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  1. Hypochlorite Oxidation of Select Androgenic Steroids

    EPA Science Inventory

    Steroid hormones are vital for regulation of various biological functions including sexual development. Elevated concentrations of natural and synthetic androgenic steroids have been shown to adversely affect normal development in indigenous aqueous species. Androgens and their s...

  2. Steroids

    MedlinePlus

    ... Got Homework? Here's Help White House Lunch Recipes Steroids KidsHealth > For Kids > Steroids Print A A A ... a good idea to avoid them. What Are Steroids? "Steroids" has more than one meaning. Your body ...

  3. Complications of intraoperative epidural steroid use in lumbar discectomy: a systematic review and meta-analysis.

    PubMed

    Akinduro, Oluwaseun O; Miller, Brandon A; Haussen, Diogo C; Pradilla, Gustavo; Ahmad, Faiz U

    2015-10-01

    OBJECT The authors' aim in this paper was to review the intraoperative use of epidural steroids in lumbar discectomy surgery with a focus on surgical complications. METHODS A comprehensive literature search was done using PubMed, MEDLINE, and the Cochrane Central Registry of Controlled Trials. Relevant papers were retrieved and analyzed. The authors performed a meta-analysis of all available data. Search terms included epidural, steroids, discectomy, lumbar disc surgery, herniated lumbar disc, methylprednisolone, and perioperative.The primary outcome was surgical complications such as wound infection or need for reoperation. Secondary outcomes were pain and postoperative narcotic usage. RESULTS Sixteen trials and 1 retrospective study (a total of 1933 patients) were eligible for inclusion in this study. In all studies, steroids were added epidurally over the nerve root before closure in cases, and control patients underwent discectomy alone. The mean age (42.7 years vs 42.4 years; RR 0.30 [95% CI -0.30 to 0.90], p = 0.32), overall complication rates (2.69% vs 1.18%; RR 1.94 [95% CI 0.72-5.26], p = 0.19), and infectious complication rates (0.94% vs 0.08%; RR 4.58 [95% CI 0.75-27.95], p = 0.10) were similar between the steroid group and control group, respectively. CONCLUSIONS There is good evidence that epidural steroids can decrease pain in the short term and decrease the usage of postoperative narcotics after lumbar spinal surgery for degenerative spinal disease. The authors' results demonstrate a trend toward increased infection with epidural steroid use, but there was not a statistically significant difference. More studies are needed to validate the long-term risk/benefit ratio of epidural steroids in lumbar discectomy. PMID:26424336

  4. Complications of intraoperative epidural steroid use in lumbar discectomy: a systematic review and meta-analysis.

    PubMed

    Akinduro, Oluwaseun O; Miller, Brandon A; Haussen, Diogo C; Pradilla, Gustavo; Ahmad, Faiz U

    2015-10-01

    OBJECT The authors' aim in this paper was to review the intraoperative use of epidural steroids in lumbar discectomy surgery with a focus on surgical complications. METHODS A comprehensive literature search was done using PubMed, MEDLINE, and the Cochrane Central Registry of Controlled Trials. Relevant papers were retrieved and analyzed. The authors performed a meta-analysis of all available data. Search terms included epidural, steroids, discectomy, lumbar disc surgery, herniated lumbar disc, methylprednisolone, and perioperative.The primary outcome was surgical complications such as wound infection or need for reoperation. Secondary outcomes were pain and postoperative narcotic usage. RESULTS Sixteen trials and 1 retrospective study (a total of 1933 patients) were eligible for inclusion in this study. In all studies, steroids were added epidurally over the nerve root before closure in cases, and control patients underwent discectomy alone. The mean age (42.7 years vs 42.4 years; RR 0.30 [95% CI -0.30 to 0.90], p = 0.32), overall complication rates (2.69% vs 1.18%; RR 1.94 [95% CI 0.72-5.26], p = 0.19), and infectious complication rates (0.94% vs 0.08%; RR 4.58 [95% CI 0.75-27.95], p = 0.10) were similar between the steroid group and control group, respectively. CONCLUSIONS There is good evidence that epidural steroids can decrease pain in the short term and decrease the usage of postoperative narcotics after lumbar spinal surgery for degenerative spinal disease. The authors' results demonstrate a trend toward increased infection with epidural steroid use, but there was not a statistically significant difference. More studies are needed to validate the long-term risk/benefit ratio of epidural steroids in lumbar discectomy.

  5. Complications of selective laser trabeculoplasty: a review

    PubMed Central

    Song, Julia

    2016-01-01

    Selective laser trabeculoplasty is a laser treatment to treat glaucoma. It was initially indicated for open-angle glaucoma but has been proven to be efficacious for various types of glaucoma. This review article summarizes the few rare complications that can be seen with selective laser trabeculoplasty. It also makes recommendations on how to avoid these problems and how to treat patients when these rare complications arise. PMID:26834456

  6. Synthetic anabolic agents: steroids and nonsteroidal selective androgen receptor modulators.

    PubMed

    Thevis, Mario; Schänzer, Wilhelm

    2010-01-01

    The central role of testosterone in the development of male characteristics, as well as its beneficial effects on physical performance and muscle growth, has led to the search for synthetic alternatives with improved pharmacological profiles. Hundreds of steroidal analogs have been prepared with a superior oral bioavailability, which should also possess reduced undesirable effects. However, only a few entered the pharmaceutical market due to severe toxicological incidences that were mainly attributed to the lack of tissue selectivity. Prominent representatives of anabolic-androgenic steroids (AAS) are for instance methyltestosterone, metandienone and stanozolol, which are discussed as model compounds with regard to general pharmacological aspects of synthetic AAS. Recently, nonsteroidal alternatives to AAS have been developed that selectively activate the androgen receptor in either muscle tissue or bones. These so-called selective androgen receptor modulators (SARMs) are currently undergoing late clinical trials (IIb) and will be prohibited by the World Anti-Doping Agency from January 2008. Their entirely synthetic structures are barely related to steroids, but particular functional groups allow for the tissue-selective activation or inhibition of androgen receptors and, thus, the stimulation of muscle growth without the risk of severe undesirable effects commonly observed in steroid replacement therapies. Hence, these compounds possess a high potential for misuse in sports and will be the subject of future doping control assays.

  7. Retention of selected steroids on a silt-loam soil.

    PubMed

    Gineys, Nathalie; Giroud, Barbara; Gineys, Mickael; Vulliet, Emmanuelle

    2012-01-01

    This study used batch-equilibrium techniques to evaluate the soil sorption and desorption of target steroids, representative of the estrogen, androgen, progestogen and corticosteroid families. The sorption kinetics exhibited an immediate rapid sorption followed by a slow process with a duration dependent on soil particle size. Adsorption and desorption isotherms could be described by the Freundlich equation, in a non-linear form (1/n < 1). High organic carbon-water partitioning coefficient (K(OC)) values indicate that a large mass fraction of the hormones will be associated with the sorbed phase. As a result of the poor linear correlation between log K(OC) and log K(OW) (octanol-water partition coefficient), it could be assumed that both hydrophobic and hydrogen bonding interactions contribute to the sorption mechanisms of the selected steroids. A hysteresis phenomenon was observed, varying with particle size, indicating strong irreversible interactions between some steroids and soil.

  8. Steroids

    NASA Astrophysics Data System (ADS)

    Frey, Felix J.; Frey, Brigitte M.; Benet, Leslie Z.

    If a radioimmunoassay, a protein binding method, or a colorimetric assay for the assessment of a steroid level is replaced by high performance liquid chromatography (HPLC), the cost for the determination of a steroid level increases at least initially because one must acquire the new HPLC equipment. Therefore, if an older method provides the same results as the new, "advanced" HPLC method, the only advantage resulting from the introduction of a high performance chromatographic assay is that gained by the manufacturer in terms of greater sales. Thus, justification for the assessment of steroids by HPLC is only obtained if the quality and/or quantity of information gained is significantly increased as compared to that provided by the conventional methods. But this evidential relation, that more and better information justifies a higher price in any case, is no longer true in health care, with the birth some years ago of the categoric imperative for the reduction of costs in the medical sector. That is, each new technology introduced for health maintenance should demonstrate at least a stabilizing impact on total medical expenditures. Therefore, after reviewing the presently available HPLC methods for the clinically important steroids, we will consider whether HPLC analyses for these steroids can be recommended without violating this vox populi.

  9. The role of endogenous cardiotonic steroids in pathogenesis of cardiovascular and renal complications of arterial hypertension.

    PubMed

    Paczula, Aneta; Więcek, Andrzej; Piecha, Grzegorz

    2016-01-01

    Endogenous cardiotonic steroids (CTS), also called digitalis-like factors, are a group of steroid hormones linking high salt intake and elevated blood pressure and in part responsible for target organ damage in arterial hypertension. CTS act primarily through their ability to inhibit the ubiquitous transport enzyme sodium-potassium adenosine triphosphatase (Na⁺/K⁺-ATPase). A portion of Na⁺/K⁺-ATPase does not seem to actively "pump" sodium and potassium but is closely associated with other key signaling proteins. Plasma concentration and urine excretion of CTS are increased in experimental models with volume expansion and on a high salt diet. Elevated plasma concentration of marinobufagenin has been shown in volume-expanded states such as essential hypertension, primary aldosteronism, chronic renal failure, congestive heart failure and pregnancy. In experimental models marinobufagenin induces heart and kidney fibrosis to the same extent as observed in uremia. Neutralization of marinobufagenin with antibodies prevents such heart remodeling. Expanding our understanding of this new class of hormones may lead to development of novel and effective therapeutic strategies in hypertensive patients with renal and cardiovascular complications. PMID:27117099

  10. The role of endogenous cardiotonic steroids in pathogenesis of cardiovascular and renal complications of arterial hypertension.

    PubMed

    Paczula, Aneta; Więcek, Andrzej; Piecha, Grzegorz

    2016-03-18

    Endogenous cardiotonic steroids (CTS), also called digitalis-like factors, are a group of steroid hormones linking high salt intake and elevated blood pressure and in part responsible for target organ damage in arterial hypertension. CTS act primarily through their ability to inhibit the ubiquitous transport enzyme sodium-potassium adenosine triphosphatase (Na⁺/K⁺-ATPase). A portion of Na⁺/K⁺-ATPase does not seem to actively "pump" sodium and potassium but is closely associated with other key signaling proteins. Plasma concentration and urine excretion of CTS are increased in experimental models with volume expansion and on a high salt diet. Elevated plasma concentration of marinobufagenin has been shown in volume-expanded states such as essential hypertension, primary aldosteronism, chronic renal failure, congestive heart failure and pregnancy. In experimental models marinobufagenin induces heart and kidney fibrosis to the same extent as observed in uremia. Neutralization of marinobufagenin with antibodies prevents such heart remodeling. Expanding our understanding of this new class of hormones may lead to development of novel and effective therapeutic strategies in hypertensive patients with renal and cardiovascular complications.

  11. Selecting a Principal: Keep It Complicated!

    ERIC Educational Resources Information Center

    Naso, Paul A.

    2011-01-01

    When searching for a new principal, many search committees tend to use the lists of competencies published in the literature and provided by state departments of education as if they were checklists. Instead, they should focus on more complicated competencies, such as acumen, judgment, and ability to manage the dilemmas of practice.

  12. Mycobacterium fortuitum skin infection as a complication of anabolic steroids: a rare case report

    PubMed Central

    Parampalli, U; Hettiarachchi, G; Ahmed, I

    2013-01-01

    Mycobacterium fortuitum is a rare cause of recurrent skin abscesses in an immunocompetent person. We report the case of a 37-year-old man presenting with multiple recurrent non-healing skin abscesses. Culture of the abscess wall yielded growth of M fortuitum. In our case, we highlight the association of anabolic steroids with non-tuberculous mycobacterial skin abscesses that fail to resolve despite repeated drainage. PMID:23317715

  13. Mycobacterium fortuitum skin infection as a complication of anabolic steroids: a rare case report.

    PubMed

    Pai, R; Parampalli, U; Hettiarachchi, G; Ahmed, I

    2013-01-01

    Mycobacterium fortuitum is a rare cause of recurrent skin abscesses in an immunocompetent person. We report the case of a 37-year-old man presenting with multiple recurrent non-healing skin abscesses. Culture of the abscess wall yielded growth of M fortuitum. In our case, we highlight the association of anabolic steroids with non-tuberculous mycobacterial skin abscesses that fail to resolve despite repeated drainage.

  14. Preoperative steroid use and the incidence of perioperative complications in patients undergoing craniotomy for definitive resection of a malignant brain tumor.

    PubMed

    Alan, Nima; Seicean, Andreea; Seicean, Sinziana; Neuhauser, Duncan; Benzel, Edward C; Weil, Robert J

    2015-09-01

    We studied the impact of preoperative steroids on 30 day morbidity and mortality of craniotomy for definitive resection of malignant brain tumors. Glucocorticoids are used to treat peritumoral edema in patients with malignant brain tumors, however, prolonged (⩾ 10 days) use of preoperative steroids as a risk factor for perioperative complications following resection of brain tumors has not been studied comprehensively. Therefore, we identified 4407 patients who underwent craniotomy to resect a malignant brain tumor between 2007 and 2012, who were reported in the National Surgical Quality Improvement Program, a prospectively collected clinical database. Metastatic brain tumors constituted 37.5% (n=1611) and primary malignant gliomas 62.5% (n=2796) of the study population. We used logistic regression to assess the association between preoperative steroid use and perioperative complications before and after 1:1 propensity score matching. Patients who received steroids constituted 22.8% of the population (n=1009). In the unmatched cohort, steroid use was associated with decreased length of hospitalization (odds ratio [OR] 0.7; 95% confidence interval [CI] 0.6-0.8), however, the risk for readmission (OR 1.5; 95% CI 1.2-1.8) was increased. In the propensity score matched cohort (n=465), steroid use was not statistically associated with any adverse outcomes. Patients who received steroids were less likely to stay hospitalized for a protracted period of time, but were more likely to be readmitted after discharge following craniotomy. As an independent risk factor, preoperative steroid use was not associated with any observed perioperative complications. The findings of this study suggest that preoperative steroids do not independently compromise the short term outcome of craniotomy for resection of malignant brain tumors.

  15. Severe viral hepatitis in a patient with chronic lymphocytic leukemia (CLL) complicated with autoimmune hemolytic anemia (AIHA), treated with steroids.

    PubMed

    Orvain, Corentin; Ducancelle, Alexandra; Eymerit-Morin, Caroline; Rousselet, Marie-Christine; Oberti, Frederic; Hunault-Berger, Mathilde; Tanguy-Schmidt, Aline

    2015-01-01

    Infectious complications are a major cause of morbidity and mortality in patients with chronic lymphocytic leukemia (CLL) due to impaired immunity secondary to the disease itself and to the immunosuppressive therapies administered to these patients. We report a 78-year-old woman with CLL who was treated with steroids for autoimmune hemolytic anemia (AIHA). A few weeks later, she was admitted for severe acute hepatitis with disseminated intravascular coagulation (DIC). Despite the symptomatic treatment of DIC, standard reanimation and probabilistic antibiotics, the patient died within 24h with severe hepatic failure. Autopsy was in favor of a disseminated viral infection with esophageal, hepatic and pulmonary cytopathologic lesions with acidophilic intranuclear inclusions suggestive of herpes virus, even though HSV 1 and 2, CMV and HHV6 PCRs were negative. This case of severe viral hepatitis with esophagitis occurring three weeks after the introduction of high-dose steroid treatment for AIHA in a CLL patient calls for anti-herpetic prophylaxis in such patients, immunodepressed by their diseases and the treatment they receive.

  16. Selective steroid oxyfunctionalisation by CYP154C5, a bacterial cytochrome P450

    PubMed Central

    2013-01-01

    Background Cytochrome P450 monooxygenases – able to regio- and stereoselectively hydroxylate non-activated carbon atoms – are important enzymes for the synthesis of valuable intermediates in the production of steroid hormones in the pharmaceutical industry. However, up to now only a few bacterial enzymes able to hydroxylate steroids have been reported. CYP154C5 from Nocardia farcinica IFM 10152, a bacterial P450 monooxygenase, was previously shown to convert testosterone to 16α-hydroxytestosterone. Since the hydroxylation at 16α-position is of special interest for the pharmaceutical industry, we have studied this enzyme in more detail to investigate its activity and selectivity in bioconversions of further steroids. Results CYP154C5 was coexpressed in Escherichia coli together with putidaredoxin and putidaredoxin reductase from Pseudomonas putida as redox partners for electron transfer and applied in bioconversions of various pregnanes and androstanes [pregnenolone (1), dehydroepiandrosterone (2), progesterone (3), androstenedione (4), testosterone (5) and nandrolone (6)]. Structure elucidation of the formed products revealed an exclusive regio- and stereoselectivity of CYP154C5, always yielding the corresponding 16α-hydroxylated steroids. Application of whole cells expressing the three components, P450, Pdx and PdR, in steroid biotransformations resulted in significantly higher conversions and total turnover numbers (TTN) compared to reactions using cell-free extracts. Additionally, considerably higher substrate loads (up to 15 mM) were tolerated by the whole-cell system. Furthermore, turnover numbers (TON) were determined for the six different steroids using whole cells. Thus, testosterone was found to be the worst substrate with a TON of only 0.8 μmol substrate consumed min-1 μmol-1 CYP154C5, while progesterone and pregnenolone were converted the fastest resulting in TON of 3.3 μmol substrate consumed min-1 μmol-1 CYP154C5. Conclusion CYP154C5

  17. [Myoanabolic steroids and selective androgen receptor modulators: mechanism of action and perspectives].

    PubMed

    Tóth, Miklós

    2009-11-01

    Interest in anabolic steroids has been renewed in the last decade with the discovery of tissue-selective androgen receptor modulators exhibiting high myotropic and small androgenic activity. An explanation put forward by us in 1982 for the mechanism of the preferential myotropic effect of nandrolone (19-nortestosterone) exploits the fundamental difference between the 5alpha-reductase concentrations in skeletal muscle and androgenic target tissue. In androgenic tissue, testosterone is converted to the more potent 5alpha-dihydrotestosterone whereas nandrolone is converted to a less potent derivative. As 5alpha-reduction is negligible in skeletal muscle, this explains why nandrolone shows a greater myotropic to androgenic ratio when compared with testosterone. Anabolic steroids that do not undergo 5alpha-reduction exert myotropic-androgenic dissociation because their effect in androgenic tissues is not amplified by 5alpha-reduction. Tissue selectivity by receptor modulators may be achieved by inducing specific conformational changes of the androgen receptor that affect its interaction with transcriptional coregulators. Anabolic activity is mediated by the stimulation of ribosomal RNA synthesis therefore regulation of this synthesis by anabolic steroids would deserve detailed studies.

  18. Complications of patient selection: recognizing the difficult patient.

    PubMed

    Goode, Richard L

    2013-11-01

    This article reviews some basic principles of patient selection for facial plastic surgery. There are patients who are not good candidates, independent of the deformity and the ability of the surgeon. Reasons include subtle and not so subtle psychiatric disorders, unrealistic expectations, lack of communication despite multiple visits, and litigious patients. Complications or suboptimal results are not well handled in these patients and often produce an uncomfortable experience for the surgeon and staff in the postoperative period. These patients are best avoided or should be provided a much longer evaluation period prior to any surgery.

  19. Cross-Sectional Study for Prevalence of Non-Steroidal Anti-Inflammatory Drug-Induced Gastrointestinal, Cardiac and Renal Complications in India: Interim Report

    PubMed Central

    Chatterjee, Suparna; Dureja, Gur Prasad; Kadhe, Ganesh; Mane, Amey; Phansalkar, Abhay A.; Sawant, Sandesh; Kapatkar, Vaibhavi

    2015-01-01

    Background Non-steroidal anti-inflammatory drugs (NSAIDs) are the most common therapeutic products used for the management of inflammation and pain. However, their use is associated with gastrointestinal (GI), cardiovascular and renal complications. Although prevalence data regarding NSAID-induced complications are available worldwide, but none of the study has assessed the prevalence of GI, cardiac and renal complications in India. This study aimed to assess the point prevalence of GI, cardiac and renal complications associated with the use of NSAIDs in India. The study also aimed to evaluate the association between the risk factors and GI, renal and cardiac complications in patients using NSAIDs. Methods This prospective, cross-sectional, multi-centric study was conducted in eight medical colleges across India (North, East, West, South and Central India). Data related to GI complications including gastric, duodenal and gastroduodenal erosions/ulcers/gastritis, renal complications including acute and chronic renal failure or cardiac complications including acute coronary syndrome (ACS), acute myocardial infarction (AMI) and cardiac failure, were collected from patients. Results The cut-off date for interim data analysis was July 7, 2014. A total of 2,140 patients out of 3,600 were enrolled from eight centers at the time of interim analysis. The NSAID-associated point prevalence of GI complications was 30.08%; cardiac complication was 42.77%; and renal complication was 27.88%. Conclusions Results of the present interim analysis show that the prevalence of GI, cardiac and renal complications among patients is high due to exaggerated usage; however, the final analysis would provide the overall prevalence of these complications.

  20. Binding Mode and Selectivity of Steroids towards Glucose-6-phosphate Dehydrogenase from the Pathogen Trypanosoma cruzi.

    PubMed

    Ortiz, Cecilia; Moraca, Francesca; Medeiros, Andrea; Botta, Maurizio; Hamilton, Niall; Comini, Marcelo A

    2016-01-01

    Glucose-6-phosphate dehydrogenase (G6PDH) plays a housekeeping role in cell metabolism by generating reducing power (NADPH) and fueling the production of nucleotide precursors (ribose-5-phosphate). Based on its indispensability for pathogenic parasites from the genus Trypanosoma, G6PDH is considered a drug target candidate. Several steroid-like scaffolds were previously reported to target the activity of G6PDH. Epiandrosterone (EA) is an uncompetitive inhibitor of trypanosomal G6PDH for which its binding site to the enzyme remains unknown. Molecular simulation studies with the structure of Trypanosoma cruzi G6PDH revealed that EA binds in a pocket close to the G6P binding-site and protrudes into the active site blocking the interaction between substrates and hence catalysis. Site directed mutagenesis revealed the important steroid-stabilizing effect of residues (L80, K83 and K84) located on helix α-1 of T. cruzi G6PDH. The higher affinity and potency of 16α-Br EA by T. cruzi G6PDH is explained by the formation of a halogen bond with the hydrogen from the terminal amide of the NADP+-nicotinamide. At variance with the human enzyme, the inclusion of a 21-hydroxypregnane-20-one moiety to a 3β-substituted steroid is detrimental for T. cruzi G6PDH inhibition. The species-specificity of certain steroid derivatives towards the parasite G6PDH and the corresponding biochemically validated binding models disclosed in this work may prove valuable for the development of selective inhibitors against the pathogen's enzyme. PMID:26999093

  1. Molecularly imprinted polymer applied to the selective isolation of urinary steroid hormones: an efficient tool in the control of natural steroid hormones abuse in cattle.

    PubMed

    Doué, Mickael; Bichon, Emmanuelle; Dervilly-Pinel, Gaud; Pichon, Valérie; Chapuis-Hugon, Florence; Lesellier, Eric; West, Caroline; Monteau, Fabrice; Le Bizec, Bruno

    2012-12-28

    The use of anabolic substances to promote growth in livestock is prohibited within the European Union as laid down in Directive 96/22/EC. Nowadays, efficient methods such as steroid profiling or isotopic deviation measurements allow to control natural steroid hormones abuse. In both cases, urine is often selected as the most relevant matrix and, due to its relatively high content of potential interferents, its preparation before analysis is considered as a key step. In this context, the use of a selective sorbent such as molecularly imprinted polymer (MIP) was investigated. A MIP was synthesized based on 17β-estradiol, methacrylic acid and acetonitrile as template, monomer and porogen, respectively. Two approaches were then tested for non-conjugated (aglycons and glucuronides deconjugated) steroid purification: (i) molecularly imprinted solid phase extraction (MISPE) and (ii) semi-preparative supercritical fluid chromatography with a commercial MIP as stationary phase (SFC-MIP). Parameters for both approaches were optimized based on the main bovine metabolites of testosterone, estradiol, nandrolone and boldenone. The MISPE protocol developed for screening purposes allowed satisfactory recoveries (upper 65% for the 12 target steroids) with sufficient purification for gas chromatography-mass spectrometry (GC-MS) analysis. For confirmatory purposes, the use of isotopic ratio mass spectrometry (IRMS) requires a higher degree of purity of the target compounds, which can be reached by the SFC-MIP protocol with three steps less compared to the official and current method. Purity, concentration and absence of isotopic fractionation of target steroids extracted from urine of treated cattle (treated with testosterone, estradiol, androstenedione, and boldenone) allowed the measurement of (13)C/(12)C isotopic ratios of corresponding metabolites and endogenous reference compounds (ERC) and proved the relevance of the strategy.

  2. Preparation and application of solid-phase microextraction fiber based on molecularly imprinted polymer for determination of anabolic steroids in complicated samples.

    PubMed

    Qiu, Lijun; Liu, Wei; Huang, Min; Zhang, Lan

    2010-11-26

    A relatively selective, chemically and physically robust SPME fiber was developed in a simple way with testosterone-imprinted polymer, and then directly coupled with gas chromatography-mass spectrometry (GC-MS) for selective extraction and analysis of anabolic steroids. The factors influencing polymerization (i.e., cross-linker, polymerization solvent, polymerization time) were optimized in detail and the polymer was characterized by scanning electron microscope, infrared spectrometer and thermogravimetric analyzer. Furthermore, the extraction performance of the MIP-coated SPME fibers such as extraction ability and selectivity was evaluated. Moreover, the interaction mode between target analytes and fiber coating was deducted. Finally, the method for extraction and determination of androsterone, stanolone, androstenedione and methyltestosterone by the homemade MIP-coated SPME fibers with GC-MS was obtained. It was applied to the simultaneous analysis of four anabolic steroids in the spiked human urine with the satisfactory recoveries.

  3. Discovery of a sulfamate-based steroid sulfatase inhibitor with intrinsic selective estrogen receptor modulator properties.

    PubMed

    Ouellet, Charles; Maltais, René; Ouellet, Étienne; Barbeau, Xavier; Lagüe, Patrick; Poirier, Donald

    2016-08-25

    Steroid sulfatase (STS), the enzyme which converts inactive sulfated steroid precursors into active hormones, is a promising therapeutic target for the treatment of estrogen-sensitive breast cancer. We report herein the synthesis and in vitro study of dual-action STS inhibitors with selective estrogen-receptor modulator (SERM) effects. A library of tetrahydroisoquinoline-N-substituted derivatives (phenolic compounds) was synthesized by solid-phase chemistry and tested on estrogen-sensitive breast cancer T-47D cells. Three phenolic compounds devoid of estrogenic activity and toxicity emerged from this screening. Their sulfamate analogs were then synthesized, tested in STS-transfected HEK-293 cells, and found to be potent inhibitors of the enzyme (IC50 of 3.9, 8.9, and 16.6 nM). When tested in T-47D cells they showed no estrogenic activity and produced a moderate antiestrogenic activity. The compounds were further tested on osteoblast-like Saos-2 cells and found to significantly stimulate their proliferation as well as their alkaline phosphatase activity, thus suggesting a SERM activity. These results are supported by molecular docking experiments. PMID:27155470

  4. Variability in risk of gastrointestinal complications with individual non-steroidal anti-inflammatory drugs: results of a collaborative meta-analysis.

    PubMed Central

    Henry, D.; Lim, L. L.; Garcia Rodriguez, L. A.; Perez Gutthann, S.; Carson, J. L.; Griffin, M.; Savage, R.; Logan, R.; Moride, Y.; Hawkey, C.; Hill, S.; Fries, J. T.

    1996-01-01

    OBJECTIVE--To compare the relative risks of serious gastrointestinal complications reported with individual non-steroidal anti-inflammatory drugs. DESIGN--Systematic review of controlled epidemiological studies that found a relation between use of the drugs and admission to hospital for haemorrhage or perforation. SETTING--Hospital and community based case-control and cohort studies. MAIN OUTCOME MEASURES--(a) Estimated relative risks of gastrointestinal complications with use of individual drugs, exposure to ibuprofen being used as reference; (b) a ranking that best summarised the sequence of relative risks observed in the studies. RESULTS--12 studies met the inclusion criteria. 11 provided comparative data on ibuprofen and other drugs. Ibuprofen ranked lowest or equal lowest for risk in 10 of the 11 studies. Pooled relative risks calculated with exposure to ibuprofen used as reference were all significantly greater than 1.0 (interval of point estimates 1.6 to 9.2). Overall, ibuprofen was associated with the lowest relative risk, followed by diclofenac. Azapropazone, tolmetin, ketoprofen, and piroxicam ranked highest for risk and indomethacin, naproxen, sulindac, and aspirin occupied intermediate positions. Higher doses of ibuprofen were associated with relative risks similar to those with naproxen and indomethacin. CONCLUSIONS--The low risk of serious gastrointestinal complications with ibuprofen seems to be attributable mainly to the low doses of the drug used in clinical practice. In higher doses ibuprofen is associated with a similar risk to other non-steroidal anti-inflammatory drugs. Use of low risk drugs in low dosage as first line treatment would substantially reduce the morbidity and mortality due to serious gastrointestinal toxicity from these drugs. PMID:8664664

  5. Sex steroids, sexual behavior, and selection attention for erotic stimuli in women using oral contraceptives.

    PubMed

    Alexander, G M; Sherwin, B B

    1993-01-01

    The relationship between sex steroids and sexual behavior was examined in 19 oral contraceptive users. Retrospective assessment of sexual attitudes were obtained and women completed daily ratings of sexual behavior and well-being for 28 days. Plasma levels of free testosterone (T), estradiol, and progesterone were measured at weekly intervals. In addition, women performed a novel selective attention task designed to measure the strength of the tendency to be distracted by sexual stimuli. Multiple regression analyses using average sexual behavior variables as dependent variables, and hormone levels sexual attitudes and well-being as predictor variables, showed that free T was strongly and positively associated with sexual desire, sexual thoughts, and anticipation of sexual activity. A role for T in attention to sexual stimuli was also supported by the positive correlation between free T and the bias for sexual stimuli in a subgroup of women. These results are consistent with the hypothesis that T may enhance cognitive aspects of women's sexual behavior. PMID:8493300

  6. Selected examples of complications after minimally invasive treatment for urolithiasis.

    PubMed

    Różański, Waldemar; Klimek, Leszek; Lipiński, Marek; Kliś, Rafał

    2012-01-01

    In recent years urologists have concentrated on the intense introduction of minimally invasive methods for the treatment of urinary tract diseases with major progress noted in the treatment of urolithiasis. Nowadays extracorporeal shockwave lithotripsy (ESWL), percutaneous nephrolithotomy (PCNL), and ureteroscopic lithotripsy (URSL) are widely used in the treatment of urinary tract lithiasis. The aim of this study is to present examples of urinary tract lithiasis as the complication after minimally invasive methods used in the treatment of urolithiasis. One should remember that even minimally invasive medical procedures using the instruments retained in long-term contact with urine may be the cause of incrustation and stone formation.

  7. Selective androgen receptor modulator activity of a steroidal antiandrogen TSAA-291 and its cofactor recruitment profile.

    PubMed

    Hikichi, Yukiko; Yamaoka, Masuo; Kusaka, Masami; Hara, Takahito

    2015-10-15

    Selective androgen receptor modulators (SARMs) specifically bind to the androgen receptor and exert agonistic or antagonistic effects on target organs. In this study, we investigated the SARM activity of TSAA-291, previously known as a steroidal antiandrogen, in mice because TSAA-291 was found to possess partial androgen receptor agonist activity in reporter assays. In addition, to clarify the mechanism underlying its tissue selectivity, we performed comprehensive cofactor recruitment analysis of androgen receptor using TSAA-291 and dihydrotestosterone (DHT), an endogenous androgen. The androgen receptor agonistic activity of TSAA-291 was more obvious in reporter assays using skeletal muscle cells than in those using prostate cells. In castrated mice, TSAA-291 increased the weight of the levator ani muscle without increasing the weight of the prostate and seminal vesicle. Comprehensive cofactor recruitment analysis via mammalian two-hybrid methods revealed that among a total of 112 cofactors, 12 cofactors including the protein inhibitor of activated STAT 1 (PIAS1) were differently recruited to androgen receptor in the presence of TSAA-291 and DHT. Prostate displayed higher PIAS1 expression than skeletal muscle. Forced expression of the PIAS1 augmented the transcriptional activity of the androgen receptor, and silencing of PIAS1 by siRNAs suppressed the secretion of prostate-specific antigen, an androgen responsive marker. Our results demonstrate that TSAA-291 has SARM activity and suggest that TSAA-291 may induce different conformational changes of the androgen receptor and recruitment profiles of cofactors such as PIAS1, compared with DHT, to exert tissue-specific activity.

  8. Selective non-steroidal inhibitors of 5 alpha-reductase type 1.

    PubMed

    Occhiato, Ernesto G; Guarna, Antonio; Danza, Giovanna; Serio, Mario

    2004-01-01

    The enzyme 5 alpha-reductase (5 alpha R) catalyses the reduction of testosterone (T) into the more potent androgen dihydrotestosterone (DHT). The abnormal production of DHT is associated to pathologies of the main target organs of this hormone: the prostate and the skin. Benign prostatic hyperplasia (BPH), prostate cancer, acne, androgenetic alopecia in men, and hirsutism in women appear related to the DHT production. Two isozymes of 5 alpha-reductase have been cloned, expressed and characterized (5 alpha R-1 and 5 alpha R-2). They share a poor homology, have different chromosomal localization, enzyme kinetic parameters, and tissue expression patterns. Since 5 alpha R-1 and 5 alpha R-2 are differently distributed in the androgen target organs, a different involvement of the two isozymes in the pathogenesis of prostate and skin disorders can be hypothesized. High interest has been paid to the synthesis of inhibitors of 5 alpha-reductase for the treatment of DHT related pathologies, and the selective inhibition of any single isozyme represents a great challenge for medical and pharmaceutical research in order to have more specific drugs. At present, no 5 alpha R-1 inhibitor is marketed for the treatment of 5 alpha R-1 related pathologies but pharmaceutical research is very active in this field. This paper will review the major classes of 5 alpha R inhibitors focusing in particular on non-steroidal inhibitors and on structural features that enhance the selectivity versus the type 1 isozyme. Biological tests to assess the inhibitory activity towards the two 5 alpha R isozymes will be also discussed. PMID:15026079

  9. Inhaled Steroids

    MedlinePlus

    ... potential for side effects than steroid pills or syrups. There have been concerns regarding the possibility of ... treatment. Learn about oral steroids (steroid pills and syrups), and more about steroid side effects. What are ...

  10. Selected luminal mucosal complications of adult celiac disease.

    PubMed

    Freeman, Hugh J

    2009-01-01

    Celiac disease is a gluten-dependent intestinal disorder that appears to be associated with several clinical conditions. Some involve the luminal mucosa of the stomach and intestinal tract and may, occasionally, complicate the course of celiac disease. Collagenous colitis has been associated with celiac disease and may lead to chronic diarrhea. Conversely, some of these clinical disorders that involve the luminal mucosa of the stomach and intestine may represent the initial clinical presentation of celiac disease. These disorders should be considered in patients with celiac disease who develop recurrent or refractory symptoms despite adherence to a strict gluten-free diet. Detection of collagenous disorders that affect the luminal mucosa of the stomach or intestinal tract may result in recognition of underlying celiac disease. PMID:21694821

  11. Promising Tools in Prostate Cancer Research: Selective Non-Steroidal Cytochrome P450 17A1 Inhibitors

    PubMed Central

    Bonomo, Silvia; Hansen, Cecilie H.; Petrunak, Elyse M.; Scott, Emily E.; Styrishave, Bjarne; Jørgensen, Flemming Steen; Olsen, Lars

    2016-01-01

    Cytochrome P450 17A1 (CYP17A1) is an important target in the treatment of prostate cancer because it produces androgens required for tumour growth. The FDA has approved only one CYP17A1 inhibitor, abiraterone, which contains a steroidal scaffold similar to the endogenous CYP17A1 substrates. Abiraterone is structurally similar to the substrates of other cytochrome P450 enzymes involved in steroidogenesis, and interference can pose a liability in terms of side effects. Using non-steroidal scaffolds is expected to enable the design of compounds that interact more selectively with CYP17A1. Therefore, we combined a structure-based virtual screening approach with density functional theory (DFT) calculations to suggest non-steroidal compounds selective for CYP17A1. In vitro assays demonstrated that two such compounds selectively inhibited CYP17A1 17α-hydroxylase and 17,20-lyase activities with IC50 values in the nanomolar range, without affinity for the major drug-metabolizing CYP2D6 and CYP3A4 enzymes and CYP21A2, with the latter result confirmed in human H295R cells. PMID:27406023

  12. Promising Tools in Prostate Cancer Research: Selective Non-Steroidal Cytochrome P450 17A1 Inhibitors.

    PubMed

    Bonomo, Silvia; Hansen, Cecilie H; Petrunak, Elyse M; Scott, Emily E; Styrishave, Bjarne; Jørgensen, Flemming Steen; Olsen, Lars

    2016-01-01

    Cytochrome P450 17A1 (CYP17A1) is an important target in the treatment of prostate cancer because it produces androgens required for tumour growth. The FDA has approved only one CYP17A1 inhibitor, abiraterone, which contains a steroidal scaffold similar to the endogenous CYP17A1 substrates. Abiraterone is structurally similar to the substrates of other cytochrome P450 enzymes involved in steroidogenesis, and interference can pose a liability in terms of side effects. Using non-steroidal scaffolds is expected to enable the design of compounds that interact more selectively with CYP17A1. Therefore, we combined a structure-based virtual screening approach with density functional theory (DFT) calculations to suggest non-steroidal compounds selective for CYP17A1. In vitro assays demonstrated that two such compounds selectively inhibited CYP17A1 17α-hydroxylase and 17,20-lyase activities with IC50 values in the nanomolar range, without affinity for the major drug-metabolizing CYP2D6 and CYP3A4 enzymes and CYP21A2, with the latter result confirmed in human H295R cells. PMID:27406023

  13. Holmium laser use in the treatment of selected dry eye syndrome complications

    NASA Astrophysics Data System (ADS)

    Kecik, Dariusz; Kecik, Tadeusz; Kasprzak, Jan; Kecik, Mariusz

    1996-03-01

    The authors present initial results of treatment selected complications of dry eye syndrome with holmium laser. The lacrimal puncta obliteration and coagulation of the corneal ulcer surface were done.

  14. Design and synthesis of polyhydroxy steroids as selective inhibitors against AKR1B10 and molecular docking.

    PubMed

    Chen, Wenli; Chen, Xinying; Zhou, Shujia; Zhang, Hong; Wang, Ling; Xu, Jun; Hu, Xiaopeng; Yin, Wei; Yan, Guangmei; Zhang, Jingxia

    2016-06-01

    AKR1B10 is a member of the human aldo-keto reductase superfamily which is highly expressed in several types of cancers, and has been regarded as a promising cancer therapeutic target. In this paper, a series of polyhydroxy steroids were designed and synthesized to selectively inhibit AKR1B10 activity. The most selective compound, novel compound 6, has an IC50 of 0.83±0.07μM and a selectivity of more than 120-fold for AKR1B10/AKR1B1. Structure-activity relation analyses indicate that hydroxyl at C-19 can significantly improve the selective inhibition of AKR1B10. The binding mode of AKR1B10 and its inhibitors were studied.

  15. Synthesis of new molecular probes for investigation of steroid biosynthesis induced by selective interaction with peripheral type benzodiazepine receptors (PBR).

    PubMed

    Campiani, Giuseppe; Ramunno, Anna; Fiorini, Isabella; Nacci, Vito; Morelli, Elena; Novellino, Ettore; Goegan, Mara; Mennini, Tiziana; Sullivan, Stephen; Zisterer, Daniela M; Williams, Clive D

    2002-09-12

    In the present study, we have synthesized and tested novel pyridopyrrolo- and pyrrolobenzoxazepine derivatives, as novel and selective peripheral type benzodiazepine receptor (PBR) ligands, and their ability to modulate steroid biosynthesis has been investigated. A subset of new ligands bind the PBR (rat brain and testis) with picomolar affinity, representing the most potent ligands that have been identified to date, and elicited effects on endogenous rate of steroidogenesis in MA10 Leydig cells, having similar potency and effect as PK11195. Several compounds, differently substituted at C-7, were used as molecular yardsticks to probe the spatial dimension of the lipophilic pocket L4 in the receptor binding site.

  16. Identification of selected in vitro generated phase-I metabolites of the steroidal selective androgen receptor modulator MK-0773 for doping control purposes.

    PubMed

    Lagojda, Andreas; Kuehne, Dirk; Krug, Oliver; Thomas, Andreas; Wigger, Tina; Karst, Uwe; Schänzer, Wilhelm; Thevis, Mario

    2016-01-01

    Research into developing anabolic agents for various therapeutic purposes has been pursued for decades. As the clinical utility of anabolic-androgenic steroids has been found to be limited because of their lack of tissue selectivity and associated off-target effects, alternative drug entities have been designed and are commonly referred to as selective androgen receptor modulators (SARMs). While most of these SARMs are of nonsteroidal structure, the drug candidate MK-0773 comprises a 4-aza-steroidal nucleus. Besides the intended therapeutic use, SARMs have been found to be illicitly distributed and misused as doping agents in sport, necessitating frequently updated doping control analytical assays. As steroidal compounds reportedly undergo considerable metabolic transformations, the phase-I metabolism of MK-0773 was simulated using human liver microsomal (HLM) preparations and electrochemical conversion. Subsequently, major metabolic products were identified and characterized employing liquid chromatography-high-resolution/high- accuracy tandem mass spectrometry with electrospray (ESI) and atmospheric pressure chemical ionization (APCI) as well as nuclear magnetic resonance (NMR) spectroscopy. MK-0773 produced numerous phase-I metabolites under the chosen in vitro incubation reactions, mostly resulting from mono- and bisoxygenation of the steroid. HLM yielded at least 10 monooxygenated species, while electrochemistry-based experiments resulted predominantly in three monohydroxylated metabolites. Elemental composition data and product ion mass spectra were generated for these analytes, ESI/APCI measurements corroborated the formation of at least two N-oxygenated metabolites, and NMR data obtained from electrochemistry-derived products supported structures suggested for three monohydroxylated compounds. Hereby, the hydroxylation of the A-ring located N- bound methyl group was found to be of particular intensity. In the absence of controlled elimination studies, the

  17. Identification of selected in vitro generated phase-I metabolites of the steroidal selective androgen receptor modulator MK-0773 for doping control purposes.

    PubMed

    Lagojda, Andreas; Kuehne, Dirk; Krug, Oliver; Thomas, Andreas; Wigger, Tina; Karst, Uwe; Schänzer, Wilhelm; Thevis, Mario

    2016-01-01

    Research into developing anabolic agents for various therapeutic purposes has been pursued for decades. As the clinical utility of anabolic-androgenic steroids has been found to be limited because of their lack of tissue selectivity and associated off-target effects, alternative drug entities have been designed and are commonly referred to as selective androgen receptor modulators (SARMs). While most of these SARMs are of nonsteroidal structure, the drug candidate MK-0773 comprises a 4-aza-steroidal nucleus. Besides the intended therapeutic use, SARMs have been found to be illicitly distributed and misused as doping agents in sport, necessitating frequently updated doping control analytical assays. As steroidal compounds reportedly undergo considerable metabolic transformations, the phase-I metabolism of MK-0773 was simulated using human liver microsomal (HLM) preparations and electrochemical conversion. Subsequently, major metabolic products were identified and characterized employing liquid chromatography-high-resolution/high- accuracy tandem mass spectrometry with electrospray (ESI) and atmospheric pressure chemical ionization (APCI) as well as nuclear magnetic resonance (NMR) spectroscopy. MK-0773 produced numerous phase-I metabolites under the chosen in vitro incubation reactions, mostly resulting from mono- and bisoxygenation of the steroid. HLM yielded at least 10 monooxygenated species, while electrochemistry-based experiments resulted predominantly in three monohydroxylated metabolites. Elemental composition data and product ion mass spectra were generated for these analytes, ESI/APCI measurements corroborated the formation of at least two N-oxygenated metabolites, and NMR data obtained from electrochemistry-derived products supported structures suggested for three monohydroxylated compounds. Hereby, the hydroxylation of the A-ring located N- bound methyl group was found to be of particular intensity. In the absence of controlled elimination studies, the

  18. Oral Steroids for Dermatitis.

    PubMed

    Fisher, Andrew D; Clarke, Jesse; Williams, Timothy K

    2015-01-01

    Contact/allergic dermatitis is frequently treated inappropriately with lower-than-recommended doses or inadequate duration of treatment with oral and intramuscular glucocorticoids. This article highlights a case of dermatitis in a Ranger Assessment and Selection Program student who was improperly treated over 2 weeks with oral steroids after being bit by Cimex lectularius, commonly known as bed bugs. The article also highlights the pitfalls of improper oral steroid dosing and provides reasoning for longer-duration oral steroid treatment.

  19. Oral Steroids for Dermatitis.

    PubMed

    Fisher, Andrew D; Clarke, Jesse; Williams, Timothy K

    2015-01-01

    Contact/allergic dermatitis is frequently treated inappropriately with lower-than-recommended doses or inadequate duration of treatment with oral and intramuscular glucocorticoids. This article highlights a case of dermatitis in a Ranger Assessment and Selection Program student who was improperly treated over 2 weeks with oral steroids after being bit by Cimex lectularius, commonly known as bed bugs. The article also highlights the pitfalls of improper oral steroid dosing and provides reasoning for longer-duration oral steroid treatment. PMID:26125159

  20. Differential inhibition of fracture healing by non-selective and cyclooxygenase-2 selective non-steroidal anti-inflammatory drugs.

    PubMed

    Gerstenfeld, Louis C; Thiede, Mark; Seibert, Karen; Mielke, Cindy; Phippard, Deborah; Svagr, Bohus; Cullinane, Dennis; Einhorn, Thomas A

    2003-07-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) specifically inhibit cyclooxygenase (COX) activity and are widely used as anti-arthritics, post-surgical analgesics, and for the relief of acute musculoskeletal pain. Recent studies suggest that non-specific NSAIDs, which inhibit both COX-1 and COX-2 isoforms, delay bone healing. The objectives of this study were 2-fold; first, to measure the relative changes in the normal expression of COX-1 and COX-2 mRNAs over a 42 day period of fracture healing and second, to compare the effects of a commonly used non-specific NSAID, ketorolac, with a COX-2 specific NSAID, Parecoxib (a pro-drug of valdecoxib), on this process. Simple, closed, transverse fractures were generated in femora of male Sprague-Dawley rats weighing approximately 450 g each. Total RNA was prepared from the calluses obtained prior to fracture and at 1, 3, 5, 7, 10, 14, 21, 35 and 42 days post-fracture and levels of COX-1 and COX-2 mRNA were measured using real time PCR. While the relative levels of COX-1 mRNA remained constant over a 21-day period, COX-2 mRNA levels showed peak expression during the first 14 days of healing and returned to basal levels by day 21. Mechanical properties of the calluses were then assessed at 21 and 35 days post-fracture in untreated animals and animals treated with either ketorolac or high or low dose parecoxib. At both 21 and 35 days after fracture, calluses in the group treated with the ketorolac showed a significant reduction in mechanical strength and stiffness when compared with controls (p<0.05). At the 21-day time point, calluses of the parecoxib treated animals showed a lower mean mechanical strength than controls, but the inhibition was not statistically significant. Based on physical analysis of the bones, 3 of 12 (25%) of the ketorolac-treated and 1 of 12 (8%) of the high dose parecoxib-treated animals showed failure to unite their fractures by 21 days, while all fractures in both groups showed union by 35 days

  1. Glucocorticoids and the non-steroidal selective glucocorticoid receptor modulator, compound A, differentially affect colon cancer-derived myofibroblasts.

    PubMed

    Drebert, Zuzanna; Bracke, Marc; Beck, Ilse M

    2015-05-01

    The glucocorticoid receptor functions as a ligand-dependent transcription factor that positively or negatively regulates the transcription of various specific target genes. Not only steroidal glucocorticoids can bind and activate the glucocorticoid receptor, but also the intensively examined non-steroidal selective glucocorticoid receptor modulators can do so, albeit with a select effector profile skewed to glucocorticoid receptor transrepression. Glucocorticoids are widely used to treat inflammatory afflictions, but also as anti-cancer therapies or adjuvants thereof. As the impact of glucocorticoids and selective glucocorticoid receptor modulators has scarcely been researched in this setting, we focused on colon cancer and its stromal environment, in particular the stromal myofibroblasts, which are known to influence cancer cells via paracrine signaling. In these myofibroblasts, the glucocorticoid dexamethasone is able to drive the glucocorticoid receptor into the nucleus and thus negatively regulates the expression of particular pro-inflammatory genes in TNFα-stimulated cells. The selective glucocorticoid receptor modulator compound A has an impaired ability to translocate GR, presumably underpinning its modest anti-inflammatory properties in these cells. Only dexamethasone, and not compound A, can upregulate the glucocorticoid receptor transactivation-dependent GILZ expression. Neither dexamethasone, nor compound A affects myofibroblast cell viability. However, compound A retards the growth of this myofibroblast cell line. Additionally, dexamethasone can inhibit the expression of Tenascin C, hepatocyte growth factor, and TGFβ, which are all factors known for their impact on colon cancer cell invasion, in a glucocorticoid receptor-dependent manner. In contrast, compound A can only slightly diminish the expression of just hepatocyte growth factor, and not tenascin C or TGFβ. Combined, our results expose new tumor microenvironment-modulating effects of

  2. Topical Steroids.

    PubMed

    Oakley, Gretchen M; Harvey, Richard J

    2016-01-01

    Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory condition with heterogeneous pathophysiology. A cornerstone of the management of this condition is the use of anti-inflammatory agents. Corticosteroids are very effective and the most commonly used, but other drugs with immunodulatory activity such as anti-IL5, doxycycline (Th2), and macrolides (anti-neutrophilic/IL8) have been shown to have efficacy. Although systemic corticosteroids have shown benefit in managing this condition, the frequency of use often required in this condition is associated with significant adverse effects. Topical corticosteroids, particularly when utilized after endoscopic sinus surgery and delivered in a high volume, high pressure manner, provide the desired anti-inflammatory effects with nearly negligible systemic absorption. Studies assessing the long-term use of second generation topical corticosteroids have demonstrated no significant effects on cortisol levels, growth rate, intraocular pressures or lens opacification, or local mucosal atrophy. Patients who often respond most favorably to corticosteroid treatment are those with a Th2-mediated, highly eosinophilic CRSwNP. However, there is a subset of patients who are steroid resistant. In the case of a predominantly neutrophilic CRSwNP, it is important to be aware that patients may respond well to the use of macrolide therapy. Additionally, the use of verapamil has shown promise in increasing steroid responsiveness in a difficult to treat group of patients with steroid resistance. Topical corticosteroids play a key role in the long term management of this complicated inflammatory condition by providing the much needed pharmacologic local control with minimal systemic adverse effects. PMID:27466854

  3. Even Incomplete Steroid Treatment Helps Preemies

    MedlinePlus

    ... medlineplus.gov/news/fullstory_161404.html Even Incomplete Steroid Treatment Helps Preemies: Study Fewer deaths, complications for ... MONDAY, Oct. 10, 2016 (HealthDay News) -- Even partial steroid treatment before birth can improve survival odds for ...

  4. [Severe hypercalcemia as a complication of intensive treatment for osteoporosis due to steroid therpay in 17-year-old girl with the nephrotic syndrome].

    PubMed

    Ksiazek, Ewelina; Majewski, Marek; Borzecka, Halina; Sikora, Przemysław; Bieniaś, Beata; Zajaczkowska, Małgorzata

    2008-01-01

    In the article, 17-year-old girl with iatrogenic severe hipercalcemia was presented. The girl was treated since the age of 12 years for steroid-sensitive minimal change disease. Due to steroid therapy osteoporosis developed and intensive treatment with active form of vitamin D and high doses of calcium was started. She was admitted to our clinic in severe general state with abdominal pain, vomiting, dehydration, muscle weakness, hypertension and mental confusion. Severe hipercalcemia with nephrocalcinosis was diagnosed. The history revealed that the girl had increased the doses of drugs intentionally. The authors emphasized the need for careful monitoring of prophylaxis and treatment for osteoporosis due to steroid therapy.

  5. Selective digital venous hypertension: A rare complication of hemodialysis arteriovenous fistula

    SciTech Connect

    Swayne, L.C.; Manstein, C.; Somers, R.; Cope, C.

    1983-04-01

    We report and document angiographically a case of selective venous hypertension, masquerading as an infection, which involved the three middle digits of the right hand in a patient with an access arteriovenous (AV) fistula. This complication arose following hemodialysis and was resolved after resection of the right radial artery at the site of AV fistula and re-anastomosis.

  6. Sequence-selective DNA recognition and enhanced cellular up-take by peptide-steroid conjugates.

    PubMed

    Ruiz García, Yara; Iyer, Abhishek; Van Lysebetten, Dorien; Pabon, Y Vladimir; Louage, Benoit; Honcharenko, Malgorzata; De Geest, Bruno G; Smith, C I Edvard; Strömberg, Roger; Madder, Annemieke

    2015-12-25

    Several GCN4 bZIP TF models have previously been designed and synthesized. However, the synthetic routes towards these constructs are typically tedious and difficult. We here describe the substitution of the Leucine zipper domain of the protein by a deoxycholic acid derivative appending the two GCN4 binding region peptides through an optimized double azide-alkyne cycloaddition click reaction. In addition to achieving sequence specific dsDNA binding, we have investigated the potential of these compounds to enter cells. Confocal microscopy and flow cytometry show the beneficial influence of the steroid on cell uptake. This unique synthetic model of the bZIP TF thus combines sequence specific dsDNA binding properties with enhanced cell-uptake. Given the unique properties of deoxycholic acid and the convergent nature of the synthesis, we believe this work represents a key achievement in the field of TF mimicry.

  7. Anabolic Steroids

    MedlinePlus

    Anabolic steroids are man-made substances related to male sex hormones. Doctors use anabolic steroids to treat some hormone problems in men, delayed ... from some diseases. Bodybuilders and athletes often use anabolic steroids to build muscles and improve athletic performance. Using ...

  8. Gonadal steroids, selective serotonin reuptake inhibitors, and mood disorders in women.

    PubMed

    Huttner, Ruby P; Shepherd, Janet E

    2003-09-01

    That gonadal steroids influence the limbic system and that they affect neurotransmitter activity is undisputed. Because of these known actions, and because ET and HT alleviate hot flushes and resultant sleep disturbances, they may improve mood and sense of well-being in healthy climacteric women. However, estrogen plus progestin did not decrease depressive symptoms in the WHI, the largest double-blind, placebo-controlled trial of hormone replacement yet performed. In addition, although several studies have suggested efficacy in this regard, neither ET nor HT has been proved to be therapeutic for major depression in perimenopausal and menopausal women. Certainly, further studies are needed on the potential of estrogen as an antidepressant. Based on current evidence, however, one cannot prescribe ET or HT as primary treatment for major depression in good conscience. When treating patients far this serious problem, one cannot rely on theory and the desire that it be borne out. As Sigmund Freud wrote: "Thus we call a belief an illusion when a wish-fulfillment is a prominent factor in its motivation, and in doing so we disregard its relation to reality, just as the illusion itself set, no store by verification". Since the initial publication of the results of the WHI, clinicians have learned to be cautious when making decisions about therapy that has not been proved in randomized controlled trials. In addition, attention has shifted away from potential global effects of ET and HT toward more specific management of each specific clinical sequela of menopause. If major depression is to be addressed in this way, SSRIs become first-line therapy, with TCAs considered second-line because of reduced tolerability. ET and HT may be added separately as appropriate, and may be helpful on an individual basis. Indeed, treatment for major depression in any person, male or female, at any age, is best chosen based on life situation and the neuropsychology of the condition, and not

  9. Tocotrienols activate the steroid and xenobiotic receptor, SXR, and selectively regulate expression of its target genes.

    PubMed

    Zhou, Changcheng; Tabb, Michelle M; Sadatrafiei, Asal; Grün, Felix; Blumberg, Bruce

    2004-10-01

    Vitamin E is an essential nutrient with antioxidant activity. Vitamin E is comprised of eight members, alpha-, beta-, gamma-, and delta-tocopherols and alpha-, beta-, gamma-, and delta-tocotrienols. All forms of vitamin E are initially metabolized by omega-oxidation, which is catalyzed by cytochrome P450 enzymes. The steroid and xenobiotic receptor (SXR) is a nuclear receptor that regulates drug clearance in the liver and intestine via induction of genes involved in drug and xenobiotic metabolism. We show here that all four tocotrienols specifically bind to and activate SXR, whereas tocopherols neither bind nor activate. Surprisingly, tocotrienols show tissue-specific induction of SXR target genes, particularly CYP3A4. Tocotrienols up-regulate expression of CYP3A4 but not UDP-glucuronosyltransferase 1A1 (UGT1A1) or multidrug resistance protein-1 (MDR1) in primary hepatocytes. In contrast, tocotrienols induce MDR1 and UGT1A1 but not CYP3A4 expression in intestinal LS180 cells. We found that nuclear receptor corepressor (NCoR) is expressed at relatively high levels in intestinal LS180 cells compared with primary hepatocytes. The unliganded SXR interacts with NCoR, and this interaction is only partially disrupted by tocotrienols. Expression of a dominant-negative NCoR enhanced the ability of tocotrienols to induce CYP3A4 in LS180 cells, suggesting that NCoR plays an important role in tissue-specific gene regulation by SXR. Our findings provide a molecular mechanism explaining how vitamin supplements affect the absorption and effectiveness of drugs. Knowledge of drug-nutrient interactions may help reduce the incidence of decreased drug efficacy. PMID:15269186

  10. Select steroid hormone glucuronide metabolites can cause Toll-like receptor 4 activation and enhanced pain

    PubMed Central

    Lewis, Susannah S.; Hutchinson, Mark R.; Frick, Morin M.; Zhang, Yingning; Maier, Steven F.; Sammakia, Tarek; Rice, Kenner C.; Watkins, Linda R.

    2014-01-01

    We have recently shown that several classes of glucuronide metabolites, including the morphine metabolite morphine-3-glucuronide and the ethanol metabolite ethyl glucuronide, cause toll like receptor 4 (TLR4)-dependent signalling in vitro and enhanced pain in vivo. Steroid hormones, including estrogens and corticosterone, are also metabolized through glucuronidation. Here we demonstrate that in silico docking predicts that corticosterone, corticosterone-21-glucuronide, estradiol, estradiol-3-glucuronide and estradiol-17-glucuronide all dock with the MD-2 component of the TLR4 receptor complex. In addition to each docking with MD-2, the docking of each was altered by pre-docking with (+)-naloxone, a TLR4 signaling inhibitor. As agonist versus antagonist activity cannot be determined from these in silico interactions, an in vitro study was undertaken to clarify which of these compounds can act in an agonist fashion. Studies using a cell line transfected with TLR4, necessary co-signaling molecules, and a reporter gene revealed that only estradiol-3-glucuronide and estradiol-17-glucuronide increased reporter gene product, indicative of TLR4 agonism. Finally, in in vivo studies, each of the 5 drugs was injected intrathecally at equimolar doses. In keeping with the in vitro results, only estradiol-3-glucuronide and estradiol-17-glucuronide caused enhanced pain. For both compounds, pain enhancement was blocked by the TLR4 antagonist lipopolysaccharide from Rhodobacter sphaeroides, evidence for the involvement in TLR4 in the resultant pain enhancement. These findings have implications for several chronic pain conditions, including migraine and tempromandibular joint disorder, in which pain episodes are more likely in cycling females when estradiol is decreasing and estradiol metabolites are at their highest. PMID:25218902

  11. A novel steroidal saponin glycoside from Fagonia indica induces cell-selective apoptosis or necrosis in cancer cells.

    PubMed

    Waheed, Abdul; Barker, James; Barton, Stephen J; Owen, Caroline P; Ahmed, Sabbir; Carew, Mark A

    2012-09-29

    Fagonia indica is a small spiny shrub of great ethnopharmacological importance in folk medicine. The aqueous decoction of aerial parts is a popular remedy against various skin lesions, including cancer. We used a biological activity-guided fractionation approach to isolate the most potent fraction of the crude extract on three cancer cell lines: MCF-7 oestrogen-dependent breast cancer, MDA-MB-468 oestrogen-independent breast cancer, and Caco-2 colon cancer cells. A series of chromatographic and spectroscopic procedures were utilised on the EtOAc fraction, which resulted in the isolation of a new steroidal saponin glycoside. The cytotoxic activity of the saponin glycoside was determined in cancer cells using the MTT and neutral red uptake assays. After 24h treatment, the observed IC(50) values of the saponin glycoside were 12.5 μM on MDA-MB-468 and Caco-2 cells, but 100 μM on MCF-7 cells. Several lines of evidence: PARP cleavage, caspase-3 cleavage, DNA ladder assays, and reversal of growth inhibition with the pan-caspase inhibitor Z-VAD-fmk, suggested stimulation of apoptosis in MDA-MB-468 and Caco-2 cells, but not in MCF-7 cells, which do not express caspase-3. The haemolytic activity of the saponin glycoside was confirmed in sheep red blood cells, with cell lysis observed at >100 μM, suggesting that, at this concentration, the saponin glycoside caused necrosis through cell lysis in MCF-7 cells. Using the DNA ladder assay, the saponin glycoside (12.5 μM) was not toxic to HUVEC (human umbilical vein endothelial cells) or U937 cells, indicating some selectivity between malignant and normal cells. We conclude that the steroidal saponin glycoside isolated from F. indica is able to induce apoptosis or necrosis in cancer cells depending on the cell type. PMID:22800968

  12. Steroidal Saponins

    NASA Astrophysics Data System (ADS)

    Sahu, N. P.; Banerjee, S.; Mondal, N. B.; Mandal, D.

    The medicinal activities of plants are generally due to the secondary metabolites (1) which often occur as glycosides of steroids, terpenoids, phenols etc. Saponins are a group of naturally occurring plant glycosides, characterized by their strong foam-forming properties in aqueous solution. The cardiac glycosides also possess this, property but are classified separately because of their specific biological activity. Unlike the cardiac glycosides, saponins generally do not affect the heart. These are classified as steroid or triterpenoid saponins depending on the nature of the aglycone. Steroidal glycosides are naturally occurring sugar conjugates of C27 steroidal compounds. The aglycone of a steroid saponin is usually a spirostanol or a furostanol. The glycone parts of these compounds are mostly oligosaccharides, arranged either in a linear or branched fashion, attached to hydroxyl groups through an acetal linkage (2, 3). Another class of saponins, the basic steroid saponins, contain nitrogen analogues of steroid sapogenins as aglycones.

  13. Steroid biochemistry.

    PubMed

    Kamrath, Clemens; Wudy, Stefan A; Krone, Nils

    2014-01-01

    Accurate analysis of steroid hormones represents an essential part in the evaluation of a patient with disorders or differences in sex development. Analytical methods based on mass spectrometry (MS) have become the state-of-the-art methodology allowing for the most specific qualitative and quantitative determination of steroid hormones and their metabolites. Liquid chromatography linked with tandem MS (LC-MS/MS) allows for rapid as well as highly specific and sensitive targeted steroid hormone analysis of multiple analytes from a single sample. Urinary steroid profile analysis by gas chromatography (GC)-MS is a non-invasive diagnostic approach and provides qualitative and quantitative data on the global excretion of steroid hormone metabolites. GC-MS remains the most powerful discovery tool for defining inborn errors of steroidogenesis, whereas LC-MS/MS represents a highly sensitive and specific method for targeted steroid hormone analysis.

  14. Steroid osteopathy

    SciTech Connect

    Conway, J.J.; Weiss, S.C.

    1984-01-01

    Patients receiving steroids or having disease processes which increase natural steroid production often demonstrate ''the classic x-ray changes'' of avascular necrosis of bone. Bone scintigraphy in these patients most frequently demonstrates an increased radionuclide localization. The literature suggests that the increased activity is related to healing of the avascular process. In a recent study of Legg-Calve-Perthes Disease (LCPD), 37 of the children had multiple studies and increased activity within the epiphysis during revascularization was extremely rare. Not only are the scintigraphic findings in steroid osteopathy dissimilar to that in healing LCPD, but the time interval for healing is much to short for that of a vascular necrosis and no patients demonstrated an avascular phase on bone scintigraphy. Of 15 children with renal transplants on steroid therapy, 9 demonstrated x-ray and clinical findings of osteopathy. In 8 of 9 instances, bone scintigraphy showed increased localization of radionuclide in the affected bone. Improvement or a return to normal occurred in those patients in whom steroids were discontinued. The following is a proposed mechanism for steroid osteopathy. Steroids affect the osteoblastic and osteoclastic activity of bone and weaken its internal structure. Ordinary stress produces microtrabecular fractures. Fractures characteristically stimulate reactive hyperemia and increase bone metabolism. The result is increased bone radiopharmaceutical localization. The importance of recognizing this concept is that steroid osteopathy is preventable by reducing the administered steroid dose. As opposed to avascular necrosis, bone changes are reversible.

  15. Treatment outcomes of intradiscal steroid injection/selective nerve root block for 161 patients with cervical radiculopathy.

    PubMed

    Ito, Keigo; Yukawa, Yasutsugu; Machino, Masaaki; Inoue, Taro; Ouchida, Jun; Tomita, Keisuke; Kato, Fumihiko

    2015-02-01

    Patients with cervical radiculopathy (CR) were treated with intradiscal injection of steroids (IDIS) and/or selective nerve root block (SNRB) at our hospital. We retrospectively report the outcomes of these nonsurgical treatments for CR. 161 patients who were followed up for >2months were enrolled in this study. Patients' clinical manifestations were classified as arm pain, arm numbness, neck and/or scapular pain, and arm paralysis. Improvement in each manifestation was classified as "disappeared," "improved," "poor," or "worsened." Responses of "disappeared" or "improved" manifestations suggested treatment effectiveness. Final clinical outcomes were evaluated using the Odom criteria. Changes in herniated disc size were evaluated by comparing the initial and final MRI scans. On the basis of these changes, the patients were divided into regression, no-change, or progression groups. We investigated the relationship between the Odom criteria and changes observed on MRI. Effectiveness rates were 89% for arm pain, 77% for arm numbness, 82% for neck and/or scapular pain, and 76% for arm paralysis. In total, 91 patients underwent repeated MRI. In 56 patients (62%), the size of the herniated disc decreased, but 31 patients (34%) exhibited no change in disc size. The regression group showed significantly better Odom criteria results than the no-change group. In conclusion, IDIS and SNRB for CR are not widely performed. However, other extremely effective therapies that can rapidly improve neuralgia should be considered before surgery. PMID:25797986

  16. Fifteen years of genomewide scans for selection: trends, lessons and unaddressed genetic sources of complication.

    PubMed

    Haasl, Ryan J; Payseur, Bret A

    2016-01-01

    Genomewide scans for natural selection (GWSS) have become increasingly common over the last 15 years due to increased availability of genome-scale genetic data. Here, we report a representative survey of GWSS from 1999 to present and find that (i) between 1999 and 2009, 35 of 49 (71%) GWSS focused on human, while from 2010 to present, only 38 of 83 (46%) of GWSS focused on human, indicating increased focus on nonmodel organisms; (ii) the large majority of GWSS incorporate interpopulation or interspecific comparisons using, for example F(ST), cross-population extended haplotype homozygosity or the ratio of nonsynonymous to synonymous substitutions; (iii) most GWSS focus on detection of directional selection rather than other modes such as balancing selection; and (iv) in human GWSS, there is a clear shift after 2004 from microsatellite markers to dense SNP data. A survey of GWSS meant to identify loci positively selected in response to severe hypoxic conditions support an approach to GWSS in which a list of a priori candidate genes based on potential selective pressures are used to filter the list of significant hits a posteriori. We also discuss four frequently ignored determinants of genomic heterogeneity that complicate GWSS: mutation, recombination, selection and the genetic architecture of adaptive traits. We recommend that GWSS methodology should better incorporate aspects of genomewide heterogeneity using empirical estimates of relevant parameters and/or realistic, whole-chromosome simulations to improve interpretation of GWSS results. Finally, we argue that knowledge of potential selective agents improves interpretation of GWSS results and that new methods focused on correlations between environmental variables and genetic variation can help automate this approach. PMID:26224644

  17. Fifteen years of genomewide scans for selection: trends, lessons and unaddressed genetic sources of complication.

    PubMed

    Haasl, Ryan J; Payseur, Bret A

    2016-01-01

    Genomewide scans for natural selection (GWSS) have become increasingly common over the last 15 years due to increased availability of genome-scale genetic data. Here, we report a representative survey of GWSS from 1999 to present and find that (i) between 1999 and 2009, 35 of 49 (71%) GWSS focused on human, while from 2010 to present, only 38 of 83 (46%) of GWSS focused on human, indicating increased focus on nonmodel organisms; (ii) the large majority of GWSS incorporate interpopulation or interspecific comparisons using, for example F(ST), cross-population extended haplotype homozygosity or the ratio of nonsynonymous to synonymous substitutions; (iii) most GWSS focus on detection of directional selection rather than other modes such as balancing selection; and (iv) in human GWSS, there is a clear shift after 2004 from microsatellite markers to dense SNP data. A survey of GWSS meant to identify loci positively selected in response to severe hypoxic conditions support an approach to GWSS in which a list of a priori candidate genes based on potential selective pressures are used to filter the list of significant hits a posteriori. We also discuss four frequently ignored determinants of genomic heterogeneity that complicate GWSS: mutation, recombination, selection and the genetic architecture of adaptive traits. We recommend that GWSS methodology should better incorporate aspects of genomewide heterogeneity using empirical estimates of relevant parameters and/or realistic, whole-chromosome simulations to improve interpretation of GWSS results. Finally, we argue that knowledge of potential selective agents improves interpretation of GWSS results and that new methods focused on correlations between environmental variables and genetic variation can help automate this approach.

  18. Interaction between use of non-steroidal anti-inflammatory drugs and selected genetic polymorphisms in ovarian cancer risk

    PubMed Central

    Pinheiro, Simone P; Gates, Margaret A; DeVivo, Immaculata; Rosner, Bernard A; Tworoger, Shelley S; Titus-Ernstoff, Linda; Hankinson, Susan E; Cramer, Daniel W

    2010-01-01

    Inflammation and non-steroidal anti-inflammatory agents (NSAIDs) may play important role in ovarian cancer. However, epidemiologic data are inconsistent, possibly reflecting inter-individual genetic differences affecting the metabolism of NSAIDs. We examined whether common polymorphisms affecting the metabolism of NSAIDs modify the association between NSAIDs and ovarian cancer risk. We genotyped 1,353 DNA samples from women who developed ovarian cancer and 1,823 samples from matched controls participating in the New England Case-Control study and the Nurses' Health Studies. Conditional logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs) associated with regular use of NSAIDs and with relevant polymorphisms on ovarian cancer risk. Multivariable unconditional logistic regression estimated the association of NSAID use across stratum of each genotype. Regular use of NSAIDs was not associated with ovarian cancer risk. Multivariable OR (95% CI) associated with use NSAIDs was 0.85 (95% CI: 0.71-1.02). Associations between NSAID use and ovarian cancer risk did not differ significantly across strata of genotypes. None of the studied polymorphisms was associated with ovarian cancer risk. The multivariable ORs (95% CI) associated with CYP2C9 and UGT1A6 variant genotypes were 0.99 (0.90-1.08) and 0.93 (0.82-1.05), respectively. The multivariable ORs (95% CI) associated with PPAR-γ, COX-2 -765G>C, and COX-2 Ex10+837T>C polymorphisms were 1.02 (0.87-1.20), 0.87 (0.75-1.00), and 0.97 (0.87-1.09), respectively. In this relatively large study, we found no convincing evidence supporting an association between NSAIDs use and ovarian cancer risk. Furthermore, data did not suggest interaction between selected polymorphisms and use of NSAIDs in relation to ovarian cancer risk. PMID:21532843

  19. Anabolic steroids.

    PubMed

    Strauss, R H

    1984-07-01

    Anabolic-androgenic steroid hormones are used by athletes in an attempt to improve performance. Side effects include decreased testosterone and sperm production, acne, balding, and increased aggression. The long-term effects are not known.

  20. Selective Non-Steroidal Glucocorticoid Receptor Agonists Attenuate Inflammation but Do Not Impair Intestinal Epithelial Cell Restitution In Vitro

    PubMed Central

    Reuter, Kerstin C.; Loitsch, Stefan M.; Dignass, Axel U.; Steinhilber, Dieter; Stein, Jürgen

    2012-01-01

    Introduction Despite the excellent anti-inflammatory and immunosuppressive action of glucocorticoids (GCs), their use for the treatment of inflammatory bowel disease (IBD) still carries significant risks in terms of frequently occurring severe side effects, such as the impairment of intestinal tissue repair. The recently-introduced selective glucocorticoid receptor (GR) agonists (SEGRAs) offer anti-inflammatory action comparable to that of common GCs, but with a reduced side effect profile. Methods The in vitro effects of the non-steroidal SEGRAs Compound A (CpdA) and ZK216348, were investigated in intestinal epithelial cells and compared to those of Dexamethasone (Dex). GR translocation was shown by immunfluorescence and Western blot analysis. Trans-repressive effects were studied by means of NF-κB/p65 activity and IL-8 levels, trans-activation potency by reporter gene assay. Flow cytometry was used to assess apoptosis of cells exposed to SEGRAs. The effects on IEC-6 and HaCaT cell restitution were determined using an in vitro wound healing model, cell proliferation by BrdU assay. In addition, influences on the TGF-β- or EGF/ERK1/2/MAPK-pathway were evaluated by reporter gene assay, Western blot and qPCR analysis. Results Dex, CpdA and ZK216348 were found to be functional GR agonists. In terms of trans-repression, CpdA and ZK216348 effectively inhibited NF-κB activity and IL-8 secretion, but showed less trans-activation potency. Furthermore, unlike SEGRAs, Dex caused a dose-dependent inhibition of cell restitution with no effect on cell proliferation. These differences in epithelial restitution were TGF-β-independent but Dex inhibited the EGF/ERK1/2/MAPK-pathway important for intestinal epithelial wound healing by induction of MKP-1 and Annexin-1 which was not affected by CpdA or ZK216348. Conclusion Collectively, our results indicate that, while their anti-inflammatory activity is comparable to Dex, SEGRAs show fewer side effects with respect to wound healing

  1. Cerebrovascular Dilation via Selective Targeting of the Cholane Steroid-Recognition Site in the BK Channel β1-Subunit by a Novel Nonsteroidal Agent

    PubMed Central

    Bukiya, Anna N.; McMillan, Jacob E.; Fedinec, Alexander L.; Patil, Shivaputra A.; Miller, Duane D.; Leffler, Charles W.; Parrill, Abby L.

    2013-01-01

    The Ca2+/voltage-gated K+ large conductance (BK) channel β1 subunit is particularly abundant in vascular smooth muscle. By determining their phenotype, BK β1 allows the BK channels to reduce myogenic tone, facilitating vasodilation. The endogenous steroid lithocholic acid (LCA) dilates cerebral arteries via BK channel activation, which requires recognition by a BK β1 site that includes Thr169. Whether exogenous nonsteroidal agents can access this site to selectively activate β1-containing BK channels and evoke vasodilation remain unknown. We performed a chemical structure database similarity search using LCA as a template, along with a two-step reaction to generate sodium 3-hydroxyolean-12-en-30-oate (HENA). HENA activated the BK (cbv1 + β1) channels cloned from rat cerebral artery myocytes with a potency (EC50 = 53 μM) similar to and an efficacy (×2.5 potentiation) significantly greater than that of LCA. This HENA action was replicated on native channels in rat cerebral artery myocytes. HENA failed to activate the channels made of cbv1 + β2, β3, β4, or β1T169A, indicating that this drug selectively targets β1-containing BK channels via the BK β1 steroid-sensing site. HENA (3–45 μM) dilated the rat and C57BL/6 mouse pressurized cerebral arteries. Consistent with the electrophysiologic results, this effect was larger than that of LCA. HENA failed to dilate the arteries from the KCNMB1 knockout mouse, underscoring BK β1’s role in HENA action. Finally, carotid artery-infusion of HENA (45 μM) dilated the pial cerebral arterioles via selective BK-channel targeting. In conclusion, we have identified for the first time a nonsteroidal agent that selectively activates β1-containing BK channels by targeting the steroid-sensing site in BK β1, rendering vasodilation. PMID:23455312

  2. Selective accumulation of meso-tetra(hydroxyphenyl)chlorin in steroid-synthesizing cells of the rat adrenal gland

    NASA Astrophysics Data System (ADS)

    Colombo-Benkmann, Mario; Muhm, Markus; Gahlen, Johannes; Vry, Magnus-Sebastian; Deubzer, Hedwig; Holloschi, Andreas; Haffner, Matthias; Heym, Christine; Senninger, Norbert

    1998-04-01

    Rat adrenal glands fluoresce intensely after systemic application of meso-tetra(hydroxyphenyl)chlorin (mTHPC). We investigated which parts of the adrenal gland accumulate mTHPC. Furthermore we examined the time course of adrenal mTHPC-accumulation. Ten male Wistar rats each were given 0.5 or 0.7 mg mTHPC kg-1 iv. Each two animals were perfused with normal saline and Zamboni fixative 6, 12, 24, 48 and 72 hours after photosensitization. Untreated animals served as controls. Fluorescence was quantified on 20 micrometer frozen sections with CCD-camera and appropriate software. Immunohistochemistry identified specific cell types with antibodies to steroid-synthesizing enzymes. The cortex exhibited an intense fluorescence, with weaker fluorescence of corticocytes in the zona glomerulosa compared to the other zones. Besides intensely fluorescing singly lying scattered cells, the medulla showed a faint mTHPC-induced fluorescence. Immunohistochemistry revealed that intramedullary cells with intense fluorescence were corticocytes, showing a positive reaction to the 21-(beta) -hydroxylase antibody. Peak accumulation of mTHPC was always observed after 24 hours. Our results indicate for the first time that only steroid synthesizing cells of the adrenal gland exhibit an intense photosensitizer-induced fluorescence. Thus mTHPC-application is an uncomplicated method to identify steroid-synthesizing cells, possibly also in other organs.

  3. Oral Steroids (Steroid Pills and Syrups)

    MedlinePlus

    ... more about steroids? How are steroid pills and syrups used? Steroid pills and syrups are very effective at reducing swelling and mucus ... liver or cause sterility Available as pills and syrups. Often necessary for treating more severe episodes of ...

  4. Relevance of the selective oestrogen receptor modulators tamoxifen, toremifene and clomiphene in doping field: endogenous steroids urinary profile after multiple oral doses.

    PubMed

    Mazzarino, Monica; Braganò, Maria Cristina; de la Torre, Xavier; Molaioni, Francesco; Botrè, Francesco

    2011-11-01

    The present study was performed to investigate the influence of the intake of selective oestrogen receptor modulators on the urinary endogenous steroids profile. For this purpose the circadian variability of luteinizing hormone, follicle-stimulating hormone, testosterone, 5α-androstan-3α,17β-diol, 5β-androstan-3α,17β-diol, epitestosterone, 4-androstenedione, androsterone and etiocholanolone were measured on eight subjects (four males and four females) by gas chromatography-mass spectrometry and chemiluminescent immunometric assay techniques before and after oral administration of multiple doses of either tamoxifen (80 mg for 2 days) or toremifene (120 mg for 2 days) or clomiphene (100 mg for 2 days). The individual baseline variability of the steroids studied was set up by collecting the urine samples every 3 h, for 3 days prior to the treatment; whereas the evaluation of the effects of the oral administration of multiple doses of selective oestrogen receptor modulators on the steroid urinary profile was assessed by collecting urine samples every three hours for at least five days from the first administration. The results of our measurements showed that, only in male subjects, the relative urinary concentrations of testosterone, epitestosterone and 4-androstenedione were significantly altered generally after the second day of drug administration. While no significant effects were recorded in both sexes on the luteinizing hormone, follicle-stimulating hormone, androsterone, etiocholanolone, 5α-androstan-3α,17β-diol and 5β-androstan-3α,17β-diol urinary levels and on testosterone/epitestosterone, 5α-androstan-3α,17β-diol/5β-androstan-3α,17β-diol and androsterone/etiocholanolone ratios.

  5. Anabolic steroids.

    PubMed

    Kuhn, Cynthia M

    2002-01-01

    The term "anabolic steroids" refers to testosterone derivatives that are used either clinically or by athletes for their anabolic properties. However, scientists have questioned the anabolic effects of testosterone and its derivatives in normal men for decades. Most scientists concluded that anabolic steroids do not increase muscle size or strength in people with normal gonadal function and have discounted positive results as unduly influenced by positive expectations of athletes, inferior experimental design, or poor data analysis. There has been a tremendous disconnect between the conviction of athletes that these drugs are effective and the conviction of scientists that they aren't. In part, this disconnect results from the completely different dose regimens used by scientists to document the correction of deficiency states and by athletes striving to optimize athletic performance. Recently, careful scientific study of suprapharmacologic doses in clinical settings - including aging, human immunodeficiency virus, and other disease states - supports the efficacy of these regimens. However, the mechanism by which these doses act remains unclear. "Anabolism" is defined as any state in which nitrogen is differentially retained in lean body mass, either through stimulation of protein synthesis and/or decreased breakdown of protein anywhere in the body. Testosterone, the main gonadal steroid in males, has marked anabolic effects in addition to its effects on reproduction that are easily observed in developing boys and when hypogonadal men receive testosterone as replacement therapy. However, its efficacy in normal men, as during its use in athletes or in clinical situations in which men are eugonadal, has been debated. A growing literature suggests that use of suprapharmacologic doses can, indeed, be anabolic in certain situations; however, the clear identification of these situations and the mechanism by which anabolic effects occur are unclear. Furthermore, the

  6. Selection of non-steroidal anti-inflammatory drug and treatment regimen for sulfur mustard-induced cutaneous lesions.

    PubMed

    Plahovinsak, Jennifer L; Buccellato, Matthew A; Reid, Frances M; Graham, John S

    2016-09-01

    The inflammatory process plays an important role in sulfur mustard (HD) injury and HD pathogenesis, suggesting that anti-inflammatory treatments applied as soon as possible following HD injury may reduce tissue damage and accelerate healing. This study used the HD dermal weanling swine model to investigate the efficacy of two non-steroidal anti-inflammatory drugs, capsaicin and diclofenac, when applied in combination with the steroid, clobetasol. The therapeutic regimen was also investigated with respect to initiation of treatment post-exposure, frequency and duration. Yorkshire-cross pigs were randomly assigned to experimental groups, corresponding to all combinations of treatment (capsaicin with clobetasol or diclofenac with clobetasol), onset time (1, 2 or 4 h post-exposure), treatment duration (1, 3 or 5 days) and frequency of applications (2, 3 or 4 per day). For each animal, two sites on the ventral abdomen were exposed to 400 μL of neat HD for 8 min to achieve superficial dermal (SD) lesions and two sites were exposed to 400 μL neat HD for 30 min to achieve deep dermal (DD) lesions. Each treatment regimen was tested against a SD and a DD injury. Untreated SD and DD lesion sites served as within-animal controls. Assessments, up to one week post-challenge, included digital photographs, clinical assessments (lesion size measurements and modified Draize scoring), transepidermal water loss (TEWL), reflectance colorimetry and histopathologic evaluations that included an estimate for depth of injury and wound healing parameters. Diclofenac plus clobetasol treatment resulted in significant reductions in lesion contracture and modified Draize scores, increased barrier function (decreased TEWL), and increased healing as determined by histopathology for both SD and DD injury when compared with untreated sites and sites treated with capsaicin plus clobetasol. An increased duration of treatment from 1 to 5 days was most commonly associated with decreased

  7. Selection of non-steroidal anti-inflammatory drug and treatment regimen for sulfur mustard-induced cutaneous lesions.

    PubMed

    Plahovinsak, Jennifer L; Buccellato, Matthew A; Reid, Frances M; Graham, John S

    2016-09-01

    The inflammatory process plays an important role in sulfur mustard (HD) injury and HD pathogenesis, suggesting that anti-inflammatory treatments applied as soon as possible following HD injury may reduce tissue damage and accelerate healing. This study used the HD dermal weanling swine model to investigate the efficacy of two non-steroidal anti-inflammatory drugs, capsaicin and diclofenac, when applied in combination with the steroid, clobetasol. The therapeutic regimen was also investigated with respect to initiation of treatment post-exposure, frequency and duration. Yorkshire-cross pigs were randomly assigned to experimental groups, corresponding to all combinations of treatment (capsaicin with clobetasol or diclofenac with clobetasol), onset time (1, 2 or 4 h post-exposure), treatment duration (1, 3 or 5 days) and frequency of applications (2, 3 or 4 per day). For each animal, two sites on the ventral abdomen were exposed to 400 μL of neat HD for 8 min to achieve superficial dermal (SD) lesions and two sites were exposed to 400 μL neat HD for 30 min to achieve deep dermal (DD) lesions. Each treatment regimen was tested against a SD and a DD injury. Untreated SD and DD lesion sites served as within-animal controls. Assessments, up to one week post-challenge, included digital photographs, clinical assessments (lesion size measurements and modified Draize scoring), transepidermal water loss (TEWL), reflectance colorimetry and histopathologic evaluations that included an estimate for depth of injury and wound healing parameters. Diclofenac plus clobetasol treatment resulted in significant reductions in lesion contracture and modified Draize scores, increased barrier function (decreased TEWL), and increased healing as determined by histopathology for both SD and DD injury when compared with untreated sites and sites treated with capsaicin plus clobetasol. An increased duration of treatment from 1 to 5 days was most commonly associated with decreased

  8. Steroid withdrawal in renal transplantation.

    PubMed

    Grenda, Ryszard

    2013-11-01

    - Early steroid withdrawal is possible in patients at high immunological risk using a combination of polyclonal antibody induction, tacrolimus, and mycophenolate mofetil- All protocols of steroid minimization showed relevant clinical benefits, however the growth-related benefit was limited to pre-pubertal patients in all but one of the studies- Adverse events of steroid withdrawal occurred in a higher incidence of post-transplant bone marrow suppression Key research points - There is no clear evidence of the impact of steroid withdrawal on the risk of recurrence of primary glomerulonephritis after renal transplantation in children, therefore further evaluation of this important issue should be performed in prospective trials- There is limited pediatric data on the risk of anti-HLA/donor-specific antibody production in steroid-free patients after renal transplantation. It is not clear whether the selection of the type of induction antibody (lymphocyte depleting versus short, two-dose administration of anti-IL2R inhibitor) is important in this term. The production of anti-HLA antibodies should then be monitored on a regular basis and analyzed in prospective trials.

  9. Epidural Steroid Injections

    MedlinePlus

    ... Assessment Tools Injection Treatments for Spinal Pain Epidural Steroid Injections Lumbar Zygapophysial (Facet) Joint Injections Surgical Options Nonsurgical Treatments Alternative Medicine Epidural Steroid Injections General Information Why Get an Epidural Steroid ...

  10. Non-steroidal anti-inflammatory drugs and the risk of cardiovascular diseases: are we going to see the revival of cyclooxygenase-2 selective inhibitors?

    PubMed

    Głuszko, Piotr; Bielińska, Aneta

    2009-04-01

    The use of non-steroidal anti-inflammatory drugs (NSAID) is associated with a number of gastrointestinal and other adverse effects. Introduction of selective cyclooxygenase-2 (COX-2) inhibitors at the end of the 20th century raised hopes for a substantial reduction in the rate of serious events such as upper gastrointestinal ulcers, bleeding and perforations. In 2004 and 2005, predictions of some pharmacologists were confirmed when the Adenomatous Polyp Prevention on VIOXX trial (APPROVE) and other randomized, double-blind, placebo-controlled trials with COX-2 inhibitors showed an increased rate of thrombotic vascular events, including myocardial infarction, in patients treated with coxibs. So far, only limited long-term data on cardiovascular risk associated with non-selective NSAID have been available; however, some studies have suggested that both selective COX-2 inhibitors and traditional NSAID increase the risk of cardiovascular events. For patients at high cardiovascular risk, contradictory warnings and recommendations have been published recently by the American Heart Association, Food and Drug Administration, and by independent experts. The current paper reviews these recommendations and discusses the therapeutic challenge to minimize the risk of serious adverse events associated with the use of NSAID.

  11. Metal-organic frameworks@graphene hybrid aerogels for solid-phase extraction of non-steroidal anti-inflammatory drugs and selective enrichment of proteins.

    PubMed

    Zhang, Xiaoqiong; Liang, Qionglin; Han, Qiang; Wan, Wei; Ding, Mingyu

    2016-06-20

    Graphene aerogel (GA)-supported metal-organic framework (MOF) particles with a three-dimensional (3D) architecture were fabricated for the first time via a facile template-free "sol-cryo" method. The prepared MOFs@graphene hybrid aerogels exhibit a 3D interconnected macroporous framework of graphene sheets with uniform dispersion of MOF particles. We also report the first attempt at using the hybrid aerogels as adsorbents for the solid-phase extraction (SPE) of non-steroidal anti-inflammatory drugs (NSAIDs) and the selective enrichment of proteins. The macroporous skeletons of GA provide both low backpressure and rapid mass transfer in SPE application, thus overcoming the obstacle of high backpressure caused by directly packing submicron or micron sized MOF particles into SPE cartridges. Excellent performances including satisfactory recoveries, high sensitivity and good reproducibility were achieved in the extraction of five NSAIDs. The hybrid aerogels also showed an interesting ability for selective enrichment of ribonuclease A (RNase A) and simultaneous exclusion of cytochrome C (Cyt C) and lysozyme (Lyz), which could be attributed to the electrostatic interactions between proteins and the positively charged coordinatively unsaturated metal sites (CUS) in MIL-101. We believe that this work will promote the application of MOFs in adsorption and separation, and our synthetic strategy could be further extended to develop other graphene-based hybrid aerogels. PMID:27156534

  12. Steroidal androgens and nonsteroidal, tissue-selective androgen receptor modulator, S-22, regulate androgen receptor function through distinct genomic and nongenomic signaling pathways.

    PubMed

    Narayanan, Ramesh; Coss, Christopher C; Yepuru, Muralimohan; Kearbey, Jeffrey D; Miller, Duane D; Dalton, James T

    2008-11-01

    Androgen receptor (AR) ligands are important for the development and function of several tissues and organs. However, the poor oral bioavailability, pharmacokinetic properties, and receptor cross-reactivity of testosterone, coupled with side effects, place limits on its clinical use. Selective AR modulators (SARMs) elicit anabolic effects in muscle and bone, sparing reproductive organs like the prostate. However, molecular mechanisms underlying the tissue selectivity remain ambiguous. We performed a variety of in vitro studies to compare and define the molecular mechanisms of an aryl propionamide SARM, S-22, as compared with dihydrotestosterone (DHT). Studies indicated that S-22 increased levator ani muscle weight but decreased the size of prostate in rats. Analysis of the upstream intracellular signaling events indicated that S-22 and DHT mediated their actions through distinct pathways. Modulation of these pathways altered the recruitment of AR and its cofactors to the PSA enhancer in a ligand-dependent fashion. In addition, S-22 induced Xenopus laevis oocyte maturation and rapid phosphorylation of several kinases, through pathways distinct from steroids. These studies reveal novel differences in the molecular mechanisms by which S-22, a nonsteroidal SARM, and DHT mediate their pharmacological effects.

  13. Adolescent Steroid Use.

    ERIC Educational Resources Information Center

    Office of Inspector General (DHHS), Washington, DC.

    The study focused on non-medical steroid use by adolescents according to data obtained from the National Institute on Drug Abuse, professional literature, 30 key informants knowledgeable in steroid issues, and 72 current or former steroid users. The findings indicated: (1) over 250,000 adolescents, primarily males, used or have used steroids, and…

  14. [Clinical use of spinal or epidural steroids].

    PubMed

    Marinangeli, F; Ciccozzi, A; Donatelli, F; Paladini, A; Varrassi, G

    2002-01-01

    Steroids, drugs with potent antiinflammatory properties on the damaged nervous roots, have been especially used as adjuvants of local anesthetics, by spinal route, in the treatments of low-back pain. Spinal route was chosen to obtain a higher local concentration of drug, with few systemic side effects and to improve drug's action mechanism. Steroids seem to interact with GABA receptors and thus control neural excitability through a stabilising effect on membranes, modification of nervous conduction and membrane hyperpolarization, in supraspinal and spinal site. Epidural steroids are especially used in the treatment of low back pain due to irritation of nervous roots. They have been administered alone or in association with local anesthetics and/or saline solution. Slow release formulations have been generally used (methylprednisolone acetate, and triamcinolone diacetate). Other indications of epidural steroids are: postoperative hemilaminectomy pain, prevention of post herpetic neuralgia, degenerative ostheoartrithis. Intra-thecal steroids have been frequently used in the treatment of lumbar radiculopathy due to discopathy, as an alternative treatment when epidural administration is ineffective. Positive results have been obtained with methylprednisolone acetate, alone or in association with local anesthetics. Complications related to intraspinal steroids injections are due to execution of the block and side effects of drugs. Complications associated with intrathecal steroids are more frequent and severe than epidural injections and include: adhesive arachnoiditis, aseptic meningitis, cauda equina syndrome. Steroidal toxicity seems to be related to the polyethylenic glycole vehicle. Anyway, slow release formulations contain less concentrated polyethylenic glycole. The epidural administration, a correct dilution of steroid with local anesthetics solution and/or saline solution, and a limited number of injections (no more than three) allows a significant reduction of

  15. Asthma and Rhinitis Induced by Selective Immediate Reactions to Paracetamol and Non-steroidal Anti-inflammatory Drugs in Aspirin Tolerant Subjects.

    PubMed

    Pérez-Alzate, Diana; Blanca-López, Natalia; Doña, Inmaculada; Agúndez, José A; García-Martín, Elena; Cornejo-García, José A; Perkins, James R; Blanca, Miguel; Canto, Gabriela

    2016-01-01

    In subjects with non-steroidal anti-inflammatory drugs (NSAIDs)- exacerbated respiratory disease (NERD) symptoms are triggered by acetyl salicylic acid (ASA) and other strong COX-1 inhibitors, and in some cases by weak COX-1 or by selective COX-2 inhibitors. The mechanism involved is related to prostaglandin pathway inhibition and leukotriene release. Subjects who react to a single NSAID and tolerate others are considered selective responders, and often present urticaria and/or angioedema and anaphylaxis (SNIUAA). An immunological mechanism is implicated in these reactions. However, anecdotal evidence suggests that selective responders who present respiratory airway symptoms may also exist. Our objective was to determine if subjects might develop selective responses to NSAIDs/paracetamol that manifest as upper/lower airways respiratory symptoms. For this purpose, we studied patients reporting asthma and/or rhinitis induced by paracetamol or a single NSAID that tolerated ASA. An allergological evaluation plus controlled challenge with ASA was carried out. If ASA tolerance was found, we proceeded with an oral challenge with the culprit drug. The appearance of symptoms was monitored by a clinical questionnaire and by measuring FEV1 and/or nasal airways volume changes pre and post challenge. From a total of 21 initial cases, we confirmed the appearance of nasal and/or bronchial manifestations in ten, characterized by a significant decrease in FEV1% and/or a decrease in nasal volume cavity after drug administration. All cases tolerated ASA. This shows that ASA tolerant subjects with asthma and/or rhinitis induced by paracetamol or a single NSAID without skin/systemic manifestations exist. Whether these patients represent a new clinical phenotype to be included within the current classification of hypersensitivity reactions to NSAIDs requires further investigation.

  16. Asthma and Rhinitis Induced by Selective Immediate Reactions to Paracetamol and Non-steroidal Anti-inflammatory Drugs in Aspirin Tolerant Subjects.

    PubMed

    Pérez-Alzate, Diana; Blanca-López, Natalia; Doña, Inmaculada; Agúndez, José A; García-Martín, Elena; Cornejo-García, José A; Perkins, James R; Blanca, Miguel; Canto, Gabriela

    2016-01-01

    In subjects with non-steroidal anti-inflammatory drugs (NSAIDs)- exacerbated respiratory disease (NERD) symptoms are triggered by acetyl salicylic acid (ASA) and other strong COX-1 inhibitors, and in some cases by weak COX-1 or by selective COX-2 inhibitors. The mechanism involved is related to prostaglandin pathway inhibition and leukotriene release. Subjects who react to a single NSAID and tolerate others are considered selective responders, and often present urticaria and/or angioedema and anaphylaxis (SNIUAA). An immunological mechanism is implicated in these reactions. However, anecdotal evidence suggests that selective responders who present respiratory airway symptoms may also exist. Our objective was to determine if subjects might develop selective responses to NSAIDs/paracetamol that manifest as upper/lower airways respiratory symptoms. For this purpose, we studied patients reporting asthma and/or rhinitis induced by paracetamol or a single NSAID that tolerated ASA. An allergological evaluation plus controlled challenge with ASA was carried out. If ASA tolerance was found, we proceeded with an oral challenge with the culprit drug. The appearance of symptoms was monitored by a clinical questionnaire and by measuring FEV1 and/or nasal airways volume changes pre and post challenge. From a total of 21 initial cases, we confirmed the appearance of nasal and/or bronchial manifestations in ten, characterized by a significant decrease in FEV1% and/or a decrease in nasal volume cavity after drug administration. All cases tolerated ASA. This shows that ASA tolerant subjects with asthma and/or rhinitis induced by paracetamol or a single NSAID without skin/systemic manifestations exist. Whether these patients represent a new clinical phenotype to be included within the current classification of hypersensitivity reactions to NSAIDs requires further investigation. PMID:27489545

  17. Anti-inflammatory effect and low ulcerogenic activity of etodolac, a cyclooxygenase-2 selective non-steroidal anti-inflammatory drug, on adjuvant-induced arthritis in rats.

    PubMed

    Tachibana, Masaki; Inoue, Naoki; Yoshida, Eri; Matsui, Masami; Ukai, Yojiro; Yano, Junichi

    2003-06-01

    Adjuvant arthritic rats are known to be more susceptible to gastric damage induced by non-steroidal anti-inflammatory drugs (NSAIDs) than are normal rats. We compared the relative gastric safety profile of etodolac with those of meloxicam, diclofenac sodium and indometacin in adjuvant arthritic rats and normal rats or mice. As a measure of the safety profiles of NSAIDs, we used the safety index, the ratio of the dose that elicits gastric mucosal lesions to the effective dose as an anti-inflammatory or analgesic compound. The anti-inflammatory or analgesic effects of NSAIDs were assessed by paw swelling in adjuvant arthritic rats, and either carrageenin-induced paw edema or brewer's yeast-induced hyperalgesia, as well as acetic acid-induced writhing, in normal rats or mice. In addition, we also investigated the effects of these NSAIDs on human COX-1 and COX-2 activity. Etodolac and other NSAIDs inhibited paw swelling and caused gastric mucosal lesions in adjuvant arthritic rats in a dose-dependent manner. Etodolac showed the highest UD(50) value and safety index among these NSAIDs in arthritic rats. In normal rats, etodolac also showed the highest UD(50) value and safety index, except when its effects were assessed by acetic acid-induced writhing. Etodolac and meloxicam showed selectivity for human COX-2 over COX-1. In contrast, diclofenac sodium and indometacin were selective for COX-1. These results suggest that etodolac, a COX-2 selective NSAID, has anti-inflammatory effects with a better safety profile for the stomach than do non-selective NSAIDs, including diclofenac sodium and indometacin, in adjuvant arthritic as well as normal rats.

  18. Asthma and Rhinitis Induced by Selective Immediate Reactions to Paracetamol and Non-steroidal Anti-inflammatory Drugs in Aspirin Tolerant Subjects

    PubMed Central

    Pérez-Alzate, Diana; Blanca-López, Natalia; Doña, Inmaculada; Agúndez, José A.; García-Martín, Elena; Cornejo-García, José A.; Perkins, James R.; Blanca, Miguel; Canto, Gabriela

    2016-01-01

    In subjects with non-steroidal anti-inflammatory drugs (NSAIDs)- exacerbated respiratory disease (NERD) symptoms are triggered by acetyl salicylic acid (ASA) and other strong COX-1 inhibitors, and in some cases by weak COX-1 or by selective COX-2 inhibitors. The mechanism involved is related to prostaglandin pathway inhibition and leukotriene release. Subjects who react to a single NSAID and tolerate others are considered selective responders, and often present urticaria and/or angioedema and anaphylaxis (SNIUAA). An immunological mechanism is implicated in these reactions. However, anecdotal evidence suggests that selective responders who present respiratory airway symptoms may also exist. Our objective was to determine if subjects might develop selective responses to NSAIDs/paracetamol that manifest as upper/lower airways respiratory symptoms. For this purpose, we studied patients reporting asthma and/or rhinitis induced by paracetamol or a single NSAID that tolerated ASA. An allergological evaluation plus controlled challenge with ASA was carried out. If ASA tolerance was found, we proceeded with an oral challenge with the culprit drug. The appearance of symptoms was monitored by a clinical questionnaire and by measuring FEV1 and/or nasal airways volume changes pre and post challenge. From a total of 21 initial cases, we confirmed the appearance of nasal and/or bronchial manifestations in ten, characterized by a significant decrease in FEV1% and/or a decrease in nasal volume cavity after drug administration. All cases tolerated ASA. This shows that ASA tolerant subjects with asthma and/or rhinitis induced by paracetamol or a single NSAID without skin/systemic manifestations exist. Whether these patients represent a new clinical phenotype to be included within the current classification of hypersensitivity reactions to NSAIDs requires further investigation. PMID:27489545

  19. Insights into cerebrovascular complications and Alzheimer disease through the selective loss of GRK2 regulation

    PubMed Central

    Obrenovich, Mark E; Morales, Ludis A; Cobb, Celia J; Shenk, Justin C; Méndez, Gina M; Fischbach, Kathryn; Smith, Mark A; Qasimov, Eldar K; Perry, George; Aliev, Gjumrakch

    2009-01-01

    Abstract Alzheimer disease (AD) and stroke are two leading causes of age-associated dementia. Increasing evidence points to vascular damage as an early contributor to the development of AD and AD-like pathology. In this review, we discuss the role of G protein-coupled receptor kinase 2 (GRK2) as it relates to individuals affected by AD and how the cardiovasculature plays a role in AD pathogenesis. The possible involvement of GRKs in AD pathogenesis is an interesting notion, which may help bridge the gap in our understanding of the heart–brain connection in relation to neurovisceral damage and vascular complications in AD, since kinases of this family are known to regulate numerous receptor functions both in the brain, myocardium, and elsewhere. The aim of this review is to discuss our findings of overexpression of GRK2 in the context of the early pathogenesis of AD, because increased levels of GRK2 immunoreactivity were found in vulnerable neurons of AD patients as well as in a two-vessel occlusion (2-VO) mammalian model of ischaemia. Also, we consider the consequences for this overexpression as a loss of G-protein coupled receptor (GPCR) regulation, as well as suggest a potential role for GPCRs and GRKs in a unifying theory of AD pathogenesis, particularly in the context of cerebrovascular disease. We synthesize this newer information and attempt to put it into context with GRKs as regulators of diverse physiological cellular functions that could be appropriate targets for future pharmacological intervention. PMID:19292735

  20. Anabolic steroid use by male adolescents.

    PubMed

    Johnson, M D; Jay, M S; Shoup, B; Rickert, V I

    1989-06-01

    Anabolic steroids have recently been used by professional and college athletes to improve athletic ability by increasing muscle size and strength. A study was done to determine the extent of steroid use and knowledge about these drugs in a population of high school male adolescents in a southern state. A self-report questionnaire, which allowed multiple answers for each question, was administered to 853 male students in six high schools. Results indicated that an average of 11% had used or were using anabolic steroids. The following were assessed: the reasons for steroid use, the sources from which the students received information about steroids, their familiarity with the physiologic effects and complications of steroid use, and the extent of their involvement in sports. The results suggest that a segment of male adolescents are using anabolic steroids without fully understanding the risks of such behavior. Health care providers need to become knowledgeable about steroids so that they may better educate adolescents about the potential deleterious effects of these agents.

  1. Selective Transcatheter Arterial Embolization for Treatment of Bleeding Complications or Reduction of Tumor Mass of Hepatocellular Adenomas

    SciTech Connect

    Erdogan, Deha; Delden, Otto M. van; Busch, Olivier R. C.; Gouma, Dirk J.; Gulik, Thomas M. van

    2007-11-15

    Hepatocellular adenomas (HCAs) are benign liver lesions which may be complicated by spontaneous intratumoral bleeding, with or without rupture into the abdominal cavity, or malignant degeneration. Recent advances in radiological interventional techniques now offer selective transcatheter arterial embolization (TAE) as an alternative approach to surgery as the initial treatment to stop the bleeding or as an elective treatment to reduce the tumor mass of the HCA. Herein, we report our initial experience using TAE in the management of HCA. Five female patients and one male patient presented with spontaneous hemorrhage of HCA. Four patients were initially treated with selective TAE to stop the bleeding. In two patients in whom the bleeding stopped spontaneously, TAE was electively undertaken 1 year after presentation to reduce the tumor mass of HCAs >5 cm. Selective TAE as initial treatment in patients with spontaneous bleeding of HCA with or without rupture is effective and will change the need for urgent laparotomy to control bleeding. Selective TAE may also be used as an elective treatment to reduce the tumor mass of larger HCAs.

  2. Estimation of the breakthrough volume of selected steroids for C-18 solid-phase extraction sorbent using retention data from micro-thin layer chromatography.

    PubMed

    Bielicka-Daszkiewicz, Katarzyna; Voelkel, Adam; Rusińska-Roszak, Danuta; Zarzycki, Paweł K

    2013-03-01

    SPE method is a very popular technique, and is commonly used for the prepurification, concentration, and isolation of different organic compounds from variable matrices. In this work, the optimization of SPE process was carried out. The breakthrough volume of solid sorbents based on octadecylsilane was determined and three methods were compared: (1) calculation one - the breakthrough volume was calculated using retention factor k determined with micro-TLC method, frontal analysis - (2) breakthrough volume was determined as volume of whole elution peak, and (3) breakthrough volume was determined as the center of peak gravity. For calculation method, the k values of key estrogens and progestogens were derived from the micro-TLC experiment reported previously. By combining these three methods, we can point the start of elution, the maximum concentration of analyte in eluate, and the whole eluent volume, which is necessary to achieve an appropriate selectivity and high extraction recovery. Proposed calculation method allows to estimate the beginning of the steroid peak, when the analyte appears in the eluate flowing from the sorbent. Such observation advances the SPE optimization protocol that was described before and was based on the correlation between raw k(SPE) and k(micro-TLC) data.

  3. Effects of selective serotonin reuptake inhibitors on three sex steroids in two versions of the aromatase enzyme inhibition assay and in the H295R cell assay.

    PubMed

    Jacobsen, Naja Wessel; Hansen, Cecilie Hurup; Nellemann, Christine; Styrishave, Bjarne; Halling-Sørensen, Bent

    2015-10-01

    Selective serotonin reuptake inhibitors are known to have a range of disorders that are often linked to the endocrine system e.g. hormonal imbalances, breast enlargement, sexual dysfunction, and menstrual cycle disorders. The mechanisms behind most of these disorders are not known in details. In this study we investigated whether the endocrine effect due to SSRI exposure could be detected in well adopted in vitro steroidogenesis assays, two versions of the aromatase enzyme inhibition assay and the H295R cell assay. The five drugs citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline, were shown to inhibit the aromatase enzyme in both types of aromatase assays. The IC50 values ranged from 3 to 600 μM. All five SSRIs, were further investigated in the H295R cell line. All compounds altered the steroid secretion from the cells, the lowest observed effect levels were 0.9 μM and 3.1 μM for sertraline and fluvoxamine, respectively. In general the H295R cell assay was more sensitive to SSRI exposure than the two aromatase assays, up to 20 times more sensitive. This indicates that the H295R cell line is a better tool for screening endocrine disrupting effects. Our findings show that the endocrine effects of SSRIs may, at least in part, be due to interference with the steroidogenesis. PMID:26162595

  4. Refuge function of marine algae complicates selection in an intertidal snail.

    PubMed

    Kemppainen, Petri; van Nes, Solveig; Ceder, Christofer; Johannesson, Kerstin

    2005-04-01

    Species with restricted gene flow often show trait-shifts from one type of environment to another. In those rock-dwelling marine gastropods that lack larval dispersal, size generally decreases in wave-exposed habitats reducing risk of dislodgement, while increases in less exposed habitats to resist crab-crushing. In Littorina fabalis, however, snails of moderately exposed shores are generally much larger (11-14 mm) than snails of sheltered shores (5-8 mm). Observations from the White Sea (where crabs are not present) indicate that in the absence of crabs snails are small (6-7 mm) in both habitats. We assumed that the optimal size for L. fabalis in the absence of crabs is less than 8 mm, and thus that increased size in moderately exposed habitats in areas with crabs might be a response to crab predation. In a crab-rich area (Sweden) we showed that crab predation is an important mortality factor for this snail species in both sheltered and moderately exposed habitats. In sheltered habitats, snails were relatively more protected from crab-predation when dwelling on their habitual substrate, fucoid algae, than if experimentally tethered to rocks below the algae. This showed that algae function as snail refuges. Snail dislodgement increased, however, with wave exposure but tethering snails in moderately exposed habitats showed that large snails survived equally well on rocks under the algae as in the canopy of the algae. Thus in sheltered habitats a small snail size is favored, probably due to life-history reasons, while increased risk of being dislodged from the algae refuges promotes a large size in moderately exposed habitats. This study shows an example of selection of a trait depends on complex interactions of different factors (life-history optimization, crab predation, wave induced dislodgement and algal refuges). PMID:15711994

  5. Antibacterial properties of cationic steroid antibiotics.

    PubMed

    Savage, Paul B; Li, Chunhong; Taotafa, Uale; Ding, Bangwei; Guan, Qunying

    2002-11-19

    Cationic steroid antibiotics have been developed that display broad-spectrum antibacterial activity. These compounds are comprised of steroids appended with amine groups arranged to yield facially amphiphilic morphology. Examples of these antibiotics are highly bactericidal, while related compounds effectively permeabilize the outer membranes of Gram-negative bacteria sensitizing these organisms to hydrophobic antibiotics. Cationic steroid antibiotics exhibit various levels of eukaryote vs. prokaryote cell selectivity, and cell selectivity can be increased via charge recognition of prokaryotic cells. Studies of the mechanism of action of these antibiotics suggest that they share mechanistic aspects with cationic peptide antibiotics. PMID:12445638

  6. A nursing perspective on the misuse of anabolic steroids.

    PubMed

    Rollo, Ian

    There is widespread use of anabolic steroids in the athletic community (Windsor and Dumitru, 1988). The potential health complications associated with this represents a serious risk to an otherwise healthy population. It is important for nurses to be knowledgeable about anabolic steroid abuse and to be able to identify users and populations most exposed to these drugs.

  7. Assisted Reproduction Technologies Impair Placental Steroid Metabolism

    PubMed Central

    Collier, Abby C.; Miyagi, Shogo J.; Yamauchi, Yasuhiro; Ward, Monika A.

    2009-01-01

    The placenta plays a vital role in pregnancy by facilitating steroid passage from maternal to fetal circulation and/or direct production of hormones. Using a murine model, we demonstrated the differences in placental steroid metabolism between pregnancies conceived naturally and with assisted reproduction technologies (ART): in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). While the ovarian steroid production was similar (estrone, 17β-estradiol) or higher (estriol) in ART pregnancies compared to mating, the levels of placental estriol were significantly lower in ART group. Placentas from ART had significantly higher activities of the steroid metabolizing enzymes UDP-glucuronosyltransferase (UGT) and sulfotransferase (SULT), which in ICSI were also coupled with decreased activity of the steroid regenerating enzymes β-glucuronidase (β-G) and Aryl sulfatase (AS). Levels of steroid metabolites androstane-3α-17β-diol glucuronide and dehydroepiandrosterone sulfate were higher in fetal compared to maternal blood in ART, but not in mating. This study demonstrates that in murine ART pregnancies, higher metabolism and clearance of steroids by the placenta may seriously affect the passage of essential hormones to the fetus. If a similar phenomenon exists in humans, this could provide a plausible explanation for obstetric and neonatal complications associated with ART, including the higher incidence of low birth weight babies. PMID:19406239

  8. The regio- and stereo-selective reduction of steroidal 4-en-3-ones using Na₂S₂O₄/NaHCO₃ and CuCl/NaBH₄.

    PubMed

    Wang, Chunli; Chen, Xiaoyu; Huang, Yaoqing; Yang, Jesse; Chen, Ying

    2013-12-20

    This paper describes the regio- and stereoselective reduction of △⁴-3-keto moiety in certain steroids using Na₂S₂O₄/NaHCO₃ and CuCl/NaBH₄, respectively. Using either one of the two reduction agents in the reaction, the 17-substituents in the D ring were observed to have clearly influenced the stereoselective reduction of 4-ene in the A ring by the so-called conformational transmission effect. Na₂S₂O₄/NaHCO₃ regioselectively reduced CC at 4-position of 17-substituted-androst-4-en-3-one derivatives to 5α-H-3-one as the main isomer. And as an extended application, Epiandrosterone (11) was further synthesized from androst-4-en-3,17-dione (AD) via four steps. The total yield from this was about 45%. In the presence of CuCl/NaBH₄, △⁴-3-keto conjugated reduction of 17-spirocyclic ethylene ketal protected androst-4-en-3-one derivatives mainly produced 3α-hydroxy-5β-H isomers, at a yield around 81%. Considering the scaffold configuration of 3α-hydroxy-5β-H moiety coincided with that of bile acid analogs, this selective reduction could also be used as an alternative method for the synthetic study of bile acids using AD and its derivatives, which are from the microorganism degradation of natural sterols, as the potential materials. Meanwhile, configurations of the reductive compounds 5b, 6b, 9, 10 and 17e were identified by X-ray diffraction. PMID:24128809

  9. Steroids as γ-secretase modulators

    PubMed Central

    Jung, Joo In; Ladd, Thomas B.; Kukar, Thomas; Price, Ashleigh R.; Moore, Brenda D.; Koo, Edward H.; Golde, Todd E.; Felsenstein, Kevin M.

    2013-01-01

    Aggregation and accumulation of Aβ42 play an initiating role in Alzheimer's disease (AD); thus, selective lowering of Aβ42 by γ-secretase modulators (GSMs) remains a promising approach to AD therapy. Based on evidence suggesting that steroids may influence Aβ production, we screened 170 steroids at 10 μM for effects on Aβ42 secreted from human APP-overexpressing Chinese hamster ovary cells. Many acidic steroids lowered Aβ42, whereas many nonacidic steroids actually raised Aβ42. Studies on the more potent compounds showed that Aβ42-lowering steroids were bonafide GSMs and Aβ42-raising steroids were inverse GSMs. The most potent steroid GSM identified was 5β-cholanic acid (EC50=5.7 μM; its endogenous analog lithocholic acid was virtually equipotent), and the most potent inverse GSM identified was 4-androsten-3-one-17β-carboxylic acid ethyl ester (EC50=6.25 μM). In addition, we found that both estrogen and progesterone are weak inverse GSMs with further complex effects on APP processing. These data suggest that certain endogenous steroids may have the potential to act as GSMs and add to the evidence that cholesterol, cholesterol metabolites, and other steroids may play a role in modulating Aβ production and thus risk for AD. They also indicate that acidic steroids might serve as potential therapeutic leads for drug optimization/development.—Jung, J. I., Ladd, T. B., Kukar, T., Price, A. R., Moore, B. D., Koo, E. H., Golde, T. E., Felsenstein, K. M. Steroids as γ-secretase modulators. PMID:23716494

  10. Reference ranges for urinary concentrations and ratios of endogenous steroids, which can be used as markers for steroid misuse, in a Caucasian population of athletes.

    PubMed

    Van Renterghem, Pieter; Van Eenoo, Peter; Geyer, Hans; Schänzer, Wilhelm; Delbeke, Frans T

    2010-02-01

    The detection of misuse with naturally occurring steroids is a great challenge for doping control laboratories. Intake of natural anabolic steroids alters the steroid profile. Thus, screening for exogenous use of these steroids can be established by monitoring a range of endogenous steroids, which constitute the steroid profile, and evaluate their concentrations and ratios against reference ranges. Elevated values of the steroid profile constitute an atypical finding after which a confirmatory IRMS procedure is needed to unequivocally establish the exogenous origin of a natural steroid. However, the large inter-individual differences in urinary steroid concentrations and the recent availability of a whole range of natural steroids (e.g. dehydroepiandrosterone and androstenedione) which each exert a different effect on the monitored parameters in doping control complicate the interpretation of the current steroid profile. The screening of an extended steroid profile can provide additional parameters to support the atypical findings and can give specific information upon the steroids which have been administered. The natural concentrations of 29 endogenous steroids and 11 ratios in a predominantly Caucasian population of athletes were determined. The upper reference values at 97.5%, 99% and 99.9% levels were assessed for male (n=2027) and female (n=1004) populations. Monitoring minor metabolites and evaluation of concentration ratios with respect to their natural abundances could improve the interpretation of the steroid profile in doping analysis.

  11. Steroid resistant asthma.

    PubMed

    Luhadia, S K

    2014-03-01

    Inspite of very safe and effective treatment, Bronchial asthmatics do not respond well in 5-10% of cases which are labelled as Refractory Asthma. Besides compliance, presence of psychogenic and trigger factors and comorbid illness, steroid insensitiveness or resistance may play a significant role in the poorly controlled/responding asthmatics. Type I Steroid resistance is due to lack of binding affinity of steroids to glucocorticoid receptors and may respond to higher doses of steroids while type II steroid resistance is because of reduced number of cells with glucocorticoid receptors, which is very rare and do not respond to even higher doses of systemic steroids and these cases require alternative/novel therapies. Future treatment of steroid resistant and severe refractory asthma is likely to be targeted towards cytokines and Bronchial Thermoplasty.

  12. Risk of upper gastrointestinal ulcer bleeding associated with selective cyclo‐oxygenase‐2 inhibitors, traditional non‐aspirin non‐steroidal anti‐inflammatory drugs, aspirin and combinations

    PubMed Central

    Lanas, A; García‐Rodríguez, L A; Arroyo, M T; Gomollón, F; Feu, F; González‐Pérez, A; Zapata, E; Bástida, G; Rodrigo, L; Santolaria, S; Güell, M; de Argila, C M; Quintero, E; Borda, F; Piqué, J M

    2006-01-01

    Background The risks and benefits of coxibs, non‐steroidal anti‐inflammatory drugs (NSAIDs), and aspirin treatment are under intense debate. Objective To determine the risk of peptic ulcer upper gastrointestinal bleeding (UGIB) associated with the use of coxibs, traditional NSAIDs, aspirin or combinations of these drugs in clinical practice. Methods A hospital‐based, case–control study in the general community of patients from the National Health System in Spain. The study included 2777 consecutive patients with endoscopy‐proved major UGIB because of the peptic lesions and 5532 controls matched by age, hospital and month of admission. Adjusted relative risk (adj RR) of UGIB determined by conditional logistic regression analysis is provided. Results Use of non‐aspirin‐NSAIDs increased the risk of UGIB (adj RR 5.3; 95% confidence interval (CI) 4.5 to 6.2). Among non‐aspirin‐NSAIDs, aceclofenac (adj RR 3.1; 95% CI 2.3 to 4.2) had the lowest RR, whereas ketorolac (adj RR 14.4; 95% CI 5.2 to 39.9) had the highest. Rofecoxib treatment increased the risk of UGIB (adj RR 2.1; 95% CI 1.1 to 4.0), whereas celecoxib, paracetamol or concomitant use of a proton pump inhibitor with an NSAID presented no increased risk. Non‐aspirin antiplatelet treatment (clopidogrel/ticlopidine) had a similar risk of UGIB (adj RR 2.8; 95% CI 1.9 to 4.2) to cardioprotective aspirin at a dose of 100 mg/day (adj RR 2.7; 95% CI 2.0 to 3.6) or anticoagulants (adj RR 2.8; 95% CI 2.1 to 3.7). An apparent interaction was found between low‐dose aspirin and use of non‐aspirin‐NSAIDs, coxibs or thienopyridines, which increased further the risk of UGIB in a similar way. Conclusions Coxib use presents a lower RR of UGIB than non‐selective NSAIDs. However, when combined with low‐dose aspirin, the differences between non‐selective NSAIDs and coxibs tend to disappear. Treatment with either non‐aspirin antiplatelet or cardioprotective aspirin has a similar risk of UGIB. PMID

  13. Bilateral rupture of the Achilles tendon in patients on steroid therapy.

    PubMed Central

    Haines, J F

    1983-01-01

    Three patients are presented who sustained bilateral rupture of the Achilles tendon while on systemic steroid therapy for chest disease; a fourth patient with polymyalgia rheumatica on steroids is also presented. This is further evidence that tendon rupture can be a direct complication of steroid treatment. The English-language literature on bilateral Achilles tendon rupture is reviewed. PMID:6651370

  14. Highly sensitive and selective analysis of urinary steroids by comprehensive two-dimensional gas chromatography combined with positive chemical ionization quadrupole mass spectrometry

    PubMed Central

    Zhang, Ying; Tobias, Herbert J.; Brenna, J. Thomas

    2014-01-01

    Comprehensive two dimensional gas chromatography (GC×GC) provides greater separation space than conventional GC. Because of fast peak elution, a time of flight mass spectrometer (TOFMS) is the usual structure-specific detector of choice. The quantitative capabilities of a novel GC×GC fast quadrupole MS were investigated with electron ionization (EI), and CH4 or NH3 positive chemical ionization (PCI) for analysis of endogenous urinary steroids targeted in anti-doping tests. Average precisions for steroid quantitative analysis from replicate urine extractions were 6% (RSD) for EI and 8% for PCI-NH3. The average limits of detection (LOD) calculated by quantification ions for 12 target steroids spiked into steroid-free urine matrix (SFUM) were 2.6 ng mL−1 for EI, 1.3 ng mL−1 for PCI-CH4, and 0.3 ng mL−1 for PCI-NH3, all in mass scanning mode. The measured limits of quantification (LOQ) with full mass scan GC×GC-qMS were comparable with the LOQ values measured by one-dimensional GC-MS in single ion monitoring (SIM) mode. PCI-NH3 yields fewer fragments and greater (pseudo)molecular ion abundances than EI or PCI-CH4. These data show a benchtop GC×GC-qMS system has the sensitivity, specificity, and resolution to analyze urinary steroids at normal urine concentrations, and that PCI-NH3, not currently available on most GC×GC-TOFMS instruments, is of particular value for generation of structure-specific ions. PMID:22606686

  15. The novel non-steroidal selective androgen receptor modulator S-101479 has additive effects with bisphosphonate, selective estrogen receptor modulator, and parathyroid hormone on the bones of osteoporotic female rats.

    PubMed

    Furuya, Kazuyuki; Yamamoto, Noriko; Ohyabu, Yuki; Makino, Akito; Morikyu, Teruyuki; Ishige, Hirohide; Kuzutani, Kazuya; Endo, Yasuhisa

    2012-01-01

    We have studied non-steroidal selective androgen receptor modulators (SARMs) to develop anti-osteoporosis drugs for males and females. Many SARMs have been studied for their anabolic effects on bone or muscle with reduced virilizing effects in male animals. However, the tissue selectivities of these agents in female animals have not been fully evaluated. We evaluated the novel SARM S-101479 from tetrahydroquinoline libraries in ovariectomized (OVX) rats. S-101479 preferentially bound to the androgen receptor with nanomolar affinity among nuclear receptors. It increased the bone mineral density (BMD) of femurs and diminished the effects on the uterus and clitoral gland in OVX rats. We then compared the effect of S-101479 on bone with those of commercial anti-osteoporosis drugs such as alendronate, raloxifene, and teriparatide. Furthermore, we evaluated the effects of combination treatments with these agents in OVX rats. After 16-week treatment, all agents significantly increased BMD, but the magnitude of bone mineral content (BMC) and/or bone size (projected bone area) were different. Alendronate, raloxifene, and teriparatide maintained BMC and bone size in this experimental dose. Only S-101479 increased BMC with bone size on single treatments. In combination treatment, S-101479 significantly increased BMC and bone size compared with single treatments of other agents. S-101479, like natural androgen, may have showed periosteal bone formation of the cortical area and indicated additive effects with commercial anti-osteoporosis drugs. These results indicate that S-101479 may be a useful anti-osteoporosis drug, particularly for patients with established severe osteoporosis.

  16. Mind Over Matter: Anabolic Steroids

    MedlinePlus

    ... Term(s): Teachers / NIDA Teaching Guide / Mind Over Matter Teaching Guide and Series / Anabolic Steroids Print Mind Over Matter: Anabolic Steroids Order Free Publication in: English Spanish Download PDF 830.69 KB Anabolic steroids are ...

  17. The Steroid Metabolome of Adrenarche

    PubMed Central

    Rege, Juilee; Rainey, William E.

    2014-01-01

    Adrenarche is an endocrine developmental process whereby humans and select nonhuman primates increase adrenal output of a series of steroids, especially dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS). The timing of adrenarche varies between primates, but in humans, serum levels of DHEAS are seen to increase around 6 years of age. This phenomenon corresponds with the development and expansion of the zona reticularis (ZR) of the adrenal gland. The physiological phenomena that trigger the onset of adrenarche are still unknown; however the biochemical pathways leading to this event have been elucidated in detail. There are numerous reviews examining the process of adrenarche, most of which, have focused on the changes within the adrenal as well as the phenotypic results of adrenarche. This article reviews the recent and past studies that show the breadth of changes in the circulating steroid metabolome that occurs during the process of adrenarche. PMID:22715193

  18. STEC:O111-HUS complicated by acute encephalopathy in a young girl was successfully treated with a set of hemodiafiltration, steroid pulse, and soluble thrombomodulin under plasma exchange.

    PubMed

    Yada, Noritaka; Fujioka, Masayuki; Bennett, Charles L; Inoki, Kazuya; Miki, Toyokazu; Watanabe, Akihiko; Yoshida, Toshiko; Hayakawa, Masaki; Matsumoto, Masanori; Fujimura, Yoshihiro

    2015-04-01

    We report a 14-year-old girl, who developed shigatoxin-producing E. coli (STEC)-HUS complicated by encephalopathy. She was successfully treated with hemodiafiltration, high-dose methylprednisolone pulse therapy, and soluble recombinant thrombomodulin under plasma exchange. von Willebrand factor multimers analysis provides potential insights into how the administered therapies might facilitate successful treatment of STEC-HUS.

  19. Pharmacology of anabolic steroids.

    PubMed

    Kicman, A T

    2008-06-01

    Athletes and bodybuilders have recognized for several decades that the use of anabolic steroids can promote muscle growth and strength but it is only relatively recently that these agents are being revisited for clinical purposes. Anabolic steroids are being considered for the treatment of cachexia associated with chronic disease states, and to address loss of muscle mass in the elderly, but nevertheless their efficacy still needs to be demonstrated in terms of improved physical function and quality of life. In sport, these agents are performance enhancers, this being particularly apparent in women, although there is a high risk of virilization despite the favourable myotrophic-androgenic dissociation that many xenobiotic steroids confer. Modulation of androgen receptor expression appears to be key to partial dissociation, with consideration of both intracellular steroid metabolism and the topology of the bound androgen receptor interacting with co-activators. An anticatabolic effect, by interfering with glucocorticoid receptor expression, remains an attractive hypothesis. Behavioural changes by non-genomic and genomic pathways probably help motivate training. Anabolic steroids continue to be the most common adverse finding in sport and, although apparently rare, designer steroids have been synthesized in an attempt to circumvent the dope test. Doping with anabolic steroids can result in damage to health, as recorded meticulously in the former German Democratic Republic. Even so, it is important not to exaggerate the medical risks associated with their administration for sporting or bodybuilding purposes but to emphasize to users that an attitude of personal invulnerability to their adverse effects is certainly misguided.

  20. Anabolic steroid abuse.

    PubMed

    Landry, G L; Primos, W A

    1990-01-01

    Anabolic steroids are capable of increasing strength and muscle bulk in certain individuals when combined with a proper diet and an intense training program. Any steroid that is anabolic is also androgenic. Anabolic steroids are fraught with numerous side effects, a few of which are potentially life threatening, and some of which are permanent. Most of the side effects are mild and reversible. Use of anabolic steroids in sports is as much a moral issue as a medical one. Drug testing has not been a very successful means to eradicate abuse in the sporting arena. Education alone is probably not the answer to stopping anabolic steroid abuse but is an essential first step in combating this problem. Use of anabolic steroids in athletes is a form of cheating, and use will likely continue, especially if the rewards for success in sports remain so high. Physicians should avoid condemning individuals who choose to use anabolic steroids and encourage discussion of use with their health providers.

  1. [Ocular hypertension after intravitreal steroid injections: Clinical update as of 2015].

    PubMed

    Dot, C; El Chehab, H; Russo, A; Agard, E

    2015-09-01

    Intravitreal injections are a therapeutic delivery method best suited to the treatment of retinal diseases. Recent years have been marked by the use of anti-VEGF agents as well as the arrival of sustained-release corticosteroid implants in France, replacing triamcinolone acetonide. A common complication of IVT steroids is secondary ocular hypertension (OHT) resulting from increased outflow resistance. This article summarizes current understanding. OHT induced by topical steroids has been described for 60 years. Intravitreal use also shows a temporary effect if the exposure is short, dose dependence, and varying incidence depending on the drug used. Sustained release formulations and discontinuing treatment have reduced the risk of induced OHT. Risk factors that induce OHT must be clearly identified prior to an injection. Most cases of OHT can be controlled medically, although differences exist between different drugs. In cases where it cannot be controlled, removal of the implant, selective laser trabeculoplasty, and filtration surgery can be discussed.

  2. STEC:O111-HUS complicated by acute encephalopathy in a young girl was successfully treated with a set of hemodiafiltration, steroid pulse, and soluble thrombomodulin under plasma exchange

    PubMed Central

    Yada, Noritaka; Fujioka, Masayuki; Bennett, Charles L; Inoki, Kazuya; Miki, Toyokazu; Watanabe, Akihiko; Yoshida, Toshiko; Hayakawa, Masaki; Matsumoto, Masanori; Fujimura, Yoshihiro

    2015-01-01

    Key Clinical Message We report a 14-year-old girl, who developed shigatoxin-producing E. coli (STEC)-HUS complicated by encephalopathy. She was successfully treated with hemodiafiltration, high-dose methylprednisolone pulse therapy, and soluble recombinant thrombomodulin under plasma exchange. von Willebrand factor multimers analysis provides potential insights into how the administered therapies might facilitate successful treatment of STEC-HUS. PMID:25914810

  3. Risk factors for anabolic-androgenic steroid use in men.

    PubMed

    Brower, K J; Blow, F C; Hill, E M

    1994-01-01

    The illicit use of anabolic steroids to enhance athletic performance and physical appearance can cause numerous psychiatric and other adverse effects. In order to prevent steroid use and its negative consequences, knowledge of risk factors is needed. We conducted an anonymous survey of 404 male weight lifters from community gymnasiums who completed a 20-min, self-administered questionnaire. The sample for this study included all 35 men who were thinking about using steroids ("high-risk" nonusers), 50 randomly selected nonusers who were not thinking about using steroids ("low-risk" nonusers) and all 49 steroid users. The three groups differed in age, training characteristics, other performance-enhancers tried, body image, acquaintance with steroid users, and perception of negative consequences. When groups were compared along a continuum from low risk to high risk and from high risk to actual use, we found increasing amounts of competitive bodybuilding, performance-enhancers tried, and steroid-using acquaintances. Groups did not differ in their use of addictive substances. Nearly three-fourths of the high-risk group felt "not big enough," compared to 21% of the low-risk group and 38% of the steroid users (p < .001). These data suggest that steroids do work to increase satisfaction with body size, and that dissatisfaction with body size may contribute to the risk of using steroids.

  4. Steroids (For Parents)

    MedlinePlus

    ... by some athletes and bodybuilders. Anabolic steroids are synthetic hormones that can boost the body's ability to ... doses every day can significantly increase levels of testosterone, which can lead to a number of health ...

  5. Preparation of novel alumina nanowire solid-phase microextraction fiber coating for ultra-selective determination of volatile esters and alcohols from complicated food samples.

    PubMed

    Zhang, Zhuomin; Ma, Yunjian; Wang, Qingtang; Chen, An; Pan, Zhuoyan; Li, Gongke

    2013-05-17

    A novel alumina nanowire (ANW) solid-phase microextraction (SPME) fiber coating was prepared by a simple and rapid anodization-chemical etching method for ultra-selective determination of volatile esters and alcohols from complicated food samples. Preparation conditions for ANW SPME fiber coating including corrosion solution concentration and corrosion time were optimized in detail for better surface morphology and higher surface area based on scanning electron microscope (SEM). Under the optimum conditions, homogeneous alumina nanowire structure of ANW SPME fiber coating was achieved with the average thickness of 20 μm around. Compared with most of commercial SPME fiber coatings, ANW SPME fiber coatings achieved the higher extraction capacity and special selectivity for volatile esters and alcohols. Finally, an efficient gas sampling technique based on ANW SPME fiber coating as the core was established and successfully applied for the ultra-selective determination of trace volatile esters and alcohols from complicated banana and fermented glutinous rice samples coupled with gas chromatography/mass spectrometry (GC/MS) detection. It was interesting that 25 esters and 2 alcohols among 30 banana volatile organic compounds (VOCs) identified and 4 esters and 7 alcohols among 13 identified VOCs of fermented glutinous rice were selectively sampled by ANW SPME fiber coatings. Furthermore, new analytical methods for the determination of some typical volatile esters and alcohols from banana and fermented glutinous rice samples at specific storage or brewing phases were developed and validated. Good recoveries for banana and fermented glutinous rice samples were achieved in range of 108-115% with relative standard deviations (RSDs) of 2.6-6.7% and 80.0-91.8% with RSDs of 0.3-1.3% (n=3), respectively. This work proposed a novel and efficient gas sampling technique of ANW SPME which was quite suitable for ultra-selectively sampling trace volatile esters and alcohols from

  6. Steroid biosynthesis in adipose tissue.

    PubMed

    Li, Jiehan; Papadopoulos, Vassilios; Vihma, Veera

    2015-11-01

    Tissue-specific expression of steroidogenic enzymes allows the modulation of active steroid levels in a local manner. Thus, the measurement of local steroid concentrations, rather than the circulating levels, has been recognized as a more accurate indicator of the steroid action within a specific tissue. Adipose tissue, one of the largest endocrine tissues in the human body, has been established as an important site for steroid storage and metabolism. Locally produced steroids, through the enzymatic conversion from steroid precursors delivered to adipose tissue, have been proven to either functionally regulate adipose tissue metabolism, or quantitatively contribute to the whole body's steroid levels. Most recently, it has been suggested that adipose tissue may contain the steroidogenic machinery necessary for the initiation of steroid biosynthesis de novo from cholesterol. This review summarizes the evidence indicating the presence of the entire steroidogenic apparatus in adipose tissue and discusses the potential roles of local steroid products in modulating adipose tissue activity and other metabolic parameters.

  7. Gonadotropin-releasing hormone agonist selectively augments thymopoiesis and prevents cell apoptosis in LPS induced thymic atrophy model independent of gonadal steroids.

    PubMed

    Ullewar, Meenal P; Umathe, Sudhir N

    2014-11-01

    Lipopolysaccharide (LPS) causes acute thymic atrophy, a phenomenon that has been linked to immune dysfunction and poor survival during sepsis. The systemic response to LPS involves a rise in glucocorticoids and proinflammatory cytokines which contribute greatly to thymic involution and apoptosis. Gonadotropin-releasing hormone (GnRH) analog exerts thymopoietic regulatory effects and possesses immunostimulant properties. We determined whether leuprolide, a GnRH analog can be useful in LPS induced thymic involution and apoptosis. Mice injected with 100 μg of LPS intraperitoneally led to involution of thymus, to decrease of CD4(+)8(+) thymocyte subset, and to fragmentation of thymic DNA. Leuprolide (100 μg/mouse, s.c.) pretreatment significantly attenuated LPS induced thymic atrophy, and also reduced LPS induced systemic rise in corticosterone levels. The observed effect of leuprolide remained unaffected in castrated and ovariectomized mice. Collectively, leuprolide has protective action independent of gonadal steroids, which was mediated by blunting of the systemic corticosteroid response in LPS induced thymic atrophy model.

  8. Complications from radiotherapy.

    PubMed

    Dhermain, Frédéric; Barani, Igor J

    2016-01-01

    Radiotherapy (RT) of the brain is associated with significant stigma in the neuro-oncology community. This is primarily because of the potentially severe complications with which it may be associated. These complications, especially in subacute and latent settings, are often unpredictable, potentially progressive, and irreversible. The onset of complications may start from the first fraction of 2 Gy, continuing over several months after end of RT with persistent drowsiness and apathy. It may also extend over many years with progressive onset of neurocognitive impairments such as memory decline, and diminished focus/attention. For long-term survivors, such as young patients irradiated for a favorable low-grade glioma, quality of life can be seriously impacted by RT. It is essential, as in the pediatric field, to propose patient-specific regimens from the very outset of therapy. The use of molecular biomarkers to better predict survival, control of comorbidities along with judicious use of medications such as steroids and antiepileptics, improved targeting with the help of modern imaging and RT techniques, modulation of the dose, and fractionation aimed at limiting integral dose to the healthy brain all have the potential to minimize treatment-related complications while maintaining the therapeutic efficacy for which RT is known. Sparing "radiosensitive" areas such as hippocampi could have a modest but measurable impact with regard to cognitive preservation, an effect that can possibly be enhanced when used in conjunction with memantine and/or donepezil. PMID:26948357

  9. Detection of designer steroids

    PubMed Central

    Yuan, Xiaohui; Forman, Barry Marc

    2005-01-01

    Illicit use of performance-enhancing steroids has proliferated among a wide range of professional and amateur athletes. This problem has attracted broad public attention and has led the United States Congress to draft legislation that proposes frequent testing of athletes. However, current testing protocols are inadequate as athletes can evade detection by using novel steroids that are unknown to authorities. We have developed a strategy that overcomes this limitation by virtue of its ability to detect “designer steroids” without prior knowledge of their existence. PMID:16604170

  10. Steroids. Building a better you?

    PubMed

    Berlin, B

    1999-03-01

    The use of anabolic steroids was first reported in the 1950s among weight lifters seeking to gain an edge in strength and muscle size. Since then, anabolic steroids have been used to augment strength and appearance. Today, steroids reach far beyond the world of professional athletes to high school locker rooms, neighborhood gyms, and suburban fitness centers. An estimated one million Americans use anabolic steroids for nonmedical purposes, supporting an illicit $400 million market.

  11. Regulation of 3β-hydroxysteroid dehydrogenase and sulphotransferase 2A1 gene expression in primary porcine hepatocytes by selected sex-steroids and plant secondary metabolites from chicory (Cichorium intybus L.) and wormwood (Artemisia sp.).

    PubMed

    Rasmussen, Martin Krøyer; Ekstrand, Bo

    2014-02-15

    In pigs the endogenously produced compound androstenone is metabolised in the liver in two steps by 3β-hydroxysteroid dehydrogenase (3β-HSD) and sulphotransferase 2A1 (SULT2A1). The present study investigated the effect of selected sex-steroids (0.01-1 μM androstenone, testosterone and estradiol), skatole (1-100 μM) and secondary plant metabolites (1-100 μM) on the expression of 3β-HSD and SULT2A1 mRNA. Additionally the effect of a global methanolic extract of dried chicory root was investigated and compared to previous obtained in vivo effects. Primary hepatocytes were isolated from the livers of piglets (crossbreed: Landrace×Yorkshire and Duroc) and cultured for 24h before treatment for an additionally 24h. RNA was isolated from the hepatocytes and specific gene expression determined by RT-PCR using TaqMan probes. The investigated sex-steroids had no effect on the mRNA expression of 3β-HSD and SULT2A1, while skatole decreased the content of SULT2A1 30% compared to control. Of the investigated secondary plant metabolites artemisinin and scoparone (found in Artemisia sp.) lowered the content of SULT2A1 by 20 and 30% compared to control, respectively. Moreover, we tested three secondary plant metabolites (lactucin, esculetin and esculin) found in chicory root. Lactucin increased the mRNA content of both 3β-HSD and SULT2A1 by 200% compared to control. An extract of chicory root was shown to decrease the expression of both 3β-HSD and SULT2A1. It is concluded that the gene expression of enzymes with importance for androstenone metabolism is regulated by secondary plant metabolites in a complex manner. PMID:24333270

  12. Regulation of 3β-hydroxysteroid dehydrogenase and sulphotransferase 2A1 gene expression in primary porcine hepatocytes by selected sex-steroids and plant secondary metabolites from chicory (Cichorium intybus L.) and wormwood (Artemisia sp.).

    PubMed

    Rasmussen, Martin Krøyer; Ekstrand, Bo

    2014-02-15

    In pigs the endogenously produced compound androstenone is metabolised in the liver in two steps by 3β-hydroxysteroid dehydrogenase (3β-HSD) and sulphotransferase 2A1 (SULT2A1). The present study investigated the effect of selected sex-steroids (0.01-1 μM androstenone, testosterone and estradiol), skatole (1-100 μM) and secondary plant metabolites (1-100 μM) on the expression of 3β-HSD and SULT2A1 mRNA. Additionally the effect of a global methanolic extract of dried chicory root was investigated and compared to previous obtained in vivo effects. Primary hepatocytes were isolated from the livers of piglets (crossbreed: Landrace×Yorkshire and Duroc) and cultured for 24h before treatment for an additionally 24h. RNA was isolated from the hepatocytes and specific gene expression determined by RT-PCR using TaqMan probes. The investigated sex-steroids had no effect on the mRNA expression of 3β-HSD and SULT2A1, while skatole decreased the content of SULT2A1 30% compared to control. Of the investigated secondary plant metabolites artemisinin and scoparone (found in Artemisia sp.) lowered the content of SULT2A1 by 20 and 30% compared to control, respectively. Moreover, we tested three secondary plant metabolites (lactucin, esculetin and esculin) found in chicory root. Lactucin increased the mRNA content of both 3β-HSD and SULT2A1 by 200% compared to control. An extract of chicory root was shown to decrease the expression of both 3β-HSD and SULT2A1. It is concluded that the gene expression of enzymes with importance for androstenone metabolism is regulated by secondary plant metabolites in a complex manner.

  13. Steroids. A Resource Guide.

    ERIC Educational Resources Information Center

    New York State Education Dept., Albany. Bureau of School Health Education and Services.

    This guide provides information on steroid use as well as prevention and intervention strategies. It is intended to serve as a supplement to drug abuse education and prevention programs in elementary and secondary schools and as the basis for local curriculum development and instructional activities. The following topics are covered: (1) history…

  14. Anabolic Steroids...What's the Hype?...

    ERIC Educational Resources Information Center

    Landry, Gregory L.; Wagner, Lauris L.

    This pamphlet uses a question-and-answer format to examine the use and abuse of anabolic steroids. It begins by explaining that all steroids are not anabolic steroids and that anabolic steroids are those used specifically to build muscles quickly. Medical uses of anabolic steroids are reviewed; how people get steroids, how they take them, and…

  15. Steroid-induced central serous retinopathy.

    PubMed

    Shah, Samidh P; Desai, Chetna K; Desai, Mira K; Dikshit, R K

    2011-09-01

    A-24 year-old male was prescribed prednisolone (60 mg/day) for left sided facial palsy. After three days of therapy, the patient complained of black spots in his vision in right eye. Fluorescein angiography of right eye showed evidence of central serous retinopathy (CSR). Prednisolone dose was withdrawn gradually and the patient improved within a week. There were no other systemic or ophthalmic diseases reported by the patient, which could have caused this condition. An improvement after dechallenge confirmed steroid-induced CSR. Recurrent CSR is known to cause permanent loss of vision. Hence, awareness regarding this adverse drug reaction (ADR) with steroids and its reporting can minimize this complication and help in better patient management.

  16. Stress, Ethanol, and Neuroactive Steroids

    PubMed Central

    Biggio, Giovanni; Concas, Alessandra; Follesa, Paolo; Sanna, Enrico; Serra, Mariangela

    2010-01-01

    Neurosteroids play a crucial role in stress, alcohol dependence and withdrawal, and other physiological and pharmacological actions by potentiating or inhibiting neurotransmitter action. This review article focuses on data showing that the interaction among stress, ethanol, and neuroactive steroids may result in plastic molecular and functional changes of GABAergic inhibitory neurotransmission. The molecular mechanisms by which stress-ethanol-neuroactive steroids interactions can produce plastic changes in GABAA receptors have been studied using different experimental models in vivo and in vitro in order to provide useful evidence and new insights into the mechanisms through which acute and chronic ethanol and stress exposure modulate the activity of GABAergic synapses. We show detailed data on a) the effect of acute and chronic stress on peripheral and brain neurosteroid levels and GABAA receptor gene expression and function; b) ethanol-stimulated brain steroidogenesis; c) plasticity of GABAA receptor after acute and chronic ethanol exposure. The implications of these new mechanistic insights to our understanding of the effects of ethanol during stress are also discussed. The understanding of these neurochemical and molecular mechanisms may shed new light on the physiopathology of diseases, such as anxiety, in which GABAergic transmission play a pivotal role. These data may also lead to the need for new anxiolytic, hypnotic and anticonvulsant selective drugs devoid of side effects. PMID:17555824

  17. Nonprescription steroids on the Internet.

    PubMed

    Clement, Christen L; Marlowe, Douglas B; Patapis, Nicholas S; Festinger, David S; Forman, Robert F

    2012-02-01

    This study evaluated the degree to which anabolic-androgenic steroids are proffered for sale over the Internet and how they are characterized on popular Web sites. Searches for specific steroid product labels (e.g., Dianabol) between March 2006 and June 2006 revealed that approximately half of the Web sites advocated their "safe" use, and roughly one third offered to sell them without prescriptions. The Web sites frequently presented misinformation about steroids and minimized their dangers. Less than 5% of the Web sites presented accurate health risk information about steroids or provided information to abusers seeking to discontinue their steroid use. Implications for education, prevention, treatment, and policy are discussed. PMID:22080724

  18. Nonprescription Steroids on the Internet

    PubMed Central

    McDonald, Christen L.; Marlowe, Douglas B.; Patapis, Nicholas S.; Festinger, David S.; Forman, Robert F.

    2008-01-01

    This study evaluated the degree to which anabolic-androgenic steroids are proffered for sale over the Internet and how they are characterized on popular websites. Searches for specific steroid product labels (e.g., Dianabol) between March and June, 2006 revealed that approximately half of the websites advocated their “safe” use, and roughly one-third offered to sell them without prescriptions. The websites frequently presented misinformation about steroids and minimized their dangers. Less than 5% of the websites presented accurate health risk information about steroids or provided information to abusers seeking to discontinue their steroid use. Implications for education, prevention, treatment and policy are discussed. PMID:22080724

  19. Pharmacokinetics of S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide in rats, a non-steroidal selective androgen receptor modulator

    PubMed Central

    KEARBEY, J. D.; WU, D.; GAO, W.; MILLER, D. D.; DALTON, J. T.

    2007-01-01

    1. S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide (also known as S-4) is a non-steroidal selective androgen receptor modulator demonstrating tissue-selective androgenic and anabolic effects. The purpose of the present study was to examine the systemic pharmacokinetics, elimination and oral bioavailability of S-4 in rats. 2. Thirty-five male Sprague–Dawley rats weighing approximately 250 g were randomly assigned to one of seven treatment groups. Intravenous doses of 0.5, 1, 10, and 30 mg kg−1 were given via a jugular catheter. Oral doses of 1, 10 and 30 mg kg−1 were administered via gavage. Plasma concentrations were determined using a validated high-performance liquid chromatography or by a high-performance liquid chromatography/mass spectrometry method. 3. Clearances ranged between 1.0 and 2.1 ml min−1 kg−1 and varied with dose. The volume of distribution was approximately 0.448 l kg−1 in all treatment groups. Oral bioavailability was also dose dependent, with the lower doses showing complete oral bioavailability. The half-life of S-4 over the dose range tested was between 2.6 and 5.3 h. 4. It was demonstrated that S-4 is rapidly absorbed, slowly cleared, and has a moderate volume of distribution in rats. The pharmacokinetics and oral bioavailability of S-4 indicate that it is an excellent candidate for clinical development. PMID:15204699

  20. Anabolic steroids and growth hormone.

    PubMed

    Haupt, H A

    1993-01-01

    Athletes are generally well educated regarding substances that they may use as ergogenic aids. This includes anabolic steroids and growth hormone. Fortunately, the abuse of growth hormone is limited by its cost and the fact that anabolic steroids are simply more enticing to the athlete. There are, however, significant potential adverse effects regarding its use that can be best understood by studying known growth hormone excess, as demonstrated in the acromegalic syndrome. Many athletes are unfamiliar with this syndrome and education of the potential consequences of growth hormone excess is important in counseling athletes considering its use. While athletes contemplating the use of anabolic steroids may correctly perceive their risks for significant physiologic effects to be small if they use the steroids for brief periods of time, many of these same athletes are unaware of the potential for habituation to the use of anabolic steroids. The result may be incessant use of steroids by an athlete who previously considered only short-term use. As we see athletes taking anabolic steroids for more prolonged periods, we are likely to see more severe medical consequences. Those who eventually do discontinue the steroids are dismayed to find that the improvements made with the steroids generally disappear and they have little to show for hours or even years of intense training beyond the psychological scars inherent with steroid use. Counseling of these athletes should focus on the potential adverse psychological consequences of anabolic steroid use and the significant risk for habituation.

  1. 77 FR 44456 - Classification of Two Steroids, Prostanozol

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-30

    .... Background In a Notice of Proposed Rulemaking (NPRM) published on November 23, 2011 (76 FR 72355), DEA... healthy individual who experiences clear physical and psychological complications (Trenton and Currier... attacks. Furthermore, anabolic steroid abuse is purported to induce psychological effects such...

  2. Orbital complications in functional endoscopic sinus surgery.

    PubMed

    Corey, J P; Bumsted, R; Panje, W; Namon, A

    1993-11-01

    Endoscopic sinus surgery can result in both minor and major complications. Among these, orbital complications--including retroorbital hematoma--are among the most feared. Injuries can be direct or indirect from pulling on diseased structures. A retrospective chart review of 616 endoscopic sinus procedures revealed eight orbital complications in seven patients. These included two medial rectus injuries, five orbital hemorrhages, and one nasolacrimal duct injury. Predisposing factors may include hypertension, lamina papyracia dehiscences, extensive polypoid disease, previous surgery, inability to visualize the maxillary ostia, violent coughing or sneezing, and chronic steroid use. Suggested management in the literature includes lateral canthotomy, steroids, and mannitol with ophthalmologic consultation. Opening of the wound by means of an external ethmoidectomy incision has also been suggested. We suggest that adding orbital decompression by means of multiple incisions into the periorbita should be added for fully effective relief. A "management" tree of decision parameters relevant to orbital complications is presented.

  3. Considerations and complications after Bells' palsy.

    PubMed

    Nemet, Arie Y; Vinker, Shlomo

    2015-12-01

    We present a retrospective, observational study of all patients diagnosed with Bells' palsy (BP) at the Central District of Clalit Health Services from 2003 through to 2012. BP is associated with several complications. We evaluated clinical characteristics including the number of patient visits to general physicians (GP), otolaryngologists, ophthalmologists and neurologists, medications prescribed in the acute phase of BP (steroids and antiviral agents), and the ophthalmic diagnoses. A total of 4463 patients with the diagnosis of BP were included. The incidence per 100,000/year was 87.0, and it increased with age. Patients had significantly more visits to all specialists at 6 months after the BP event. Steroid treatment was prescribed to 50.4% of the patients and antiviral agents to 65.5%. Both treatments were associated with older patient age and female sex. The rate of post BP lagophthalmos and keratitis was 3.45% and 0.63% at 1-3 months, respectively, and both were more likely to develop in older patients. Steroid and/or antiviral treatments were not associated with a decrease in ophthalmic complications. BP may cause ophthalmic complications at a low rate, which are associated with older age. Steroids and antiviral agents appeared to have no effect on ophthalmic complications. PMID:26314659

  4. Steroid Receptor-Associated Immunophilins: A Gateway to Steroid Signalling

    PubMed Central

    Ratajczak, Thomas; Cluning, Carmel; Ward, Bryan K

    2015-01-01

    The steroid receptor-associated immunophilins FKBP51, FKBP52, CyP40 and PP5 have specific roles in steroid receptor function that impact steroid hormone-binding affinity, nucleocytoplasmic shuttling and transcriptional activation of target genes in a tissue-specific manner. Aberrant expression of these functionally unique immunophilins has the potential to cause steroid-based diseases, including breast and prostate cancer, diabetes and related metabolic disorders, male and female infertility and major depressive disorders. This review addresses the function of these proteins as co-chaperones in steroid receptor-Hsp90 complexes and extensively covers current knowledge of the link between the steroid receptor-associated immunophilins and human disease. An improved understanding of their mechanisms of action has revealed opportunities for molecular therapies to enhance or inhibit cellular processes under immunophilin control that contribute both to human health and disease. PMID:26224894

  5. Selection of background electrolyte for CZE analysis by a chemometric approach. Part I. Separation of a mixture of acidic non-steroidal anti-inflammatory drugs.

    PubMed

    Furlanetto, Sandra; Lanteri, Silvia; Orlandini, Serena; Gotti, Roberto; Giannini, Iacopo; Pinzauti, Sergio

    2007-03-12

    This paper is the first part of the presentation of a chemometric approach for the rapid selection of a suitable background electrolyte (BGE) in CZE analysis of small drug molecules. The strategy is based on principal component analysis and experimental design. In this first section, the approach is applied to the analysis of a mixture of six arylpropionic anti-inflammatory drugs. Initially, 222 possible aqueous background electrolytes (objects) were characterized using as descriptors pH, conductivity, ionic strength and relative viscosity. In order to allow the dissociation of the acidic analytes, this original data set was reduced to 154 background electrolytes with pH values higher than or equal to 5. Principal component analysis made it possible to graphically represent the new set of objects, described by the four variables, in a two-dimensional space. Among these electrolytes, Kennard-Stone algorithm selected ten objects to be tested by CZE, covering homogeneously principal component space. CZE analyses were carried out with the selected electrolytes, and 0.1 M borax was identified as the most suitable one for the specified application. Finally, the characteristics of the analysis were finely tuned by means of a response surface study, which allowed the best conditions to be determined: borax concentration, 0.09 M; methanol, 6% (v/v); temperature, 24 degrees C, voltage, 20 kV. Applying these conditions, a baseline resolution among the six compounds was obtained in less than 10 min.

  6. Benzo[c]quinolizin-3-ones: a novel class of potent and selective nonsteroidal inhibitors of human steroid 5alpha-reductase 1.

    PubMed

    Guarna, A; Machetti, F; Occhiato, E G; Scarpi, D; Comerci, A; Danza, G; Mancina, R; Serio, M; Hardy, K

    2000-10-01

    The synthesis and biological evaluation of a series of novel, selective inhibitors of isoenzyme 1 of human 5alpha-reductase (5alphaR) (EC 1.3.99.5) are reported. The inhibitors are 4aH- (19-29) or 1H-tetrahydrobenzo[c]quinolizin-3-ones (35-47) bearing at positions 1, 4, 5, and 6 a methyl group and at position 8 a hydrogen, methyl group, or chlorine atom. All these compounds were tested toward 5alphaR-1 and 5alphaR-2 expressed in CHO cells (CHO 1827 and CHO 1829, respectively) resulting in selective inhibitors of the type 1 isoenzyme, with inhibitory potencies (IC(50)) ranging from 7.6 to 9100 nM. The inhibitors of the 4aH-series, having a double bond at position 1,2, were generally less active than the corresponding inhibitors of the 1H-series having the double bond at position 4,4a on the A ring. The presence of a methyl group at position 4 (as in compounds 39-40 and 45-47), associated with a substituent at position 8, determined the highest inhibition potency (IC(50) from 7.6 to 20 nM). Compounds 39 and 40, having K(i) values of 5.8+/-1.8 and 2.7+/-0.6 nM, respectively, toward 5alphaR-1 expressed in CHO cells, were also tested toward native 5alphaR-1 in human scalp and 5alphaR-2 in human prostate homogenates, in comparison with finasteride and the known 5alphaR-1-selective inhibitor LY191704, and their mechanism of inhibition was determined. They both inhibited the enzyme through a reversible competitive mechanism and again were selective inhibitors of 5alphaR-1 with IC(50) values of 41 nM. These specific features make these inhibitors suitable candidates for further development as drugs in the treatment of DHT-dependent disorders such as acne and androgenic alopecia in men and hirsutism in women. PMID:11020287

  7. First synthesis of thia steroids from cholic acid.

    PubMed

    Ibrahim-Ouali, Malika; Rocheblave, Luc

    2010-10-01

    Heterosteroids remain interesting due to their potential biological activities. This prompted us to synthesize novel thia steroids possessing the heteroatom in the A-ring. We set out to describe a new and versatile method for preparing 3-thia steroids from cholic acid via a selective oxidation of one hydroxyl group, a Baeyer-Villiger oxidation and a photolysis as the key steps. The characteristic (1)H and (13)C NMR spectroscopic features of the synthesized compounds are reported.

  8. Selective adsorption mechanisms of antilipidemic and non-steroidal anti-inflammatory drug residues on functionalized silica-based porous materials in a mixed solute.

    PubMed

    Suriyanon, Nakorn; Permrungruang, Jutima; Kaosaiphun, Jidanan; Wongrueng, Aunnop; Ngamcharussrivichai, Chawalit; Punyapalakul, Patiparn

    2015-10-01

    The selective adsorption mechanisms of naproxen (NAP), acetaminophen (ACT), and clofibric acid (CFA) on silica-based porous materials were examined by single and mixed-batch adsorption. Effects of the types and densities of surface functional groups on adsorption capacities were determined, including the role of hydrophobic and hydrophilic dissolved organic matters (DOMs). Hexagonal mesoporous silica (HMS), superparamagnetic HMS (HMS-SP) and SBA-15 were functionalized and applied as adsorbents. Compared with powdered activated carbon (PAC), amine-functionalized HMS had a better adsorption capacity for CFA, but PAC possessed a higher adsorption capacity for the other pharmaceuticals than HMS and its two derivatives. In contrast to PAC, the adsorption capacity of the mesoporous silicas varied with the solution pH, being highest at pH 5. Electrostatic interactions and hydrogen bonding were found to be the main mechanisms. Increase in grafted amine group density on silica surfaces can enhance the CFA adsorption capacity. Further, hydrophilic DOM can decrease CFA adsorption capacities on amino-grafted adsorbents by adsorption site competition, while hydrophobic DOM can interfere with CFA adsorption by the interaction between hydrophobic DOM and CFA. Finally, in a competitive adsorption study, the adsorption capacity of hydrophilic adsorbents for acidic pharmaceuticals varied with their pKa values.

  9. Selective adsorption mechanisms of antilipidemic and non-steroidal anti-inflammatory drug residues on functionalized silica-based porous materials in a mixed solute.

    PubMed

    Suriyanon, Nakorn; Permrungruang, Jutima; Kaosaiphun, Jidanan; Wongrueng, Aunnop; Ngamcharussrivichai, Chawalit; Punyapalakul, Patiparn

    2015-10-01

    The selective adsorption mechanisms of naproxen (NAP), acetaminophen (ACT), and clofibric acid (CFA) on silica-based porous materials were examined by single and mixed-batch adsorption. Effects of the types and densities of surface functional groups on adsorption capacities were determined, including the role of hydrophobic and hydrophilic dissolved organic matters (DOMs). Hexagonal mesoporous silica (HMS), superparamagnetic HMS (HMS-SP) and SBA-15 were functionalized and applied as adsorbents. Compared with powdered activated carbon (PAC), amine-functionalized HMS had a better adsorption capacity for CFA, but PAC possessed a higher adsorption capacity for the other pharmaceuticals than HMS and its two derivatives. In contrast to PAC, the adsorption capacity of the mesoporous silicas varied with the solution pH, being highest at pH 5. Electrostatic interactions and hydrogen bonding were found to be the main mechanisms. Increase in grafted amine group density on silica surfaces can enhance the CFA adsorption capacity. Further, hydrophilic DOM can decrease CFA adsorption capacities on amino-grafted adsorbents by adsorption site competition, while hydrophobic DOM can interfere with CFA adsorption by the interaction between hydrophobic DOM and CFA. Finally, in a competitive adsorption study, the adsorption capacity of hydrophilic adsorbents for acidic pharmaceuticals varied with their pKa values. PMID:26025186

  10. About Steroids (Inhaled and Oral Corticosteroids)

    MedlinePlus

    ... dose-inhalers ( inhaled steroids ), oral forms (pills or syrups) , injections (shots) and intravenous (IV) solutions. Healthcare providers ... slowly decreased. Inhaled steroids and steroid pills and syrups are often prescribed for people with a chronic ...

  11. Complications of glioma surgery.

    PubMed

    Jackson, Christina; Westphal, Manfred; Quiñones-Hinojosa, Alfredo

    2016-01-01

    Even with current advances in adjunctive therapies, including radiation, chemotherapy, and various clinical trials of gene therapy and immunotherapy, surgical resection remains one of the most effective treatment for intra-axial gliomas. Survival in these patients has been shown to be related to the extent of resection. In some cases, it can provide cures of long-term remission; in others, it can provide disease control when combined with the above adjunctive treatments. However, surgical resection carries its own risks and complications. These complications can be broadly divided into neurologic, regional, and systemic, including direct cortical and vascular injury, surgical wound complications, and postsurgical medical complications. Certain patient characteristics, including Karnofsky performance status score (KPS) and pathology of the tumor, have been shown to have an impact on the risk of postsurgical complications. Advancement in preoperative and intraoperative adjunct technology such as cortical mapping and navigation has improved the surgeon's ability to safely and maximally resect the tumors. It is therefore important to understand the perioperative complications after craniotomy and tumor resection and factors affecting morbidity and mortality in order for surgeons to optimally select and counsel patients who will benefit the most from surgical resection. This chapter will focus on the complications associated with craniotomy for intrinsic glioma and ways of avoiding these events.

  12. A guide to understanding the steroid pathway: new insights and diagnostic implications.

    PubMed

    Greaves, Ronda F; Jevalikar, Ganesh; Hewitt, Jacqueline K; Zacharin, Margaret R

    2014-10-01

    Steroid analysis has always been complicated requiring a clear understanding of both the clinical and analytical aspects in order to accurately interpret results. The literature relating to this specialised area spans many decades and the intricacies of the steroid pathway have evolved with time. A number of key changes, including discovery of the alternative androgen pathway, have occurred in the last decade, potentially changing our understanding and approach to investigating disorders of sexual development. Such investigation usually occurs in specialised paediatric centres and although preterm infants represent only a small percentage of the patient population, consideration of the persistence of the foetal adrenal zone is an additional important consideration when undertaking steroid hormone investigations. The recent expanded role of mass spectrometry and molecular diagnostic methods provides significant improvements for accurate steroid quantification and identification of enzyme deficiencies. However analysis of steroids and interpretation of results remain complicated. This review aims to provide an insight into the complexities of steroid measurement in children and offers an updated guide to interpretation, of serum and urine steroids through the presentation of a refined steroid pathway.

  13. Roles of Steroids in Nematodes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The inability of nematodes to biosynthesize steroids de novo and the resulting dependence of parasitic nematodes upon their hosts have enhanced the importance of elucidating the metabolism of sterols and the hormonal and other functions of steroids in nematodes. Biochemical research has revealed th...

  14. Pd-catalyzed steroid reactions.

    PubMed

    Czajkowska-Szczykowska, Dorota; Morzycki, Jacek W; Wojtkielewicz, Agnieszka

    2015-05-01

    We review the most important achievements of the last decade in the field of steroid synthesis in the presence of palladium catalysts. Various palladium-catalyzed cross-coupling reactions, including Heck, Suzuki, Stille, Sonogashira, Negishi and others, are exemplified with steroid transformations.

  15. Blood chemistry of current and previous anabolic steroid users.

    PubMed

    O'Connor, J S; Baldini, F D; Skinner, J S; Einstein, M

    1990-02-01

    While the use of anabolic-androgenic steroids appears to be increasing, little is known about the long-term effects of these drugs. This study compared selected blood profiles of current and former steroid-using athletes to expected values for non-drug-using populations. The results are consistent with previous research findings that steroids can have acute negative effects on liver function, lipoprotein fractions, and testosterone production. The results suggest that side effects vary widely among individuals and are drug and dose dependent. Normal function appears to return after drug use is discontinued. These data emphasize the difficulty physicians have interpreting clinical tests when dealing with those who use or have used anabolic steroids. Clearly more research is needed regarding the effects of these drugs.

  16. Do oral steroids aid recovery in children with Bell's palsy?

    PubMed

    Ismail, Abdul Qader; Alake, Oluwaseyi; Kallappa, Chetana

    2014-10-01

    There is growing evidence that steroids are not beneficial for treatment of paediatric patients with Bell's palsy. To investigate, we conducted a retrospective longitudinal study examining notes of 100 children, over 12 years coded for facial nerve palsy. Of the 79 diagnosed with Bell's palsy, all recovered, and for 46 patients we had data on interval from onset of symptoms to resolution (median duration in treated group = 5 weeks, range = 39; median duration in untreated group = 6 weeks, range = 11; P = .86). From our results, we conclude that all children with Bell's palsy recovered, with or without steroid treatment, with no statistically significant difference in symptoms duration. Complications of unresolved Bell's palsy can have important long-term functional and psychosocial consequences. Therefore, we need further research on use of steroids in children with complete/severe cases; it would be a shame to omit treatment due to "absence of evidence" rather than "evidence of absence."

  17. Do oral steroids aid recovery in children with Bell's palsy?

    PubMed

    Ismail, Abdul Qader; Alake, Oluwaseyi; Kallappa, Chetana

    2014-10-01

    There is growing evidence that steroids are not beneficial for treatment of paediatric patients with Bell's palsy. To investigate, we conducted a retrospective longitudinal study examining notes of 100 children, over 12 years coded for facial nerve palsy. Of the 79 diagnosed with Bell's palsy, all recovered, and for 46 patients we had data on interval from onset of symptoms to resolution (median duration in treated group = 5 weeks, range = 39; median duration in untreated group = 6 weeks, range = 11; P = .86). From our results, we conclude that all children with Bell's palsy recovered, with or without steroid treatment, with no statistically significant difference in symptoms duration. Complications of unresolved Bell's palsy can have important long-term functional and psychosocial consequences. Therefore, we need further research on use of steroids in children with complete/severe cases; it would be a shame to omit treatment due to "absence of evidence" rather than "evidence of absence." PMID:24141272

  18. Steroid signaling activation and intracellular localization of sex steroid receptors.

    PubMed

    Giraldi, Tiziana; Giovannelli, Pia; Di Donato, Marzia; Castoria, Gabriella; Migliaccio, Antimo; Auricchio, Ferdinando

    2010-12-01

    In addition to stimulating gene transcription, sex steroids trigger rapid, non-genomic responses in the extra-nuclear compartment of target cells. These events take place within seconds or minutes after hormone administration and do not require transcriptional activity of sex steroid receptors. Depending on cell systems, activation of extra-nuclear signaling pathways by sex steroids fosters cell cycle progression, prevents apoptosis, leads to epigenetic modifications and increases cell migration through cytoskeleton changes. These findings have raised the question of intracellular localization of sex steroid receptors mediating these responses. During the past years, increasing evidence has shown that classical sex steroid receptors localized in the extra-nuclear compartment or close to membranes of target cells induce these events. The emerging picture is that a process of bidirectional control between signaling activation and sex steroid receptor localization regulates the outcome of hormonal responses in target cells. This mechanism ensures cell cycle progression in estradiol-treated breast cancer cells, and its derangement might occur in progression of human proliferative diseases. These findings will be reviewed here together with unexpected examples of the relationship between sex steroid receptor localization, signaling activation and biological responses in target cells. We apologize to scientists whose reports are not mentioned or extensively discussed owing to space limitations.

  19. Contraceptives and other steroid drugs: their production from steroidal sapogenins.

    PubMed

    Fazli, F R

    1968-01-01

    Sterols, steroidal sapogenins, steroidal alkaloids and alkaloidal amines derived from plant sources provide the starting materials for steroid production. Sarmentogenin (III) a cardiac glycoside, was first used, but the source was limited. Hecogenin (IV), a saponin (Agave sislana), was manufactured to cortisone by the process of Spensley et al. Introduction of an oxygen atom at carbon 11 by microbiological means gave a new series of starting compounds, among them, diosgenin (V) which converts to progesterone, to 11 hydroxyprogesterone by fermentation, cortisone, hydrocortisone and delta compounds. Reviews on the development, physiological and biochemical aspects of oral contraceptives were mentioned. A steroid with activity equivalent to progesterone was made by Ehrenstein in a 12-step synthesis from a cardiac aglycone strophanthidin. Estradiol converted to 19-nor testosterone by Birch and Mukherji provided a breakthrough in production of 19-nor steroids and led to production of 19-nor progesterone (VI) with a higher activity than progesterone. 19-nor-17alpha-ethynyltestosterone (VIII), its acetate derivative, and a related compound (I) account for 80% of consumption of oral contraceptives in the United States. Reviews of nor-steroids by Colton and Kilmstra, and of the chemical developments leading to currently used steroid contraceptives by Djerassi are mentioned.

  20. [Anabolic steroids and sports].

    PubMed

    Kopera, H

    1986-09-30

    Anabolic steroids are derivatives of androgens with less androgenic and stronger anabolic actions. They should be used for therapeutic indications only. Their misuse to improve physical performance is unethical (doping), illegal and of doubtful pharmacological value. Together with intense muscular exercise and high-protein diet, anabolics due to their anabolic and anti-catabolic actions possibly increase physical performance and enhance recovery in athletes where added strength is a great advantage. In most sport disciplines a beneficial effect has not been demonstrated. Like all active drugs, anabolics can cause side-effects. They depend on structure, dosage and duration of administration. The misuse by athletes of high doses during long periods should be a particular motivation for doctors, teachers and coaches to discourage athletes from using anabolic drugs. The dangers of overdosing and long-term use are emphasized, search for untoward side- and after- effects by regular and careful controls is recommended.

  1. Steroids and the scientist.

    PubMed

    Gustafsson, Jan-Ake

    2005-06-01

    Our interest in nuclear receptors (NRs) originated from early studies on hepatic steroid metabolism. We discovered a new hypothalamo-pituitary-liver axis, imprinted neonatally by androgens and operating through sexually differentiated GH secretory patterns. Male and female patterns have opposite effects on sexually differentiated hepatic genes, explaining sexually dimorphic liver patterns. To further understand steroid action, we purified the glucocorticoid receptor (GR) leading to our discovery of the NR three-domain structure, with separable DNA binding domain and ligand binding domains and a third domain now known to have transcriptional regulatory properties. Knowledge of this domain structure has been immensely important for deciphering NR actions. Using this first purified NR, we collaborated with Keith Yamamoto and first demonstrated specific NR binding to DNA. This also was the first demonstration of a mammalian transcription factor, a breakthrough that led to discovery of NR response elements. In further collaboration with Yamamoto, we cloned the first NR cDNA sequences, leading to cloning of the superfamily of NR genes. With Yamamoto and Kaptein, we determined the first three-dimensional NR structure, that of DNA binding domain. Later work on orphan receptors resulted in the first discovery of: 1) endogenous ligands for an orphan receptor (fatty acids as activators of peroxisomal proliferator-activated receptor alpha); 2) liver X receptor beta (OR-1) and its role in central nervous system cholesterol homeostasis; and 3) estrogen receptor beta, leading to a paradigm shift in understanding of estrogen signaling, of importance in endocrinology, immunology, and oncology and to development of estrogen receptor beta agonists for treatment of autoimmune diseases, prostate disease, depression, and ovulatory dysfunction.

  2. Topical Steroid-Damaged Skin

    PubMed Central

    Abraham, Anil; Roga, Gillian

    2014-01-01

    Topical steroids, commonly used for a wide range of skin disorders, are associated with side effects both systemic and cutaneous. This article aims at bringing awareness among practitioners, about the cutaneous side effects of easily available, over the counter, topical steroids. This makes it important for us as dermatologists to weigh the usefulness of topical steroids versus their side effects, and to make an informed decision regarding their use in each individual based on other factors such as age, site involved and type of skin disorder. PMID:25284849

  3. Use of pre-operative steroids in liver resection: a systematic review and meta-analysis

    PubMed Central

    Richardson, Arthur J; Laurence, Jerome M; Lam, Vincent WT

    2014-01-01

    Background By attenuating the systemic inflammatory response to major surgery, the pre-operative administration of steroids may reduce the incidence of complications. Methods A systematic review was conducted to identify randomized controlled trials (RCT) comparing pre-operative steroid administration with placebo during a liver resection. Meta-analyses were performed. Results Five RCTs were identified including a total of 379 patients. Pre-operative steroids were associated with statistically significant reductions in the levels of serum bilirubin and interleukin 6 (IL-6) on post-operative day one. There was a trend towards a lower incidence of post-operative complications and prothrombin time (PT), but this did not reach statistical significance. Conclusion Pre-operative steroids may be associated with a clinically significant benefit in liver resection. PMID:23461716

  4. Steroids in Athletics: One University's Experience.

    ERIC Educational Resources Information Center

    Lopez, Mike

    1990-01-01

    Presents an account of one university's experience in conducting an investigation into possible steroid use by student athletes and the development of a program to deal with the problem. Discusses why athletes use steroids and how steroids are taken. Concludes it is likely many steroid-related deaths of athletes go undetected. (Author/ABL)

  5. Symmetry adapted cluster-configuration interaction calculation of the photoelectron spectra of famous biological active steroids

    NASA Astrophysics Data System (ADS)

    Abyar, Fatemeh; Farrokhpour, Hossein

    2014-11-01

    The photoelectron spectra of some famous steroids, important in biology, were calculated in the gas phase. The selected steroids were 5α-androstane-3,11,17-trione, 4-androstane-3,11,17-trione, cortisol, cortisone, corticosterone, dexamethasone, estradiol and cholesterol. The calculations were performed employing symmetry-adapted cluster/configuration interaction (SAC-CI) method using the 6-311++G(2df,pd) basis set. The population ratios of conformers of each steroid were calculated and used for simulating the photoelectron spectrum of steroid. It was found that more than one conformer contribute to the photoelectron spectra of some steroids. To confirm the calculated photoelectron spectra, they compared with their corresponding experimental spectra. There were no experimental gas phase Hesbnd I photoelectron spectra for some of the steroids of this work in the literature and their calculated spectra can show a part of intrinsic characteristics of this molecules in the gas phase. The canonical molecular orbitals involved in the ionization of each steroid were calculated at the HF/6-311++g(d,p) level of theory. The spectral bands of each steroid were assigned by natural bonding orbital (NBO) calculations. Knowing the electronic structures of steroids helps us to understand their biological activities and find which sites of steroid become active when a modification is performing under a biological pathway.

  6. Nalbuphine hydrochloride dependence in anabolic steroid users.

    PubMed

    Wines, J D; Gruber, A J; Pope, H G; Lukas, S E

    1999-01-01

    Nalbuphine hydrochloride, a nonscheduled opioid agonist/antagonist analgesic, is currently approved for the treatment of pain. Recently, nalbuphine dependence was reported in three anabolic steroid users in Britain. To further document this phenomenon, we conducted interviews on eleven subjects who reported nalbuphine use. Eight subjects were clinically dependent on nalbuphine, and seven of the subjects who were asked about tolerance and withdrawal with nalbuphine acknowledged these symptoms. Eight subjects, who had never used drugs intravenously before, reported using nalbuphine by this route. Nalbuphine-related morbidity was extensive and included medical complications and psychiatric symptoms. Nalbuphine users also exhibited a high rate of comorbid Axis I disorders, including other substance misuse. Virtually all subjects described widespread nalbuphine use in the gymnasiums they frequented. These observations, together with the recent increase in nalbuphine-related articles in the lay press, suggest that nalbuphine may represent a new drug of abuse among athletes, especially those using anabolic steroids, and that nalbuphine's scheduling status may need to be re-evaluated.

  7. Probing Steroidal Substrate Specificity of Cytochrome P450 BM3 Variants.

    PubMed

    Liu, Xing; Wang, Zhi-Biao; Wang, Ya-Nan; Kong, Jian-Qiang

    2016-01-01

    M01A82W, M11A82W and M01A82WS72I are three cytochrome P450 BM3 (CYP102A1) variants. They can catalyze the hydroxylation of testosterone (TES) and norethisterone at different positions, thereby making them promising biocatalysts for steroid hydroxylation. With the aim of obtaining more hydroxylated steroid precursors it is necessary to probe the steroidal substrate diversity of these BM3 variants. Here, three purified BM3 variants were first incubated with eight steroids, including testosterone (TES), methyltestosterone (MT), cholesterol, β-sitosterol, dehydroepiandrosterone (DHEA), diosgenin, pregnenolone and ergosterol. The results indicated that the two 3-keto-Δ⁴-steroids TES and MT can be hydroxylated at various positions by the three BM3 mutants, respectively. On the contrary, the three enzymes displayed no any activity toward the remaining six 3-hydroxy-Δ⁵-steroids. This result indicates that the BM3 mutants prefer 3-keto-Δ⁴-steroids as hydroxylation substrates. To further verify this notion, five other substrates, including two 3-hydroxy-Δ⁵-steroids and three 3-keto-Δ⁴-steroids, were carefully selected to incubate with the three BM3 variants. The results indicated the three 3-keto-Δ⁴-steroids can be metabolized to form hydroxysteroids by the three BM3 variants. On the other hand, the two 3-hydroxy-Δ⁵-steroids cannot be hydroxylated at any position by the BM3 mutants. These results further support the above conclusion, therefore demonstrating the 3-keto-Δ⁴-steroid substrate preference of BM3 mutants, and laying a foundation for microbial production of more hydroxylated steroid intermediates using BM3 variants. PMID:27294908

  8. [Anabolic steroids in athletes].

    PubMed

    Yesalis, C E; Wright, J E; Lombardo, J A

    1992-01-01

    The use of anabolic-androgenic steroids (AS) to enhance appearance as well as physical/physiological capacities has increased dramatically over the past four decades in all age groups from early adolescence to adulthood. Although higher AS use rates are reported by elite and competitive athletes, a significant number of recreational athletes appear to be using AS. The scientific literature is inconsistent and at times at odds with the conventional wisdom and empirical experiences of the athletic community regarding the ergogenic effects of AS. However, individuals experienced in weight training, with an adequate diet, and who continue training during AS administration seem to consistently increase their strength and lean mass over what would have been expected from training alone. Previous research documenting deleterious but transient and mostly asymptomatic acute changes in physiology, risk factors and behavior has been inconclusive regarding the long term health impact. The abuse of AS constitutes a special challenge to society. AS are not euphorigenic or mood altering immediately following administration, as are other illicit drugs; the appetite for AS has been created predominantly by our societal fixations on winning and physical appearance. Consequently any successful intervention in this area must go beyond education, law enforcement and drug testing, and attempt to change a social environment which currently encourages the use of AS.

  9. Cervical Meningomyelitis After Lumbar Epidural Steroid Injection

    PubMed Central

    Kim, Joon-Sung; Kim, Ji Yeon

    2015-01-01

    Epidural steroid injections (ESI) are a common treatment for back pain management. ESI-related complications have increased with the growing number of procedures. We report a case of cervical meningomyelitis followed by multiple lumbar ESI. A 60-year-old male with diabetes mellitus presented to our hospital with severe neck pain. He had a history of multiple lumbar injections from a local pain clinic. After admission, high fever and elevated inflammatory values were detected. L-spine magnetic resonance imaging (MRI) revealed hematoma in the S1 epidural space. Antibiotic treatment began under the diagnosis of a lumbar epidural abscess. Despite the treatment, he started to complain of weakness in both lower extremities. Three days later, the weakness progressed to both upper extremities. C-spine MRI revealed cervical leptomeningeal enhancement in the medulla oblongata and cervical spinal cord. Removal of the epidural abscess was performed, but there was no neurological improvement. PMID:26161360

  10. Pneumococcal hemolytic uremic syndrome and steroid resistant nephrotic syndrome

    PubMed Central

    Groves, Andrew P.; Reich, Patrick; Sigdel, Binayak; Davis, T. Keefe

    2016-01-01

    Pneumococcal-associated hemolytic uremic syndrome (pHUS) is a rare but severe complication of invasive Streptococcus pneumoniae infection. We report the case of a 12-year-old female with steroid-resistant nephrotic syndrome treated with adrenocorticotrophic hormone (H.P. Acthar® Gel), who developed pneumococcal pneumonia and subsequent pHUS. While nephrotic syndrome is a well-known risk factor for invasive pneumococcal disease, this is the first reported case of pHUS in an adolescent patient with nephrotic syndrome, and reveals novel challenges in the diagnosis, treatment and potential prevention of this complication. PMID:27478599

  11. Hepatic manifestations of non-steroidal inflammatory bowel disease therapy

    PubMed Central

    Hirten, Robert; Sultan, Keith; Thomas, Ashby; Bernstein, David E

    2015-01-01

    Inflammatory bowel disease (IBD) is composed of Crohn’s disease and ulcerative colitis and is manifested by both bowel-related and extraintestinal manifestations. Recently the number of therapeutic options available to treat IBD has dramatically increased, with each new medication having its own mechanism of action and side effect profile. A complete understanding of the hepatotoxicity of these medications is important in order to distinguish these complications from the hepatic manifestations of IBD. This review seeks to evaluate the hepatobiliary complications of non-steroid based IBD medications and aide providers in the recognition and management of these side-effects. PMID:26644815

  12. Giant aortic arch aneurysm complicating Kawasaki's disease

    PubMed Central

    Hakim, Kaouthar; Boussada, Rafik; Chaker, Lilia; Ouarda, Fatma

    2014-01-01

    Kawasaki disease (KD) is a common acute vasculitis in pediatric population that usually involves small- and middle-sized arteries, commonly coronary arteries. Although the incidence and natural course of coronary aneurysms after KD are well documented in studies, related reports on peripheral arterial and aortic aneurysms are scarce. We report the occurrence of a giant aortic aneurysm involving the horizontal part of aortic arch in a 28-month-old boy diagnosed with KD. This complication was managed by steroids therapy in the beginning. Because of mechanical complication and potential risk of rupture, surgery was undertaken. PMID:25298695

  13. [Steroid receptors and mechanism of action of sex steroids].

    PubMed

    Guiochon-Mantel, A; Milgrom, E

    1999-01-01

    Steroid hormone receptors define a large family of proteins. Recently, a new estradiol receptor has been identified. This discovery suggests the existence of a previously unrecognized pathway of estrogen signalling. Moreover, it implies important pharmacological consequences. Receptors activation induces the modulation of transcription of specific genes. Proteins involved in this effect have been identified: coactivators, corepressors and cointegrators. Their mechanism of action have been characterized. They modify histone acetylation of the corresponding promotor. Sex steroid receptors are located in the nucleus. This nuclear localization is in fact a dynamic situation, resulting from a continuous shuttling of the receptor between the cytoplasm and the nucleus. Non genomic effects of steroids have also been described. PMID:10542957

  14. Competitive Agonists and Antagonists of Steroid Nuclear Receptors: Evolution of the Concept or Its Reversal.

    PubMed

    Smirnova, O V

    2015-10-01

    The mechanisms displaying pure and mixed steroid agonist/antagonist activity as well as principles underlying in vivo action of selective steroid receptor modulators dependent on tissue or cell type including interaction with various types of nuclear receptors are analyzed in this work. Mechanisms of in vitro action for mixed agonist/antagonist steroids are discussed depending on: specific features of their interaction with receptor hormone-binding pocket; steroid-dependent allosteric modulation of interaction between hormone-receptor complex and hormone response DNA elements; features of interacting hormone-receptor complex with protein transcriptional coregulators; level and tissue-specific composition of transcriptional coregulators. A novel understanding regarding context-selective modulators replacing the concept of steroid agonists and antagonists is discussed.

  15. Alligators, contaminants and steroid hormones.

    PubMed

    Guillette, Louis J; Edwards, Thea M; Moore, Brandon C

    2007-01-01

    Steroids are essential for successful reproduction in all vertebrate species. Over the last several decades, extensive research has indicated that exposure to various environmental pollutants can disrupt steroidogenesis and steroid signaling. Although steroidogenesis is regulated by the hypothalamic-pituitary axis, it is also modified by various paracrine and autocrine factors. Furthermore, the classical two-cell model of steroidogenesis in the developing ovarian follicle, involving the granulosa and theca cells in mammals, may not be universal. Instead, birds and probably reptiles use the two thecal compartments (theca interna and theca externa) as sites of steroid production. We have documented that embryonic or juvenile exposure to a complex mixture of contaminants from agricultural and storm water runoff leads to altered steroid hormone profiles in American alligators. Our observations suggest that alterations in plasma steroid hormone concentrations are due in part to altered gene expression, modified hepatic biotransformation and altered gonadal steroidogenesis. Future studies must examine the interplay between endocrine and paracrine regulation in the development and expression of gonadal steroidogenesis in individuals exposed to endocrine disrupting contaminants at various life stages if we are to fully understand potential detrimental outcomes.

  16. Steroidal Saponins in Oat Bran.

    PubMed

    Yang, Junli; Wang, Pei; Wu, Wenbin; Zhao, Yantao; Idehen, Emmanuel; Sang, Shengmin

    2016-02-24

    Saponins are one type of widespread defense compound in the plant kingdom and have been exploited for the production of lead compounds with diverse pharmacological properties in drug discovery. Oats contain two unique steroidal saponins, avenacoside A, 1, and avenacoside B, 2. However, the chemical composition, the levels of these saponins in commercial oat products, and their health effects are still largely unknown. In this study, we directly purified 5 steroidal saponins (1-5) from a methanol extract of oat bran, characterized their structures by analyzing their MS and NMR spectra, and also tentatively identified 11 steroidal saponins (6-16) on the basis of their tandem mass spectra (MS(n), n = 2-3). Among the five purified saponins, 5 is a new compound and 4 is purified from oats for the first time. Using HPLC-MS techniques, a complete profile of oat steroidal saponins was determined, and the contents of the two primary steroidal saponins, 1 and 2, were quantitated in 15 different commercial oat products. The total levels of these two saponins vary from 49.6 to 443.0 mg/kg, and oat bran or oatmeal has higher levels of these two saponins than cold oat cereal. Furthermore, our results on the inhibitory effects of 1 and 2 against the growth of human colon cancer cells HCT-116 and HT-29 showed that both had weak activity, with 2 being more active than 1. PMID:26852819

  17. Bioconversion of steroid glycosides by Nocardia restricta.

    PubMed

    Belic, I; Kastelic-Suhadolc, T; Kralj, B

    1985-09-01

    The bioconversion of steroid alkaloid tomatine by Nocardia restricta yields the conjugate with lactic acid. We studied the bioconversion of some steroid glycosides without a nitrogen atom in the molecule to determine the effect of the nitrogen atom. The glycosides were of three different types: sterol glycosides, bufadienolide rhamnoside and steroid saponine. The results of bioconversions showed that Nocardia restricta converts steroid glycosides differently according to the sugar bound to the steroid aglycone. It can be concluded that in the absence of a nitrogen atom in the steroid molecule no conjugation with lactic acid by Nocardia restricta occurs. PMID:4046605

  18. The relationship between anabolic androgenic steroids and muscle dysmorphia: a review.

    PubMed

    Rohman, Lebur

    2009-01-01

    This review explores the condition of muscle dysmorphia (MD) and its relationship with anabolic androgenic steroids (AAS). Particular emphasis is placed upon whether anabolic steroids are a predisposing, precipitating or perpetuating factor of MD. Furthermore, psychiatric complications of AAS abuse are examined. The current evidence from the literature suggests that AAS (ab)use is possibly a perpetuating factor in the evolution of MD. Psychiatric complications of AAS include mood and behavior changes, perceptual abnormalities, and withdrawal symptoms. In addition, there appears to be a credible dependence theory to AAS in fruition. PMID:19391018

  19. Hypoglycemia: The neglected complication

    PubMed Central

    Kalra, Sanjay; Mukherjee, Jagat Jyoti; Venkataraman, Subramanium; Bantwal, Ganapathi; Shaikh, Shehla; Saboo, Banshi; Das, Ashok Kumar; Ramachandran, Ambady

    2013-01-01

    Hypoglycemia is an important complication of glucose-lowering therapy in patients with diabetes mellitus. Attempts made at intensive glycemic control invariably increases the risk of hypoglycemia. A six-fold increase in deaths due to diabetes has been attributed to patients experiencing severe hypoglycemia in comparison to those not experiencing severe hypoglycemia Repeated episodes of hypoglycemia can lead to impairment of the counter-regulatory system with the potential for development of hypoglycemia unawareness. The short- and long-term complications of diabetes related hypoglycemia include precipitation of acute cerebrovascular disease, myocardial infarction, neurocognitive dysfunction, retinal cell death and loss of vision in addition to health-related quality of life issues pertaining to sleep, driving, employment, recreational activities involving exercise and travel. There is an urgent need to examine the clinical spectrum and burden of hypoglycemia so that adequate control measures can be implemented against this neglected life-threatening complication. Early recognition of hypoglycemia risk factors, self-monitoring of blood glucose, selection of appropriate treatment regimens with minimal or no risk of hypoglycemia and appropriate educational programs for healthcare professionals and patients with diabetes are the major ways forward to maintain good glycemic control, minimize the risk of hypoglycemia and thereby prevent long-term complications. PMID:24083163

  20. DHHC-7 and -21 are palmitoylacyltransferases for sex steroid receptors.

    PubMed

    Pedram, Ali; Razandi, Mahnaz; Deschenes, Robert J; Levin, Ellis R

    2012-01-01

    Classical estrogen, progesterone, and androgen receptors (ERs, PRs, and ARs) localize outside the nucleus at the plasma membrane of target cells. From the membrane, the receptors signal to activate kinase cascades that are essential for the modulation of transcription and nongenomic functions in many target cells. ER, PR, and AR trafficking to the membrane requires receptor palmitoylation by palmitoylacyltransferase (PAT) protein(s). However, the identity of the steroid receptor PAT(s) is unknown. We identified the DHHC-7 and -21 proteins as conserved PATs for the sex steroid receptors. From DHHC-7 and -21 knockdown studies, the PATs are required for endogenous ER, PR, and AR palmitoylation, membrane trafficking, and rapid signal transduction in cancer cells. Thus the DHHC-7 and -21 proteins are novel targets to selectively inhibit membrane sex steroid receptor localization and function. PMID:22031296

  1. Prenatal and postnatal steroid therapy and child neurodevelopment.

    PubMed

    Friedman, Smadar; Shinwell, Eric S

    2004-09-01

    In recent years, scientific evidence has accumulated on the potential neuro-toxic effects of perinatal steroid therapy on the incompletely developed brain; therefore, much effort has been directed toward finding the optimal regimen that may reduce lung disease without incurring significant brain injury in fetuses and preterm infants. Current recommendations of the NIH endorse a single course of prenatal steroids in cases of imminent preterm delivery. Postnatal steroid therapy should be limited, according to the American Association of Pediatrics Guide-lines, to selected clinical cases after the first week of life. These cautions aim to decrease possible harmful effects that could affect short- and long-term neuro-developmental outcome in this high-risk population.

  2. An inside perspective on anabolic steroid abuse

    PubMed Central

    Schaive, Chad; Kohler, Tobias S.

    2016-01-01

    Steroid abuse is common across gyms across the world. This unique article features an inside perspective/opinion in a question and answer format from a former steroid user/high level body builder. PMID:27141450

  3. An inside perspective on anabolic steroid abuse.

    PubMed

    Schaive, Chad; Kohler, Tobias S

    2016-04-01

    Steroid abuse is common across gyms across the world. This unique article features an inside perspective/opinion in a question and answer format from a former steroid user/high level body builder. PMID:27141450

  4. [Medico-legal assessment of selected cases of perinatal complications resulting in death of the woman during childbirth. Medical error or therapeutic failure?].

    PubMed

    Chowaniec, Małgorzata; Chowaniec, Czesław; Jabłoński, Christian; Nowak, Agnieszka

    2005-01-01

    Medico-legal estimation of therapeutic management in cases of perinatal complications, especially those resulting in death of the women during childbirth is usually very difficult. The authors have investigated medical documentation supported by the results of autopsies of cases chosen from the casuistry of the Forensic Medicine Department, Medical University of Silesia, Katowice. Considering the limits of professional liability and legal responsibility of physicians, close attention was paid to standard therapeutic management and increased risk in treatment with regard to that relating to typical salubrious complications. The presented cases of deaths of women during childbirth can be the succeeding opinion in broad discussion on medical errors as well as an attempt to standardise and differentiate the medical error from therapeutic failure which occurred within the reach of risk in the undertaken treatment.

  5. Detection of endogenous steroid abuse in cattle: results from population studies in the UK.

    PubMed

    Scarth, J P; Clarke, A; Teale, P; Mill, A; Macarthur, R; Kay, J

    2011-01-01

    The use of steroids as growth-promoting agents in food production is banned under European Union legislation. Detecting the abuse of testosterone, nandrolone, boldenone, oestradiol and progesterone is complicated by the fact that these steroids are known to be endogenous in certain situations. In this study, the concentrations of characteristic metabolites of each of these steroids were quantified in populations of untreated steers and heifers. Steroid concentration population data were then used by a statistical model (the Chebyshev inequality) to produce threshold concentrations for screening and confirming the abuse of these steroids in steer and non-pregnant heifer urine. In addition to thresholds based on testing one animal (a '1 out of 1' approach), new methods based on testing multiple animals from a herd (a 'y out of n' approach) allowed threshold concentrations to be significantly reduced and hence false compliances to be minimised. In the majority of cases, the suggested thresholds were found to be capable of confirming the abuse of endogenous steroids in steers and heifers. In the case of oestradiol abuse in the female, however, confirmation based on a threshold is not possible and alternative methods such as gas chromatography-combustion-isotope ratio mass spectrometry are required. In addition to the steer and heifer populations, a small number of pregnant animals were also tested, yielding insights into the biosynthetic pathways of some of the steroids.

  6. The effects of anabolic steroids on rat tendon. An ultrastructural, biomechanical, and biochemical analysis.

    PubMed

    Inhofe, P D; Grana, W A; Egle, D; Min, K W; Tomasek, J

    1995-01-01

    Forty-eight male rats were randomly separated into four groups: a control group, a group treated with anabolic steroids, a group treated with daily exercise, and a group treated with both steroids and exercise. At 6 weeks, biomechanical, ultrastructural, and biochemical testing was performed on the Achilles tendons of half of the rats in each group. The remaining rats continued in the experimental protocol, but steroid administration was discontinued. Similar testing was then performed on the remaining rats at 12 weeks. Testing showed anabolic steroids produced a stiffer tendon that absorbs less energy and fails with less elongation; tendon strength was unaffected. Effects were entirely reversible on discontinuation of the steroids. Light microscopic analysis revealed no changes in the appearance of the fibrils. No change in fibril diameter or shape was noted on electron microscopic analysis. Biochemical testing revealed no change in qualitative immunofluorescence staining with Type III collagen or fibronectin. Abuse of anabolic steroids is a widespread problem among competitive athletes; consequently, complications after their use are seen with increasing frequency. Knowledge of the effects of these drugs on tendon and the musculotendinous unit may prove helpful in counseling athletes who use anabolic steroids.

  7. Sex steroids and their receptors in lampreys.

    PubMed

    Bryan, Mara B; Scott, Alexander P; Li, Weiming

    2008-01-01

    The use of steroids and their receptors as ligand-gated transcription factors is thought to be an important step in vertebrate evolution. The lamprey is the earliest-evolving vertebrate to date in which sex steroids and their receptors have been demonstrated to have hormonal roles similar to those found in jawed vertebrates. Sex steroids and their receptors have been examined in several lamprey species, and the majority of studies have focused on the sea lamprey, Petromyzon marinus. While classical steroids appear to be present in lampreys, their function, concentrations, and synthesis have not been determined conclusively. The only classical steroid that is thought to act as a hormone in both males and females is estradiol. Recent research has established that lampreys produce and circulate 15alpha-hydroxylated steroids, and that these steroids respond to upstream stimulation within the hypothalamic-pituitary-gonadal axis. In particular, 15alpha-hydroxyprogesterone is highly sensitive and responds in great magnitude to stimulation, and is likely a hormone. Lampreys also appear to use androstenedione, a precursor to vertebrate androgens, as their main androgen, and a receptor for androstenedione has recently been described. Non-classical steroids are prevalent in many aquatic vertebrates, and the non-classical steroids found in the sea lamprey may represent an evolutionary artifact, or alternatively may be a way to avoid endocrine disruption when ingesting the body fluids of host fish. The lamprey will continue to be an interesting model for examining the evolution of steroid hormones, steroid receptors, and steroid function.

  8. Adolescents and Steroids: A User Perspective.

    ERIC Educational Resources Information Center

    Office of Inspector General (DHHS), Washington, DC.

    Anabolic-androgenic steroids ("steroids") are synthetic derivatives of the natural male hormone testosterone. They were first used non-medically by elite athletes seeking to improve performance. More recently, however, steroid use has filtered down to high school and junior high school levels. The purpose of this study was to describe adolescent…

  9. The real risks of steroid injection for plantar fasciitis, with a review of conservative therapies.

    PubMed

    Tatli, Yusuf Ziya; Kapasi, Sameer

    2009-03-01

    This article presents a review of conservative therapies for plantar fasciitis pain reduction with a discussion of steroid therapy risks. The therapies reviewed include orthoses, stretching, extracorporeal shockwave, BTX-A, and corticosteroid injection/iontophoresis. These modes were included based on the availability of double blinded randomized controlled trials. We noted the following findings. Orthoses, regardless of type, can improve pain levels. Plantar stretching shows limited short-term benefit (1 month), but can reflect significant long-term improvement (10 months). Extracorporeal shockwave therapy shows equivocal benefit with some studies showing significant improvement and others showing none. Although BTX-A injections were the least studied, significant pain improvement was demonstrated in the short and long term. Steroid injection/iontophoresis showed significant improvement in the short term (1 month). Steroid therapy, when coupled with plantar stretching, can provide efficacious pain relief; however, steroid injections should be combined with ultrasound monitoring to reduce complications.

  10. Adverse effects of anabolic steroids.

    PubMed

    Hickson, R C; Ball, K L; Falduto, M T

    1989-01-01

    Anabolic steroids are used therapeutically for various disorders and as ergogenic aids by athletes to augment strength, muscular development, and to enhance performance. There is a wide range of concomitant temporary and permanent adverse effects with steroid administration. Several well-documented adverse actions of these hormones may develop rapidly within several weeks or less (i.e. altered reproductive function) or require up to several years of steroid intake (i.e. liver carcinoma). More recent studies indicate that glucose intolerance, insulin resistance, increased cardiovascular disease risk profiles, cerebral dangers, musculoskeletal injuries, prostate cancer, psychosis and schizophrenic episodes, among others, accompany anabolic steroid intake. There is, at present, no evidence to support the claim that athletes are less susceptible to adverse effects than those individuals receiving hormone treatment in a clinical setting. Based on the available information which has accumulated primarily from cross-sectional, short term longitudinal, and case studies, there is a need: (a) to develop a comprehensive battery of specific and sensitive markers of adverse effects, particularly those that would be able to detect the onset of adverse actions; and (b) to conduct controlled long term longitudinal studies in order to fully understand the extensiveness and mechanisms involved in the occurrence of adverse effects.

  11. Structural classification of steroid-binding sites on proteins by coarse-grained atomic environment and its correlation with their biological function.

    PubMed

    Hori-Tanaka, Yasuha; Yura, Kei; Takai-Igarashi, Takako; Tanaka, Hiroshi

    2015-04-01

    Steroid hormone is extensively used for transmitting variety of biological signals in organisms. Natural steroid hormone is synthesized from cholesterol in adrenal cortex and in sexual gland in vertebrates. Appropriately dosed synthetic steroid hormones can be used for medication. Despite their positive effects as medicine, they sometimes cause significant side effects due to their wide range of actions, and the studies for discovering the mechanisms of side effects were carried out aiming to reduce the side effects. The fundamental cause of the side effects seems to be interactions between the steroid and a non-target protein. To understand the possible range of interaction of steroid molecule, we gathered all the three-dimensional structures of protein-steroid complex determined by X-ray crystallography, compared the atomic environments of the steroid-binding sites in proteins and classified the pattern of steroid binding. Protein Data Bank contained 871 structures of steroid-protein complexes in 382 entries. For this study, we selected 832 steroid binding proteins. Using a newly developed method to describe the atomic environments of these steroid molecules and their function, we were able to separate the environments into six patterns. This classification had a potential to predict the function of function-unknown proteins with a co-crystallized steroid molecule. We speculated that the proteins grouped into the same pattern of nuclear receptors were the candidates of non-targeted proteins causing a side effect by a therapeutic prescription of steroid hormone.

  12. Evaluation of steroidomics by liquid chromatography hyphenated to mass spectrometry as a powerful analytical strategy for measuring human steroid perturbations.

    PubMed

    Jeanneret, Fabienne; Tonoli, David; Rossier, Michel F; Saugy, Martial; Boccard, Julien; Rudaz, Serge

    2016-01-22

    This review presents the evolution of steroid analytical techniques, including gas chromatography coupled to mass spectrometry (GC-MS), immunoassay (IA) and targeted liquid chromatography coupled to mass spectrometry (LC-MS), and it evaluates the potential of extended steroid profiles by a metabolomics-based approach, namely steroidomics. Steroids regulate essential biological functions including growth and reproduction, and perturbations of the steroid homeostasis can generate serious physiological issues; therefore, specific and sensitive methods have been developed to measure steroid concentrations. GC-MS measuring several steroids simultaneously was considered the first historical standard method for analysis. Steroids were then quantified by immunoassay, allowing a higher throughput; however, major drawbacks included the measurement of a single compound instead of a panel and cross-reactivity reactions. Targeted LC-MS methods with selected reaction monitoring (SRM) were then introduced for quantifying a small steroid subset without the problems of cross-reactivity. The next step was the integration of metabolomic approaches in the context of steroid analyses. As metabolomics tends to identify and quantify all the metabolites (i.e., the metabolome) in a specific system, appropriate strategies were proposed for discovering new biomarkers. Steroidomics, defined as the untargeted analysis of the steroid content in a sample, was implemented in several fields, including doping analysis, clinical studies, in vivo or in vitro toxicology assays, and more. This review discusses the current analytical methods for assessing steroid changes and compares them to steroidomics. Steroids, their pathways, their implications in diseases and the biological matrices in which they are analysed will first be described. Then, the different analytical strategies will be presented with a focus on their ability to obtain relevant information on the steroid pattern. The future technical

  13. Refractory strictures despite steroid injection after esophageal endoscopic resection

    PubMed Central

    Hanaoka, Noboru; Ishihara, Ryu; Uedo, Noriya; Takeuchi, Yoji; Higashino, Koji; Akasaka, Tomofumi; Kanesaka, Takashi; Matsuura, Noriko; Yamasaki, Yasushi; Hamada, Kenta; Iishi, Hiroyasu

    2016-01-01

    Background: Although steroid injection prevents stricture after esophageal endoscopic submucosal dissection (ESD), some patients require repeated sessions of endoscopic balloon dilation (EBD). We investigated the risk for refractory stricture despite the administration of steroid injections to prevent stricture in patients undergoing esophageal ESD. Refractory stricture was defined as the requirement for more than three sessions of EBD to resolve the stricture. In addition, the safety of steroid injections was assessed based on the rate of complications. Patients and methods: We analyzed data from 127 consecutive patients who underwent esophageal ESD and had mucosal defects with a circumferential extent greater than three-quarters of the esophagus. To prevent stricture, steroid injection was performed. EBD was performed whenever a patient had symptoms of dysphagia. Results: The percentage of patients with a tumor circumferential extent greater than 75 % was significantly higher in those with refractory stricture than in those without stricture (P = 0.001). Multivariate analysis adjusted for age, sex, history of radiation therapy, tumor location, and tumor diameter showed that a tumor circumferential extent greater than 75 % was an independent risk factor for refractory stricture (adjusted odds ratio [OR] 5.49 [95 %CI 1.91 – 15.84], P = 0.002). Major adverse events occurred in 3 patients (2.4 %): perforation during EBD in 2 patients and delayed perforation after EBD in 1 patient. The patient with delayed perforation underwent esophagectomy because of mediastinitis. Conclusions: A tumor circumferential extent greater than 75 % is an independent risk factor for refractory stricture despite steroid injections. The development of more extensive interventions is warranted to prevent refractory stricture. PMID:27004256

  14. Influences of sex steroids on experimental carcinogenesis.

    PubMed

    Lucier, G W; Rumbaugh, R C

    1983-01-01

    Sex steroids can apparently modify hepatic function in at least two ways (Figure 1). First, the liver contains specific receptor proteins for either androgens or oestrogens. Several studies, using effects on the monooxygenase system as an indicator of hormone action, have shown good correlations between the presence of sex-steroid receptors and hepatic response to these hormones. In general, androgens induce the activities of drug biotransformation reactions, whereas oestrogens depress them. Second, the endocrine milieu, during a critical period of early development, apparently programmes the hypothalamic-pituitary axis to release factors which cause certain aspects of liver biochemistry to undergo sex differentiation. Selected components of the cytochrome P-450 system exhibit sex differences, and these differences are imprinted by neonatal androgens and are initiated and maintained by the pituitary gland. Corresponding to sex differentiation of the hepatic monooxygenase system are significant sex differences in responses to hepatocarcinogens such as N-2-fluorenylacetamide and N-hydroxy-N-2-fluorenylacetamide. Higher incidences of hepatocellular carcinomas in males appear to result from exposure to neonatal androgens.

  15. Synthesis and Antiproliferative Activity of Steroidal Thiosemicarbazone Platinum (Pt(II)) Complexes

    PubMed Central

    Huang, Yanmin; Kong, Erbin; Gan, Chunfang; Liu, Zhiping; Lin, Qifu; Cui, Jianguo

    2015-01-01

    Steroidal compounds exhibit particular physiological activities. In this paper, some steroidal thiosemicarbazones platinum (Pt(II)) complexes were synthesized by the condensation of steroidal ketones with thiosemicarbazide using estrone, chenodeoxycholic acid, and 7-deoxycholic acid as starting materials and complexation of steroidal thiosesemicarbazones with Pt(II). The complexes were characterized by IR, NMR, and MS, and their antiproliferative activities were evaluated. The results showed that some steroidal thiosemicarbazones platinum (Pt(II)) complexes displayed moderate cytotoxicity to HeLa and Bel-7404 cells. Thereinto, complex 6 showed an excellent inhibited selectivity to HeLa cells with an IC50 value of 9.2 μM and SI value of 21.7. At the same time, all compounds were almost inactive to HEK293T (normal kidney epithelial cells). The information obtained from the studies may be useful for the design of novel chemotherapeutic drugs. PMID:26635511

  16. Avoiding and treating dermal filler complications.

    PubMed

    Lemperle, Gottfried; Rullan, Peter P; Gauthier-Hazan, Nelly

    2006-09-01

    All fillers are associated with the risk of both early and late complications. Early side effects such as swelling, redness, and bruising occur after intradermal or subdermal injections. The patient has to be aware of and accept these risks. Adverse events that last longer than 2 weeks can be attributable to technical shortcomings (e.g., too superficial an implantation of a long-lasting filler substance). Such adverse events can be treated with intradermal 5-fluorouracil, steroid injections, vascular lasers, or intense pulsed light, and later with dermabrasion or shaving. Late adverse events also include immunologic phenomena such as late-onset allergy and nonallergic foreign body granuloma. Both react well to intralesional steroid injections, which often have to be repeated to establish the right dose. Surgical excisions shall remain the last option and are indicated for hard lumps in the lips and visible hard nodules or hard granuloma in the subcutaneous fat.

  17. [Complications after dermal fillers and their treatment].

    PubMed

    Lemperle, G; Gauthier-Hazan, N; Wolters, M

    2006-12-01

    All dermal fillers are associated with the risk of both early and late complications. Early side effects such as swelling, redness, and bruising occur after intradermal or subdermal injections. The patient has to be aware of these risks and be prepared to accept them. Adverse events that last longer than 2 weeks can be attributable to technical shortcomings (e.g., the implantation of a long-lasting filler substance was too superficial). Such adverse events can be treated with intradermal 5-fluorouracil and steroid injections, vascular lasers, or intense pulsed light, and later with dermabrasion or shaving. Late adverse events also include immunological phenomena such as late-onset allergy and non-allergic foreign body granulomas. Both react well to intralesional steroid injections, which often have to be repeated to establish the right dose. Surgical excisions should remain the last option and are indicated for hard lumps in the lips and visible hard nodules or hard granulomas in the subcutaneous fat.

  18. Avoiding and treating dermal filler complications.

    PubMed

    Lemperle, Gottfried; Rullan, Peter P; Gauthier-Hazan, Nelly

    2006-09-01

    All fillers are associated with the risk of both early and late complications. Early side effects such as swelling, redness, and bruising occur after intradermal or subdermal injections. The patient has to be aware of and accept these risks. Adverse events that last longer than 2 weeks can be attributable to technical shortcomings (e.g., too superficial an implantation of a long-lasting filler substance). Such adverse events can be treated with intradermal 5-fluorouracil, steroid injections, vascular lasers, or intense pulsed light, and later with dermabrasion or shaving. Late adverse events also include immunologic phenomena such as late-onset allergy and nonallergic foreign body granuloma. Both react well to intralesional steroid injections, which often have to be repeated to establish the right dose. Surgical excisions shall remain the last option and are indicated for hard lumps in the lips and visible hard nodules or hard granuloma in the subcutaneous fat. PMID:16936549

  19. Steroids and endocrine disruptors--History, recent state of art and open questions.

    PubMed

    Hampl, Richard; Kubátová, Jana; Stárka, Luboslav

    2016-01-01

    This introductory chapter provides an overview of the levels and sites at which endocrine disruptors (EDs) affect steroid actions. In contrast to the special issue of Journal of Steroid Biochemistry and Molecular Biology published three years ago and devoted to EDs as such, this paper focuses on steroids. We tried to point to more recent findings and opened questions. EDs interfere with steroid biosynthesis and metabolism either as inhibitors of relevant enzymes, or at the level of their expression. Particular attention was paid to enzymes metabolizing steroid hormones to biologically active products in target cells, such as aromatase, 5α-reductase and 3β-, 11β- and 17β-hydroxysteroid dehydrogenases. An important target for EDs is also steroid acute regulatory protein (StAR), responsible for steroid precursor trafficking to mitochondria. EDs influence receptor-mediated steroid actions at both genomic and non-genomic levels. The remarkable differences in response to various steroid-receptor ligands led to a more detailed investigation of events following steroid/disruptor binding to the receptors and to the mapping of the signaling cascades and nuclear factors involved. A virtual screening of a large array of EDs with steroid receptors, known as in silico methods (≡computer simulation), is another promising approach for studying quantitative structure activity relationships and docking. New data may be expected on the effect of EDs on steroid hormone binding to selective plasma transport proteins, namely transcortin and sex hormone-binding globulin. Little information is available so far on the effects of EDs on the major hypothalamo-pituitary-adrenal/gonadal axes, of which the kisspeptin/GPR54 system is of particular importance. Kisspeptins act as stimulators for hormone-induced gonadotropin secretion and their expression is regulated by sex steroids via a feed-back mechanism. Kisspeptin is now believed to be one of the key factors triggering puberty in

  20. Molecular properties of steroids involved in their effects on the biophysical state of membranes.

    PubMed

    Wenz, Jorge J

    2015-10-01

    The activity of steroids on membranes was studied in relation to their ordering, rigidifying, condensing and/or raft promoting ability. The structures of 82 steroids were modeled by a semi-empirical procedure (AM1) and 245 molecular descriptors were next computed on the optimized energy conformations. Principal component analysis, mean contrasting and logistic regression were used to correlate the molecular properties with 212 cases of documented activities. It was possible to group steroids based on their properties and activities, indicating that steroids having similar molecular properties have similar activities on membranes. Steroids having high values of area, partition coefficient, volume, number of rotatable bonds, molar refractivity, polarizability or mass displayed ordering, rigidifying, condensing and/or raft promoting activity on membranes higher than those steroids having low values in such molecular properties. After a variable selection procedure circumventing correlation problems among descriptors, area and log P were found as the most relevant properties in governing and predicting the activity of steroids on membranes. A logistic regression model as a function of the area and log P of the steroids is proposed, which is able to predict correctly 92.5% of the cases. A rationale of the findings is discussed.

  1. Marked elevation of adrenal steroids, especially androgens, in saliva of prepubertal autistic children.

    PubMed

    Majewska, Maria Dorota; Hill, Martin; Urbanowicz, Ewa; Rok-Bujko, Paulina; Bieńkowski, Przemysław; Namysłowska, Irena; Mierzejewski, Paweł

    2014-06-01

    Autism is diagnosed on the basis of behavioral manifestations, but its biomarkers are not well defined. A strong gender bias typifying autism (it is 4-5 times more prevalent in males) suggests involvement of steroid hormones in autism pathobiology. In order to evaluate the potential roles of such hormones in autism, we compared the salivary levels of 22 steroids in prepubertal autistic male and female children from two age groups (3-4 and 7-9 years old) with those in healthy controls. The steroids were analyzed using gas chromatography-mass spectrometry and radioimmunoassay. Statistical analysis (ANOVA) revealed that autistic children had significantly higher salivary concentrations of many steroid hormones (both C21 and C19) than control children. These anomalies were more prominent in older autistic children and in boys. The levels of androgens (androstenediol, dehydroepiandrosterone, androsterone and their polar conjugates) were especially increased, indicative of precocious adrenarche and predictive of early puberty. The concentrations of the steroid precursor, pregnenolone, and of several pregnanolones were also higher in autistic than in healthy children, but cortisol levels were not different. Some steroids, whose levels are raised in autism (allopregnanolone, androsterone, pregnenolone, dehydroepiandrosterone and their sulfate conjugates) are neuroactive and modulate GABA, glutamate, and opioid neurotransmission, affecting brain development and functioning. These steroids may contribute to autism pathobiology and symptoms such as elevated anxiety, sleep disturbances, sensory deficits, and stereotypies among others. We suggest that salivary levels of selected steroids may serve as biomarkers of autism pathology useful for monitoring the progress of therapy.

  2. Steroid toxicity and detoxification in ascomycetous fungi.

    PubMed

    Cvelbar, Damjana; Zist, Vanja; Kobal, Katja; Zigon, Dušan; Zakelj-Mavrič, Marija

    2013-02-25

    In the last couple of decades fungal infections have become a significant clinical problem. A major interest into fungal steroid action has been provoked since research has proven that steroid hormones are toxic to fungi and affect the host/fungus relationship. Steroid hormones were found to differ in their antifungal activity in ascomycetous fungi Hortaea werneckii, Saccharomyces cerevisiae and Aspergillus oryzae. Dehydroepiandrosterone was shown to be the strongest inhibitor of growth in all three varieties of fungi followed by androstenedione and testosterone. For their protection, fungi use several mechanisms to lower the toxic effects of steroids. The efficiency of biotransformation in detoxification depended on the microorganism and steroid substrate used. Biotransformation was a relatively slow process as it also depended on the growth phase of the fungus. In addition to biotransformation, steroid extrusion out of the cells contributed to the lowering of the active intracellular steroid concentration. Plasma membrane Pdr5 transporter was found to be the most effective, followed by Snq2 transporter and vacuolar transporters Ybt1 and Ycf1. Proteins Aus1 and Dan1 were not found to be involved in steroid import. The research of possible targets of steroid hormone action in fungi suggests that steroid hormones inhibit ergosterol biosynthesis in S. cerevisiae and H. werneckii. Results of this inhibition caused changes in the sterol content of the cellular membrane. The presence of steroid hormones most probably causes the degradation of the Tat2 permease and impairment of tryptophan import.

  3. Sexual functioning of male anabolic steroid abusers.

    PubMed

    Moss, H B; Panzak, G L; Tarter, R E

    1993-02-01

    The effects of anabolic steroid use on male sexual behavior were assessed using a structured clinical interview administered to male body builders currently using steroids, and to two comparison groups (body builders with a past but not current history of steroid use, and a group of "natural" body builders who had never used steroids). Current anabolic steroid users had a significantly higher coital and orgasmic frequency than did comparison athletes. They also reported a significantly higher incidence of erectile difficulties during the past month. Beliefs concerning the sexually stimulating effects of steroids did not correlate with the frequencies of specific sexual behaviors. The data support the contention that anabolic steroids, as androgenic compounds, enhance sexual desire.

  4. Adverse effects of anabolic steroids in athletes.

    PubMed

    Kibble, M W; Ross, M B

    1987-09-01

    The effects of anabolic steroid use on athletic performance and the adverse effects associated with the use of anabolic steroids are reviewed. Anabolic steroids increase protein synthesis in skeletal muscles and reverse catabolic processes. Because of these properties, some athletes use anabolic steroids in an attempt to improve their athletic performance. However, studies indicate that increases in muscle mass and strength during anabolic steroid administration are observed only in athletes who already are weight-trained and who continue intensive training while maintaining high-protein, high-calorie diets. Adverse effects attributed to anabolic steroid use occur frequently. Serious adverse effects include hepatic and endocrine dysfunction; cardiovascular and behavioral changes also are reported. Some of the adverse effects associated with the use of these agents are irreversible, particularly in women. The use of anabolic steroids to improve athletic performance has become prevalent. However, the reported benefits are tempered by numerous adverse reactions.

  5. An atypical presentation of adult-onset Still’s disease complicated by pulmonary hypertension and macrophage activation syndrome treated with immunosuppression: a case-based review of the literature

    PubMed Central

    Manson, Daniel K.; Horn, Evelyn M.; Haythe, Jennifer

    2016-01-01

    Abstract Pulmonary arterial hypertension (PAH) is a known complication of rheumatologic diseases, but it is only rarely associated with adult-onset Still’s disease (AOSD). We describe the case of a 30-year-old woman who presented in a pulmonary hypertension crisis and was found to have underlying AOSD with PAH and nonspecific interstitial pneumonia (NSIP) with a course complicated by macrophage activation syndrome (MAS). She dramatically improved with steroids, cyclosporine A, and anakinra, with total resolution of the MAS and significant improvement of her pulmonary arterial pressures. While there are only select case reports of AOSD associated with PAH, this is the first reported case of (1) AOSD complicated by both PAH and MAS and (2) AOSD complicated by biopsy-proven NSIP. Clinically, this case highlights the efficacy of immunosuppressive agents in the treatment of PAH and MAS from underlying AOSD and supports their use in this setting. PMID:27162622

  6. Neuropeptides and steroid hormones in arthritis.

    PubMed

    Cerinic, M M; Konttinen, Y; Generini, S; Cutolo, M

    1998-05-01

    Primary afferent nociceptive and peptidergic efferent nerves are sensitized in arthritis and thus easily stimulated by mechanical and chemical stimuli. This leads to increased or disturbed release of neuropeptides from nerve terminals. This local (at the site of stimulation), expanded (expanded and additional receptive fields), and remote (cross-spinal reflexes) neuropeptide release leads to disturbed tissue homeostasis and neurogenic inflammation. In arthritis, raised levels of neuropeptides were detected in the synovial fluid, whereas nerve fibers were lacking in the synovial tissue. It has been hypothesized that cycles of nerve fiber destruction and degeneration follow the cycles of joint inflammation. This evidence suggests that the peripheral nervous system, through its neuropeptides, may contribute to the generation of inflammation, i.e., "neurogenic inflammation." Altered hypothalamic-pituitary-adrenocortical axis function and sex hormone status have been suggested to contribute to the development and persistence of arthritis. In particular, current evidence indicates that glucocorticoid secretion is closely and reciprocally interrelated with inflammation, and that an adrenal insufficiency is present in many forms of immune-mediated arthritis. Conversely, gonadal steroids seem to play a central role as predisposing factors in many forms of arthritis, with estrogens involved as immuno-enhancing hormones and androgens as natural immunosuppressors. Functional receptors for sex hormones have been described in cells involved in the immune response and, after activation, the hormone-receptor complex might modulate the expression of selected cytokines. The possibility of targeting the efferent nerves with specific peptides and replacement therapies with selected steroid hormones may represent a new and potentially efficient and natural system of modulation of the arthritis.

  7. Steroid hormones in cluster headaches.

    PubMed

    Stillman, Mark

    2006-04-01

    For decades, glucocorticoid therapy has been a well-recognized abortive treatment for cluster headaches. However, the role of steroid hormones, including both glucocorticoids and sex steroids, in the pathophysiology and therapy of cluster headaches has been a topic of much debate and speculation. Current research now points to the importance of cortisol and testosterone in the pathogenesis of cluster headaches, and they appear to be linked mechanistically to another hormone, melatonin. Melatonin, unlike cortisol or testosterone, is not a product of the hypothalamic pituitary axis but of the retinohypothalamic pineal axis, and is the major biomarker of circadian rhythms. The regulation of steroids and melatonin in the pathogenesis of cluster headaches in turn depends on the sympathetic nervous system. Accumulated evidence suggests sympathetic dysfunction--embodied in the Horner sign so commonly seen in the cluster headache--as a necessary ingredient in the inception of the cluster headache. Sympathetic dysfunction now is thought to be associated with the hypercortisolism, hypotestosteronism, and lower-than-normal melatonin levels in the active cluster patient. Future research may hold the key to a fuller explanation of the complex interaction of hormonal systems in the cluster headache.

  8. Novel approach to the preparation of hemisuccinates of steroids bearing tertiary alcohol group.

    PubMed

    Longin, Ondřej; Černý, Ivan; Drašar, Pavel

    2015-05-01

    17β-O-Hemisuccinates of typical representatives of Anabolic-Androgenic Steroids, 17β-hydroxy-17-methylandrostan-4-en-3-one, 17β-hydroxy-17-methyl-2-oxa-5α-androstan-3-one, 17β-hydroxy-17-methyl-5α-androstano-[3,2-c]pyrazole, were prepared. Several methods for the hemisuccinate preparation were tested. The indirect method using 1-ethyl-3-(dimethylaminopropyl)carbodiimide coupling reagent to form an ester bond of steroid with 2-(trimethylsilyl)ethyl hydrogen butanedioate was finally applied. Using the selectively removable protecting group, the desired hemisuccinates of steroids bearing tertiary alcohol group were obtained.

  9. [Diffuse alveolar hemorrhage (DAH): an underestimated pulmonary complication after hematopoietic stem cell transplantation].

    PubMed

    Kretzschmar, M; Steinke, K; Steinbrich, W

    2005-08-17

    Diffuse alvedar haemorrhage (DAH): a severe complication post haematopoietic stemcell transplantation (HSCT) with high mortality. Early diagnose and distinction from other pulmonary complications is essential. Radiologic imaging provides first cues to diagnose. Confirmation of diagnose by BAL. Therapeutic approach with high dose steroids

  10. Marine steroids as potential anticancer drug candidates: In silico investigation in search of inhibitors of Bcl-2 and CDK-4/Cyclin D1.

    PubMed

    Saikia, Surovi; Kolita, Bhaskor; Dutta, Partha P; Dutta, Deep J; Neipihoi; Nath, Shyamalendu; Bordoloi, Manobjyoti; Quan, Pham Minh; Thuy, Tran Thu; Phuong, Doan Lan; Long, Pham Quoc

    2015-10-01

    Star fishes (Asteroidea) are rich in polar steroids with diverse structural characteristics. The structural modifications of star fish steroids occur at 3β, 4β, 5α, 6α (or β), 7α (or β), 8, 15α (or β) and 16β positions of the steroidal nucleus and in the side chain. Widely found polar steroids in starfishes include polyhydroxysteroids, steroidal sulfates, glycosides, steroid oligoglycosides etc. Bioactivity of these steroids is less studied; only a few reports like antibacterial, cytotoxic activity etc. are available. In continuation of our search for bioactive molecules from natural sources, we undertook in silico screening of steroids from star fishes against Bcl-2 and CDK-4/Cyclin D1 - two important targets of progression and proliferation of cancer cells. We have screened 182 natural steroids from star fishes occurring in different parts of the world and their 282 soft-derivatives by in silico methods. Their physico-chemical properties, drug-likeliness, binding potential with the selected targets, ADMET (absorption, distribution, metabolism, toxicity) were predicted. Further, the results were compared with those of existing steroidal and non steroidal drugs and inhibitors of Bcl-2 and CDK-4/Cyclin D1. The results are promising and unveil that some of these steroids can be potent leads for cancer treatments.

  11. [Sequential changes of serum steroid levels in puerperium].

    PubMed

    Yamaguchi, Y; Kimura, T; Yanaihara, T; Nakayama, T

    1983-10-01

    To examine daily changes in blood hormone levels during the postpartum period, twenty steroids including free and conjugated pregnenolone (P5), 16 alpha OH-P5(16P5), dehydroepiandrosterone (DHA), 16 alpha OH-DHA(16DHA), estrone(E1), estradiol(E2), estriol(E3), estetrol(E4) and free progesterone(P4), 16 alpha OH - P4(16P4), 20 alpha-dihydro-P4(20P4) and cortisol(F) were measured simultaneously by RIA. Seven patients who delivered a healthy child vaginally were selected for this study. The steroid levels in maternal blood were measured daily until the 7th post partum day and were compared to those at delivery. Levels of free and conjugated E1, E2, P5, free E3 and 16P4 dropped rapidly within 24 hours and reached approximately 10% of those at delivery. Conjugated E2, E4, 16P5, and P4, 20P4 levels also dropped after delivery to less than 17% of those at delivery within 72 hours. However, the levels of these steroids were maintained at more than 20% of those at delivery until the 7th postpartum day. These results provide further information on the significance of the steroids in maternal blood during pregnancy. PMID:6226753

  12. The Effect of Steroid Therapy on Postoperative Inflammatory Response after Endovascular Abdominal Aortic Aneurysm Repair

    PubMed Central

    Aoki, Atsushi; Omoto, Tadashi; Iizuka, Hirofumi; Kawaura, Hiroyuki

    2016-01-01

    Objectives: Unexpected systemic inflammatory response with high fever and increase in C-reactive protein (CRP) occurred frequently after endovascular abdominal aortic aneurysm repair (EVAR). This excessive inflammatory response affects the postoperative course. We evaluated the effects of steroid on the postoperative inflammatory response after EVAR. Methods: Steroid therapy, intravenous infusion of methylprednisolone 1000 mg just after the anesthesia induction, was started since December 2012. After induction of the steroid therapy, 25 patients underwent EVAR with steroid therapy (Group S). These patients were compared with the 65 patients who underwent EVAR without steroid therapy (Group C) in white blood cell count (WBC), CRP and maximum body temperature (BT) on postoperative day 1–5. Results: There was no significant difference in age, female gender, operation time, maximum aneurysm diameter between the two groups. There was no postoperative infective complication in the both groups. WBC did not differ between the two groups; however, CRP was significantly suppressed in Group S than in Group C on POD 1, 3 and 5. Also BT was significantly lower in Group S than Group C on POD 1, 2 and 3. Conclusions: Steroid pretreatment before implantation of the stent graft reduces the early postoperative inflammatory response after EVAR, without increasing postoperative infection. (This is a translation of Jpn J Vasc Surg 2015; 24: 861–865.)

  13. Dose-sensitive steroid-induced hyperglycaemia.

    PubMed

    Gannon, Craig; Dando, Nicholas

    2010-10-01

    Steroids cause significant but under-appreciated and poorly managed glucose intolerance. In this case we describe a patient with steroid-induced hyperglycaemia who obtained a large positive impact on glycaemic control from a small reduction in her steroid dose, sufficient to alleviate the need for insulin. Developments in the treatment of steroid-induced hyperglycaemia may mean that a more active approach needs to be considered when treating steroid-related diabetes in patients whose management is palliative. We advise checking for steroid-induced hyperglycaemia by testing capillary blood glucose values 2 hours after the lunchtime meal and recommend a single morning dose of long-acting insulin to treat the condition.

  14. Failure to thrive and life-threatening complications due to inherited selective cobalamin malabsorption effectively managed in a juvenile Australian shepherd dog

    PubMed Central

    Gold, Ashley J.; Scott, Michael A.; Fyfe, John C.

    2015-01-01

    A juvenile Australian shepherd dog exhibited failure to grow, inappetence, weakness, nonregenerative anemia, neutropenia, and cobalamin deficiency. DNA testing confirmed homozygosity of an amnionless mutation (AMN c.3G > A). Clinical signs resolved with supportive care and parenteral cobalamin supplementation. Inherited selective intestinal cobalamin malabsorption requiring lifelong parenteral supplementation should be considered in Australian shepherds, giant schnauzers, border collies, and beagles that fail to thrive. PMID:26483576

  15. Interaction of JAK with steroid receptor function

    PubMed Central

    Gupta, Nibedita; Mayer, Doris

    2013-01-01

    The function of steroid receptors is not only regulated by steroid hormones, but also by multiple cellular signaling cascades activated by membrane-bound receptors which are stimulated by growth factors or cytokines. Cross-talk between JAK and steroid receptors plays a central role in the regulation of a multitude of physiological processes and aberrant signaling is involved in the development of numerous diseases including cancer. In this review we provide a brief summary of the knowledge of interactions between JAK and the function of steroid receptors in normal cells and tissues and in diseases. PMID:24416641

  16. Steroid metabolism by monkey and human spermatozoa

    SciTech Connect

    Rajalakshmi, M.; Sehgal, A.; Pruthi, J.S.; Anand-Kumar, T.C.

    1983-05-01

    Freshly ejaculated spermatozoa from monkey and human were washed and incubated with tritium labelled androgens or estradiol to study the pattern of spermatozoa steroid metabolism. When equal concentrations of steroid substrates were used for incubation, monkey and human spermatozoa showed very similar pattern of steroid conversion. Spermatozoa from both species converted testosterone mainly to androstenedione, but reverse conversion of androstenedione to testosterone was negligible. Estradiol-17 beta was converted mainly to estrone. The close similarity between the spermatozoa of monkey and men in their steroid metabolic pattern indicates that the rhesus monkey could be an useful animal model to study the effect of drugs on the metabolic pattern of human spermatozoa.

  17. Steroids and brain atrophy in multiple sclerosis.

    PubMed

    Zivadinov, Robert

    2005-06-15

    In this review, we focus on different pathogenetic mechanisms of corticosteroids that induce short- and long-term brain volume fluctuations in a variety of systemic conditions and disorders, as well as on corticosteroid-induced immunomodulatory, immunosuppressive and anti-inflammatory mechanisms that contribute to the slowdown of brain atrophy progression in patients with multiple sclerosis (MS). It appears that chronic low-dose treatment with corticosteroids may contribute to irreversible loss of brain tissue in a variety of autoimmune diseases. This side effect of steroid therapy is probably mediated by steroid-induced protein catabolism mechanism. Evidence is mounting that high-dose corticosteroids may induce reversible short-term brain volume changes due to loss of intracellular water and reduction of abnormal vascular permeability, without there having been axonal loss. Other apoptotic and selective inhibiting mechanisms have been proposed to explain the nature of corticosteroid-induced brain volume fluctuations. It has been shown that chronic use of high dose intravenous methylprednisolone (IVMP) in patients with MS may limit brain atrophy progression over the long-term via different immunological mechanisms, including downregulation of adhesion molecule expression on endothelial cells, decreased cytokine and matrix metalloproteinase secretion, decreased autoreactive T-cell-mediated inflammation and T-cell apoptosis induction, blood-brain barrier closure, demyelination inhibition and, possibly, remyelination promotion. Studies in nonhuman primates have confirmed that short-term brain volume fluctuations may be induced by corticosteroid treatment, but that they are inconsistent, potentially reversible and probably dependent upon individual susceptibility to the effects of corticosteroids. Further longitudinal studies are needed to elucidate pathogenetic mechanisms contributing to brain volume fluctuations in autoimmune diseases and multiple sclerosis.

  18. Steroid Refractory Autoimmune Haemolytic Anaemia Secondary to Sarcoidosis Successfully Treated with Rituximab and Mycophenolate Mofetil.

    PubMed

    Green, Sarah; Partridge, Erica; Idedevbo, Edore; Borg, Anton

    2016-01-01

    Autoimmune haemolytic anaemia is not a well-recognised complication of sarcoidosis. We describe the case of a 30-year-old female who presented with acute warm haemolytic anaemia and widespread lymphadenopathy. Sarcoidosis was diagnosed on lymph node biopsy and further investigation. The haemolytic anaemia responded only to a high dose of steroids. Evidence regarding treatment of steroid refractory autoimmune haemolysis secondary to sarcoidosis is lacking. Based on the emergent evidence that both disorders share common immunopathogenic mechanisms involving Th1 and Th17 lymphocytes, our patient was given rituximab and mycophenolate mofetil to successfully suppress the haemolysis and sarcoid activity. PMID:27563474

  19. Steroid Refractory Autoimmune Haemolytic Anaemia Secondary to Sarcoidosis Successfully Treated with Rituximab and Mycophenolate Mofetil

    PubMed Central

    Idedevbo, Edore; Borg, Anton

    2016-01-01

    Autoimmune haemolytic anaemia is not a well-recognised complication of sarcoidosis. We describe the case of a 30-year-old female who presented with acute warm haemolytic anaemia and widespread lymphadenopathy. Sarcoidosis was diagnosed on lymph node biopsy and further investigation. The haemolytic anaemia responded only to a high dose of steroids. Evidence regarding treatment of steroid refractory autoimmune haemolysis secondary to sarcoidosis is lacking. Based on the emergent evidence that both disorders share common immunopathogenic mechanisms involving Th1 and Th17 lymphocytes, our patient was given rituximab and mycophenolate mofetil to successfully suppress the haemolysis and sarcoid activity. PMID:27563474

  20. 76 FR 72355 - Classification of Two Steroids, Prostanozol and Methasterone, as Schedule III Anabolic Steroids...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-23

    ... steroids and ] depend on several factors (e.g., age, sex, anabolic steroid used, the amount used, and the.... Evaluation of Statutory Factors for Classification as an Anabolic Steroid DEA is proposing by this NPRM to... interaction with DNA. In this study, transcription of a reporter gene provides information as to a...

  1. Steroidal esters from Ferula sinkiangensis.

    PubMed

    Li, Guangzhi; Li, Xiaojin; Cao, Li; Shen, Liangang; Zhu, Jun; Zhang, Jing; Wang, Junchi; Zhang, Lijing; Si, Jianyong

    2014-09-01

    Two new steroidal esters with an unusual framework, Sinkiangenorin A and B, a new organic acid glycoside, Sinkiangenorin C, and four known lignin compounds were isolated from the seeds of Ferula sinkiangensis. The structures of these compounds were established by spectroscopic analysis and single-crystal X-ray diffraction. All of the isolated compounds were tested against Hela, K562 and AGS human cancer cell lines. Sinkiangenorin C showed cytotoxic activity against AGS cells with an IC50 of 36.9 μM. PMID:24979220

  2. Steroid abuse in female athletes.

    PubMed

    Honour, J W

    1997-06-01

    Drug abuse in sport attracts considerable media and public interest, particularly around the time of major international events such as the Olympic Games. From a scientific viewpoint the benefits of drugs to sportspersons have been difficult to address. In the case of steroids, the experiments required for proof, particularly in women, are unethical. Drug testing is an expensive mechanism for deterrence, but there are areas in the scenario where validation data are lacking and improvements to the procedures are needed. Testing standards for women cannot be based on results from tests in men, and regulations need revision to take account of new data. PMID:9263702

  3. Into the world of steroids

    PubMed Central

    2010-01-01

    Evolution of steroids such as sex hormones and ecdysteroids occurred independently in the animal and plant kingdoms. Plants use phytoecdysteroids (PEs) to control defense interactions with some predators; furthermore, PEs can exert beneficial influence on many aspects of mammalian metabolism. Endocrine disrupting compounds such as the estrogen agonist bisphenol A (BPA) are widespread in the environment, posing a potential hormonal risk to animals and plants. Adverse BPA effects on reproductive development and function are coupled with other toxic effects. BPA bioremediation techniques could be developed by exploiting some tolerant plant species. PMID:20671439

  4. Steroid Receptor Coactivator-2 Expression in Brain and Physical Associations with Steroid Receptors

    PubMed Central

    Yore, Mackensie A.; Im, DaEun; Webb, Lena K.; Zhao, Yingxin; Chadwick, Joseph G.; Molenda-Figueira, Heather A.; Haidacher, Sigmund J.; Denner, Larry; Tetel, Marc J.

    2010-01-01

    Estradiol and progesterone bind to their respective receptors in the hypothalamus and hippocampus to influence a variety of behavioral and physiological functions, including reproduction and cognition. Work from our lab and others has shown that the nuclear receptor coactivators, steroid receptor coactivator-1 (SRC-1) and SRC-2, are essential for efficient estrogen receptor (ER) and progestin receptor (PR) transcriptional activity in brain and for hormone-dependent behaviors. While the expression of SRC-1 in brain has been studied extensively, little is known about the expression of SRC-2 in brain. In the present studies, we found that SRC-2 was highly expressed throughout the hippocampus, amygdala and hypothalamus, including the medial preoptic area (MPOA), ventral medial nucleus (VMN), arcuate nucleus (ARC), bed nucleus of the stria terminalis, supraoptic nucleus and suprachiasmatic nucleus. In order for coactivators to function with steroid receptors, they must be expressed in the same cells. Indeed, SRC-2 and ERα were coexpressed in many cells in the MPOA, VMN and ARC, all brain regions known to be involved in female reproductive behavior and physiology. While in vitro studies indicate that SRC-2 physically associates with ER and PR, very little is known about receptor-coactivator interactions in brain. Therefore, we used pull-down assays to test the hypotheses that SRC-2 from hypothalamic and hippocampal tissue physically associate with ER and PR subtypes in a ligand-dependent manner. SRC-2 from both brain regions interacted with ERα bound to agonist, but not in the absence of ligand or in the presence of the selective ER modulator, tamoxifen. Analysis by mass spectrometry confirmed these ligand-dependent interactions between ERα and SRC-2 from brain. In dramatic contrast, SRC-2 from brain showed little to no interaction with ERβ. Interestingly, SRC-2 from both brain regions interacted with PR-B, but not PR-A, in a ligand-dependent manner. Taken together

  5. Activated p38 MAPK in Peripheral Blood Monocytes of Steroid Resistant Asthmatics

    PubMed Central

    Li, Ling-bo; Leung, Donald Y. M.; Goleva, Elena

    2015-01-01

    Steroid resistance is a significant problem in management of chronic inflammatory diseases, including asthma. Accessible biomarkers are needed to identify steroid resistant patients to optimize their treatment. This study examined corticosteroid resistance in severe asthma. 24 asthmatics with forced expiratory volume in one second of less then 80% predicted were classified as steroid resistant or steroid sensitive based on changes in their lung function following a week of treatment with oral prednisone. Heparinised blood was collected from patients prior to oral prednisone administration. Phosphorylated mitogen activated kinases (MAPK) (extracellular regulated kinase (ERK), p38 and jun kinase (JNK)) were analyzed in whole blood samples using flow cytometry. Activation of phospho-p38 MAPK and phospho-mitogen- and stress-activated protein kinase 1 (MSK1) in asthmatics’ peripheral blood mononuclear cells (PBMC) were confirmed by Western blot. Dexamethasone suppression of the LPS-induced IL-8 mRNA production by steroid resistant asthmatics PBMC in the presence of p38 and ERK inhibitors was evaluated by real time PCR. Flow cytometry analysis identified significantly stronger p38 phosphorylation in CD14+ monocytes from steroid resistant than steroid sensitive asthmatics (p = 0.014), whereas no difference was found in phosphorylation of ERK or JNK in CD14+ cells from these two groups of asthmatics. No difference in phosphorylated p38, ERK, JNK was detected in CD4+, CD8+ T cells, B cells and NK cells from steroid resistant vs. steroid sensitive asthmatics. P38 MAPK pathway activation was confirmed by Western blot, as significantly higher phospho-p38 and phospho-MSK1 levels were detected in the PBMC lysates from steroid resistant asthmatics. P38 inhibitor significantly enhanced DEX suppression of LPS-induced IL-8 mRNA by PBMC of steroid resistant asthmatics. This is the first report demonstrating selective p38 MAPK pathway activation in blood monocytes of steroid

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

    PubMed Central

    Leme, J. G.; Bechara, G. H.; Sudo, L. S.

    1977-01-01

    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. PMID:607989

  7. Steroids

    MedlinePlus

    ... hormones that your adrenal glands make to fight stress associated with illnesses and injuries. They reduce inflammation and affect the immune system. You may need to take corticosteroids to treat Arthritis Asthma Autoimmune diseases such as lupus and multiple sclerosis ...

  8. Central line complications

    PubMed Central

    Kornbau, Craig; Lee, Kathryn C; Hughes, Gwendolyn D; Firstenberg, Michael S

    2015-01-01

    Central venous access is a common procedure performed in many clinical settings for a variety of indications. Central lines are not without risk, and there are a multitude of complications that are associated with their placement. Complications can present in an immediate or delayed fashion and vary based on type of central venous access. Significant morbidity and mortality can result from complications related to central venous access. These complications can cause a significant healthcare burden in cost, hospital days, and patient quality of life. Advances in imaging, access technique, and medical devices have reduced and altered the types of complications encountered in clinical practice; but most complications still center around vascular injury, infection, and misplacement. Recognition and management of central line complications is important when caring for patients with vascular access, but prevention is the ultimate goal. This article discusses common and rare complications associated with central venous access, as well as techniques to recognize, manage, and prevent complications. PMID:26557487

  9. CONTAMINANT INTERACTIONS WITH STEROID RECEPTORS: EVIDENCE FOR RECEPTOR BINDING.

    EPA Science Inventory

    Steroid receptors are important determinants of endocrine disrupter consequences. As the most frequently proposed mechanism of endocrine-disrupting contaminant (EDC) action, steroid receptors are not only targets of natural steroids but are also commonly sites of nonsteroidal com...

  10. [Sex steroids and bone tissue].

    PubMed

    Ribot, C; Tremollieres, F

    1995-01-01

    The precise mechanism of action of sexual steroids in the regulation of bone tissue is still poorly understood. Besides the indirect action via the production of calciotropic hormones, the fact that receptors respond to oestrogens as well as to androgens and progesterone is evidence that sexual steroids have a direct action in regulating bone activity. The anti-osteoclastic action of oestrogens, via the modulation in osteoblastic production of different substances such as interleukin-1 and -6, TGF beta, GM-CSF which inhibit osteoclastogenesis and bone resorption activity, is well documented. More recently, the direct role in osteoclast inhibition was suggested by the observation that osteoclasts carry oestrogen receptors. Likewise, certain in vivo and in vitro data suggest that oestrogens could also have a positive effect on bone formation regulation. For androgens, currently available data show that in vitro stimulation of bone formation, with increased proliferation and cell differentiation, could be mediated by TGF beta. The role of progesterone is more recently known. In vivo, progesterone increases cell growth and IFGF-II secretion by non-transformed human osteoblasts. The number of potential mechanisms which have already been demonstrated suggest the complexity of sex hormone regulation which leads to the final situation of physiological calcium sparing in the skeleton while maintaining skeletal structure. PMID:7747921

  11. Environmental Stress and Atopic Dermatitis: Cure with Steroid-Free Treatment and Mutual Trust in a Good Life Style

    NASA Astrophysics Data System (ADS)

    Kimata, H.

    Atopic Dermatitis (AD) is a chronic inflammatory skin diseasewith severe itching. The exact causes for AD still remain to be elucidated. However, there are at least following 3 causes: 1) allergy, 2) bacterial infection, and 3) environmental stress. These 3 causes are mixed in AD, and consequently symptoms of AD are very complex. In addition, patients with AD are reluctant to take steroid ointment treatment. This is due to the fact that steroid is an anti-inflammatory and immunosuppressive drug. Thus steroid ointment treatment only temporally improved AD by reduction of inflammation, while it failed to cure bacterial infection. Patients had to apply steroid ointment for long-term, which caused many side effects, including enhancement of IgE production, aggravation of skin infection, and rebound phenomenon. Rebound was aggravation of symptoms upon cessation of steroid ointment use. Enhancement of IgE production augmented allergic responses, while aggravation of skin infecti on worsened skin symptoms. Collectively, lone-term use of steroid ointment complicated AD instead of cure. Patients with AD suffered from these side effects, and they did not trust steroid treatment. Recently, tacrolimus ointment was widely used instead of steroid ointment. However, tacrolimus was more potent immunosuppressive drug, and US FDA warned cancer concern. Therefore, steroid- and tacrolimus-free treatment was considered safer and ideal. Patients with AD were susceptible to stress, which worsened symptoms. Recently, new environmental stress emerged, and patients with AD were suffering from them. In this article, I describe the effect of environmental stress on allergic responses, and explain the details of cases of AD with steroid-free treatment and mutual trust, which resulted in cure of AD.

  12. Regulation of TRP channels by steroids: Implications in physiology and diseases.

    PubMed

    Kumar, Ashutosh; Kumari, Shikha; Majhi, Rakesh Kumar; Swain, Nirlipta; Yadav, Manoj; Goswami, Chandan

    2015-09-01

    While effects of different steroids on the gene expression and regulation are well established, it is proven that steroids can also exert rapid non-genomic actions in several tissues and cells. In most cases, these non-genomic rapid effects of steroids are actually due to intracellular mobilization of Ca(2+)- and other ions suggesting that Ca(2+) channels are involved in such effects. Transient Receptor Potential (TRP) ion channels or TRPs are the largest group of non-selective and polymodal ion channels which cause Ca(2+)-influx in response to different physical and chemical stimuli. While non-genomic actions of different steroids on different ion channels have been established to some extent, involvement of TRPs in such functions is largely unexplored. In this review, we critically analyze the literature and summarize how different steroids as well as their metabolic precursors and derivatives can exert non-genomic effects by acting on different TRPs qualitatively and/or quantitatively. Such effects have physiological repercussion on systems such as in sperm cells, immune cells, bone cells, neuronal cells and many others. Different TRPs are also endogenously expressed in diverse steroid-producing tissues and thus may have importance in steroid synthesis as well, a process which is tightly controlled by the intracellular Ca(2+) concentrations. Tissue and cell-specific expression of TRP channels are also regulated by different steroids. Understanding of the crosstalk between TRP channels and different steroids may have strong significance in physiological, endocrinological and pharmacological context and in future these compounds can also be used as potential biomedicine.

  13. Enantiomer selective glucuronidation of the non-steroidal pure anti-androgen bicalutamide by human liver and kidney: role of the human UDP-glucuronosyltransferase (UGT)1A9 enzyme

    PubMed Central

    Grosse, Laurent; Campeau, Anne-Sophie; Caron, Sarah; Morin, Frédéric-Alexandre; Meunier, Kim; Trottier, Jocelyn; Caron, Patrick; Verreault, Mélanie; Barbier, Olivier

    2013-01-01

    Bicalutamide (Casodex®) is a non-steroidal pure anti-androgen used in the treatment of localized prostate cancer. It is a racemate drug and its activity resides in the (R)-enantiomer, with little in the (S)-enantiomer. A major metabolic pathway for bicalutamide is glucuronidation catalyzed by UDP-glucuronosyltransferase (UGT) enzymes. While (S)bicalutamide is directly glucuronidated, (R)bicalutamide requires hydroxylation prior to glucuronidation. The contribution of human tissues and UGT isoforms in the metabolism of these enantiomers has not been extensively investigated. In this study, both (R) and/or (S)bicalutamide were converted into glucuronide (-G) derivatives following incubation of pure and racemic solutions with microsomal extracts from human liver and kidney. Intestinal microsomes exhibited only low reactivity with these substrates. Km values of liver and kidney samples for (S)bicalutamide glucuronidation were similar, and lower than values obtained with the (R)-enantiomer. Among the 16 human UGTs tested, UGT1A8 and UGT1A9 were able to form both (S) and (R)bicalutamide-G from pure or racemic substrates. UGT2B7 was also able to form (R)bicalutamide-G. Kinetic parameters of the recombinant UGT2B7, UGT1A8 and UGT1A9 enzymes support a predominant role of the UGT1A9 isoform in bicalutamide metabolism. Accordingly, (S)bicalutamide inhibited the ability of human liver and kidney microsomes to glucuronidate the UGT1A9 probe substrate, propofol. In conclusion, the present study provides the first comprehensive analysis of in vitro bicalutamide glucuronidation by human tissues and UGTs, and identifies UGT1A9 as a major contributor for (R) and (S) glucuronidation in the human liver and kidney. PMID:23527766

  14. [Mechanism, diagnosis, and treatment of steroid myopathy].

    PubMed

    Kohsaka, Hitoshi

    2013-11-01

    Steroid myopathy, characterized by muscle atrophy and weakness, is an adverse effect of high-dose steroid therapy. Weakness of proximal muscle that interferes with activities of daily living is a serious problem for patients with steroid myopathy. Here, we outline the pathogenic mechanism, diagnosis, and treatment of steroid myopathy. Recent studies have shown that steroid-mediated induction of ubiquitin ligases (atrogin-1, muscle RING finger-1) and suppression of mammalian/mechanistic target of rapamycin cause an imbalance between anabolism and catabolism of muscle proteins, resulting in muscle atrophy. Despite the progress in understanding the pathogenic mechanism, the diagnosis and treatment of steroid myopathy has not yet been established. Small changes in muscle enzymes, including CK, LDH, and aldolase, make it difficult to define diagnostic criteria. Furthermore, since there is no drug available for treating the disorder, the patients have no opinion except waiting for spontaneous recovery with steroid tapering and exercising. To address these issues, we introduce novel approaches involving branched-chain amino acids that aim at treatment and assessment of steroid myopathy. PMID:24200615

  15. [Mechanism, diagnosis, and treatment of steroid myopathy].

    PubMed

    Kohsaka, Hitoshi

    2013-11-01

    Steroid myopathy, characterized by muscle atrophy and weakness, is an adverse effect of high-dose steroid therapy. Weakness of proximal muscle that interferes with activities of daily living is a serious problem for patients with steroid myopathy. Here, we outline the pathogenic mechanism, diagnosis, and treatment of steroid myopathy. Recent studies have shown that steroid-mediated induction of ubiquitin ligases (atrogin-1, muscle RING finger-1) and suppression of mammalian/mechanistic target of rapamycin cause an imbalance between anabolism and catabolism of muscle proteins, resulting in muscle atrophy. Despite the progress in understanding the pathogenic mechanism, the diagnosis and treatment of steroid myopathy has not yet been established. Small changes in muscle enzymes, including CK, LDH, and aldolase, make it difficult to define diagnostic criteria. Furthermore, since there is no drug available for treating the disorder, the patients have no opinion except waiting for spontaneous recovery with steroid tapering and exercising. To address these issues, we introduce novel approaches involving branched-chain amino acids that aim at treatment and assessment of steroid myopathy.

  16. Psychological Characteristics of Adolescent Steroid Users.

    ERIC Educational Resources Information Center

    Burnett, Kent F.; Kleiman, Mark E.

    1994-01-01

    Used Millon Adolescent Personality Inventory and Profile of Mood States to assess psychological characteristics in 72 adolescent males: 24 adolescent athletes who reported steroid use, 24 athletes with no steroid use, and 24 nonathletes. Although some personality variables differentiated between athletes and nonathletes, no personality variables…

  17. Steroids Update, Part 1 and Part 2.

    ERIC Educational Resources Information Center

    Miller, Calvin; Duda, Marty

    1986-01-01

    Part 1 of this two-part article describes the views of a physician who believes that athletes who want to take steroids are best protected by receiving a prescription and monitoring. Part 2 discusses the more general view of physicians that steroids should not be prescribed but perhaps should be monitored. (MT)

  18. Behavioural manifestations of anabolic steroid use.

    PubMed

    Trenton, Adam J; Currier, Glenn W

    2005-01-01

    The use of anabolic androgenic steroids (AAS) for gains in strength and muscle mass is relatively common among certain subpopulations, including athletes, bodybuilders, adolescents and young adults. Adverse physical effects associated with steroid abuse are well documented, but more recently, increased attention has been given to the adverse psychiatric effects of these compounds. Steroids may be used in oral, 17alpha-alkylated, or intramuscular, 17beta-esterified, preparations. Commonly, steroid users employ these agents at levels 10- to 100-fold in excess of therapeutic doses and use multiple steroids simultaneously, a practice known as 'stacking'. Significant psychiatric symptoms including aggression and violence, mania, and less frequently psychosis and suicide have been associated with steroid abuse. Long-term steroid abusers may develop symptoms of dependence and withdrawal on discontinuation of AAS. Treatment of AAS abusers should address both acute physical and behavioural symptoms as well as long-term abstinence and recovery. To date, limited information is available regarding specific pharmacological treatments for individuals recovering from steroid abuse. This paper reviews the published literature concerning the recognition and treatment of behavioural manifestations of AAS abuse.

  19. Steroids: To Test or to Educate?

    ERIC Educational Resources Information Center

    LaFee, Scott

    2006-01-01

    In February 2005, The Dallas Morning News published a multipart series on steroid use among high school students in Texas. The paper's four-month investigation was wide-ranging, but shined a particular spotlight upon alleged abuses in the 13,700-student Grapevine-Colleyville Independent School District, north of Dallas. Use of steroids and other…

  20. Canine Lipomas Treated with Steroid Injections: Clinical Findings

    PubMed Central

    Lamagna, Barbara; Greco, Adelaide; Guardascione, Anna; Navas, Luigi; Ragozzino, Manuela; Paciello, Orlando; Brunetti, Arturo; Meomartino, Leonardo

    2012-01-01

    Lipomas are common benign tumours of fat cells. In most cases, surgical excision is curative and simple to perform; however, such a procedure requires general anaesthesia and may be associated with delayed wound healing, seroma formation and nerve injury in deep and intramuscular tumours. The objective of this study was to evaluate treatment of subcutaneous, subfascial or intermuscular lipomas using intralesional steroid injections in dogs. Fifteen dogs presenting with lipomas were selected for treatment with ultrasound-guided intralesional injection of triamcinolone acetonide at a dose of 40 mg/mL. Nine subcutaneous and subfascial tumours showed a complete regression. The other lipomas decreased in diameter, achieving, in some cases, remission of discomfort and regression of lameness. Steroid injection was a relatively safe and effective treatment for lipomas in dogs; only six dogs experienced polyuria/polydipsia for about 2 weeks post-treatment. PMID:23226250

  1. [Anabolic steroids and their abuse in sports].

    PubMed

    Bruno, M

    1990-11-15

    Anabolic steroids increase protein synthesis in skeletal muscles and reverse catabolic processes. Because of these properties some athletes use anabolic steroids in an attempt to improve their athletic performance. However, the latest studies indicate that limited increases in muscle mass and strength during anabolic steroid administration are observed only in athletes who already are weight-trained and who continue intensive training while consuming high-protein, high-calorie diets. Adverse effects attributed to anabolic steroid use occur frequently. Serious adverse effects include hepatic and endocrine dysfunction; cardiovascular and behavioral changes are also reported. Some of the adverse effects associated with the use of these agents are irreversible, particularly in women. The use of anabolic steroids to improve athletic performance has become prevalent; however the limited benefits reported are offset by numerous adverse reactions.

  2. Pregnancy Complications: Anemia

    MedlinePlus

    ... Close X Home > Complications & Loss > Pregnancy complications > Anemia Anemia E-mail to a friend Please fill in ... anemia at a prenatal care visit . What causes anemia? Usually, a woman becomes anemic (has anemia) because ...

  3. Extraintestinal Complications: Kidney Disorders

    MedlinePlus

    ... Extraintestinal Complications: Kidney Disorders Go Back Extraintestinal Complications: Kidney Disorders Email Print + Share The kidneys filter the ... but some less serious ones occur more frequently. Kidney stones These are probably the most commonly encountered ...

  4. Pregnancy Complications: Preexisting Diabetes

    MedlinePlus

    ... Home > Complications & Loss > Pregnancy complications > Preexisting diabetes Preexisting diabetes E-mail to a friend Please fill in ... and your baby are healthy. What is preexisting diabetes? About 9 out of 100 women (9 percent) ...

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

    PubMed Central

    Shu, H-J; Zeng, C-M; Wang, C; Covey, D F; Zorumski, C F; Mennerick, S

    2006-01-01

    Background and purpose: Neuroactive steroids are potent modulators of GABAA 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 GABAA receptors because cyclodextrins form inclusion complexes with at least some steroids that are active at the GABAA receptor, such as (3α,5α)-3-hydroxypregnan-20-one (3α5αP, allopregnanolone). Experimental approach: To assess the versatility of cyclodextrins as steroid modulators, we investigated interactions between γ-cyclodextrin and neuroactive steroids of different structural classes. Key results: Both a bioassay based on electrophysiological assessment of GABAA receptor function and optical measurements of cellular accumulation of a fluorescent steroid analogue suggest that γ-cyclodextrin sequesters steroids rather than directly influencing GABAA receptor function. Neither a 5β-reduced A/B ring fusion nor a sulphate group at carbon 3 affected the presumed inclusion complex formation between steroid and γ-cyclodextrin. Apparent dissociation constants for interactions between natural steroids and γ-cyclodexrin ranged from 10-60 μM. Although γ-cyclodextrin accommodates a range of natural and synthetic steroids, C11 substitutions reduced inclusion complex formation. Using γ-cyclodextrin to remove steroid not directly bound to GABAA receptors, we found that cellular retention of receptor-unbound steroid rate limits potentiation by 3α- hydroxysteroids but not inhibition by sulphated steroids. Conclusions and implications: We conclude that γ-cyclodextrins can be useful, albeit non-specific, tools for terminating the actions of multiple classes of naturally occurring neuroactive steroids. PMID:17160009

  6. Steroids in house sparrows (Passer domesticus): Effects of POPs and male quality signalling.

    PubMed

    Nossen, Ida; Ciesielski, Tomasz M; Dimmen, Malene V; Jensen, Henrik; Ringsby, Thor Harald; Polder, Anuschka; Rønning, Bernt; Jenssen, Bjørn M; Styrishave, Bjarne

    2016-03-15

    At high trophic levels, environmental contaminants have been found to affect endocrinological processes. Less attention has been paid to species at lower trophic levels. The house sparrow (Passer domesticus) may be a useful model for investigating effects of POPs in mid-range trophic level species. In male house sparrows, ornamental traits involved in male quality signalling are important for female selection. These traits are governed by endocrinological systems, and POPs may therefore interfere with male quality signalling. The aim of the present study was to use the house sparrow as a mid-range trophic level model species to study the effects of environmental contaminants on endocrinology and male quality signalling. We analysed the levels of selected PCBs, PBDEs and OCPs and investigated the possible effects of these contaminants on circulating levels of steroid hormones (4 progestagens, 4 androgens and 3 estrogens) in male and female adult house sparrows from a population on the island Leka, Norway. Plasma samples were analysed for steroid hormones by GC-MS and liver samples were analysed for environmental contaminants by GC-ECD and GC-MS. In males, we also quantified ornament traits. It was hypothesised that POPs may have endocrine disrupting effects on the local house sparrow population and can thus interfere with the steroid hormone homeostasis. Among female house sparrows, bivariate correlations revealed negative relationships between POPs and estrogens. Among male sparrows, positive relationships between dihydrotestosterone levels and PCBs were observed. In males, positive relationships were also found between steroids and beak length, and between steroids and ornamental traits such as total badge size. This was confirmed by a significant OPLS model between beak length and steroids. Although sparrows are in the mid-range trophic levels, the present study indicates that POPs may affect steroid homeostasis in house sparrows, in particular for females. For

  7. Steroid Injection and Nonsteroidal Anti-inflammatory Agents for Shoulder Pain

    PubMed Central

    Sun, Yaying; Chen, Jiwu; Li, Hong; Jiang, Jia; Chen, Shiyi

    2015-01-01

    Abstract Advantages and possible risks associated with steroid injection compared with nonsteroidal anti-inflammatory drugs (NSAIDs) for shoulder pain are not fully understood. To compare the efficiency and safety of steroid injection versus NSAIDs for patients with shoulder pain. PubMed, Embase, and the Cochrane Library were searched through July 2015. Study eligibility criteria, participants, and interventions: randomized controlled trials (RCTs) that assessed steroid injection versus NSAIDs for patients with shoulder pain. Study appraisal and synthesis methods: predefined primary efficacy outcome was functional improvement; and secondary efficacy outcomes included pain relief and complications. Relative risks (RRs) and standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using a random-effects model accounting for clinical heterogeneity. Eight RCTs involving 465 participants were included in the meta-analysis. Five trials compared steroid injection with oral NSAIDs, and 3 compared steroids injection with NSAIDs injection. Compared with steroid injection, oral NSAIDs were less effective in 4 or 6 weeks for functional improvement (SMD 0.61; 95% CI, 0.08–1.14; P = 0.01), while there was no significant difference in pain relief (SMD 0.45; 95% CI, −0.50–1.40; P < 0.00001) or complication rate (RR 1.10; 95% CI, 0.26–4.58; P = 0.29). Meta-analysis was not performed for NSAIDs injection due to considerable heterogeneity. Conflicting results were observed in favor of either steroid or NSAIDs injection. Not all diseases that can lead to shoulder pain were included, detailed intervention protocols were inconsistent across studies, and some estimated data were input into comparison while some data were lost, which could exert an influence on pooled results. Steroid injection, compared with oral NSAIDs, provides slightly more improvement in shoulder function without superiority in pain relief or risk of complications at

  8. Neuroactive steroids with perfluorobenzoyl group.

    PubMed

    Cerný, Ivan; Buděšínský, Miloš; Pouzar, Vladimír; Vyklický, Vojtěch; Krausová, Barbora; Vyklický, Ladislav

    2012-10-01

    During an initial study in searching for the alternative derivatives suitable for photolabeling of neuroactive steroids, perfluorobenzoates and perfluorobenzamides in position 17 of 5β-androstan-3α-ol were synthesized from the corresponding 17-hydroxy and 17-amino derivatives. After transformation into glutamates or sulfates, 17α-epimers had comparable inhibitory activity at NMDA receptors to the natural neurosteroid (20-oxo-5β-pregnan-3β-yl sulfate), however, were more potent (2- to 36-fold) than their 17β-substituted analogs. In one case, fluorine in position 4' of perfluorobenzoate group was substituted with azide and activity of the final glutamate was retained comparing with the corresponding perfluorobenzoate. The series was expanded with perfluorobenzoyl derivatives of pregnanolone: Perfluorobenzamide of glutamate and perfluorobenzoate of 11α-hydroxy pregnanolone were prepared and tested. From nine tested compounds, four of them exhibit very good inhibition activity and can serve as promising leads for photolabeling experiments.

  9. Complications of mandibular fractures.

    PubMed

    Zweig, Barry E

    2009-03-01

    Before any definitive treatment of mandibular fractures, the patient needs to be evaluated for more potentially life-threatening injuries. Complications can and do occur with treatment of mandibular fractures and can occur during any of the phases of treatment. The development of an accurate diagnosis and appropriate treatment plan is vital in achieving optimal success and decreasing complications. Knowledge of the anatomy and the principles of bone healing is also an important factor in preventing complications. To limit long-term untoward effects, complications should be recognized early and the appropriate treatment should be started before a minor complication becomes a complex one that is more difficult to manage.

  10. [Non-steroid anti-inflammatory drugs and adverse gastrointestinal effects. An unresolved problem].

    PubMed

    López, A

    1999-01-01

    Non-steroid anti-inflammatory drugs are a class of medicine widely used throughout the world. This is a pharmacological group in continuous growth, to which some new molecules have been added in recent years. The great drawback of non-steroid anti-inflammatory drugs are their adverse effects, outstanding of which due to their frequency and importance being those that occur in the gastrointestinal tract. By means of a search in Medline and other databases, this work reviews the latest data published on the incidence of dyspepsia, gastroduodenal lesions, gastrointestinal complications and mortality associated with consumption of non-steroid anti-inflammatory drugs. Similarly, a brief description is made of the mechanism of lesions to the stomach of the non-steroid anti-inflammatory drugs and the different risk factors that condition the appearance of adverse effects at the gastrointestinal level. Finally, an analysis is made of the preventive strategy and the different medicines that can be used to this end and a contrast is made of the evidence extracted from the different published studies and the reality of the use of the different "gastroprotectors". This review concludes with a series of questions that still remain unresolved concerning treatment with non-steroid anti-inflammatory drugs and their lesions to the stomach.

  11. Collision-induced dissociation pathways of anabolic steroids by electrospray ionization tandem mass spectrometry.

    PubMed

    Guan, Fuyu; Soma, Lawrence R; Luo, Yi; Uboh, Cornelius E; Peterman, Scott

    2006-04-01

    Anabolic steroids are structurally similar compounds, and their product-ion spectra obtained by tandem mass spectrometry under electrospray ionization conditions are quite difficult to interpret because of poly-ring structures and lack of a charge-retaining center in their chemical structures. In the present study, the fragmentation of nine anabolic steroids of interest to the racing industry was investigated by using triple quadrupole mass spectrometer, Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer, and a linear ion trap instrument. With the aid of an expert system software (Mass Frontier version 3.0), accurate mass measurements, and multiple stage tandem mass spectrometric (MS(n)) experiments, fragmentation pathways were elucidated for boldenone, methandrostenolone, tetrahydrogestrinone (THG), trenbolone, normethandrolone and mibolerone. Small differences in the chemical structures of the steroids, such as an additional double-bond or a methyl group, result in significantly different fragmentation pathways. The fragmentation pathways proposed in this paper allow interpretation of major product ions of other anabolic steroids reported by other researchers in a recent publication. The proposed fragmentation pathways are helpful for characterization of new steroids. The approach used in this study for elucidation of the fragmentation pathways is helpful in interpretation of complicated product-ion spectra of other compounds, drugs and their metabolites. PMID:16488153

  12. Up-regulation of steroid biosynthesis by retinoid signaling: Implications for aging

    PubMed Central

    Manna, Pulak R.; Stetson, Cloyce L.; Daugherty, Carol; Shimizu, Ikue; Syapin, Peter J.; Garrel, Ghislaine; Cohen-Tannoudji, Joelle; Huhtaniemi, Ilpo; Slominski, Andrzej T.; Pruitt, Kevin; Stocco, Douglas M.

    2015-01-01

    Retinoids (vitamin A and its derivatives) are critical for a spectrum of developmental and physiological processes, in which steroid hormones also play indispensable roles. The StAR protein predominantly regulates steroid biosynthesis in steroidogenic tissues. We reported that regulation of retinoid, especially atRA and 9-cis RA, responsive StAR transcription is largely mediated by an LXR-RXR/RAR heterodimeric motif in the mouse StAR promoter. Herein we demonstrate that retinoids are capable of enhancing StAR protein, P-StAR, and steroid production, in granulosa, adrenocortical, glial, and epidermal cells. Whereas transient expression of RARα and RXRα enhanced 9-cis RA-treated StAR gene transcription, silencing of RXRα with siRNA, decreased StAR and steroid levels. An oligonucleotide probe encompassing an LXR-RXR/RAR motif bound to adrenocortical and epidermal keratinocyte NEs in EMSAs. ChIP studies revealed association of RARα and RXRα with the StAR proximal promoter. Further studies demonstrated that StAR mRNA levels decreased in diseased and elderly men and women skin tissues and that atRA could restore steroidogenesis in epidermal keratinocytes of aged individuals. These findings provide novel insights into the relevance of retinoid signaling in the up-regulation of steroid biosynthesis in various target tissues, and indicate that retinoid therapy may have important implications in age-related complications and diseases. PMID:26303142

  13. Anabolic-androgenic steroids. Current issues.

    PubMed

    Yesalis, C E; Bahrke, M S

    1995-05-01

    The use of drugs to enhance physical performance has been observed for thousands of years. Today, individuals continue to use a variety of substances, including anabolic-androgenic steroids, in the hope of enhancing their performance and appearance. Rumours persist regarding the incidence of the nonmedical use of anabolic steroids by athletes and nonathletes: however, true estimates are now available based on the results of systematic surveys. Although the vast majority of the athletic community accepts that anabolic steroids enhance performance and appearance, the extent to which this occurs and the factors influencing such effects remain incompletely understood and documented. Refinement of our knowledge of the ergogenic effects of anabolic steroids is not without merit; however, the existing scientific evidence coupled with an overwhelming number of anecdotal accounts argues against devoting significant resources to this area of investigation at present. The short term health effects of anabolic steroids have been increasingly studied and reviewed, and while anabolic steroid use has been associated with several adverse and even fatal effects, the incidence of serious effects thus far reported has been extremely low. The long term effects of anabolic steroid use are generally unknown. Unfortunately, the lack of scientific information on long term health effects has impeded, if not precluded, the formation of effective health education and drug abuse prevention strategies. Consequently, efforts should be expanded in the areas of prevention and education.

  14. Investigations into the feasibility of routine ultra high performance liquid chromatography-tandem mass spectrometry analysis of equine hair samples for detecting the misuse of anabolic steroids, anabolic steroid esters and related compounds.

    PubMed

    Gray, Bobby P; Viljanto, Marjaana; Bright, Jane; Pearce, Clive; Maynard, Steve

    2013-07-17

    The detection of the abuse of anabolic steroids in equine sport is complicated by the endogenous nature of some of the abused steroids, such as testosterone and nandrolone. These steroids are commonly administered as intramuscular injections of esterified forms of the steroid, which prolongs their effects and improves bioavailability over oral dosing. The successful detection of an intact anabolic steroid ester therefore provides unequivocal proof of an illegal administration, as esterified forms are not found endogenously. Detection of intact anabolic steroid esters is possible in plasma samples but not, to date, in the traditional doping control matrix of urine. The analysis of equine mane hair for the detection of anabolic steroid esters has the potential to greatly extend the time period over which detection of abuse can be monitored. Equine mane hair samples were incubated in 0.1M phosphate buffer (pH 9.5) before anabolic steroids (testosterone, nandrolone, boldenone, trenbolone and stanozolol), anabolic steroid esters (esters of testosterone, nandrolone, boldenone and trenbolone) and associated compounds (fluticasone propionate and esters of hydroxyprogesterone) were extracted by liquid-liquid extraction with a mix of hexane and ethyl acetate (7:3, v:v). Further sample clean up by solid phase extraction was followed by derivatisation with methoxylamine HCL and analysis by UHPLC-MS/MS. Initial method development was performed on a representative suite of four testosterone esters (propionate, phenylpropionate, isocaproate and decanoate) and the method was later extended to include a further 18 compounds. The applicability of the method was demonstrated by the analysis of mane hair samples collected following the intramuscular administration of 500 mg of Durateston(®) (mixed testosterone esters) to a Thoroughbred mare (560 kg). The method was subsequently used to successfully detect boldenone undecylenate and stanozolol in hair samples collected following

  15. Video-assisted thoracic surgery complications

    PubMed Central

    Kozak, Józef

    2014-01-01

    Video-assisted thoracic surgery (VATS) is a miniinvasive technique commonly applied worldwide. Indications for VATS are very broad and include the diagnosis of mediastinal, lung and pleural diseases, as well as large resection procedures such as pneumonectomy. The most frequent complication is prolonged postoperative air leak. The other significant complications are bleeding, infections, postoperative pain and recurrence at the port site. Different complications of VATS procedures can occur with variable frequency in various diseases. Despite the large number of their types, such complications are rare and can be avoided through the proper selection of patients and an appropriate surgical technique. PMID:25561984

  16. Steroid plant hormones: effects outside plant kingdom.

    PubMed

    Zhabinskii, Vladimir N; Khripach, Natalia B; Khripach, Vladimir A

    2015-05-01

    Brassinosteroids (BS) are the first group of steroid-hormonal compounds isolated from and acting in plants. Among numerous physiological effects of BS growth stimulation and adaptogenic activities are especially remarkable. In this review, we provide evidence that BS possess similar types of activity also beyond plant kingdom at concentrations comparable with those for plants. This finding allows looking at steroids from a new point of view: how common are the mechanisms of steroid bioregulation in different types of organisms from protozoa to higher animals.

  17. A review on determination of steroids in biological samples exploiting nanobio-electroanalytical methods.

    PubMed

    Yadav, Saurabh K; Chandra, Pranjal; Goyal, Rajendra N; Shim, Yoon-Bo

    2013-01-31

    The applications of nanomaterial modified sensors, molecularly imprinting polymer based, aptamer based, and immunosensors have been described in the determination of steroids using electroanalytical techniques. After a brief description of the steroids and assays in biological fluids, the principles of electrochemical detection with the advantages and the limitations of the various sensors are presented. The nanomaterial modified sensors catalyze the oxidation/reduction of steroids and are suitable for sensing them in environmental samples and biological fluids. The determination of steroids based on their reduction has been found more useful in comparison to oxidation as the common metabolites present in the biological fluids do not undergo reduction in the usual potential window and hence, do not interfere in the determination. The sensors based on immunosensors and aptamers were found more sensitive and selective for steroid determination. Conducting polymer modified bio-sensors and microchip devices are suggested as possible future prospects for the ultra sensitive and simultaneous determination of steroids and their metabolites in various samples.

  18. Integration of ligand and structure-based virtual screening for identification of leading anabolic steroids.

    PubMed

    Alvarez-Ginarte, Yoanna María; Montero-Cabrera, Luis Alberto; García-de la Vega, José Manuel; Bencomo-Martínez, Alberto; Pupo, Amaury; Agramonte-Delgado, Alina; Marrero-Ponce, Yovani; Ruiz-García, José Alberto; Mikosch, Hans

    2013-11-01

    Parallel ligand- and structure-based virtual screenings of 269 steroids with anabolic activity evaluated in vivo were performed. The quantitative structure-activity relationship (QSAR) model expressed by selected descriptors as the octanol-water partition coefficient, the molar volume and the quantum mechanical calculated charge values on atoms C1, C2, C5, C9, C10, C14 and C17 of the steroid skeleton, expresses structural features of anabolic steroids (AS) contributing to the transport and steroid-receptor interaction. On the other hand, computational simulations of a candidate ligand binding to a receptor study (a "docking" procedure) predict the association of these AS with the human androgen receptor (AR). Fourteen compounds were identified as lead; the most potent was the 7α-methylestr-4-en-3, 17-dione. It was concluded that a good anabolic activity requires hydrogen bonding interactions between both Arg752 and Gln711 residues in the cycles A with O3 atom of the steroid and either Asn705 and Thr877 residues in the cycles D of steroid with O17 atom.

  19. Antiangiogenic Steroids in Human Cancer Therapy.

    PubMed

    Pietras, Richard J; Weinberg, Olga K

    2005-03-01

    Despite advances in the early detection of tumors and in the use of chemotherapy, radiotherapy and surgery for disease management, the worldwide mortality from human cancer remains unacceptably high. The treatment of cancer may benefit from the introduction of novel therapies derived from natural products. Natural products have served to provide a basis for many of the pharmaceutical agents in current use in cancer therapy. Emerging research indicates that progressive growth and spread of many solid tumors depends, in part, on the formation of an adequate blood supply, and this process of tumor-associated angiogenesis is reported to have prognostic significance in several human cancers. This review focuses on the potential application in antitumor therapy of naturally-occurring steroids that target tumor-associated angiogenesis. Squalamine, a 7,24 dihydroxylated 24-sulfated cholestane steroid conjugated to a spermidine at position C-3, is known to have strong antiangiogenic activity in vitro, and it significantly disrupts tumor proliferation and progression in laboratory studies. Work on the interactions of squalamine with vascular endothelial cells indicate that it binds with cell membranes, inhibits the membrane Na(+)/H(+) exchanger and may further function as a calmodulin chaperone. These primary actions appear to promote inhibition of several vital steps in angiogenesis, such as blockade of mitogen-induced actin polymerization, cell-cell adhesion and cell migration, leading to suppression of endothelial cell proliferation. Preclinical studies with squalamine have shown additive benefits in tumor growth delay when squalamine is combined with cisplatin, paclitaxel, cyclophosphamide, genistein or radiation therapy. This compound has also been assessed in early phase clinical trials in cancer; squalamine was found to exhibit little systemic toxicity and was generally well tolerated by treated patients with various solid tumor malignancies, including ovarian, non

  20. Simultaneous bilateral septic arthritis of the knee after intraarticular steroid injection: A clinical report.

    PubMed

    Munigangaiah, Sudarshan; O'Sullivan, Theresa A; Lenehan, Brian

    2014-07-01

    Osteoarthritis of knee is one of the common problems in elderly population. Intraarticular corticosteroid injection is a conservative management modality in osteoarthritis of knee. Septic arthritis is an infective complication of intraarticular corticosteroid injection. Septic arthritis in rheumatoid arthritis patients have worse prognosis because of delay in diagnosis. A higher rate of infectious complications following intraarticular injection is expected in immunocompromised and rheumatoid patients. We would like to report an extremely rare case of simultaneous bilateral knee septic arthritis after bilateral knee intraarticular steroid injection in a rheumatoid arthritis patient. Patient was treated successfully with multiple bilateral knee arthroscopic washouts and long-term intravenous antibiotics. This case report emphasizes the increased risk of infection in rheumatoid arthritis patients and a risk benefit assessment on individual basis before carrying out intraarticular steroid injection. Patient should be aware of this increased risk of infection.

  1. Prevalence of Use of Anabolic Steroids by Bodybuilders Using Three Methods in a City of Iran

    PubMed Central

    Nakhaee, Mohammad Reza; Pakravan, Faezeh; Nakhaee, Nouzar

    2013-01-01

    Background The prevalence of substance use among bodybuilding athletes has been poorly studied in Iran. This study was conducted to examine the prevalence of drug use, especially anabolic steroids, among bodybuilding athletes. Methods This cross-sectional study was conducted in the first half of 2013 among body building athletes referring to gyms located in Kerman, Iran. Five gyms were selected randomly and 380 athletes were invited to complete a self-administered anonymous questionnaire, consecutively. The questionnaire included two parts; baseline characteristics and substance related questions. The prevalence of anabolic steroids was estimated based on three methods; self-report, projective question, and crosswise model. Findings We enrolled 298 male athletes in the final analysis. Mean ± SD age of subjects was 25.9 ± 8.4. The most frequent recent (past 30 days) drug use was waterpipe smoking (45%). The second most frequently used drug was alcohol (26.5%, recent use). Based on self-reports, the prevalence of lifetime anabolic steroid use was calculated to be 24.5%. The corresponding figure based on crosswise method was obtained to be 56.8%. Participants believed that a median of 40% of athletes had used anabolic steroids in their lifetime. The prevalence of anabolic steroid was higher in single and less educated individuals (P < 0.05). The main reason for using anabolic steroids was to increase muscle size. Conclusion The prevalence of drug use, especially tobacco, alcohol, and anabolic steroids, was high among bodybuilding athletes. We could not rely on self-reports to examine anabolic steroid use. PMID:24494162

  2. Use of steroids for self-enhancement: an epidemiologic/societal perspective.

    PubMed

    Yesalis, C E

    2001-03-01

    Humans are basically competitive. For centuries, athletes have used various substances to enhance performance, increase strength, and prolong endurance. In the early 1940s, research indicating that testosterone improved a sense of well-being, appearance, and sexual performance led to the use of anabolic steroid hormones by a select few athletes. Today, even among high school students, the use of androgenic steroid hormones is prevalent, with 1% to 2% of adolescent girls and 4% to 6% of adolescent boys having used an anabolic steroid at least once. An estimated 1 million people in the United States are current of former users of anabolic-androgenic steroid hormones, with men having a higher prevalence of use than women. Androgenic steroid use has been associated with the use of other illicit drugs, cigarette smoking, and alcohol use. Nevertheless, anabolic-androgenic steroid hormones appear to have legitimate uses in certain patients. In HIV-infected, hypogonadal men, anabolic steroid hormones optimize muscle strength and muscle mass when combined with resistance exercise. Although a large number of people have used these drugs for many years, no studies of the long-term health effects have been done. However, when taken in supraphysiologic doses, these drugs are known to cause a wide range of acute adverse effects. When used in less then supraphysiologic doses in eugonadal or hypogonadal HIV-infected patients, these drugs reverse HIV-related hypogonadism, muscle wasting, and perhaps lipodystrophy. Provided that the oral preparations are not used and patients are closely monitored, anabolic-androgenic steroid hormones offer HIV-infected patients a better quality of life and an improved sense of well-being.

  3. Characteristics of Steroid Users in an Adolescent School Population.

    ERIC Educational Resources Information Center

    Adlaf, Edward M.; Smart, Reginald G.

    1992-01-01

    Examined rates of steroid use among Ontario adolescent students. Findings from 3,892 students revealed that 1.1 percent reported using steroids over past year. Steroid users were significantly more likely to use stimulants, caffeine, and relaxants than were nonsteroid users. Demographically, steroid users were significantly more likely to be male…

  4. 21 CFR 1308.34 - Exempt anabolic steroid products.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 9 2014-04-01 2014-04-01 false Exempt anabolic steroid products. 1308.34 Section... SUBSTANCES Exempt Anabolic Steroid Products § 1308.34 Exempt anabolic steroid products. The list of compounds, mixtures, or preparations that contain an anabolic steroid that have been exempted by the...

  5. 21 CFR 1308.34 - Exempt anabolic steroid products.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 9 2012-04-01 2012-04-01 false Exempt anabolic steroid products. 1308.34 Section... SUBSTANCES Exempt Anabolic Steroid Products § 1308.34 Exempt anabolic steroid products. The list of compounds, mixtures, or preparations that contain an anabolic steroid that have been exempted by the...

  6. 21 CFR 1308.34 - Exempt anabolic steroid products.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Exempt anabolic steroid products. 1308.34 Section... SUBSTANCES Exempt Anabolic Steroid Products § 1308.34 Exempt anabolic steroid products. The list of compounds, mixtures, or preparations that contain an anabolic steroid that have been exempted by the...

  7. 21 CFR 1308.34 - Exempt anabolic steroid products.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 9 2013-04-01 2013-04-01 false Exempt anabolic steroid products. 1308.34 Section... SUBSTANCES Exempt Anabolic Steroid Products § 1308.34 Exempt anabolic steroid products. The list of compounds, mixtures, or preparations that contain an anabolic steroid that have been exempted by the...

  8. 21 CFR 1308.34 - Exempt anabolic steroid products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Exempt anabolic steroid products. 1308.34 Section... SUBSTANCES Exempt Anabolic Steroid Products § 1308.34 Exempt anabolic steroid products. The list of compounds, mixtures, or preparations that contain an anabolic steroid that have been exempted by the...

  9. Facial Filler Complications.

    PubMed

    Woodward, Julie; Khan, Tanya; Martin, John

    2015-11-01

    The use of facial fillers has greatly expanded over the past several years. Along with increased use comes a rise in documented complications, ranging from poor cosmetic result to nodules, granulomas, necrosis, and blindness. Awareness of the potential types of complications and options for management, in addition to the underlying facial anatomy, are imperative to delivering the best patient care. This article defines the complications and how to treat them and provides suggestions to avoid serious adverse outcomes.

  10. Plasma steroid-binding proteins: primary gatekeepers of steroid hormone action

    PubMed Central

    2016-01-01

    Biologically active steroids are transported in the blood by albumin, sex hormone-binding globulin (SHBG), and corticosteroid-binding globulin (CBG). These plasma proteins also regulate the non-protein-bound or ‘free’ fractions of circulating steroid hormones that are considered to be biologically active; as such, they can be viewed as the ‘primary gatekeepers of steroid action’. Albumin binds steroids with limited specificity and low affinity, but its high concentration in blood buffers major fluctuations in steroid concentrations and their free fractions. By contrast, SHBG and CBG play much more dynamic roles in controlling steroid access to target tissues and cells. They bind steroids with high (~nM) affinity and specificity, with SHBG binding androgens and estrogens and CBG binding glucocorticoids and progesterone. Both are glycoproteins that are structurally unrelated, and they function in different ways that extend beyond their transportation or buffering functions in the blood. Plasma SHBG and CBG production by the liver varies during development and different physiological or pathophysiological conditions, and abnormalities in the plasma levels of SHBG and CBG or their abilities to bind steroids are associated with a variety of pathologies. Understanding how the unique structures of SHBG and CBG determine their specialized functions, how changes in their plasma levels are controlled, and how they function outside the blood circulation provides insight into how they control the freedom of steroids to act in health and disease. PMID:27113851

  11. Conjugation of steroids with PAMAM nanoparticles.

    PubMed

    Chanphai, P; Bekale, L; Tajmir-Riahi, H A

    2015-12-01

    We studied the binding process between polyamidoamine PAMAN-G4 dendrimer and testosterone and its aliphatic (alip) and aromatic (arom) dimers in aqueous solution at pH 7.4. Multiple spectroscopic methods, transmission electron microscopy (TEM) and molecular modeling were used to characterize the steroid binding process to PAMAM-G4 nanoparticles. Thermodynamic parameters ΔS, ΔH and ΔG showed steroid-PAMAM bindings occur via hydrophobic, H-bonding and van der Waals contacts. The binding affinity is testosterone>testosterone-aromatic dimer>testosterone-aliphatic dimer. Transmission electron microscopy showed significant changes in carrier morphology with major changes in the diameter of the polymer aggregate as steroid encapsulation occurred. Modeling also showed that testosterone is located in the interior cavity of PAMAM with the free binding energy of -9.36 kcal/mol, indicating of spontaneous steroid-polymer interaction at room temperature. PMID:26590896

  12. Steroids/Nutritional Supplements/Antibiotics

    MedlinePlus

    ... that prednisone may also somehow stimulate muscle protein production. Because of this sugar effect, catabolic steroids are ... suppressing the immune cells that rush in to clean up and remove "leaky" muscle cells and debris. ...

  13. Antifungal Activity of C-27 Steroidal Saponins

    PubMed Central

    Yang, Chong-Ren; Zhang, Ying; Jacob, Melissa R.; Khan, Shabana I.; Zhang, Ying-Jun; Li, Xing-Cong

    2006-01-01

    As part of our search for new antifungal agents from natural resources, 22 C-27 steroidal saponins and 6 steroidal sapogenins isolated from several monocotyledonous plants were tested for their antifungal activity against the opportunistic pathogens Candida albicans, Candida glabrata, Candida krusei, Cryptococcus neoformans, and Aspergillus fumigatus. The results showed that the antifungal activity of the steroidal saponins was associated with their aglycone moieties and the number and structure of monosaccharide units in their sugar chains. Within the 10 active saponins, four tigogenin saponins (compounds 1 to 4) with a sugar moiety of four or five monosaccharide units exhibited significant activity against C. neoformans and A. fumigatus, comparable to the positive control amphotericin B. The antifungal potency of these compounds was not associated with cytotoxicity to mammalian cells. This suggests that the C-27 steroidal saponins may be considered potential antifungal leads for further preclinical study. PMID:16641439

  14. Severe Cholestasis and Bile Acid Nephropathy From Anabolic Steroids Successfully Treated With Plasmapheresis.

    PubMed

    Flores, Avegail; Nustas, Rosemary; Nguyen, Hoang-Lan; Rahimi, Robert S

    2016-01-01

    Severe cholestasis with anabolic androgenic steroids is well-known to cause acute liver injury. Treatment is usually supportive after withdrawal of the offending agent. Acute kidney injury (AKI) frequently occurs in acute liver injury and may complicate management and prognosis. We highlight the use of plasmapheresis resulting in rapid improvement in cholestatic jaundice with resolution of AKI. Plasmapheresis should be considered in special cases in which there is progressive clinical decline despite supportive care. PMID:26958570

  15. Severe Cholestasis and Bile Acid Nephropathy From Anabolic Steroids Successfully Treated With Plasmapheresis

    PubMed Central

    Flores, Avegail; Nustas, Rosemary; Nguyen, Hoang-Lan

    2016-01-01

    Severe cholestasis with anabolic androgenic steroids is well-known to cause acute liver injury. Treatment is usually supportive after withdrawal of the offending agent. Acute kidney injury (AKI) frequently occurs in acute liver injury and may complicate management and prognosis. We highlight the use of plasmapheresis resulting in rapid improvement in cholestatic jaundice with resolution of AKI. Plasmapheresis should be considered in special cases in which there is progressive clinical decline despite supportive care. PMID:26958570

  16. The postanesthetic period. Complications.

    PubMed

    Malamed, S F

    1987-01-01

    Postanesthetic complications can occur even in the best of circumstances. Proper preparation of the staff, aggressive monitoring of the recovering patient, and early recognition and management of the complications are essential if the outcome is to be successful. In reviewing postanesthetic complications, two factors are present in the overwhelming majority of situations--hypoxia and hypercarbia--often the direct result of inadequate monitoring during the postanesthetic period. The anesthetic procedure is not over once the anesthetic agents are discontinued. The skillful anesthetist is aware of the possibilities of postoperative complications and prevents problems by employing enhanced monitoring techniques during the recovery phase.

  17. Steroids' transformations in Penicillium notatum culture.

    PubMed

    Bartmańska, Agnieszka; Dmochowska-Gładysz, Jadwiga; Huszcza, Ewa

    2005-03-01

    The application of Penicillium notatum genus for biotransformations of steroids has been investigated. The reactions observed include insertion of an oxygen atom into D-ring of steroids, 15alpha-hydroxylation of 17alpha-methyl testosterone derivatives, ester bond hydrolysis, and degradation of a testosterone derivatives side chain. Microbial production of testolactones, the biologically active compounds, was also achieved using this strain in up to 98% yield. PMID:15763598

  18. Steroids in the assessment of prenatal development.

    PubMed Central

    Chamberlain, G.; Kitchin, Y.

    1976-01-01

    Methods for identifying the fetus at risk and monitoring fetal well-being as pregnancy progresses are now an established part of prenatal care in the Western World. In this short review the use of steroids in the assessment of prenatal development is discussed. The metabolism of oestrogens, progestogens, corticosteroids and androgens during pregnancy is outlined and the relative merits, in terms of usefulness and practicability, of urinary and plasma steroid assays are discussed. PMID:792854

  19. Transient neurologic syndrome after spinal anesthesia with epidural steroid treatment

    PubMed Central

    Cöcelli, L. Pirbudak; Erkutlu, Ibrahim; Karakurum, Gunhan; Avci, Neslihan; Gül, Rauf; Öner, Ünsal

    2009-01-01

    Background: Transient neurologic syndrome (TNS) is a rare complication of spinal and epidural anesthesia. It is defined as paradoxic postoperative back pain radiating to the lower extremities with no neurologic deficits. Because it is a self-limited disease, the treatment is usually symptomatic and consists of NSAIDs and injections of a neuromuscular-blocking drug at the trigger points. The syndrome may be resistant to this treatment regimen and may last for several months, resulting in a long convalescence. Case summary: A 63-year-old Turkish woman (height, 165 cm; weight, 71 kg) underwent hemorrhoidectomy in the jackknife position using spinal anesthesia. No adverse events occurred during puncture or surgery or in the immediate postoperative recovery period. Recovery from the sensory and motor block was normal. Twenty-four hours after surgery, lower limb and plantar pain developed with no sensory or motor deficit. Neurologic examination revealed normal motor and sensory function. Electroneuromyography showed partial denervation potential of muscles innervated by the left sciatic nerve. The symptoms were suggestive of TNS. Combination oral NSAID treatment with amitriptyline (25 mg/d) and gabapentin (1200 mg/d) was initiated. Because the pain still persisted 6 weeks after surgery, epidural steroid injection with triamcinolone acetate (80 mg) with isotonic saline was administered, resulting in definite pain relief (visual analog scale score = 0). Conclusions: Epidural steroid treatment was effective in this patient with TNS resistant to treatment with NSAIDs, amitriptyline, and gabapentin. Future studies are needed to evaluate this treatment. PMID:24683240

  20. Inhalational Steroids and Iatrogenic Cushing’s Syndrome

    PubMed Central

    A.V, Raveendran

    2014-01-01

    Bronchial asthma (BA) and Allergic rhinitis (AR) are common clinical problems encountered in day to day practice, where inhalational corticosteroids (ICS) or intranasal steroids (INS) are the mainstay of treatment. Iatrogenic Cushing syndrome (CS) is a well known complication of systemic steroid administration. ICS /INS were earlier thought to be safe, but now more and more number of case reports of Iatrogenic Cushing syndrome have been reported, especially in those who are taking cytochrome P450 (CYP 450) inhibitors. Comparing to the classical clinical features of spontaneous Cushing syndrome, iatrogenic Cushing syndrome is more commonly associated with osteoporosis, increase in intra-ocular pressure, benign intracranial hypertension, aseptic necrosis of femoral head and pancreatitis, where as hypertension, hirsuitisum and menstrual irregularities are less common. Endocrine work up shows low serum cortisol level with evidence of HPA (hypothalamo-pituitary-adrenal) axis suppression. In all patients with features of Cushing syndrome with evidence of adrenal suppression always suspect iatrogenic CS. Since concomitant administration of cytochrome P450 inhibitors in patients on ICS/INS can precipitate iatrogenic CS, avoidance of CYP450 inhibitors, its dose reduction or substitution of ICS are the available options. Along with those, measures to prevent the precipitation of adrenal crisis has to be taken. An update on ICS-/INS- associated iatrogenic CS and its management is presented here. PMID:25674177

  1. Steroidal saponins from Tribulus terrestris.

    PubMed

    Kang, Li-Ping; Wu, Ke-Lei; Yu, He-Shui; Pang, Xu; Liu, Jie; Han, Li-Feng; Zhang, Jie; Zhao, Yang; Xiong, Cheng-Qi; Song, Xin-Bo; Liu, Chao; Cong, Yu-Wen; Ma, Bai-Ping

    2014-11-01

    Sixteen steroidal saponins, including seven previously unreported compounds, were isolated from Tribulus terrestris. The structures of the saponins were established using 1D and 2D NMR spectroscopy, mass spectrometry, and chemical methods. They were identified as: 26-O-β-d-glucopyranosyl-(25R)-furost-4-en-2α,3β,22α,26-tetrol-12-one (terrestrinin C), 26-O-β-d-glucopyranosyl-(25R)-furost-4-en-22α,26-diol-3,12-dione (terrestrinin D), 26-O-β-d-glucopyranosyl-(25S)-furost-4-en-22α,26-diol-3,6,12-trione (terrestrinin E), 26-O-β-d-glucopyranosyl-(25R)-5α-furostan-3β,22α,26-triol-12-one (terrestrinin F), 26-O-β-d-glucopyranosyl-(25R)-furost-4-en-12β,22α,26-triol-3-one (terrestrinin G), 26-O-β-d-glucopyranosyl-(1→6)-β-d-glucopyranosyl-(25R)-furost-4-en-22α,26-diol-3,12-dione (terrestrinin H), and 24-O-β-d-glucopyranosyl-(25S)-5α-spirostan-3β,24β-diol-12-one-3-O-β-d-glucopyranosyl-(1→4)-β-d-galactopyranoside (terrestrinin I). The isolated compounds were evaluated for their platelet aggregation activities. Three of the known saponins exhibited strong effects on the induction of platelet aggregation.

  2. Steroidal saponins from Tribulus terrestris.

    PubMed

    Su, Lan; Chen, Gang; Feng, Sheng-Guang; Wang, Wei; Li, Zhi-Feng; Chen, Huan; Liu, Ying-Xue; Pei, Yue-Hu

    2009-01-01

    Five new steroidal saponins were isolated from the fruits of Tribulus terrestris. Their structures were fully established by spectroscopic and chemical analysis as (23S,25S)-5alpha-spirostane-24-one-3beta,23-diol-3-O-{alpha-l-rhamnopyranosyl-(1-->2)-O-[beta-d-glucopyranosyl-(1-->4)]-beta-d-galactopyranoside} (1), (24S,25S)-5alpha-spirostane-3beta,24-diol-3-O-{alpha-l-rhamnopyranosyl-(1-->2)-O-[beta-d-glucopyranosyl-(1-->4)]-beta-d-galactopyranoside} (2), 26-O-beta-d-glucopyranosyl-(25R)-5alpha-furostan-2alpha,3beta,22alpha,26-tetraol-3-O-{beta-d-glucopyranosyl-(1-->2)-O-beta-d-glucopyranosyl-(1-->4)-beta-d-galactopyranoside} (3), 26-O-beta-d-glucopyranosyl-(25R)-5alpha-furostan-20(22)-en-2alpha,3beta,26-triol-3-O-{beta-d-glucopyranosyl-(1-->2)-O-beta-d-glucopyranosyl-(1-->4)-beta-d-galactopyranoside} (4), and 26-O-beta-d-glucopyranosyl-(25S)-5alpha-furostan-12-one-22-methoxy-3beta,26-diol-3-O-{alpha-l-rhamnopyranosyl-(1-->2)-O-[beta-d-glucopyranosyl-(1-->4)]-beta-d-galactopyranoside} (5). The isolated compounds were evaluated for cytostatic activity against HL-60 cells.

  3. Steroidal saponins from Dioscorea preussii.

    PubMed

    Tabopda, Turibio Kuiate; Mitaine-Offer, Anne-Claire; Tanaka, Chiaki; Miyamoto, Tomofumi; Mirjolet, Jean-François; Duchamp, Olivier; Ngadjui, Bonaventure Tchaleu; Lacaille-Dubois, Marie-Aleth

    2014-09-01

    Three new steroidal saponins, named diospreussinosides A-C (1-3), along with two known ones (4, 5) were isolated from rhizomes of Dioscorea preussii. Their structures were elucidated mainly by 1D and 2D NMR spectroscopic analysis and mass spectrometry as (25S)-17α,25-dihydroxyspirost-5-en-3β-yl-O-α-L-rhamnopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranoside (1), (25S)-17α,25-dihydroxyspirost-5-en-3β-yl-O-α-L-rhamnopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→4)-[α-L-rhamnopyranosyl-(1→2)]-β-D-glucopyranoside (2), and (24S,25R)-17α,24,25-trihydroxyspirost-5-en-3β-yl-O-α-L-rhamnopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→4)-[α-L-rhamnopyranosyl-(1→2)]-β-D-glucopyranoside (3). The spirostane-type skeleton of compound 3 possessing an unusual dihydroxylation pattern on the F-ring is reported for the first time. Cytotoxicity of compounds 2-5 was evaluated against two human colon carcinoma cell lines (HT-29 and HCT 116).

  4. Mitochondrial Fusion Is Essential for Steroid Biosynthesis

    PubMed Central

    Cooke, Mariana; Soria, Gastón; Cornejo Maciel, Fabiana; Gottifredi, Vanesa; Podestá, Ernesto J.

    2012-01-01

    Although the contribution of mitochondrial dynamics (a balance in fusion/fission events and changes in mitochondria subcellular distribution) to key biological process has been reported, the contribution of changes in mitochondrial fusion to achieve efficient steroid production has never been explored. The mitochondria are central during steroid synthesis and different enzymes are localized between the mitochondria and the endoplasmic reticulum to produce the final steroid hormone, thus suggesting that mitochondrial fusion might be relevant for this process. In the present study, we showed that the hormonal stimulation triggers mitochondrial fusion into tubular-shaped structures and we demonstrated that mitochondrial fusion does not only correlate-with but also is an essential step of steroid production, being both events depend on PKA activity. We also demonstrated that the hormone-stimulated relocalization of ERK1/2 in the mitochondrion, a critical step during steroidogenesis, depends on mitochondrial fusion. Additionally, we showed that the SHP2 phosphatase, which is required for full steroidogenesis, simultaneously modulates mitochondrial fusion and ERK1/2 localization in the mitochondrion. Strikingly, we found that mitofusin 2 (Mfn2) expression, a central protein for mitochondrial fusion, is upregulated immediately after hormone stimulation. Moreover, Mfn2 knockdown is sufficient to impair steroid biosynthesis. Together, our findings unveil an essential role for mitochondrial fusion during steroidogenesis. These discoveries highlight the importance of organelles’ reorganization in specialized cells, prompting the exploration of the impact that organelle dynamics has on biological processes that include, but are not limited to, steroid synthesis. PMID:23029265

  5. Biosynthesis and metabolism of steroids in molluscs.

    PubMed

    Fernandes, Denise; Loi, Barbara; Porte, Cinta

    2011-11-01

    Molluscs are the second most diverse animal group, they are ecologically important and they are considered excellent indicators of ecosystem health. Some species have been widely used in pollution biomonitoring programs; however, their endocrinology is still poorly known. Despite some studies reporting the presence of (vertebrate-type) steroids in molluscs, information regarding enzymatic pathways involved in steroid synthesis and further catabolism of those steroids is still fragmentary. Regarding steroidogenesis, a number of excellent studies were performed in the 70s using different radio-labelled steroid precursors and detecting the formation of different metabolites. But, since then a long gap of research exist until the late 90s when the 'endocrine disruption' issue raised the need of a better knowledge of mollusc (and invertebrate) endocrinology in order to assess alterations caused by pollutants. Here we summarize past and recent studies dealing with steroid biosynthesis and metabolism in different mollusc species. Most of these studies suggest the involvement of steroids in mollusc reproduction. However, the knowledge is still fragmentary and many questions remain to be answered.

  6. Anabolic steroid use in high school students.

    PubMed

    Pallesen, Ståle; Jøsendal, Ola; Johnsen, Bjørn-Helge; Larsen, Svein; Molde, Helge

    2006-01-01

    A total of 1351 high school students (52.3% males, 47.7% females) with mean age 17.5 years (SD = 2.2) from randomized school classes in Hordaland County, Norway, participated in an Internet survey conducted in 2004 about the lifetime use of anabolic steroids and personal acquaintance with at least one user of anabolic steroids. In addition to questions about anabolic steroids the participants completed the Hospital Anxiety and Depression Scale and the Alcohol Use Disorders Identification Test. They also answered questions about demography, smoking, and narcotic use. The lifetime prevalence for use of anabolic steroids was 3.6% for males and 0.6% for females. In all, 27.9% of the respondents reported having at least one acquaintance that used or had used anabolic steroids. Use of anabolic steroids and having acquaintances using such drugs were strongly related to use of other drugs such as alcohol, nicotine, and narcotics. Implications for prevention are discussed and the study's limitations are noted. PMID:17118811

  7. Mitochondrial benzodiazepine receptors regulate steroid biosynthesis

    SciTech Connect

    Mukhin, A.G.; Papadopoulos, V.; Costa, E.; Krueger, K.E. )

    1989-12-01

    Recent observations on the steroid synthetic capability within the brain open the possibility that benzodiazepines may influence steroid synthesis in nervous tissue through interactions with peripheral-type benzodiazepine recognition sites, which are highly expressed in steroidogenic cells and associated with the outer mitochondrial membrane. To examine this possibility nine molecules that exhibit a greater than 10,000-fold difference in their affinities for peripheral-type benzodiazepine binding sites were tested for their effects on a well-established steroidogenic model system, the Y-1 mouse adrenal tumor cell line. 4{prime}-Chlorodiazepam, PK 11195, and PK 14067 stimulated steroid production by 2-fold in Y-1 cells, whereas diazepam, flunitrazepam, zolpidem, and PK 14068 displayed a lower (1.2- to 1.5-fold) maximal stimulation. In contrast, clonazepam and flumazenil did not stimulate steroid synthesis. The potencies of these compounds to inhibit {sup 3}H-labeled PK 11195 binding to peripheral-type benzodiazepine recognition sites correlated with their potencies to stimulate steroid production. Similar findings were observed in bovine and rat adrenocortical cell preparations. These results suggest that ligands of the peripheral-type benzodiazepine recognition site acting on this mitochondrial receptor can enhance steroid production. This action may contribute specificity to the pharmacological profile of drugs preferentially acting on the benzodiazepine recognition site associated with the outer membrane of certain mitochondrial populations.

  8. New steroid derivative with hypoglycemic activity

    PubMed Central

    Lauro, Figueroa-Valverde; Francisco, Díaz-Cedillo; Lenin, Hau-Heredia; Elodia, García-Cervera; Eduardo, Pool-Gómez; Marcela, Rosas-Nexticapa; Bety, Sarabia-Alcocer

    2014-01-01

    Data indicates that some steroid derivatives may induce changes on glucose levels; nevertheless, data are very confusing. Therefore, more pharmacological data are needed to characterize the activity induced by the steroid derivatives on glucose levels. The aim of this study was to synthesize a new steroid derivative for evaluate its hypoglycemic activity. The effects of steroid derivative on glucose concentration were evaluated in a diabetic animal model using glibenclamide and metformin as controls. In addition, the pregnenolone-dihydrotestosterone conjugate was bound to Tc-99m using radioimmunoassay methods, to evaluate the pharmacokinetics of the steroid derivative over time. The results showed that the pregnenolone-dihydrotestosterone conjugate induces changes on the glucose levels in similar form than glibenclamide. Other data showed that the biodistribution of Tc-99m-steroid derivativein brain was higher in comparison with spleen, stomach, intestine liver and kidney. In conclusion, the pregnenolone-dihydrotestosterone conjugate exerts hypoglycemic activity and this phenomenon could depend of its physicochemical properties which could be related to the degree of lipophilicity of the steroidderivative. PMID:25550906

  9. Mitochondrial fusion is essential for steroid biosynthesis.

    PubMed

    Duarte, Alejandra; Poderoso, Cecilia; Cooke, Mariana; Soria, Gastón; Cornejo Maciel, Fabiana; Gottifredi, Vanesa; Podestá, Ernesto J

    2012-01-01

    Although the contribution of mitochondrial dynamics (a balance in fusion/fission events and changes in mitochondria subcellular distribution) to key biological process has been reported, the contribution of changes in mitochondrial fusion to achieve efficient steroid production has never been explored. The mitochondria are central during steroid synthesis and different enzymes are localized between the mitochondria and the endoplasmic reticulum to produce the final steroid hormone, thus suggesting that mitochondrial fusion might be relevant for this process. In the present study, we showed that the hormonal stimulation triggers mitochondrial fusion into tubular-shaped structures and we demonstrated that mitochondrial fusion does not only correlate-with but also is an essential step of steroid production, being both events depend on PKA activity. We also demonstrated that the hormone-stimulated relocalization of ERK1/2 in the mitochondrion, a critical step during steroidogenesis, depends on mitochondrial fusion. Additionally, we showed that the SHP2 phosphatase, which is required for full steroidogenesis, simultaneously modulates mitochondrial fusion and ERK1/2 localization in the mitochondrion. Strikingly, we found that mitofusin 2 (Mfn2) expression, a central protein for mitochondrial fusion, is upregulated immediately after hormone stimulation. Moreover, Mfn2 knockdown is sufficient to impair steroid biosynthesis. Together, our findings unveil an essential role for mitochondrial fusion during steroidogenesis. These discoveries highlight the importance of organelles' reorganization in specialized cells, prompting the exploration of the impact that organelle dynamics has on biological processes that include, but are not limited to, steroid synthesis.

  10. Rapid steroid hormone actions via membrane receptors.

    PubMed

    Schwartz, Nofrat; Verma, Anjali; Bivens, Caroline B; Schwartz, Zvi; Boyan, Barbara D

    2016-09-01

    Steroid hormones regulate a wide variety of physiological and developmental functions. Traditional steroid hormone signaling acts through nuclear and cytosolic receptors, altering gene transcription and subsequently regulating cellular activity. This is particularly important in hormonally-responsive cancers, where therapies that target classical steroid hormone receptors have become clinical staples in the treatment and management of disease. Much progress has been made in the last decade in detecting novel receptors and elucidating their mechanisms, particularly their rapid signaling effects and subsequent impact on tumorigenesis. Many of these receptors are membrane-bound and lack DNA-binding sites, functionally separating them from their classical cytosolic receptor counterparts. Membrane-bound receptors have been implicated in a number of pathways that disrupt the cell cycle and impact tumorigenesis. Among these are pathways that involve phospholipase D, phospholipase C, and phosphoinositide-3 kinase. The crosstalk between these pathways has been shown to affect apoptosis and proliferation in cardiac cells, osteoblasts, and chondrocytes as well as cancer cells. This review focuses on rapid signaling by 17β-estradiol and 1α,25-dihydroxy vitamin D3 to examine the integrated actions of classical and rapid steroid signaling pathways both in contrast to each other and in concert with other rapid signaling pathways. This new approach lends insight into rapid signaling by steroid hormones and its potential for use in targeted drug therapies that maximize the benefits of traditional steroid hormone-directed therapies while mitigating their less desirable effects. PMID:27288742

  11. Determination of steroid hormones in human plasma by GC-triple quadrupole MS.

    PubMed

    Matysik, Silke; Schmitz, Gerd

    2015-07-01

    A fast and sensitive GC-MS/MS method is proposed to determine pregnenolone, dehydroepiandrosterone (DHEA), testosterone and dihydrotestosterone from human plasma. Steroids were extracted by liquid/liquid extraction, and derivatized with N-methyl-N-trimethylsilyl-trifluoracetamide. Electron ionization at 30eV was applied to generate high abundant precursor ions. Specific precursor/product transitions were generated a priori for each compound of interest and these assays were then used to selectively detect and quantify these steroids. Using the selected reaction monitoring mode, detection limits in the pg/ml (subnmol/l) range could be achieved for all four steroid compounds. The method was validated for imprecision, and recovery and applied in a pilot study in patients with hypercholesterolemia. Associations of increased cholesterol biosynthesis and low testosterone and dihydrotestosterone concentrations were found.

  12. Steroid Hydroxylation by Basidiomycete Peroxygenases: a Combined Experimental and Computational Study

    PubMed Central

    Babot, Esteban D.; del Río, José C.; Cañellas, Marina; Sancho, Ferran; Lucas, Fátima; Guallar, Víctor; Kalum, Lisbeth; Lund, Henrik; Gröbe, Glenn; Scheibner, Katrin; Ullrich, René; Hofrichter, Martin; Martínez, Angel T.

    2015-01-01

    The goal of this study is the selective oxyfunctionalization of steroids under mild and environmentally friendly conditions using fungal enzymes. With this purpose, peroxygenases from three basidiomycete species were tested for the hydroxylation of a variety of steroidal compounds, using H2O2 as the only cosubstrate. Two of them are wild-type enzymes from Agrocybe aegerita and Marasmius rotula, and the third one is a recombinant enzyme from Coprinopsis cinerea. The enzymatic reactions on free and esterified sterols, steroid hydrocarbons, and ketones were monitored by gas chromatography, and the products were identified by mass spectrometry. Hydroxylation at the side chain over the steroidal rings was preferred, with the 25-hydroxyderivatives predominating. Interestingly, antiviral and other biological activities of 25-hydroxycholesterol have been reported recently (M. Blanc et al., Immunity 38:106–118, 2013, http://dx.doi.org/10.1016/j.immuni.2012.11.004). However, hydroxylation in the ring moiety and terminal hydroxylation at the side chain also was observed in some steroids, the former favored by the absence of oxygenated groups at C-3 and by the presence of conjugated double bonds in the rings. To understand the yield and selectivity differences between the different steroids, a computational study was performed using Protein Energy Landscape Exploration (PELE) software for dynamic ligand diffusion. These simulations showed that the active-site geometry and hydrophobicity favors the entrance of the steroid side chain, while the entrance of the ring is energetically penalized. Also, a direct correlation between the conversion rate and the side chain entrance ratio could be established that explains the various reaction yields observed. PMID:25862224

  13. [Determination by high performance chromatography, steroid saponins in a biologically active food supplements containing the extract of Tribulus terrestris].

    PubMed

    Kozlova, O I; Perederiaev, O I; Ramenskaia, G V

    2011-01-01

    Steroidal saponins are bioactive substances of Tribulus terrestris and can be used to assess the quality of raw materials and processed products from them. For this purpose has been developed the method of qualitative and quantitative determination of steroidal saponins by high performance liquid chromatography with spectrophotometric and mass-selective detection and optimal conditions of sample preparation (70% methanol extraction with sonication and heating); also has been studied steroidal saponins composition of Tribulus terrestris (protodioscin, tribulosaponin B, metilprotodiostsin, terrestrozin H, prototribestin, gracillin and others were found).

  14. Fountain of steroid from an ectopic ACTH-producing tumour

    PubMed Central

    Lo, Tom Edward Ngo; Jimeno, Cecilia Alegado

    2013-01-01

    This case is of a 39-year-old Filipino woman who within 2 months developed, Cushing's features she had no known comorbidities and no history of steroid intake. The patient also presented with hyperpigmentation of knuckles and toes, metabolic alkalosis and persistent hypokalaemia noted as proximal muscle weakness. The patient was referred to our institution for acutely worsening behavioural and psychiatric changes. Work-up for endogenous Cushing's syndrome revealed a significant adrenocorticotropic hormone production from an ectopic source. Further imaging was requested to locate the tumour, but the patient eventually succumbed to the drastic complications of hypercortisolism. On autopsy, the patient was found to have an ectopic well-differentiated neuroendocrine tumour located at the pancreatic head with metastasis to the right hepatic lobe. PMID:23861274

  15. [Complications of laparoscopic cholecystectomy].

    PubMed

    Kyzer, S; Ramadan, E; Chaimoff, C

    1992-04-15

    92% of our first 60 laparoscopic cholecystectomies were successful. Postoperative complications included fever in 10 cases (17%), urinary retention in 5 (8%), intraabdominal abscess in 2 (3%), biliary leakage in 1 (2%) and unexplained abdominal pain in 10 (17%). Although laparoscopic cholecystectomy has obvious advantages, it also has major as well as minor complications. PMID:1398315

  16. Facial flap complications.

    PubMed

    Zoumalan, Richard A; Murakami, Craig S

    2012-06-01

    Knowledge of fundamental concepts can help decrease the chance of complications in plastic surgery. Local flap reconstruction for facial defects has many pitfalls. This article describes common complications in local flap reconstruction of the face and describes strategies that prevent problems.

  17. Bulimia Nervosa - medical complications.

    PubMed

    Mehler, Philip S; Rylander, Melanie

    2015-01-01

    As with anorexia nervosa, there are many medical complications associated with bulimia nervosa. In bulimia nervosa, these complications are a direct result of both the mode and the frequency of purging behaviours. For the purposes of this article, we will review in detail the many complications of the two major modes of purging, namely, self-induced vomiting and laxative abuse; these two account for more than 90% of purging behaviours in bulimia nervosa. Some of these complications are potentially extremely dangerous and need to be well understood to effectively treat patients with bulimia nervosa. Other methods of purging, such as diuretic abuse, are much less frequently utilized and will only be mentioned briefly. In a subsequent article, the treatments of these medical complications will be presented.

  18. Anorexia nervosa - medical complications.

    PubMed

    Mehler, Philip S; Brown, Carrie

    2015-01-01

    In contrast to other mental health disorders, eating disorders have a high prevalence of concomitant medical complications. Specifically, patients suffering from anorexia nervosa (AN) have a litany of medical complications which are commonly present as part of their eating disorders. Almost every body system can be adversely, affected by this state of progressive malnutrition. Moreover, some of the complications can have permanent adverse effects even after there is a successful program of nutritional rehabilitation and weight restoration. Within this article we will review all body systems affected by AN. There is also salient information about both, how to diagnose these medical complications and which are the likely ones to result in permanent sequelae if not diagnosed and addressed early in the course of AN. In a subsequent article, the definitive medical treatment for these complications will be presented in a clinically practical manner.

  19. [Complications in pediatric anesthesia].

    PubMed

    Becke, K

    2014-07-01

    As in adult anesthesia, morbidity and mortality could be significantly reduced in pediatric anesthesia in recent decades. This fact cannot conceal the fact that the incidence of anesthetic complications in children is still much more common than in adults and sometimes with a severe outcome. Newborns and infants in particular but also children with emergency interventions and severe comorbidities are at increased risk of potential complications. Typical complications in pediatric anesthesia are respiratory problems, medication errors, difficulties with the intravenous puncture and pulmonal aspiration. In the postoperative setting, nausea and vomiting, pain, and emergence delirium can be mentioned as typical complications. In addition to the systematic prevention of complications in pediatric anesthesia, it is important to quickly recognize disturbances of homeostasis and treat them promptly and appropriately. In addition to the expertise of the performing anesthesia team, the institutional structure in particular can improve quality and safety in pediatric anesthesia. PMID:25004872

  20. [Complications after dermal fillers and their treatment].

    PubMed

    Lemperle, G; Gauthier-Hazan, N; Wolters, M

    2006-12-01

    All dermal fillers are associated with the risk of both early and late complications. Early side effects such as swelling, redness, and bruising occur after intradermal or subdermal injections. The patient has to be aware of these risks and be prepared to accept them. Adverse events that last longer than 2 weeks can be attributable to technical shortcomings (e.g., the implantation of a long-lasting filler substance was too superficial). Such adverse events can be treated with intradermal 5-fluorouracil and steroid injections, vascular lasers, or intense pulsed light, and later with dermabrasion or shaving. Late adverse events also include immunological phenomena such as late-onset allergy and non-allergic foreign body granulomas. Both react well to intralesional steroid injections, which often have to be repeated to establish the right dose. Surgical excisions should remain the last option and are indicated for hard lumps in the lips and visible hard nodules or hard granulomas in the subcutaneous fat. PMID:17219319

  1. [Complications of blepharoplasty].

    PubMed

    Morax, S

    2004-06-01

    Blepharoplasty complications are infrequent, most often minor and transitory, rarely major and permanent with functional or esthetic consequences. Treatment is above all preventive: screening at risk patients with a history of ophthalmic problems, but also general illnesses that would contraindicate blepharoplasty. Patients must be informed of possible risks through informative booklets with the most important points underlined. Complications can be purely ophthalmological, the more serious sequelae being partial or complete visual loss due to ischemic optical neuropathy, with very poor prognosis, or more rarely compression of the ocular globe by intraorbital hemorrhage, which has a better prognosis provided the origins are quickly recognized and treated immediately. Other visual complications include oculomotor problems, keratoconjunctivitis sicca, epiphora, and chemosis of lymphatic origin. Eyelid complications are more frequent: ptosis on the upper eyelid or lagophthalmia caused by incorrect resection of the skin, scarring and eyelid fold anomalies. The most serious esthetic complication is the malposition of the lower eyelid, which can manifest as retraction, lagophthalmia, ectropion, deformation of the external canthus, or lower eyelid tissue relaxation. These malpositions are quite often minor, sometimes reversible, but at times major, with psychological, esthetic and functional consequences that are difficult for the patient. Other local complications also arise: enophthalmia with a sunken lid, as well as under- and overcorrection. General complications can include scarring related to pigmentation problems and residual hematomas, and exceptionally infections going as far as the orbital fat tissue. Finally, other complications are related to new laser surgical techniques that are responsible for ectropion of the lower eyelid and even burns or residual redness, or complications related to periocular injections of filling material. A comprehensive review of

  2. [Ocular complications of giant cell arteritis].

    PubMed

    Liozon, E; Ly, K-H; Robert, P-Y

    2013-07-01

    Permanent visual loss (PVL) is the most dreaded complication of giant cell arteritis (GCA). It results from anterior ischemic optic neuropathy or, less commonly, retinal artery occlusion. This complication still occurs in 14 to 20% of patients and is typically devastating and permanent, although it is highly preventable by an early diagnosis of giant cell arteritis and appropriate glucocorticoid treatment. Transient ischemic symptoms such as amaurosis fugax, episodes of blurred vision or diplopia may occur, either heralding visual loss or remaining isolated. In studies, the main predictors of PVL are jaw claudication, amaurosis fugax, lack of systemic "B" symptoms, a modestly increased ESR and a higher haemoglobin level. The evaluation of a GCA patient with PVL includes emergency fundoscopy completed by fluorescein angiography, immediate erythrocyte sedimentation rate, C-reactive protein, and complete blood count. Treatment is extremely urgent mainly because, if left untreated, GCA is associated with visual loss in the fellow eye within days in up to 50% of individuals. Treatment may begin with high-dose intravenous methylprednisolone, followed by oral prednisone administered at 1 mg/kg per day. Daily adjunctive aspirin orally may be added since it has been shown, in retrospective studies, to protect against stroke and visual loss. Although treatment duration of complicated GCA is not codified, an initial PVL deserves close monitoring of patient's systemic symptoms, ESR and CRP to avoid relapses due to a significant risk of late recurrence of visual loss during steroid tapering. PMID:23523078

  3. Anabolic steroids and cardiovascular risk.

    PubMed

    Angell, Peter; Chester, Neil; Green, Danny; Somauroo, John; Whyte, Greg; George, Keith

    2012-02-01

    Recent reports from needle exchange programmes and other public health initiatives have suggested growing use of anabolic steroids (AS) in the UK and other countries. Data indicate that AS use is not confined to body-builders or high-level sportsmen. Use has spread to professionals working in emergency services, casual fitness enthusiasts and subelite sportsmen and women. Although the precise health consequences of AS use is largely undefined, AS use represents a growing public health concern. Data regarding the consequences of AS use on cardiovascular health are limited to case studies and a modest number of small cohort studies. Numerous case studies have linked AS use with a variety of cardiovascular disease (CVD) events or endpoints, including myocardial infarction, stroke and death. Large-scale epidemiological studies to support these links are absent. Consequently, the impact of AS use upon known CVD risk factors has been studied in relatively small, case-series studies. Data relating AS use to elevated blood pressure, altered lipid profiles and ECG abnormalities have been reported, but are often limited in scope, and other studies have often produced equivocal outcomes. The use of AS has been linked to the appearance of concentric left ventricular hypertrophy as well as endothelial dysfunction but the data again remains controversial. The mechanisms responsible for the negative effect of AS on cardiovascular health are poorly understood, especially in humans. Possibilities include direct effects on myocytes and endothelial cells, reduced intracellular Ca2+ levels, increased release of apoptogenic factors, as well as increased collagen crosslinks between myocytes. New data relating AS use to cardiovascular health risks are emerging, as novel technologies are developed (especially in non-invasive imaging) that can assess physiological structure and function. Continued efforts to fully document the cardiovascular health consequences of AS use is important to

  4. Steroidal saponins from Chlorophytum deistelianum.

    PubMed

    Tabopda, Turibio Kuiate; Mitaine-Offer, Anne-Claire; Paululat, Thomas; Delemasure, Stéphanie; Dutartre, Patrick; Ngadjui, Bonaventure Tchaleu; Lacaille-Dubois, Marie-Aleth

    2016-06-01

    Phytochemical investigation of the aerial parts of Chlorophytum deistelianum led to the isolation of four previously undescribed steroidal saponins called chlorodeistelianosides A-D with five known ones. Their structures were established mainly by extensive 1D and 2D NMR spectroscopic techniques and mass spectrometry as (25R)-3β-[(β-D-glucopyranosyl-(1→3)-[α-L-rhamnopyranosyl-(1→4)]-β-D-xylopyranosyl-(1→3)-[β-D-glucopyranosyl-(1→2)]-β-D-glucopyranosyl-(1→4)-β-D-galactopyranosyl)oxy]-5α-spirostan-12-one, (24S,25S)-24-[(β-D-glucopyranosyl)oxy]-3β-[(β-d-glucopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-β-D-glucopyranosyl-(1→4)-β-D-galactopyranosyl)oxy]-5α-spirostan-12-one, (25R)-26-[(β-D-glucopyranosyl)oxy]-2α-hydroxy-22α-methoxy-5α-furostan-3β-yl β-D-glucopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-β-D-glucopyranosyl-(1→4)-β-D-galactopyranoside, and (25R)-26-[(β-D-glucopyranosyl)oxy]-3β-[(β-D-glucopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-β-D-glucopyranosyl-(1→4)-β-D-galactopyranosyl)oxy]-5α-furost-20(22)-en-12-one. Cytotoxicity of most compounds was evaluated against one human cancer cell line (SW480) and one rat cardiomyoblast cell line (H9c2). Among them, three known spirostane-type glycosides exhibited cytotoxicity on both cell lines with IC50 ranging from 8 to 10 μM. PMID:27012932

  5. Steroidal glycoalkaloids in Solanum chacoense.

    PubMed

    Mweetwa, Alice M; Hunter, Danielle; Poe, Rebecca; Harich, Kim C; Ginzberg, Idit; Veilleux, Richard E; Tokuhisa, James G

    2012-03-01

    Potato (Solanum tuberosum L.), a domesticated species that is the fourth most important world agricultural commodity, requires significant management to minimize the effects of herbivore and pathogen damage on crop yield. A wild relative, Solanum chacoense Bitt., has been of interest to plant breeders because it produces an abundance of novel steroidal glycoalkaloid compounds, leptines and leptinines, which are particularly effective deterrents of herbivory by the Colorado potato beetle (Leptinotarsa decemlineata Say). Biochemical approaches were used in this study to investigate the formation and accumulation of SGAs in S. chacoense. SGA contents were determined in various organs at different stages of organ maturity during a time course of plant development. Leptines and leptinines were the main contributors to the increased levels in SGA concentration measured in the aerial versus the subterranean organs of S. chacoense accession 8380-1. Leptines were not detected in aboveground stolons until the stage where shoots had formed mature chlorophyllous leaves. To gain insights into SGA biosynthesis, the abundance of SGAs and steady-state transcripts of genes coding for enzymes of the central terpene and SGA-specific pathways in various plant organs at anthesis were compared. For two genes of primary terpene metabolism, transcript and SGA abundances were correlated, although with some discrepancies. For genes associated with SGA biosynthesis, transcripts were not detected in some tissues containing SGAs; however these transcripts were detected in the progenitor tissues, indicating the possibility that under our standard growth conditions, SGA biosynthesis is largely limited to highly proliferative tissues such as shoot, root and floral meristems.

  6. Complications Following Radical Nephroureterectomy.

    PubMed

    Raman, Jay D; Jafri, Syed M

    2016-05-01

    Radical nephroureterectomy (RNU) is the gold standard treatment strategy for bulky, high-grade, or muscle-invasive upper tract urothelial carcinoma (UTUC). Many patients with UTUC who require RNU are elderly, comorbid, and at risk for perioperative complications. Recognition of likelihood and extent of such complications guides preoperative counseling, decision-making process for major surgery, and perioperative care. A critical review of such data is essential, given the inevitable impact of complications on hospital duration, need for readmission, resource utilization, and costs associated with management. PMID:26968416

  7. Steroid contraceptive use and pregnancy outcome.

    PubMed

    Pardthaisong, T; Gray, R H; McDaniel, E B; Chandacham, A

    1988-07-01

    Contraceptive use in relation to pregnancy outcome was studied in 8,816 births in Chiang Mai, northern Thailand, by examination of newborn infants and interviews with their mothers. Four thousand twenty-three women used no contraception before the index pregnancy, 1,229 used the injectable contraceptive Depo Provera (DMPA), and 3,038 used oral contraceptives prior to or during pregnancy. No differences were observed between these groups with respect to still births, multiple pregnancies, and birthweight. Women who used oral contraceptives had unexpectedly low rates of major defects and may have been affected by self-selection bias, whereas the noncontraceptors had rates similar to other populations. There was a significantly increased association of polysyndactyly among infants of DMPA users relative to the other groups, which was most pronounced in offspring of women under age 30 years, and persisted after exclusion of subjects with a family history or infants with multiple abnormalities. However, in five out of the ten polysyndactyly cases, the last injection of DMPA occurred more than 9 months before conception, and only three cases had definite gestational exposure. The association of chromosomal anomalies was also significantly increased in infants of mothers who used DMPA. The unrelated nature of these defects, the lack of confirmation from other studies, the distant preconceptional exposure to DMPA in many cases, and chance effects due to multiple statistical comparisons make a causal association unlikely. Other birth defects that had been previously reported in some publications to be associated with progestational steroid exposure, such as neural tube defects, heart malformations, and limb reduction defects, were not found in this study.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Anabolic-androgenic steroids and the adolescent.

    PubMed

    Rogol, A D; Yesalis, C E

    1992-03-01

    This article has reviewed some of the hormonal and behavioral maturation that occurs during adolescence, which are characterized by remarkable physical changes and behavioral vulnerability. Risk taking of many varieties is common and drugs (including anabolic-androgenic steroids) form a part of the prevailing culture in many places. These steroids probably are not severe health hazards when taken intermittently and in low to moderate doses. The 17-alkylated derivatives are clearly the more likely to cause hepatotoxicity. Thus, the scare tactics formerly used (severe constitutional side effects) are doomed to failure. The tenuous link between these drugs and objective behavioral and addictive effects must be strengthened before health strategies based on this issue can be validated. Clearly, the lack of scientific information has impeded, if not precluded, the formulation of an effective health education strategy. The most potent deterrent to the use of steroid drugs by athletes must be the moral issue of fair play and maintaining a "level playing field." We strongly support directed research in these areas and hope that the credibility of the scientific community can be regained after its faulted "stop steroid use" campaigns based on the lack of steroid efficacy in bringing about desired results or on their dire consequences have been replaced with credible evidence to refute their use on these and other grounds.

  9. Reproductive Steroid Regulation of Mood and Behavior.

    PubMed

    Schiller, Crystal Edler; Johnson, Sarah L; Abate, Anna C; Rubinow, David R; Schmidt, Peter J

    2016-01-01

    In this article, we examine evidence supporting the role of reproductive steroids in the regulation of mood and behavior in women and the nature of that role. In the first half of the article, we review evidence for the following: (i) the reproductive system is designed to regulate behavior; (ii) from the subcellular to cellular to circuit to behavior, reproductive steroids are powerful neuroregulators; (iii) affective disorders are disorders of behavioral state; and (iv) reproductive steroids affect virtually every system implicated in the pathophysiology of depression. In the second half of the article, we discuss the diagnosis of the three reproductive endocrine-related mood disorders (premenstrual dysphoric disorder, postpartum depression, and perimenopausal depression) and present evidence supporting the relevance of reproductive steroids to these conditions. Existing evidence suggests that changes in reproductive steroid levels during specific reproductive states (i.e., the premenstrual phase of the menstrual cycle, pregnancy, parturition, and the menopause transition) trigger affective dysregulation in susceptible women, thus suggesting the etiopathogenic relevance of these hormonal changes in reproductive mood disorders. Understanding the source of individual susceptibility is critical to both preventing the onset of illness and developing novel, individualized treatments for reproductive-related affective dysregulation. © 2016 American Physiological Society. Compr Physiol 6:1135-1160, 2016e. PMID:27347888

  10. Review of Androgenic Anabolic Steroid Use

    SciTech Connect

    T. Borges; G. Eisele; C. Byrd

    2001-07-31

    An area that has been overlooked within personnel security evaluations is employee use of androgenic-anabolic steroids (AAS). Current drug testing within the federal government does not include testing for anabolic steroids, and the difficulties to implement such testing protocols-not to mention the cost involved-make AAS testing highly improbable. The basis of this report is to bring to the forefront the damage that anabolic steroids can cause from both a physical and a psychological standpoint. Most individuals who use AASs do so to increase their muscle mass because they wish to gain some type of competitive edge during athletic competition or they wish to enhance their physical features for self-satisfaction and self-esteem (i.e., body building). Security officers are one group of men who often take high doses of anabolic steroids, according to the Second Report of the Senate Standing Committee (1990). The negative psychological characteristics for AAS use is extensive and includes prominent hostility, aggressiveness, irritability, euphoria, grandiose beliefs, hyperactivity, reckless behavior, increased sexual appetite, unpredictability, poor impulse control, mood fluctuations, and insomnia. The drug may invoke a sense of power and invincibility (Leckman and Scahill, 1990). Depressive symptoms, such as anhedonia, fatigue, impaired concentration, decreased libido, and even suicidality (Pope and Katz, 1992) have been noted with steroid withdrawal. It appears that long-term users of AAS experience similar characteristics as other substance abusers (i.e., craving, dependence, and withdrawal symptoms).

  11. Glucosylation of steroidal saponins by cyclodextrin glucanotransferase.

    PubMed

    Wang, Yong-ze; Feng, Bing; Huang, Hong-zhi; Kang, Li-ping; Cong, Yue; Zhou, Wen-bin; Zou, Peng; Cong, Yu-wen; Song, Xin-Bo; Ma, Bai-ping

    2010-10-01

    It is known that the sugar chains of steroidal saponins play an important role in the biological and pharmacological activities. In order to synthesize steroidal saponins with novel sugar chains in one step for further studies on pharmacological activity, we here describe the glucosylation of steroidal saponins, and 5 compounds, timosaponin AIII (1), saponin Ta (2), saponin Tb (3), trillin (4) and cantalasaponin I (5), were converted into their glucosylated products by Toruzyme 3.0 L, a cyclodextrin glucanotransferase (CGTase). 12 glucosylated products were isolated and their structures elucidated on the basis of spectral data; they were all characterized as new compounds. The results showed that Toruzyme 3.0 L had the specific ability to add the α-D-glucopyranosyl group to the glucosyl group linked at the sugar chains of steroidal saponins, and the glucosyl group was the only acceptor. This is the first report of steroidal saponins with different degrees of glucosylation. The substrates and their glucosylated derivatives were evaluated for their cytotoxicity against HL-60 human promyelocytic leukemia cell by MTT assay. The substrates all exhibited high cytotoxicity (IC(50) < 10 µmol/L), excluding compound 5 (IC(50) > 150 µmol/L), and the cytotoxicity of most of the products showed no obvious changes compared with those of their substrates.

  12. Complications of stomas: their aetiology and management.

    PubMed

    Watson, Angus J M; Nicol, Laura; Donaldson, Susan; Fraser, Cathie; Silversides, Andrew

    2013-03-01

    The formation of a stoma is an essential part of many colorectal operations. Despite the frequency with which these surgeries are performed and the number of specialists involved in stoma care, complications are still common. This article investigates the most common complications, explains the reasons for their occurrence and suggests potential management options. Common stoma complications were identified by the colorectal/ stoma clinical nurse specialist (CSCNS) and a literature search was performed using a variety of online databases, including Medline and CINAHL using the keywords stoma, complications, prolapse, ischaemia, retraction, hernia and stenosis. Articles used were selected on the basis of relevance to the topic. The commonest complications of stomas included skin irritation, prolapse, retraction, ischaemia, hernia and stenosis.

  13. Intratympanic steroids as a salvage treatment for sudden sensorineural hearing loss? A meta-analysis.

    PubMed

    Ng, Jia Hui; Ho, Roger Chun Man; Cheong, Crystal Shuk Jin; Ng, Adele; Yuen, Heng Wai; Ngo, Raymond Yeow Seng

    2015-10-01

    Sudden sensorineural hearing loss is typically treated with systemic steroids. The aim of this meta-analysis was to evaluate the efficacy of salvage intratympanic steroid treatment in patients who have initial treatment failure with systemic steroids. A MEDLINE literature search was performed, supported by searches of Web of Science, Biosis, and Science Direct. Articles of all languages were included. Selection of relevant publications was conducted independently by three authors. Only randomized controlled trials were considered. In one arm of the studies, the patients received salvage intratympanic steroids. In the other arm, patients did not receive further treatment. The standard difference in mean (SDM) amount of improvement in hearing threshold between patients who did and did not receive salvage intratympanic steroids was calculated. From an initial 184 studies found via the search strategy, 5 studies met inclusion criteria and were included. There was a statistically significant greater reduction in hearing threshold on pure-tone audiometry in patients who received salvage intratympanic steroids than in those who did not (SDM = -0.401, p = 0.005). Subgroup analysis showed that administration by intratympanic injection (SDM = -0.375, p = 0.013) rather than a round window catheter (SDM = -0.629, p = 0.160) yielded significant improvement in outcome. The usage of dexamethasone yielded better outcomes (SDM = -0.379, p = 0.039) than the use of methylprednisolone (SDM = -0.459, p = 0.187). No serious side effect of treatment was reported. In patients who have failed initial treatment with systemic steroids, additional treatment with salvage intratympanic dexamethasone injections demonstrate a statistically significant reduction in the hearing thresholds as compared to controls.

  14. Optimization of a pre-MEKC separation SPE procedure for steroid molecules in human urine samples.

    PubMed

    Olędzka, Ilona; Kowalski, Piotr; Dziomba, Szymon; Szmudanowski, Piotr; Bączek, Tomasz

    2013-01-01

    Many steroid hormones can be considered as potential biomarkers and their determination in body fluids can create opportunities for the rapid diagnosis of many diseases and disorders of the human body. Most existing methods for the determination of steroids are usually time- and labor-consuming and quite costly. Therefore, the aim of analytical laboratories is to develop a new, relatively low-cost and rapid implementation methodology for their determination in biological samples. Due to the fact that there is little literature data on concentrations of steroid hormones in urine samples, we have made attempts at the electrophoretic determination of these compounds. For this purpose, an extraction procedure for the optimized separation and simultaneous determination of seven steroid hormones in urine samples has been investigated. The isolation of analytes from biological samples was performed by liquid-liquid extraction (LLE) with dichloromethane and compared to solid phase extraction (SPE) with C18 and hydrophilic-lipophilic balance (HLB) columns. To separate all the analytes a micellar electrokinetic capillary chromatography (MECK) technique was employed. For full separation of all the analytes a running buffer (pH 9.2), composed of 10 mM sodium tetraborate decahydrate (borax), 50 mM sodium dodecyl sulfate (SDS), and 10% methanol was selected. The methodology developed in this work for the determination of steroid hormones meets all the requirements of analytical methods. The applicability of the method has been confirmed for the analysis of urine samples collected from volunteers--both men and women (students, amateur bodybuilders, using and not applying steroid doping). The data obtained during this work can be successfully used for further research on the determination of steroid hormones in urine samples. PMID:24232737

  15. Efficacy comparison of oral steroid, intratympanic steroid, hyperbaric oxygen and oral steroid + hyperbaric oxygen treatments in idiopathic sudden sensorineural hearing loss cases.

    PubMed

    Alimoglu, Yalcin; Inci, Ender; Edizer, Deniz Tuna; Ozdilek, Alper; Aslan, Mehmet

    2011-12-01

    Idiopathic sudden sensorineural hearing loss is a rare disorder of unknown pathogenesis in which hearing is lost partially or totally. About 60 treatment modalities have been described. We aimed to compare the efficacy of hyperbaric oxygen, oral steroid, intratympanic steroid therapy and their combinations in idiopathic sudden sensorineural hearing loss patients. Files of patients who were followed up between 2004 and 2010 in our clinic were examined retrospectively. Patients were divided into four groups according to the therapy received: Oral steroid, oral steroid + hyperbaric oxygen, intratympanic steroid and hyperbaric oxygen. Treatment success was assessed by Siegel criteria and mean gains using pre-treatment and post-treatment audiograms. 217 patients and 219 ears were examined. The proportion of patients responding to therapy was the highest in the oral steroid + hyperbaric oxygen group with 86.88% (53/61) followed by the oral steroid group with 63.79% (37/58), the intratympanic steroid group with 46,51% (20/43) and the hyperbaric oxygen group with 43.85% (25/57). The proportion of patients who had complete recovery was the highest in the oral steroid + hyperbaric oxygen group with 42.6% (26/61) followed by the oral steroid group with 19.0% (11/58), the hyperbaric oxygen group with 17.5% (10/57) and the intratympanic steroid group with 11.6% (5/43). The oral steroid + hyperbaric oxygen group has the highest mean hearing gain among all groups (p < 0.05). Idiopathic sudden sensorineural hearing loss patients receiving oral steroid + hyperbaric oxygen combination therapy have a higher likelihood of recovery than patients receiving oral steroids, hyperbaric oxygen or intratympanic steroids alone.

  16. Pertussis (Whooping Cough) Complications

    MedlinePlus

    ... CDC Cancel Submit Search The CDC Pertussis (Whooping Cough) Note: Javascript is disabled or is not supported ... friendly Fact Sheet Pertussis Vaccination Pregnancy and Whooping Cough Clinicians Disease Specifics Treatment Clinical Features Clinical Complications ...

  17. Complications of Measles (Rubeola)

    MedlinePlus

    ... Links Measles and Rubella Initiative World Health Organization Pan American Health Organization Complications of Measles Language: English ... Links Measles and Rubella Initiative World Health Organization Pan American Health Organization Language: English Español (Spanish) File ...

  18. Intestinal Complications of IBD

    MedlinePlus

    ... treated with topical creams or sitz baths. MALABSORPTION & MALNUTRITION Another complication in people with Crohn’s disease is ... the gut that absorbs most nutrients. Malabsorption and malnutrition usually do not develop unless the disease is ...

  19. Infection and Other Complications

    MedlinePlus

    ... Stage 3 Infection and Other Complications NLN Position Papers Lymphedema Awareness Campaign Education Kits Educational Videos What ... Patients (8) LymphLink Articles (175) FAQ's (6) Position Papers (9) LSAP Perspective (9) Become a member now » ...

  20. Dental Implant Complications.

    PubMed

    Liaw, Kevin; Delfini, Ronald H; Abrahams, James J

    2015-10-01

    Dental implants have increased in the last few decades thus increasing the number of complications. Since many of these complications are easily diagnosed on postsurgical images, it is important for radiologists to be familiar with them and to be able to recognize and diagnose them. Radiologists should also have a basic understanding of their treatment. In a pictorial fashion, this article will present the basic complications of dental implants which we have divided into three general categories: biomechanical overload, infection or inflammation, and other causes. Examples of implant fracture, loosening, infection, inflammation from subgingival cement, failure of bone and soft tissue preservation, injury to surround structures, and other complications will be discussed as well as their common imaging appearances and treatment. Lastly, we will review pertinent dental anatomy and important structures that are vital for radiologists to evaluate in postoperative oral cavity imaging.

  1. New pentahydroxylated steroids from the South China Sea gorgonian Subergorgia suberosa.

    PubMed

    Liao, Xiao-Jian; Tang, Li-Dan; Liang, Yuan-Wei; Jian, Shui-Lian; Xu, Shi-Hai; Liu, Yong-Hong

    2012-02-01

    Two new pentahydroxylated steroids, (3β,12β,16β,23E)-cholesta-5,23-diene-3,12,16,20,25-pentaol (1) and (3β,12β,16β)-cholesta-5,25(26)-diene-3,12,16,20,24-pentaol (2), were isolated from the EtOH extract of the South China Sea gorgonian Subergorgia suberosa. In addition, four known steroids were detected. The structures of these compounds were established by spectroscopic methods and comparison of their data with those of the related known compounds. In addition, the cyctotoxicities of the compounds were evaluated against selected cancer cell lines.

  2. On complicity theory.

    PubMed

    Kline, A David

    2006-04-01

    The received account of whistleblowing, developed over the last quarter century, is identified with the work of Norman Bowie and Richard DeGeorge. Michael Davis has detailed three anomalies for the received view: the paradoxes of burden, missing harm and failure. In addition, he has proposed an alternative account of whistleblowing, viz., the Complicity Theory. This paper examines the Complicity Theory. The supposed anomalies rest on misunderstandings of the received view or misreadings of model cases of whistleblowing, for example, the Challenger disaster and the Ford Pinto. Nevertheless, the Complicity Theory is important for as in science the contrast with alternative competing accounts often helps us better understand the received view. Several aspects of the received view are reviewed and strengthened through comparison with Complicity Theory, including why whistleblowing needs moral justification. Complicity Theory is also critiqued. The fundamental failure of Complicity Theory is its failure to explain why government and the public encourage and protect whistleblowers despite the possibility of considerable harm to the relevant company in reputation, lost jobs, and lost shareholder value.

  3. Neurologic complications of vaccinations.

    PubMed

    Miravalle, Augusto A; Schreiner, Teri

    2014-01-01

    This chapter reviews the most common neurologic disorders associated with common vaccines, evaluates the data linking the disorder with the vaccine, and discusses the potential mechanism of disease. A literature search was conducted in PubMed using a combination of the following terms: vaccines, vaccination, immunization, and neurologic complications. Data were also gathered from publications of the American Academy of Pediatrics Committee on Infectious Diseases, the World Health Organization, the US Centers for Disease Control and Prevention, and the Vaccine Adverse Event Reporting System. Neurologic complications of vaccination are rare. Many associations have been asserted without objective data to support a causal relationship. Rarely, patients with a neurologic complication will have a poor outcome. However, most patients recover fully from the neurologic complication. Vaccinations have altered the landscape of infectious disease. However, perception of risk associated with vaccinations has limited the success of disease eradication measures. Neurologic complications can be severe, and can provoke fear in potential vaccines. Evaluating whether there is causal link between neurologic disorders and vaccinations, not just temporal association, is critical to addressing public misperception of risk of vaccination. Among the vaccines available today, the cost-benefit analysis of vaccinations and complications strongly argues in favor of vaccination.

  4. Complications of auricular correction

    PubMed Central

    Staindl, Otto; Siedek, Vanessa

    2008-01-01

    The risk of complications of auricular correction is underestimated. There is around a 5% risk of early complications (haematoma, infection, fistulae caused by stitches and granulomae, allergic reactions, pressure ulcers, feelings of pain and asymmetry in side comparison) and a 20% risk of late complications (recurrences, telehone ear, excessive edge formation, auricle fitting too closely, narrowing of the auditory canal, keloids and complete collapse of the ear). Deformities are evaluated less critically by patients than by the surgeons, providing they do not concern how the ear is positioned. The causes of complications and deformities are, in the vast majority of cases, incorrect diagnosis and wrong choice of operating procedure. The choice of operating procedure must be adapted to suit the individual ear morphology. Bandaging technique and inspections and, if necessary, early revision are of great importance for the occurence and progress of early complications, in addition to operation techniques. In cases of late complications such as keloids and auricles that are too closely fitting, unfixed full-thickness skin flaps have proved to be the most successful. Large deformities can often only be corrected to a limited degree of satisfaction. PMID:22073079

  5. Complications of auricular correction.

    PubMed

    Staindl, Otto; Siedek, Vanessa

    2007-01-01

    The risk of complications of auricular correction is underestimated. There is around a 5% risk of early complications (haematoma, infection, fistulae caused by stitches and granulomae, allergic reactions, pressure ulcers, feelings of pain and asymmetry in side comparison) and a 20% risk of late complications (recurrences, telehone ear, excessive edge formation, auricle fitting too closely, narrowing of the auditory canal, keloids and complete collapse of the ear). Deformities are evaluated less critically by patients than by the surgeons, providing they do not concern how the ear is positioned. The causes of complications and deformities are, in the vast majority of cases, incorrect diagnosis and wrong choice of operating procedure. The choice of operating procedure must be adapted to suit the individual ear morphology. Bandaging technique and inspections and, if necessary, early revision are of great importance for the occurence and progress of early complications, in addition to operation techniques. In cases of late complications such as keloids and auricles that are too closely fitting, unfixed full-thickness skin flaps have proved to be the most successful. Large deformities can often only be corrected to a limited degree of satisfaction. PMID:22073079

  6. Psychological and behavioural effects of endogenous testosterone and anabolic-androgenic steroids. An update.

    PubMed

    Bahrke, M S; Yesalis, C E; Wright, J E

    1996-12-01

    Endogenous testosterone levels have been linked to aggressive behaviour in both animals and humans. Studies administering moderate doses of exogenous testosterone for contraceptive and clinical purposes reveal essentially no adverse effects on male sexual and aggressive behaviour. However, investigations and case reports of athletes, usually involving higher doses, demonstrate an association between anabolic-androgenic steroid use and affective and psychotic syndromes and psychological dependence. Efforts to study the psychological and behavioural effects of anabolic-androgenic steroids are complicated by a variety of methodological limitations. Only 3 prospective, blinded studies demonstrating aggression or adverse overt behaviour resulting from anabolic-androgenic steroid use have been reported. With estimates of over 1 million past or current users in the US, an extremely small percentage of individuals using anabolic-androgenic steroids appear to experience mental disturbances severe enough to result in clinical treatment and medical case reports. Even among those so affected, the roles of previous psychiatric history, genetic susceptibility to addictions or mental disorders, environmental and peer influences, and individual expectations remain unclear.

  7. Steroid-sparing effect of omalizumab for allergic bronchopulmonary aspergillosis and cystic fibrosis.

    PubMed

    Zirbes, Jacquelyn M; Milla, Carlos E

    2008-06-01

    Allergic bronchopulmonary aspergillosis (ABPA) is a complication commonly encountered in patients with CF that produces significant respiratory morbidity. Chronic airway colonization with Aspergillus induces strong inflammatory responses with high IgE levels. Current guidelines for therapy include prolonged courses of systemic corticosteroids as the main therapeutic strategy. However this has the potential to induce significant detrimental side effects in children. Omalizumab is a humanized monoclonal antibody directed against IgE that prevents its binding to high- and low-affinity receptors on effector cells. It has been shown to be effective in improving asthma control in patients with a strong allergic component. We present our long term experience with the use of Anti-IgE therapy in three children with CF and ABPA (mean age at start of therapy 14.2 years) who were steroid dependent. All three were already experiencing significant side effects from chronic steroid therapy. After the start of Omalizumab these children have experienced significant and sustained clinical improvements at the same time that they were discontinued from chronic systemic steroids. Our experience suggests that IgE blockade has tremendous potential as a strategy to control this disease in steroid dependent patients.

  8. Parenteral nutrition: risks, complications, and management.

    PubMed

    Worthington, Patricia H; Gilbert, Karen A

    2012-01-01

    Parenteral nutrition is a life-saving modality, but one that also carries risks for potentially life-threatening complications. Comprehensive management of patients receiving parenteral nutrition includes careful selection of candidates, individualizing formulas to meet patients' unique needs, monitoring response to therapy, and implementing strategies designed to avoid complications. Measures to mitigate the risk of central line-associated bloodstream infections are particularly important. As with all complex therapies, a collaborative, multidisciplinary approach promotes optimal outcomes. PMID:22222292

  9. Pathological changes in anabolic androgenic steroid users.

    PubMed

    Lusetti, Monia; Licata, Manuela; Silingardi, Enrico; Reggiani Bonetti, Luca; Palmiere, Cristian

    2015-07-01

    Several classes of recreational and prescription drugs have additional effects on the heart and vasculature, which may significantly contribute to morbidity and mortality in chronic users. The study presented herein focuses on pathological changes involving the heart possibly due to anabolic androgenic steroid use. The role these hormones may play in their occurrence of sudden cardiac death is also investigated. 98 medico-legal cases including 6 anabolic androgenic steroid users were retrospectively reviewed. Autopsies, histology, immunohistochemistry, biochemistry and toxicology were performed in all cases. Pathological changes consisted of various degrees of interstitial and perivascular fibrosis as well as fibroadipous metaplasia and perineural fibrosis within the myocardium of the left ventricle. Within the limits of the small number of investigated cases, our results appear to confirm former observations on this topic and suggest anabolic androgenic steroid's potential causative role in the pathogenesis of sudden cardiac deaths in chronic users.

  10. Effect of topical steroid treatment on idiopathic granulomatous mastitis: clinical and radiologic evaluation.

    PubMed

    Gunduz, Yasemin; Altintoprak, Fatih; Tatli Ayhan, Lacin; Kivilcim, Taner; Celebi, Fehmi

    2014-01-01

    Idiopathic granulomatous mastitis (IGM) is a rare inflammatory, noncaseating, chronic granulomatous benign disease. The etiology of IGM is still unknown. It is postulated to be an autoimmune localized response. The use of a course of oral steroids provides an important regression of breast mass and skin lesions. Topical corticosteroids are used to treat many skin diseases, but no study is available on the sole use of topical steroids for treating IGM. Eleven women with IGM were treated with topical steroid and evaluated using mammography, ultrasonography, and dynamic MRI. At the end of the 12th week, patients were clinically and radiologically evaluated for the regression of breast and skin lesions. Pre- and post-treatment time-intensity curve patterns (TICs) were also compared. During the topical steroid treatment, the inflammation signs in the affected breast had markedly disappeared, the fistulas had become inactive, and the fistula orifices and/or skin erosions had closed in nine patients. The median follow-up period was 17 months (range: 12-48 months). Recurrence was observed in two patients (2/11) at 5 and 8 months, which were treated again topically. The inflammatory findings of the breast skin completely resolved after 8 weeks of treatment, and no side effects or steroid-related complications occurred. In the pretreatment period, TICs from enhancing areas showed a Type 1 pattern in three cases, a Type 2 pattern in five cases, and a Type 3 pattern in three cases. After topical steroid treatment, TIC was not changed only in one patient (Type 2). Type 1 patterns were determined in seven cases and Type 2 patterns in two cases. In addition, in two patients, TICs were not determined due to complete healing. Our MRI findings showed that topical steroid therapy may be useful because it affects mammary parenchyma as well as mammary skin. Further studies with a greater number of patients are needed to determine the topical steroid therapy dosing and duration, and

  11. Characteristic Steroids from the South China Sea Gorgonian Muricella sibogae and Their Cytotoxicities.

    PubMed

    Zhang, Xing-Wang; Tang, Xu-Li; Liu, Bao-Sheng; Li, Ping-Lin; Li, Guo-Qiang

    2016-02-01

    Twenty-four steroid-based natural products, 9,10-secosteroids (1-10), 1,4-dien-3-one steroids (11-19), and 4-en-3-one steroids (20-24), containing varying side-chains, were isolated from the South China Sea gorgonian Muricella sibogae. The structures of one new 9,10-secosteroid, sibogol D (1), and two new 1,4-dien-3-one steroids, sibogols E and F (11 and 12), were elucidated by extensive spectroscopic analyses and by comparison with the literature data. Cytotoxicities for all the isolates were evaluated against four selected tumor cell lines, HL-60, HCT116, K562, and P388. Compounds 3, 9, and 13 exhibited potent cytotoxic activities against the HL-60 cell line, with IC50 values ranging from 1.27 to 10.05 μM, and compound 3 was also cytotoxic against HCT116 with an IC50 value of 5.8 μM. The bioassay results also indicated a potential relationship between structural patterns and activity. The newly presented series of 1,4-dien-3-one and 4-en-3-one types of steroids relating to the unique 9,10-secosteroids in biogenesis were found in this species for the first time, which is of considerable chemotaxonomic significance.

  12. Steroid modulation of the chloride ionophore in rat brain: structure-activity requirements, regional dependence and mechanism of action

    SciTech Connect

    Gee, K.W.; Bolger, M.B.; Brinton, R.E.; Coirini, H.; McEwen, B.S.

    1988-08-01

    Further in vitro studies of steroids active at the gamma-aminobutyric acidA (GABAA) receptor regulated Cl- channel labeled by (35S)-t-butylbicyclophosphorothionate ((35S)TBPS) reveal additional structural requirements necessary for activity. Evaluation of selected steroids for activity against TBPS-induced convulsions show similar requirements for activity. Interestingly, steroids (e.g., 5 alpha-pregnan-3 alpha, 20 alpha-diol) were identified that have high potency but limited efficacy as modulators of (35S)TBPS binding. These characteristics are reminiscent of the clinically useful benzodiazepines (BZs) such as clonazepam. However, interactions between the prototypical anesthetic-barbiturate, sodium pentobarbital, and steroids active at the Cl- channel suggest that they do not share a common site of action as allosteric modulators of (35S)TBPS and BZ receptor binding. The most potent steroid evaluated, 5 alpha-pregnan-3 alpha-ol-20-one, modulates (35S)TBPS binding at low concentrations (IC50 approximately 17 nM) in a regionally dependent manner. All (35S)TBPS binding sites appear to be functionally coupled to a steroid modulatory site. Because several of the active steroids are metabolites of progesterone, their ability to inhibit the binding of (3H)promegestrone to the cytosolic progestin receptor in rat uterus was evaluated. Those steroids showing potent activity at the GABAA receptor-Cl- ionophore were inactive at the intracellular progestin receptor. Such specificity coupled with their high potency provide additional support for the hypothesis that some of these steroids may be involved in the homeostatic regulation of brain excitability via the GABAA-BZ receptor complex.

  13. A new steroidal saponin from Agave attenuata.

    PubMed

    Mendes, Tatiana Paz; Silva, Graziela de Medeiros; da Silva, Bernadete Pereira; Parente, José Paz

    2004-04-01

    A new steroidal saponin was isolated from the leaves of Agave attenuata. Its structure was established as (3beta,beta,25S)-spirostan-3-yl O-beta-D-glucopyranosyl-(1 --> 2)-beta-D-glucopyranosyl-(1 --> 2)-O-[beta-D-glucopyranosyl-(1 --> 3)]-beta-D-glucopyranosyl-(1 --> 4)-beta-D-galactopyranoside. The structural identification was performed using detailed analyses of 1H- and 13C-NMR spectra including 2D NMR spectroscopic techniques (COSY, HETCOR, and COLOC) and chemical conversions. The hemolytic activity of the steroidal saponin was evaluated using an in vitro assay.

  14. A new steroidal saponin from Agave shrevei.

    PubMed

    Pereira Da Silva, Bernadete; Valente, Ana Paula; Paz Parente, José

    2006-04-01

    A new steroidal saponin was isolated from the leaves of Agave shrevei. Its structure was established as 3-[O-beta-D-glucopyranosyl-(1-->2)-O-[O-beta-D-glucopyranosyl-(1-->4)-O-[O-beta-D-glucopyranosyl-(1-->6)]-O-beta-D-glucopyranosyl-(1-->4)-beta-D-galactopyranosyl)-oxy]-(3beta,5alpha,25R)-spirostane. The structural identification was performed using detailed analyses of 1H- and 13C-NMR spectra including 2D NMR spectroscopic techniques (COSY, HETCOR, HMBC, and HMQC) and chemical conversions. The haemolytic activity of the steroidal saponin was evaluated using an in vitro assay.

  15. Postoperative surgical complications of lymphadenohysterocolpectomy

    PubMed Central

    Marin, F; Pleşca, M; Bordea, CI; Voinea, SC; Burlănescu, I; Ichim, E; Jianu, CG; Nicolăescu, RR; Teodosie, MP; Maher, K; Blidaru, A

    2014-01-01

    Rationale The current standard surgical treatment for the cervix and uterine cancer is the radical hysterectomy (lymphadenohysterocolpectomy). This has the risk of intraoperative accidents and postoperative associated morbidity. Objective The purpose of this article is the evaluation and quantification of the associated complications in comparison to the postoperative morbidity which resulted after different types of radical hysterectomy. Methods and results Patients were divided according to the type of surgery performed as follows: for cervical cancer – group A- 37 classic radical hysterectomies Class III Piver - Rutledge -Smith ( PRS ), group B -208 modified radical hysterectomies Class II PRS and for uterine cancer- group C -79 extended hysterectomies with pelvic lymphadenectomy from which 17 patients with paraaortic lymphnode biopsy . All patients performed preoperative radiotherapy and 88 of them associated radiosensitization. Discussion Early complications were intra-abdominal bleeding ( 2.7% Class III PRS vs 0.48% Class II PRS), supra-aponeurotic hematoma ( 5.4% III vs 2.4% II) , dynamic ileus (2.7% III vs 0.96% II) and uro - genital fistulas (5.4% III vs 0.96% II).The late complications were the bladder dysfunction (21.6% III vs 16.35% II) , lower limb lymphedema (13.5% III vs 11.5% II), urethral strictures (10.8% III vs 4.8% II) , incisional hernias ( 8.1% III vs 7.2% II), persistent pelvic pain (18.91% III vs 7.7% II), bowel obstruction (5.4% III vs 1.4% II) and deterioration of sexual function (83.3% III vs 53.8% II). PRS class II radical hysterectomy is associated with fewer complications than PRS class III radical hysterectomy , except for the complications of lymphadenectomy . A new method that might reduce these complications is a selective lymphadenectomy represented by sentinel node biopsy . In conclusion PRS class II radical hysterectomy associated with neoadjuvant radiotherapy is a therapeutic option for the incipient stages of cervical cancer

  16. Bell's Palsy: Treatment with Steroids and Antiviral Drugs

    MedlinePlus

    ... PATIENTS and their FAMILIES BELL’S PALSY: TREATMENT WITH STEROIDS AND ANTIVIRAL DRUGS This information sheet is provided to help you understand the role of steroids and antiviral drugs for treating Bell’s palsy. Neurologists ...

  17. Certain Steroids Raise Risk for Serious Staph Infections

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_159290.html Certain Steroids Raise Risk for Serious Staph Infections Study finds ... to infection," he added. Glucocorticoids -- a form of steroids -- are powerful immunosuppressive drugs used to treat a ...

  18. Metabolomics in diabetic complications.

    PubMed

    Filla, Laura A; Edwards, James L

    2016-04-01

    With a global prevalence of 9%, diabetes is the direct cause of millions of deaths each year and is quickly becoming a health crisis. Major long-term complications of diabetes arise from persistent oxidative stress and dysfunction in multiple metabolic pathways. The most serious complications involve vascular damage and include cardiovascular disease as well as microvascular disorders such as nephropathy, neuropathy, and retinopathy. Current clinical analyses like glycated hemoglobin and plasma glucose measurements hold some value as prognostic indicators of the severity of complications, but investigations into the underlying pathophysiology are still lacking. Advancements in biotechnology hold the key to uncovering new pathways and establishing therapeutic targets. Metabolomics, the study of small endogenous molecules, is a powerful toolset for studying pathophysiological processes and has been used to elucidate metabolic signatures of diabetes in various biological systems. Current challenges in the field involve correlating these biomarkers to specific complications to provide a better prediction of future risk and disease progression. This review will highlight the progress that has been made in the field of metabolomics including technological advancements, the identification of potential biomarkers, and metabolic pathways relevant to macro- and microvascular diabetic complications.

  19. Osteoarticular complications of brucellosis.

    PubMed Central

    Colmenero, J D; Reguera, J M; Fernández-Nebro, A; Cabrera-Franquelo, F

    1991-01-01

    Two hundred and sixty three patients with a diagnosis of brucellosis between January 1984 and December 1987 were studied prospectively. Sixty five patients (25%) developed osteoarticular complications. These patients had a more prolonged course than those with no complications. Spondylitis in 38 (58%) and sacroiliitis in 29 (45%) were the most prevalent. There were no significant laboratory, serological, or bacteriological differences between patients with and without osteoarticular complications. At diagnosis 47 patients (72%) showed radiographic abnormalities, commonly in axial sites but rarely in peripheral sites. Radionuclide bone scan was positive with no radiographic abnormalities in 17 (26%) of cases. Fifty seven patients received medical treatment alone, 51 (89%) being cured with a single course of treatment. Treatment failed or there was a relapse in six patients (11%), of whom five had spondylitis. Eight of the 65 patients (12%), all of whom had spondylitis and paravertebral or epidural abscesses, also required surgical treatment. Images PMID:1994863

  20. Ophthalmic complications of dengue.

    PubMed

    Chan, David P L; Teoh, Stephen C B; Tan, Colin S H; Nah, Gerard K M; Rajagopalan, Rajesh; Prabhakaragupta, Manjunath K; Chee, Caroline K L; Lim, Tock H; Goh, Kong Y

    2006-02-01

    We report 13 cases of ophthalmic complications resulting from dengue infection in Singapore. We performed a retrospective analysis of a series of 13 patients with dengue fever who had visual impairment. Investigations included Humphrey automated visual field analyzer, Amsler charting, fundus fluorescein angiography, and optical coherence tomography. Twenty-two eyes of 13 patients were affected. The mean age of patients was 31.7 years. Visual acuity varied from 20/25 to counting fingers only. Twelve patients (92.3%) noted central vision impairment. Onset of visual impairment coincided with the nadir of serum thrombocytopenia. Ophthalmologic findings include macular edema and blot hemorrhages (10), cotton wool spots (1), retinal vasculitis (4), exudative retinal detachment (2), and anterior uveitis (1). All patients recovered visual acuity to 20/30 or better with residual central scotoma by 12 weeks. These new complications suggest a widening spectrum of ophthalmic complications in dengue infection.

  1. Central retinal artery occlusion as an iatrogenic complication of treatment of central giant cell granuloma of the mandible.

    PubMed

    Bhushan, Gauri; Gupta, Swati; Bhushan, Urvashi; Raina, Usha Kaul

    2015-05-01

    Although intralesional steroid injection as a management option for central giant cell granuloma (CGCG) of the mandible is considered safe, central retinal artery occlusion (CRAO) is a dreaded and previously unreported complication of this treatment modality. The present report discusses an iatrogenic case of CRAO that occurred during treatment of CGCG of the mandible. This complication occurred because of high injection pressure, which led to the opening of an anastomosis between the external and internal carotid arteries, leading to retrograde migration of steroid particles. This report also highlights the importance of being aware of such communications.

  2. [Orbital complications of sinusitis].

    PubMed

    Šuchaň, M; Horňák, M; Kaliarik, L; Krempaská, S; Koštialová, T; Kovaľ, J

    2014-12-01

    Orbital complications categorised by Chandler are emergency. They need early diagnosis and agresive treatment. Stage and origin of orbital complications are identified by rhinoendoscopy, ophtalmologic examination and CT of orbite and paranasal sinuses. Periorbital cellulitis and early stage of orbital cellulitis can be treated conservatively with i. v. antibiotics. Monitoring of laboratory parameters and ophtalmologic symptoms is mandatory. Lack of improvement or worsening of symptoms within 24-48 hours and advanced stages of orbital complications are indicated for surgery. The purpose of the study is to evaluate epidemiology, clinical features and management of sinogenic orbital complications. Retrospective data of 8 patients with suspicion of orbital complication admited to hospital from 2008 to 2013 were evaluated. Patients were analyzed in terms of gender, age, CT findings, microbiology, clinical features, stage and treatment. Male and female were afected in rate 1,66:1. Most of patients were young adult in 3rd. and 4th. decade of life (62,5 %). Acute and chronic sinusitis were cause of orbital complication in the same rate. The most common origin of orbital complication was ethmoiditis (62,5 %), than maxillary (25 %) and frontal (12,5 %) sinusitis. Polysinusitis with affection of ethmoidal, maxillary and frontal sinuses (75 %) was usual CT finding. Staphylococcus epidermidis and Staphylococcus aureus were etiological agens in half of cases. Periorbital oedema (100 %), proptosis, chemosis (50 %), diplopia and glaucoma (12,5 %) were observed. Based on examinations, diagnosis of periorbital oedema/preseptal cellulitis was made in 3 (37,5 %), orbital cellulitis in 3 (37,5 %) and subperiosteal abscess in 2 cases (25 %). All patients underwent combined therapy - i. v. antibiotics and surgery within 24 hours. Eradication of disease from ostiomeatal complex (OMC), drainage of affected sinuses and drainage of subperiosteal abscess were done via fuctional endonasal

  3. Complications of cosmetic tattoos.

    PubMed

    De Cuyper, Christa

    2015-01-01

    Cosmetic tattoos, which are better known as permanent make-up, have become popular in the last decades. This same procedure can be used to camouflage pathological skin conditions, to mask scars and to complete the aesthetic results of plastic and reconstructive surgeries. The risks and complications of tattooing procedures include infections and allergic reactions. Scarring can occur. Fanning and fading of the colorants and dissatisfaction with colour and shape are not unusual. Different lasers can offer solutions for the removal of unwanted cosmetic tattoos, but complications due to the laser treatment, such as paradoxical darkening and scarring, can arise.

  4. Interactions between the gonadal steroids and the immune system.

    PubMed

    Grossman, C J

    1985-01-18

    The immune system is regulated by the gonadal steroids estrogen, androgen, and progesterone, but the circulating levels of these steroids can also be affected by immune system function. Such interactions appear to be mediated through the hypothalamic-pituitary-gonadal-thymic axis and depend on pituitary luteinizing hormone released by thymic factors under the control of the gonadal steroids.

  5. ent-Steroids: novel tools for studies of signaling pathways.

    PubMed

    Covey, Douglas F

    2009-07-01

    Membrane receptors are often modulated by steroids and it is necessary to distinguish the effects of steroids at these receptors from effects occurring at nuclear receptors. Additionally, it may also be mechanistically important to distinguish between direct effects caused by binding of steroids to membrane receptors and indirect effects on membrane receptor function caused by steroid perturbation of the membrane containing the receptor. In this regard, ent-steroids, the mirror images of naturally occurring steroids, are novel tools for distinguishing between these various actions of steroids. The review provides a background for understanding the different actions that can be expected of steroids and ent-steroids in biological systems, references for the preparation of ent-steroids, a short discussion about relevant forms of stereoisomerism and the requirements that need to be fulfilled for the interaction between two molecules to be enantioselective. The review then summarizes results of biophysical, biochemical and pharmacological studies published since 1992 in which ent-steroids have been used to investigate the actions of steroids in membranes and/or receptor-mediated signaling pathways.

  6. The Incidence of Anabolic Steroid Use among Competitive Bodybuilders.

    ERIC Educational Resources Information Center

    Tricker, Ray; And Others

    1989-01-01

    Investigated incidence of anabolic steroid use among 380 competitive male and female bodybuilders in Kansas and Missouri. Results indicated more than half (54 percent) of the male bodybuilders were using steroids on a regular basis compared to 10 percent of the female competitors. Found main reason for use of steroids was desire to win. (Author/TE)

  7. Hypercholesterolemia in Male Power Lifters Using Anabolic-Androgenic Steroids.

    ERIC Educational Resources Information Center

    Cohen, Jonathan C.; And Others

    1988-01-01

    Measurement of serum cholesterol concentrations in male power lifters who used anabolic-androgenic steroids for eight weeks, three years, or eight years indicated that mean serum cholesterol levels increased with drug use, but decreased promptly to near pre-steroid levels after steroid use ended. (Author/CB)

  8. Steroids and Other Ergogenic Aids: A Resource Guide.

    ERIC Educational Resources Information Center

    Virginia State Dept. of Education, Richmond.

    Steroids have become one of society's "short cuts" to athletic prowess and success. This guide includes information and teaching materials for educators and others who work with youth on how to teach that steroids are drugs, that drugs can harm and kill, and that a "no-use" policy applies to steroids as well as to alcohol and other drugs. It is…

  9. Sox and Drugs: Baseball, Steroids and Physics

    NASA Astrophysics Data System (ADS)

    Tobin, Roger

    2008-03-01

    The sports world is in an uproar over performance-enhancing drugs. In the United States steroids in baseball have received the most attention, in part because the purported effects are much more dramatic than in any other sport. From 1995-2003 a few players hit home runs at rates 20-50% higher than the best sluggers of the preceding century. Could steroids really increase home-run performance that much? I will describe a model that combines estimates of the physiological effects of steroids, known baseball physics, and reasonable models of batting effectiveness for highly skilled hitters. A 10% increase in muscle mass, which can reasonably be expected from steroid use, increases the speed of a batted ball by 3%. Because home runs are relatively rare events on the tail of a batter's range distribution, even this modest change in ball speed can increase the proportion of batted balls that result in home runs by 30 -- 70%, enough to account for the record-shattering performances of the recent past. I will also describe some of the attention -- both welcome and not -- that comes to the unsuspecting physicist who wades into such emotionally troubled waters.

  10. Sex Steroid Actions in Male Bone

    PubMed Central

    Laurent, Michaël R.; Claessens, Frank; Gielen, Evelien; Lagerquist, Marie K.; Vandenput, Liesbeth; Börjesson, Anna E.; Ohlsson, Claes

    2014-01-01

    Sex steroids are chief regulators of gender differences in the skeleton, and male gender is one of the strongest protective factors against osteoporotic fractures. This advantage in bone strength relies mainly on greater cortical bone expansion during pubertal peak bone mass acquisition and superior skeletal maintenance during aging. During both these phases, estrogens acting via estrogen receptor-α in osteoblast lineage cells are crucial for male cortical and trabecular bone, as evident from conditional genetic mouse models, epidemiological studies, rare genetic conditions, genome-wide meta-analyses, and recent interventional trials. Genetic mouse models have also demonstrated a direct role for androgens independent of aromatization on trabecular bone via the androgen receptor in osteoblasts and osteocytes, although the target cell for their key effects on periosteal bone formation remains elusive. Low serum estradiol predicts incident fractures, but the highest risk occurs in men with additionally low T and high SHBG. Still, the possible clinical utility of serum sex steroids for fracture prediction is unknown. It is likely that sex steroid actions on male bone metabolism rely also on extraskeletal mechanisms and cross talk with other signaling pathways. We propose that estrogens influence fracture risk in aging men via direct effects on bone, whereas androgens exert an additional antifracture effect mainly via extraskeletal parameters such as muscle mass and propensity to fall. Given the demographic trends of increased longevity and consequent rise of osteoporosis, an increased understanding of how sex steroids influence male bone health remains a high research priority. PMID:25202834

  11. Preventing Anabolic Steroid Use: Guidelines and Activities.

    ERIC Educational Resources Information Center

    Nutter, June; Rauhe, Betty

    1997-01-01

    Information about anabolic steroids should be included in the school health curriculum as early as possible. The paper presents suggestions for planning education programs and offers a variety of activities and strategies appropriate for many age groups, including case studies, story completion, posters, demonstrations, projects, creative writing,…

  12. Neuroactive steroids and peripheral myelin proteins.

    PubMed

    Magnaghi, V; Cavarretta, I; Galbiati, M; Martini, L; Melcangi, R C

    2001-11-01

    The present review summarizes observations obtained in our laboratories which underline the importance of neuroactive steroids (i.e., progesterone (PROG), dihydroprogesterone (5alpha-DH PROG), tetrahydroprogesterone (3alpha, 5alpha-TH PROG), testosterone (T), dihydrotestosterone (DHT) and 5alpha-androstan-3alpha,17beta-diol (3alpha-diol)) in the control of the gene expression of myelin proteins (i.e. glycoprotein Po (Po) and the peripheral myelin protein 22 (PMP22)) in the peripheral nervous system. Utilizing different in vivo (aged and adult male rats) and in vitro (Schwann cell cultures) experimental models, we have observed that neuroactive steroids are able to stimulate the mRNA levels of Po and PMP22. The effects of these neuroactive steroids, which are able to interact with classical (progesterone receptor, PR, and androgen receptor, AR) and non-classical (GABA(A) receptor) steroid receptors is further supported by our demonstration in sciatic nerve and/or Schwann cells of the presence of these receptors. On the basis of the observations obtained in the Schwann cells cultures, we suggest that the stimulatory effect of neuroactive steroids on Po is acting through PR, while that on PMP22 needs the GABA(A) receptor. The present findings might be of importance for the utilization of specific receptor ligands as new therapeutical approaches for the rebuilding of the peripheral myelin, particularly in those situations in which the synthesis of Po and PMP22 is altered (i.e. demyelinating diseases like Charcot-Marie-Tooth type 1A and type 1B, hereditary neuropathy with liability to pressure palsies and the Déjérine-Sottas syndrome, aging, and after peripheral injury). PMID:11744100

  13. Synthesis, characterization, biological evaluation and molecular docking of steroidal spirothiazolidinones

    NASA Astrophysics Data System (ADS)

    Shamsuzzaman; Abdul Baqi, Khan A. A.; Ali, Abad; Asif, Mohd; Mashrai, Ashraf; Khanam, Hena; Sherwani, Asif; Yaseen, Zahid; Owais, Mohammad

    2015-04-01

    The present work describes a convenient synthesis of steroidal spirothiazolidinone derivatives (3, 10-12) in a two-step process. All the newly synthesized compounds have been characterized by means of elemental analyses, IR, 1H NMR, 13C NMR and MS. Lipinski's 'Rule of Five' analysis and biological score predicted higher intrinsic quality of the synthesized compounds and revealed that these compounds have good passive oral absorption. The DNA binding studies of the synthesized compounds with CT-DNA were carried out by UV-vis and fluorescence spectroscopy. The molecular docking study suggested electrostatic interaction between synthesized compounds and nucleotide base pairs. The antitumor activity was tested in vitro against human leukemia cancer cell (Jurkat) and blood peripheral mononuclear normal cell (PBMCs) lines by MTT method. In addition, apoptosis and nonenzymatic degradation of DNA have been investigated. The acetylcholinesterase (AChE) inhibitor activities of the derivatives were also evaluated using Ellman's method. The present study has shown that steroidal spirothiazolidinone derivatives (3, 10-12) can be used as template to design more potent and selective cytotoxic and AChE inhibition agents through modification and derivatization.

  14. Characterization of a novel non-steroidal glucocorticoid receptor antagonist

    SciTech Connect

    Li, Qun-Yi; Zhang, Meng; Hallis, Tina M.; DeRosier, Therese A.; Yue, Jian-Min; Ye, Yang; Mais, Dale E.; Wang, Ming-Wei

    2010-01-15

    Selective antagonists of the glucocorticoid receptor (GR) are desirable for the treatment of hypercortisolemia associated with Cushing's syndrome, psychic depression, obesity, diabetes, neurodegenerative diseases, and glaucoma. NC3327, a non-steroidal small molecule with potent binding affinity to GR (K{sub i} = 13.2 nM), was identified in a high-throughput screening effort. As a full GR antagonist, NC3327 greatly inhibits the dexamethasone (Dex) induction of marker genes involved in hepatic gluconeogenesis, but has a minimal effect on matrix metalloproteinase 9 (MMP-9), a GR responsive pro-inflammatory gene. Interestingly, the compound recruits neither coactivators nor corepressors to the GR complex but competes with glucocorticoids for the interaction between GR and a coactivator peptide. Moreover, NC3327 does not trigger GR nuclear translocation, but significantly blocks Dex-induced GR transportation to the nucleus, and thus appears to be a 'competitive' GR antagonist. Therefore, the non-steroidal compound, NC3327, may represent a new class of GR antagonists as potential therapeutics for a variety of cortisol-related endocrine disorders.

  15. Medical complications following splenectomy.

    PubMed

    Buzelé, R; Barbier, L; Sauvanet, A; Fantin, B

    2016-08-01

    Splenectomy is attended by medical complications, principally infectious and thromboembolic; the frequency of complications varies with the conditions that led to splenectomy (hematologic splenectomy, trauma, presence of portal hypertension). Most infectious complications are caused by encapsulated bacteria (Meningococcus, Pneumococcus, Hemophilus). These occur mainly in children and somewhat less commonly in adults within the first two years following splenectomy. Post-splenectomy infections are potentially severe with overwhelming post-splenectomy infection (OPSI) and this justifies preventive measures (prophylactic antibiotics, appropriate immunizations, patient education) and demands prompt antibiotic management with third-generation cephalosporins for any post-splenectomy fever. Thromboembolic complications can involve both the caval system (deep-vein thrombophlebitis, pulmonary embolism) and the portal system. Portal vein thrombosis occurs more commonly in patients with myeloproliferative disease and cirrhosis. No thromboembolic prophylaxis is recommended apart from perioperative low molecular weight heparin. However, some authors choose to prescribe a short course of anti-platelet medication if the post-splenectomy patient develops significant thrombocytosis. Thrombosis of the portal or caval venous system requires prolonged warfarin anticoagulation for 3 to 6 months. Finally, some studies have suggested an increase in the long-term incidence of cancer in splenectomized patients. PMID:27289254

  16. Interpreting Dream Complications.

    ERIC Educational Resources Information Center

    Gollub, Dan

    1984-01-01

    Explains different complications, i.e., emotional behavior, speech, and symbolism, suggesting that emotional behavior in dreams is either genuine or opposite from emotional reality. Dream speech delineates boundaries between the conscious and unconscious. Symbolism in dreams presents abstract concepts visually. (BH)

  17. Complicating Visual Culture

    ERIC Educational Resources Information Center

    Daiello, Vicki; Hathaway, Kevin; Rhoades, Mindi; Walker, Sydney

    2006-01-01

    Arguing for complicating the study of visual culture, as advocated by James Elkins, this article explicates and explores Lacanian psychoanalytic theory and pedagogy in view of its implications for art education practice. Subjectivity, a concept of import for addressing student identity and the visual, steers the discussion informed by pedagogical…

  18. Complications of collagen fillers.

    PubMed

    Lucey, Patricia; Goldberg, David J

    2014-12-01

    As the skin ages, a deficiency in collagen occurs, thus injectable collagen products have become a sensible and popular option for dermal filling and volume enhancement. Several types of collagen have been developed over the years, including animal sources such as bovine and porcine collagen, as well as human-based sources derived from pieces of the patient's own skin, cadaver skin, and later cultured from human dermal fibroblasts. While collagen overall has a relatively safe, side effect profile, there are several complications, both early and late onset, that practitioners and patients should be aware of. Early complications, occurring within days of the procedure, can be divided into non-hypersensitivity and hypersensitivity reactions. The non-hypersensitive reactions include injection site reactions, discoloration, maldistribution, infection, skin necrosis, and the very rare but dreaded risk of vision loss, whereas the hypersensitivity reactions present usually as delayed type IV reactions, but can also rarely present as an immediate type I reaction. Late complications, occurring within weeks to even years after injection, include granuloma formation, foreign body reactions, and infection secondary to atypical mycobacteria or biofilms. This review will give a detailed overview of the complications secondary to cutaneous collagen injections.

  19. Treatment of complicated grief

    PubMed Central

    Rosner, Rita; Pfoh, Gabriele; Kotoučová, Michaela

    2011-01-01

    Following the death of a loved one, a small group of grievers develop an abnormal grieving style, termed complicated or prolonged grief. In the effort to establish complicated grief as a disorder in DSM and ICD, several attempts have been made over the past two decades to establish symptom criteria for this form of grieving. Complicated grief is different from depression and PTSD yet often comorbid with other psychological disorders. Meta-analyses of grief interventions show small to medium effect sizes, with only few studies yielding large effect sizes. In this article, an integrative cognitive behavioral treatment manual for complicated grief disorder (CG-CBT) of 25 individual sessions is described. Three treatment phases, each entailing several treatment strategies, allow patients to stabilize, explore, and confront the most painful aspects of the loss, and finally to integrate and transform their grief. Core aspects are cognitive restructuring and confrontation. Special attention is given to practical exercises. This article includes the case report of a woman whose daughter committed suicide. PMID:22893810

  20. Complicating Methodological Transparency

    ERIC Educational Resources Information Center

    Bridges-Rhoads, Sarah; Van Cleave, Jessica; Hughes, Hilary E.

    2016-01-01

    A historical indicator of the quality, validity, and rigor of qualitative research has been the documentation and disclosure of the behind-the-scenes work of the researcher. In this paper, we use what we call "methodological data" as a tool to complicate the possibility and desirability of such transparency. Specifically, we draw on our…

  1. Neurological Complications of Transplantation

    PubMed Central

    Pruitt, Amy A.; Graus, Francesc; Rosenfeld, Myrna R.

    2013-01-01

    Hematopoietic cell transplantation (HCT) is the preferred treatment for an expanding range of neoplastic and nonmalignant conditions. Increasing numbers of solid organ transplantations (SOTs) add an additional population of immunosuppressed patients with multiple potential neurological problems. While the spectrum of neurological complications varies with conditioning procedure and hematopoietic cell or solid organ source, major neurological complications occur with all transplantation procedures. This 2 part review emphasizes a practical consultative approach to central and peripheral nervous system problems related to HCT or SOT with clinical and neuroimaging examples from the authors’ institutional experience with the following conditions: the diversity of manifestations of common infections such as varicella zoster virus, Aspergillus, and progressive multifocal leukoencephalopathy (PML), drug therapy-related complications, stroke mechanisms, the spectrum of graft versus host disease (GVHD), and neurologically important syndromes of immune reconstitution inflammatory syndrome (IRIS), posterior reversible encephalopathy syndrome (PRES), and posttransplantation lymphoproliferative disorder (PTLD). These complications preferentially occur at specific intervals after HCT and SOT, and neurological consultants must recognize an extensive spectrum of syndromes in order to effect timely diagnosis and expedite appropriate treatment. PMID:23983885

  2. Complications and Treatments

    MedlinePlus

    ... successfully cure SCD. Complications from hydroxyurea therapy and stem cell transplants are rare but can be serious or life-threatening. People with SCD and their families should ask their doctors about the benefits and risks of each. Read more about treatment ...

  3. [A case of broncho-pulmonary aspergillosis complicated by bronchial asthma attack].

    PubMed

    Katayama, Nobuyuki; Fujimura, Masaki; Kasahara, Kazuo; Yasui, Masahide; Kita, Toshiyuki; Abo, Miki; Yoshimi, Yuzou; Nishitsuji, Masaru; Nomura, Satoshi; Nakao, Shinji

    2003-04-01

    A 55-year-old man was hospitalized for the treatment of severe asthma. However, his condition improved with steroid chemotherapy under artificial ventilation, but high fever and multiple patchy shadows of the lung that were not responsive to antibiotics appeared. We detected aspergillus hyphae, probably inhaled with a quantity of dust in the attic of his workplace, in the sputum. We diagnosed invasive broncho-pulmonary aspergillosis complicated with allergic broncho-pulmonary aspergillosis. His condition improved with anti-fungal drug treatment. We consider that the causes of invasive broncho-pulmonary aspergillosis in this case were massive inhalation of aspergillus conidia, artifical ventilation and steroid chemotherapy.

  4. Neurological complications in adult spinal deformity surgery.

    PubMed

    Iorio, Justin A; Reid, Patrick; Kim, Han Jo

    2016-09-01

    The number of surgeries performed for adult spinal deformity (ASD) has been increasing due to an aging population, longer life expectancy, and studies supporting an improvement in health-related quality of life scores after operative intervention. However, medical and surgical complication rates remain high, and neurological complications such as spinal cord injury and motor deficits can be especially debilitating to patients. Several independent factors potentially influence the likelihood of neurological complications including surgical approach (anterior, lateral, or posterior), use of osteotomies, thoracic hyperkyphosis, spinal region, patient characteristics, and revision surgery status. The majority of ASD surgeries are performed by a posterior approach to the thoracic and/or lumbar spine, but anterior and lateral approaches are commonly performed and are associated with unique neural complications such as femoral nerve palsy and lumbar plexus injuries. Spinal morphology, such as that of hyperkyphosis, has been reported to be a risk factor for complications in addition to three-column osteotomies, which are often utilized to correct large deformities. Additionally, revision surgeries are common in ASD and these patients are at an increased risk of procedure-related complications and nervous system injury. Patient selection, surgical technique, and use of intraoperative neuromonitoring may reduce the incidence of complications and optimize outcomes. PMID:27250041

  5. Improved Steroids Detection and Evidence for Their Regiospecific Decompositions Using Anion Attachment Mass Spectrometry.

    PubMed

    Dumont, Quentin; Bárcenas, Mariana; Dossmann, Héloïse; Bailloux, Isabelle; Buisson, Corinne; Mechin, Nathalie; Molina, Adeline; Lasne, Françoise; Rannulu, Nalaka S; Cole, Richard B

    2016-04-01

    Nonpolar anabolic steroids are doping agents that typically do not provide strong signals by electrospray ionization-mass spectrometry (ESI-MS) owing especially to the low polarity of the functional groups present. We have investigated the addition of anions, in ammonium salt form, to anabolic steroid samples as ionization enhancers and have confirmed that lower instrumental limits of detection (as low as 10 ng/mL for fluoxymesterone-M) are obtained by fluoride anion attachment mass spectrometry, as compared to ESI(+)/(-) or atmospheric pressure photoionization (APPI)(+). Moreover, collision-induced decomposition (CID) spectra of precursor fluoride adducts of the bifunctional steroid "reduced pregnenolone" (containing two hydroxyl groups) and its d4-analogue provide evidence of regiospecific decompositions after attachment of fluoride anion to a specific hydroxyl group of the steroid. This type of charting of specific CID reaction pathways can offer value to selected reaction monitoring experiments (SRM) as it may result in a gain in selectivity in detection as well as in improvements in quantification. PMID:26926765

  6. Steroid atrophy scarring treated with fat grafting in a patient with complex regional pain syndrome: A case report.

    PubMed

    Strickland, Leah R; Collawn, Sherry S

    2016-06-01

    Subcutaneous atrophy is a known complication of steroid injections. Excellent results with fat grafting for the treatment of steroid atrophy have been documented. However, the benefit of treating steroid-induced subcutaneous atrophy in an extremity diagnosed with complex regional pain syndrome (CRPS) has not been described. CRPS, known formerly as reflex sympathetic dystrophy or RSD, causalgia, or reflex neurovascular dystrophy, is a severe, progressive musculoskeletal pain syndrome characterized by pain which is disproportionate to the severity of the inciting event, edema, or skin changes. Common treatment modalities include pharmacotherapy, physical therapy, and nerve blocks-each therapy producing varying results. We present a literature review of CRPS and the case of a 15-year-old female who developed CRPS of the left lower leg after arthroscopic debridement with retrograde drilling of an osteochondral lesion. Steroid atrophy of the involved area following a saphenous nerve block complicated the patient's treatment course. The area of atrophy was treated with autologous fat grafting. Following the adipose injection procedure, the patient experienced almost complete resolution of her CPRS-associated pain symptoms, along with improved cosmetic appearance of the area. PMID:26735938

  7. Androgenic anabolic steroids also impair right ventricular function.

    PubMed

    Kasikcioglu, Erdem; Oflaz, Huseyin; Umman, Berrin; Bugra, Zehra

    2009-05-01

    Chronic anabolic steroid use suppresses left ventricular functions. However, there is no information regarding the chronic effects of anabolic steroids on right ventricular function which also plays a key role in global cardiac function. The main objective of the present study was to investigate the effects of androgenic anabolic steroids usage among athletes on remodeling the right part of the heart. Androgenic-anabolic steroids-using bodybuilders had smaller diastolic velocities of both ventricles than drug-free bodybuilders and sedentary counterparts. This study shows that androgenic anabolic steroids-using bodybuilders exhibited depressed diastolic functions of both ventricles.

  8. Drug interaction study of natural steroids from herbs specifically toward human UDP-glucuronosyltransferase (UGT) 1A4 and their quantitative structure activity relationship (QSAR) analysis for prediction.

    PubMed

    Xu, Min; Dong, Peipei; Tian, Xiangge; Wang, Chao; Huo, Xiaokui; Zhang, Baojing; Wu, Lijun; Deng, Sa; Ma, Xiaochi

    2016-08-01

    The wide application of herbal medicines and foods containing steroids has resulted in the high risk of herb-drug interactions (HDIs). The present study aims to evaluate the inhibition potential of 43 natural steroids from herb medicines toward human UDP- glucuronosyltransferases (UGTs). A remarkable structure-dependent inhibition toward UGT1A4 was observed in vitro. Some natural steroids such as gitogenin, tigogenin, and solasodine were found to be the novel selective inhibitors of UGT1A4, and did not inhibit the activities of major human CYP isoforms. To clarify the possibility of the in vivo interaction of common steroids and clinical drugs, the kinetic inhibition type and related kinetic parameters (Ki) were measured. The target compounds 2-6 and 15, competitively inhibited the UGT1A4-catalyzed trifluoperazine glucuronidation reaction, with Ki values of 0.6, 0.18, 1.1, 0.7, 0.8, and 12.3μM, respectively. And this inhibition of steroids towards UGT1A4 was also verified in human primary hepatocytes. Furthermore, a quantitative structure-activity relationship (QSAR) of steroids with inhibitory effects toward human UGT1A4 isoform was established using the computational methods. Our findings elucidate the potential for in vivo HDI effects of steroids in herbal medicine and foods, with the clinical dr ugs eliminated by UGT1A4, and reveal the vital pharamcophoric requirement of natural steroids for UGT1A4 inhibition activity. PMID:27208893

  9. Drug interaction study of natural steroids from herbs specifically toward human UDP-glucuronosyltransferase (UGT) 1A4 and their quantitative structure activity relationship (QSAR) analysis for prediction.

    PubMed

    Xu, Min; Dong, Peipei; Tian, Xiangge; Wang, Chao; Huo, Xiaokui; Zhang, Baojing; Wu, Lijun; Deng, Sa; Ma, Xiaochi

    2016-08-01

    The wide application of herbal medicines and foods containing steroids has resulted in the high risk of herb-drug interactions (HDIs). The present study aims to evaluate the inhibition potential of 43 natural steroids from herb medicines toward human UDP- glucuronosyltransferases (UGTs). A remarkable structure-dependent inhibition toward UGT1A4 was observed in vitro. Some natural steroids such as gitogenin, tigogenin, and solasodine were found to be the novel selective inhibitors of UGT1A4, and did not inhibit the activities of major human CYP isoforms. To clarify the possibility of the in vivo interaction of common steroids and clinical drugs, the kinetic inhibition type and related kinetic parameters (Ki) were measured. The target compounds 2-6 and 15, competitively inhibited the UGT1A4-catalyzed trifluoperazine glucuronidation reaction, with Ki values of 0.6, 0.18, 1.1, 0.7, 0.8, and 12.3μM, respectively. And this inhibition of steroids towards UGT1A4 was also verified in human primary hepatocytes. Furthermore, a quantitative structure-activity relationship (QSAR) of steroids with inhibitory effects toward human UGT1A4 isoform was established using the computational methods. Our findings elucidate the potential for in vivo HDI effects of steroids in herbal medicine and foods, with the clinical dr ugs eliminated by UGT1A4, and reveal the vital pharamcophoric requirement of natural steroids for UGT1A4 inhibition activity.

  10. Fourth-Generation Progestins Inhibit 3β-Hydroxysteroid Dehydrogenase Type 2 and Modulate the Biosynthesis of Endogenous Steroids

    PubMed Central

    Louw-du Toit, Renate; Perkins, Meghan S.; Snoep, Jacky L.; Storbeck, Karl-Heinz; Africander, Donita

    2016-01-01

    Progestins used in contraception and hormone replacement therapy are synthetic compounds designed to mimic the actions of the natural hormone progesterone and are classed into four consecutive generations. The biological actions of progestins are primarily determined by their interactions with steroid receptors, and factors such as metabolism, pharmacokinetics, bioavailability and the regulation of endogenous steroid hormone biosynthesis are often overlooked. Although some studies have investigated the effects of select progestins on a few steroidogenic enzymes, studies comparing the effects of progestins from different generations are lacking. This study therefore explored the putative modulatory effects of progestins on de novo steroid synthesis in the adrenal by comparing the effects of select progestins from the respective generations, on endogenous steroid hormone production by the H295R human adrenocortical carcinoma cell line. Ultra-performance liquid chromatography/tandem mass spectrometry analysis showed that the fourth-generation progestins, nestorone (NES), nomegestrol acetate (NoMAC) and drospirenone (DRSP), unlike the progestins selected from the first three generations, modulate the biosynthesis of several endogenous steroids. Subsequent assays performed in COS-1 cells expressing human 3βHSD2, suggest that these progestins modulate the biosynthesis of steroid hormones by inhibiting the activity of 3βHSD2. The Ki values determined for the inhibition of human 3βHSD2 by NES (9.5 ± 0.96 nM), NoMAC (29 ± 7.1 nM) and DRSP (232 ± 38 nM) were within the reported concentration ranges for the contraceptive use of these progestins in vivo. Taken together, our results suggest that newer, fourth-generation progestins may exert both positive and negative physiological effects via the modulation of endogenous steroid hormone biosynthesis. PMID:27706226

  11. Complications of percutaneous vertebroplasty

    PubMed Central

    Saracen, Agnieszka; Kotwica, Zbigniew

    2016-01-01

    Abstract Percutaneous vertebroplasty (PVP) is a minimally invasive procedure widely used for the treatment of pain due to vertebral fractures of different origins—osteoporotic, traumatic, or neoplastic. PVP is minimally invasive, but the complications are not rare; however, they are in most cases not significant clinically. The most frequent is cement leakage, which can occur onto veins, paravertebral soft tissue, into the intervertebral disk, or to the spinal canal, affecting foraminal area or epidural space. We analyzed results of treatment and complications of vertebroplasty performed with the use of polimethylomethylacrylate cement (PMMA) on 1100 vertebrae, with a special regard to the severity of complication and eventual clinical manifestation. One thousand one hundred PVP were analyzed, performed in 616 patients. There were 468 (76%) women and 148 men (24%), 24 to 94-year old, mean age 68 years. From 1100 procedures, 794 treated osteporotic and 137 fractures due to malignant disease, 69 PVP were made in traumatic fractures. One hundred patients had painful vertebral hemangiomas. Seven hundred twenty-six (66%) lesions were in thoracic, and 374 (34%) in lumbar area. Results of treatment were assessed using 10 cm Visual Analogue Scale (VAS) 12 hours after surgery, 7 days, 30 days, and then each 6 months, up to 3 years. Before surgery all patients had significant pain 7 to 10 in VAS scale, mean 8.9 cm. Twelve  hours after surgery 602 (97.7%) reported significant relief of pain, with mean VAS of 2,3 cm. Local complications occurred in 50% of osteoporotic, 34% of neoplastic, 16% of traumatic fractures, and 2% of vertebral hemangiomas. The most common was PMMA leakage into surrounding tissues—20%; paravertebral vein embolism—13%; intradiscal leakage—8%; and PMMA leakage into the spinal canal—0.8%. Results of treatment did not differ between patients with and without any complications. From 104 patients who had chest X-ray or CT study performed

  12. Gym and tonic: a profile of 100 male steroid users.

    PubMed Central

    Evans, N A

    1997-01-01

    OBJECTIVE: To identify unsupervised anabolic steroid regimens used by athletes. METHODS: 100 athletes attending four gymnasia were surveyed using an anonymous self administered questionnaire. RESULTS: Anabolic steroid doses ranged from 250 to 3200 mg per week and users combined different drugs to achieve these doses. Injectable and oral preparations were used in cycles lasting four to 12 weeks. Eighty six per cent of users admitted to the regular use of drugs other than steroids for various reasons, including additional anabolic effects, the minimisation of steroid related side effects, and withdrawal symptoms. Acne, striae, and gynaecomastia were the most commonly reported subjective side effects. CONCLUSIONS: Multiple steroids are combined in megadoses and self administered in a cyclical fashion. Polypharmacy is practised by over 80% of steroid users. Skeletal muscle hypertrophy along with acne, striae, and gynaecomastia are frequent physical signs associated with steroid use. Images Figure 2 PMID:9132214

  13. Therapeutic Potential of Steroidal Alkaloids in Cancer and Other Diseases.

    PubMed

    Jiang, Qi-Wei; Chen, Mei-Wan; Cheng, Ke-Jun; Yu, Pei-Zhong; Wei, Xing; Shi, Zhi

    2016-01-01

    Steroidal alkaloids are a class of secondary metabolites isolated from plants, amphibians, and marine invertebrates. Evidence accumulated in the recent two decades demonstrates that steroidal alkaloids have a wide range of bioactivities including anticancer, antimicrobial, anti-inflammatory, antinociceptive, etc., suggesting their great potential for application. It is therefore necessary to comprehensively summarize the bioactivities, especially anticancer activities and mechanisms of steroidal alkaloids. Here we systematically highlight the anticancer profiles both in vitro and in vivo of steroidal alkaloids such as dendrogenin, solanidine, solasodine, tomatidine, cyclopamine, and their derivatives. Furthermore, other bioactivities of steroidal alkaloids are also discussed. The integrated molecular mechanisms in this review can increase our understanding on the utilization of steroidal alkaloids and contribute to the development of new drug candidates. Although the therapeutic potentials of steroidal alkaloids look promising in the preclinical and clinical studies, further pharmacokinetic and clinical studies are mandated to define their efficacy and safety in cancer and other diseases.

  14. Steroid sulfatase. Biosynthesis and processing in normal and mutant fibroblasts.

    PubMed

    Conary, J; Nauerth, A; Burns, G; Hasilik, A; von Figura, K

    1986-07-01

    Antibodies raised against steroid sulfatase purified from human placenta were used to follow the biosynthesis of this enzyme in human skin fibroblasts. Steroid sulfatase is synthesized as a membrane-bound Mr-63 500 polypeptide with asparagine-linked oligosaccharide chains. Within 2 days, newly synthesized steroid sulfatase is processed to a mature Mr-61 000 form. The decrease in size is due to processing of the oligosaccharide chains, which are cleavable by endoglucosaminidase H in both the early and the mature form of steroid sulfatase. The processing involves mannosidase(s) sensitive to 1-deoxy-manno-nojirimycin. The half-life of the steroid sulfatase polypeptides is 4 days. Synthesis of steroid-sulfatase-related polypeptides and steroid sulfatase activity were not detectable in fibroblasts from four patients with X-linked ichthyosis. PMID:2942400

  15. Chemical derivatization for enhancing sensitivity during LC/ESI-MS/MS quantification of steroids in biological samples: a review.

    PubMed

    Higashi, Tatsuya; Ogawa, Shoujiro

    2016-09-01

    Sensitive and specific methods for the detection, characterization and quantification of endogenous steroids in body fluids or tissues are necessary for the diagnosis, pathological analysis and treatment of many diseases. Recently, liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS) has been widely used for these purposes due to its specificity and versatility. However, the ESI efficiency and fragmentation behavior of some steroids are poor, which lead to a low sensitivity. Chemical derivatization is one of the most effective methods to improve the detection characteristics of steroids in ESI-MS/MS. Based on this background, this article reviews the recent advances in chemical derivatization for the trace quantification of steroids in biological samples by LC/ESI-MS/MS. The derivatization in ESI-MS/MS is based on tagging a proton-affinitive or permanently charged moiety on the target steroid. Introduction/formation of a fragmentable moiety suitable for the selected reaction monitoring by the derivatization also enhances the sensitivity. The stable isotope-coded derivatization procedures for the steroid analysis are also described.

  16. Efficacy and safety of steroid injections for shoulder and elbow tendonitis: a meta-analysis of randomised controlled trials

    PubMed Central

    Gaujoux-Viala, C; Dougados, M; Gossec, L

    2009-01-01

    Objectives: To assess the efficacy and safety of steroid injections for patients with tendonitis of the shoulder or elbow. Methods: A systematic review of the literature using PubMed, EMBASE, the Cochrane library and manual searches was performed until April 2008. All randomised controlled trials (RCTs) reporting the efficacy on pain or functional disability, and/or the safety of steroid injections, versus placebo, non-steroidal anti-inflammatory drugs (NSAIDs) or physiotherapy in patients with tendonitis were selected. Pooled effect size (ES) was calculated by meta-analysis using the Mantel–Haenszel method. Results: In all, 20 RCTs were analysed (744 patients treated by injections and 987 patients treated by controls; 618 shoulders and 1113 elbows). The pooled analysis indicated only short-term effectiveness of steroids versus the pooled controls for pain and function (eg, pain at week 1–3 ES = 1.18 (95% CI 0.27 to 2.09), pain at week 4–8 ES = 1.30 (95% CI 0.55 to 2.04), pain at week 12–24 ES = −0.38 (95% CI −0.85 to 0.08) and pain at week 48 ES = 0.07 (95% CI −0.60 to 0.75)). Sensitivity analyses indicated similar results whatever the localisation, type of steroid and type of comparator except for NSAIDs: steroid injections were not significantly better than NSAIDs in the short-term. Steroid injections appeared more effective than pooled other treatments in acute or subacute tendonitis. The main side effects were transient pain after injection (10.7% of corticosteroid injections) and skin modification (4.0%). Conclusions: Steroid injections are well tolerated and more effective for tendonitis in the short-term than pooled other treatments, though similar to NSAIDs. No long-term benefit was shown. PMID:19054817

  17. Bereavement and Complicated Grief

    PubMed Central

    Ghesquiere, Angela; Glickman, Kim

    2013-01-01

    Bereavement is a common experience in adults age 60 and older. Loss of a loved one usually leads to acute grief characterized by yearning and longing, decreased interest in ongoing activities, and frequent thoughts of the deceased. For most, acute grief naturally evolves into a state of integrated grief, where the bereaved is able to reengage with everyday activities and find interest or pleasure. About 7% of bereaved older adults, however, will develop the mental health condition of Complicated Grief (CG). In CG, the movement from acute to integrated grief is derailed, and grief symptoms remain severe and impairing. This article reviews recent publications on the diagnosis of CG, risk factors for the condition, and evidenced-based treatments for CG. Greater attention to complicated grief detection and treatment in older adults is needed. PMID:24068457

  18. Synergistic Effects of Calcineurin Inhibitors and Steroids on Steroid Sensitivity of Peripheral Blood Mononuclear Cells.

    PubMed

    Takeuchi, Hironori; Iwamoto, Hitoshi; Nakamura, Yuki; Hirano, Toshihiko; Konno, Osamu; Kihara, Yu; Chiba, Naokazu; Yokoyama, Takayoshi; Takano, Kiminori; Toraishi, Tatsunori; Okuyama, Kiyoshi; Ikeda, Chie; Tanaka, Sachiko; Onda, Kenji; Soga, Akiko; Kikuchi, Yukiko; Kawaguchi, Takashi; Kawachi, Shigeyuki; Unezaki, Sakae; Shimazu, Motohide

    2015-02-01

    The steroid receptor (SR) complex contains FKBP51 and FKBP52, which bind to tacrolimus (TAC) and cyclophilin 40, which, in turn, bind to cyclosporine (CYA); these influence the intranuclear mobility of steroid-SR complexes. Pharmacodynamic interactions are thought to exist between steroids and calcineurin inhibitors (CNIs) on the SR complex. We examined the effect of CNIs on steroid sensitivity. Methylprednisolone (MPSL) sensitivity was estimated as the concentration inhibiting mitosis in 50% (IC50) of peripheral blood mononuclear cells and as the area under the MPSL concentration-proliferation suppressive rate curves (CPS-AUC) in 30 healthy subjects. MPSL sensitivity was compared between the additive group (AG) as the MPSL sensitivity that was a result of addition of the proliferation suppressive rate of CNIs to that of MPSL and the mixed culture group (MCG) as MPSL sensitivity of mixed culture with both MPSL and CNIs in identical patients. IC50 values of MPSL and cortisol sensitivity were examined before and 2 months after CNI administration in 23 renal transplant recipients. IC50 and CPS-AUC values of MPSL were lower in the MCG than in the AG with administration of TAC and CYA. The CPS-AUC ratio of MCG and AG was lower in the TAC group. IC50 values of MPSL and cortisol tended to be lower after administration of TAC and CYA, and a significant difference was observed in the IC50 of cortisol after TAC administration. Steroid sensitivity increased with both TAC and CYA. Furthermore, TAC had a greater effect on increasing sensitivity. Thus, concomitant administration of CNIs and steroids can increase steroid sensitivity. PMID:26858893

  19. Synergistic Effects of Calcineurin Inhibitors and Steroids on Steroid Sensitivity of Peripheral Blood Mononuclear Cells.

    PubMed

    Takeuchi, Hironori; Iwamoto, Hitoshi; Nakamura, Yuki; Hirano, Toshihiko; Konno, Osamu; Kihara, Yu; Chiba, Naokazu; Yokoyama, Takayoshi; Takano, Kiminori; Toraishi, Tatsunori; Okuyama, Kiyoshi; Ikeda, Chie; Tanaka, Sachiko; Onda, Kenji; Soga, Akiko; Kikuchi, Yukiko; Kawaguchi, Takashi; Kawachi, Shigeyuki; Unezaki, Sakae; Shimazu, Motohide

    2015-02-01

    The steroid receptor (SR) complex contains FKBP51 and FKBP52, which bind to tacrolimus (TAC) and cyclophilin 40, which, in turn, bind to cyclosporine (CYA); these influence the intranuclear mobility of steroid-SR complexes. Pharmacodynamic interactions are thought to exist between steroids and calcineurin inhibitors (CNIs) on the SR complex. We examined the effect of CNIs on steroid sensitivity. Methylprednisolone (MPSL) sensitivity was estimated as the concentration inhibiting mitosis in 50% (IC50) of peripheral blood mononuclear cells and as the area under the MPSL concentration-proliferation suppressive rate curves (CPS-AUC) in 30 healthy subjects. MPSL sensitivity was compared between the additive group (AG) as the MPSL sensitivity that was a result of addition of the proliferation suppressive rate of CNIs to that of MPSL and the mixed culture group (MCG) as MPSL sensitivity of mixed culture with both MPSL and CNIs in identical patients. IC50 values of MPSL and cortisol sensitivity were examined before and 2 months after CNI administration in 23 renal transplant recipients. IC50 and CPS-AUC values of MPSL were lower in the MCG than in the AG with administration of TAC and CYA. The CPS-AUC ratio of MCG and AG was lower in the TAC group. IC50 values of MPSL and cortisol tended to be lower after administration of TAC and CYA, and a significant difference was observed in the IC50 of cortisol after TAC administration. Steroid sensitivity increased with both TAC and CYA. Furthermore, TAC had a greater effect on increasing sensitivity. Thus, concomitant administration of CNIs and steroids can increase steroid sensitivity.

  20. Thrombophilia and Pregnancy Complications

    PubMed Central

    Simcox, Louise E.; Ormesher, Laura; Tower, Clare; Greer, Ian A.

    2015-01-01

    There is a paucity of strong evidence associated with adverse pregnancy outcomes and thrombophilia in pregnancy. These problems include both early (recurrent miscarriage) and late placental vascular-mediated problems (fetal loss, pre-eclampsia, placental abruption and intra-uterine growth restriction). Due to poor quality case-control and cohort study designs, there is often an increase in the relative risk of these complications associated with thrombophilia, particularly recurrent early pregnancy loss, late fetal loss and pre-eclampsia, but the absolute risk remains very small. It appears that low-molecular weight heparin has other benefits on the placental vascular system besides its anticoagulant properties. Its use is in the context of antiphospholipid syndrome and recurrent pregnancy loss and also in women with implantation failure to improve live birth rates. There is currently no role for low-molecular weight heparin to prevent late placental-mediated complications in patients with inherited thrombophilia and this may be due to small patient numbers in the studies involved in summarising the evidence. There is potential for low-molecular weight heparin to improve pregnancy outcomes in women with prior severe vascular complications of pregnancy such as early-onset intra-uterine growth restriction and pre-eclampsia but further high quality randomised controlled trials are required to answer this question. PMID:26633369

  1. Pleuropulmonary complications of pancreatitis

    PubMed Central

    Kaye, Michael D.

    1968-01-01

    Pancreatitis, in common with many other upper abdominal diseases, often leads to pleuropulmonary complications. Radiological evidence of pleuropulmonary abnormality was found in 55% of 58 cases examined retrospectively. The majority of such abnormalities are not specific for pancreatitis; but a particular category of pleural effusions, rich in pancreatic enzymes, is a notable exception. A patient with this type of effusion, complicated by a spontaneous bronchopleural fistula and then by an empyema, is reported. The literature relating to pancreatic enzyme-rich pleural effusions (pathognomonic of pancreatitis) is reviewed. Of several possible mechanisms involved in pathogenesis, transdiaphragmatic lymphatic transfer of pancreatic enzymes, intrapleural rupture of mediastinal extensions of pseudocysts, and diaphragmatic perforation are the most important. The measurement of pleural fluid amylase, at present little employed in this country, has considerable diagnostic value. Enzyme-rich effusions are more commonly left-sided, are often blood-stained, are frequently associated with pancreatic pseudocysts, and—if long standing—may be complicated by a bronchopleural fistula. Images PMID:4872925

  2. Thrombophilia and Pregnancy Complications.

    PubMed

    Simcox, Louise E; Ormesher, Laura; Tower, Clare; Greer, Ian A

    2015-01-01

    There is a paucity of strong evidence associated with adverse pregnancy outcomes and thrombophilia in pregnancy. These problems include both early (recurrent miscarriage) and late placental vascular-mediated problems (fetal loss, pre-eclampsia, placental abruption and intra-uterine growth restriction). Due to poor quality case-control and cohort study designs, there is often an increase in the relative risk of these complications associated with thrombophilia, particularly recurrent early pregnancy loss, late fetal loss and pre-eclampsia, but the absolute risk remains very small. It appears that low-molecular weight heparin has other benefits on the placental vascular system besides its anticoagulant properties. Its use is in the context of antiphospholipid syndrome and recurrent pregnancy loss and also in women with implantation failure to improve live birth rates. There is currently no role for low-molecular weight heparin to prevent late placental-mediated complications in patients with inherited thrombophilia and this may be due to small patient numbers in the studies involved in summarising the evidence. There is potential for low-molecular weight heparin to improve pregnancy outcomes in women with prior severe vascular complications of pregnancy such as early-onset intra-uterine growth restriction and pre-eclampsia but further high quality randomised controlled trials are required to answer this question.

  3. [Respiratory complications after transfusion].

    PubMed

    Bernasinski, M; Mertes, P-M; Carlier, M; Dupont, H; Girard, M; Gette, S; Just, B; Malinovsky, J-M

    2014-05-01

    Respiratory complications of blood transfusion have several possible causes. Transfusion-Associated Circulatory Overload (TACO) is often the first mentioned. Transfusion-Related Acute Lung Injury (TRALI), better defined since the consensus conference of Toronto in 2004, is rarely mentioned. French incidence is low. Non-hemolytic febrile reactions, allergies, infections and pulmonary embolism are also reported. The objective of this work was to determine the statistical importance of the different respiratory complications of blood transfusion. This work was conducted retrospectively on transfusion accidents in six health centers in Champagne-Ardenne, reported to Hemovigilance between 2000 and 2009 and having respiratory symptoms. The analysis of data was conducted by an expert committee. Eighty-three cases of respiratory complications are found (316,864 blood products). We have counted 26 TACO, 12 TRALI (only 6 cases were identified in the original investigation of Hemovigilance), 18 non-hemolytic febrile reactions, 16 cases of allergies, 5 transfusions transmitted bacterial infections and 2 pulmonary embolisms. Six new TRALI were diagnosed previously labeled TACO for 2 of them, allergy and infection in 2 other cases and diagnosis considered unknown for the last 2. Our study found an incidence of TRALI 2 times higher than that reported previously. Interpretation of the data by a multidisciplinary committee amended 20% of diagnoses. This study shows the imperfections of our system for reporting accidents of blood transfusion when a single observer analyses the medical records.

  4. Complications of vasectomy.

    PubMed Central

    Awsare, Ninaad S.; Krishnan, Jai; Boustead, Greg B.; Hanbury, Damian C.; McNicholas, Thomas A.

    2005-01-01

    INTRODUCTION: Vasectomy is a common method of sterilisation. However, it is less popular than tubal ligation world-wide. It is also a frequent cause of litigation relating to its complications. This article reviews the early and late risks associated with the procedure. PATIENTS AND METHODS: Data collection was done using the internet to search Medline for obtaining evidence-based medicine reviews. Cross-references were obtained from key articles. Websites of government bodies and medical associations were searched for guidelines relating to vasectomy. DISCUSSION: Early complications include haematoma, wound and genito-urinary infections, and traumatic fistulae. Vasectomy failure occurs in 0-2% of patients. Late recanalisation causes failure in 0.2% of vasectomies. Significant chronic orchalgia may occur in up to 15% of men after vasectomy, and may require epididyectomy or vasectomy reversal. Antisperm antibodies develop in a significant proportion of men post-vasectomy, but do not increase the risk of immune-complex or atherosclerotic heart disease. Similarly, vasectomy does not enhance risk of testicular or prostate cancer. Vasectomy has a lower mortality as compared to tubal occlusion, but is still significantly high in non-industrialised countries because of infections. CONCLUSIONS: Vasectomy, though safe and relatively simple, requires a high level of expertise to minimise complications. Adequate pre-operative counselling is essential to increase patient acceptability of this method of permanent contraception. PMID:16263006

  5. Unusual complication after genioplasty.

    PubMed

    Avelar, Rafael Linard; Sá, Carlos Diego Lopes; Esses, Diego Felipe Silveira; Becker, Otávio Emmel; Soares, Eduardo Costa Studart; de Oliveira, Rogerio Belle

    2014-01-01

    Facial beauty depends on shape, proportion, and harmony between the facial thirds. The chin is one of the most important components of the inferior third and has an important role on the definition of facial aesthetic and harmony in both frontal and lateral views. There are 2 principal therapeutic approaches that one can choose to treat mental deformities, alloplastic implants, and mental basilar ostectomy, also known as genioplasty. The latest is more commonly used because of great versatility in the correction of three-dimensional deformities of the chin and smaller taxes of postoperative complications. Possible transoperative and postoperative complications of genioplasty include mental nerve lesion, bleeding, damage to tooth roots, bone resorption of the mobilized segment, mandibular fracture, ptosis of the lower lip, and failure to stabilize the ostectomized segment. The study presents 2 cases of displacement of the osteotomized segment after genioplasty associated with facial trauma during postoperative orthognathic surgery followed by rare complications with no reports in the literature. PMID:24621765

  6. Evidence for the contribution of non-covalent steroid interactions between DNA and topoisomerase in the genotoxicity of steroids.

    PubMed

    Snyder, Ronald D; Holt, Patrick A; Maguire, Jon M; Trent, John O

    2015-04-01

    Fifty two steroids and 9 Vitamin D analogs were docked into ten crystallographically-defined DNA dinucleotide sites and two human topoisomerase II ATP binding sites using two computational programs, Autodock and Surflex. It is shown that both steroids and Vitamin D analogs exhibit a propensity for non-covalent intercalative binding to DNA. A higher predicted binding affinity was found, however, for steroids and the ATP binding site of topoisomerase; in fact these drugs exhibited among the highest topo II binding observed in over 1370 docked drugs. These findings along with genotoxicity data from 26 additional steroids not subjected to docking analysis, support a mechanism wherein the long known, but poorly understood, clastogenicity of steroids may be attributable to inhibition of topoisomerase. A "proof of principle" experiment with dexamethasone demonstrated this to be the likely mechanism of clastogenicity of, at least, this steroid. The generality of this proposed mechanism of genotoxicity across the steroids and vitamin-D analogs is discussed.

  7. Polyhydroxylated steroids from the bamboo coral Isis hippuris.

    PubMed

    Chen, Wei-Hua; Wang, Shang-Kwei; Duh, Chang-Yih

    2011-01-01

    In previous studies on the secondary metabolites of the Taiwanese octocoral Isis hippuris, specimens have always been collected at Green Island. In the course of our studies on bioactive compounds from marine organisms, the acetone-solubles of the Taiwanese octocoral I. hippuris collected at Orchid Island have led to the isolation of five new polyoxygenated steroids: hipposterone M-O (1-3), hipposterol G (4) and hippuristeroketal A (5). The structures of these compounds were determined on the basis of their spectroscopic and physical data. The anti-HCMV (human cytomegalovirus) activity of 1-5 and their cytotoxicity against selected cell lines were evaluated. Compound 2 exhibited inhibitory activity against HCMV, with an EC(50) value of 6.0 μg/mL.

  8. Steroid and triterpenoid oligoglycosides of marine origin.

    PubMed

    Minale, L; Iorizzi, M; Palagiano, E; Riccio, R

    1996-01-01

    Saponins have been considered for a long time typical metabolites of plant origin. It has been only in the last two decades that the world-wide investigation of marine organisms as sources of new bioactive metabolites disclosed the wide distribution of these molecules also among marine animals. Today saponins are recognized as the most common characteristic metabolites in two classes of the phylum Echinodermata (Holothuroidea and Asteroidea). Furthermore, several steroid and triterpenoid oligoglycosides have been isolated from different species of marine sponges, more rarely Anthozoans, and also from fishes of the genus Pardachirus, where they have been shown to act as shark repellents. This communication offers a general view of the distribution of steroid and triterpenoid oligoglycosides among marine organisms and focuses on a number of recent examples to discuss structural characteristics, biological activities, and methods of investigation. PMID:8957306

  9. Acute bile nephropathy secondary to anabolic steroids.

    PubMed

    Alkhunaizi, Ahmed M; ElTigani, Mohamed A; Rabah, Rola S; Nasr, Samih H

    2016-02-01

    Renal dysfunction in cholestatic liver disease is multifactorial. Acute kidney injury may develop secondary to renal vasoconstriction in the setting of peripheral vasodilation and relative hypovolemia, tubular obstruction by bile casts, and direct tubular toxicity from bile. Anabolic steroids are frequently used by athletes to boost endurance and increase muscle mass. These agents are a recently recognized cause of hepatotoxicity and jaundice and may lead to acute kidney injury. To increase awareness about this growing problem and to characterize the pathology of acute kidney injury in this setting, we report on a young male who developed acute kidney injury in the setting of severe cholestatic jaundice related to ingestion of anabolic steroids used for bodybuilding. Kidney biopsy showed bile casts within distal tubular lumina, filamentous bile inclusions within tubular cells, and signs of acute tubular injury. This report supports the recently re-emerged concept of bile nephropathy cholemic nephrosis.

  10. Steroid hormone sulphation in lead workers.

    PubMed Central

    Apostoli, P; Romeo, L; Peroni, E; Ferioli, A; Ferrari, S; Pasini, F; Aprili, F

    1989-01-01

    The metabolism of steroid hormones has been investigated in 10 workers exposed to lead and in 10 non-exposed subjects to determine whether lead interferes with the first or second phase reactions of steroid hormone biotransformation, or both. In the exposed workers blood lead concentrations (PbB) ranged from 45 to 69 micrograms/100 ml; in the controls PbB was less than 25 micrograms/100 ml. No statistical differences were found for the total amount of the urinary hormone metabolites, but a drop of about 50% was observed for the sulphated portion. It is suggested that lead interferes with the mechanisms of sulphoconjugation through an effect on the cytosol enzymes sulphotransferase and sulphokinase. PMID:2930732

  11. Acute bile nephropathy secondary to anabolic steroids.

    PubMed

    Alkhunaizi, Ahmed M; ElTigani, Mohamed A; Rabah, Rola S; Nasr, Samih H

    2016-02-01

    Renal dysfunction in cholestatic liver disease is multifactorial. Acute kidney injury may develop secondary to renal vasoconstriction in the setting of peripheral vasodilation and relative hypovolemia, tubular obstruction by bile casts, and direct tubular toxicity from bile. Anabolic steroids are frequently used by athletes to boost endurance and increase muscle mass. These agents are a recently recognized cause of hepatotoxicity and jaundice and may lead to acute kidney injury. To increase awareness about this growing problem and to characterize the pathology of acute kidney injury in this setting, we report on a young male who developed acute kidney injury in the setting of severe cholestatic jaundice related to ingestion of anabolic steroids used for bodybuilding. Kidney biopsy showed bile casts within distal tubular lumina, filamentous bile inclusions within tubular cells, and signs of acute tubular injury. This report supports the recently re-emerged concept of bile nephropathy cholemic nephrosis. PMID:26587777

  12. Estetrol: a unique steroid in human pregnancy.

    PubMed

    Holinka, Christian F; Diczfalusy, Egon; Coelingh Bennink, Herjan J T

    2008-05-01

    Estetrol (E(4)) is an estrogenic steroid molecule synthesized exclusively by the fetal liver during human pregnancy and reaching the maternal circulation through the placenta. Its function is presently unknown. After its discovery in the mid-1960s, E(4) research revealed rather unique properties of this steroid and spawned a large body of state-of-the art publications. Nevertheless, 20 years later experimental work was virtually abandoned. In recent years based on new data, E(4) has experienced a vita nova, a revival of preclinical and clinical research activities with the goal to elucidate its physiological function and explore its potential for therapeutic use in humans. This review is intended to offer an historical account of the discovery of E(4) and the preclinical studies conducted during the heyday of E(4) research that ended in the mid-1980s. PMID:18462934

  13. Cytotoxic steroidal saponins from Agave sisalana.

    PubMed

    Chen, Pi-Yu; Chen, Chin-Hui; Kuo, Ching-Chuan; Lee, Tzong-Huei; Kuo, Yueh-Hsiung; Lee, Ching-Kuo

    2011-06-01

    Two new steroidal saponins, 8 and 10, along with 7 known steroidal sapogenins and saponins (1-7) and a furostanol saponin (9) were isolated from Agave sisalana Perrine ex Engelm. The structures of these two new compounds were identified and characterized by 1D and 2D NMR spectroscopy and mass spectrometry. In addition, acid hydrolysis and GC-FID were used to confirm the sugar moieties of 8 and 10. The cytotoxic effects of 1-10 on MCF-7, NCI-H460, and SF-268 cancer cells were evaluated, and among them, compound 10 proved to be the most cytotoxic with IC₅₀ values of 1.2, 3.8, and 1.5 µM, respectively.

  14. Peptic ulcer disease and other complications in patients receiving dexamethasone palliation for brain metastasis

    SciTech Connect

    Penzner, R.D.; Lipsett, J.A.

    1982-11-01

    A retrospective analysis was done of 106 patients who received radiation therapy for brain metastasis. Dexamethasone therapy was instituted in 97 patients. Peptic ulcer disease developed in 5 of 89 patients (5.6 percent) who received a dosage of at least 12 mg a day, but did not occur in patients who received a lower dose or in those who did not receive steroids. The interval between institution of dexamethasone therapy and the development of peptic ulcer disease ranged from three to nine weeks. Two patients had perforated ulcers, one of whom required surgical resection. Peptic ulcer disease contributed to the general deterioration and death of three of the five patients. Overall, in 14 of the 89 patients (15.7 percent) a complication of steroid therapy developed in the form of peptic ulcer disease, steroid myopathy or diabetes mellitus (or a combination of these).

  15. Relationships between structure, ionization profile and sensitivity of exogenous anabolic steroids under electrospray ionization and analysis in human urine using liquid chromatography-tandem mass spectrometry.

    PubMed

    Cha, Eunju; Kim, Sohee; Kim, Hee Won; Lee, Kang Mi; Kim, Ho Jun; Kwon, Oh-Seung; Lee, Jaeick

    2016-04-01

    The relationships between the ionization profile, sensitivity, and structures of 64 exogenous anabolic steroids (groups I-IV) was investigated under electrospray ionization (ESI) conditions. The target analytes were ionized as [M + H](+) or [M + H-nH2 O](+) in the positive mode, and these ions were used as precursor ions for selected reaction monitoring analysis. The collision energy and Q3 ions were optimized based on the sensitivity and selectivity. The limits of detection (LODs) were 0.05-20 ng/mL for the 64 steroids. The LODs for 38 compounds, 14 compounds and 12 compounds were in the range of 0.05-1, 2-5 and 10-20 ng/mL, respectively. Steroids including the conjugated keto-functional group at C3 showed good proton affinity and stability, and generated the [M + H](+) ion as the most abundant precursor ion. In addition, the LODs of steroids using the [M + H](+) ion as the precursor ion were mostly distributed at low concentrations. In contrast, steroids containing conjugated/unconjugated hydroxyl functional groups at C3 generated [M + H - H2 O](+) or [M + H - 2H2 O](+) ions, and these steroids showed relatively high LODs owing to poor stability and multiple ion formation. An LC-MS/MS method based on the present ionization profile was developed and validated for the determination of 78 steroids (groups I-V) in human urine.

  16. Relationships between structure, ionization profile and sensitivity of exogenous anabolic steroids under electrospray ionization and analysis in human urine using liquid chromatography-tandem mass spectrometry.

    PubMed

    Cha, Eunju; Kim, Sohee; Kim, Hee Won; Lee, Kang Mi; Kim, Ho Jun; Kwon, Oh-Seung; Lee, Jaeick

    2016-04-01

    The relationships between the ionization profile, sensitivity, and structures of 64 exogenous anabolic steroids (groups I-IV) was investigated under electrospray ionization (ESI) conditions. The target analytes were ionized as [M + H](+) or [M + H-nH2 O](+) in the positive mode, and these ions were used as precursor ions for selected reaction monitoring analysis. The collision energy and Q3 ions were optimized based on the sensitivity and selectivity. The limits of detection (LODs) were 0.05-20 ng/mL for the 64 steroids. The LODs for 38 compounds, 14 compounds and 12 compounds were in the range of 0.05-1, 2-5 and 10-20 ng/mL, respectively. Steroids including the conjugated keto-functional group at C3 showed good proton affinity and stability, and generated the [M + H](+) ion as the most abundant precursor ion. In addition, the LODs of steroids using the [M + H](+) ion as the precursor ion were mostly distributed at low concentrations. In contrast, steroids containing conjugated/unconjugated hydroxyl functional groups at C3 generated [M + H - H2 O](+) or [M + H - 2H2 O](+) ions, and these steroids showed relatively high LODs owing to poor stability and multiple ion formation. An LC-MS/MS method based on the present ionization profile was developed and validated for the determination of 78 steroids (groups I-V) in human urine. PMID:26268571

  17. Steroidal saponins from Hemerocallis fulva var. kwanso.

    PubMed

    Konishi, T; Fujiwara, Y; Konoshima, T; Kiyosawa, S; Nishi, M; Miyahara, K

    2001-03-01

    Two steroidal saponins, hemeroside A and B, were isolated from the aerial part of Hemerocallis fulva var. kwanso for the first time. The structures of these compounds were established as 24S-hydroxy-neotokorogenin 1-O-alpha-L-arabinopyranosyl 24-O-beta-D-glucopyranoside (1) and isorhodeasapogenin 3-O-beta-D-glucopyranosyl-(1-->3)-[beta-D-xylopyranosyl-(1-->2)]-beta-D-glucopyranosyl-(1-->4)-beta-D-galactopyranoside (2) through NMR experiments. PMID:11253923

  18. Blood steroid concentrations in domestic Mongolian horses.

    PubMed

    Haffner, John C; Fecteau, Kellie A; Eiler, Hugo; Tserendorj, Tsek; Hoffman, Rhonda M; Oliver, Jack W

    2010-07-01

    Traditionally, analysis of blood cortisol alone has been used to evaluate adrenal function. Currently, multisteroid analyses are considered more informative than analysis of a single hormone to assess adrenal function. The objective of the present research was to create a database for steroid reference values for domestic Mongolian horses. Seven adrenal steroid levels were determined in the blood of 18 colts, 34 stallions, 25 geldings, 17 fillies, and 29 mares. Results were as follows (lowest and highest group median, in nanograms per milliliter): progesterone: <0.030 (fillies), 4.30 (mares), and 0.070 (all horses); 17-OH-progesterone: 0.070 (colts), 0.520 (mares), and 0.110 (all horses); androstenedione: 0.101 (colts), 0.256 (stallions), and 0.181 (all horses); testosterone: <0.040 (mares, stallions, and fillies), 0.040 (geldings and colts), and <0.40 (all horses); estradiol: 0.066 (stallions), 0.093 (fillies), and 0.085 (all horses); cortisol: 23.040 (colts), 70.210 (geldings), and 50.770 (all horses); and aldosterone: 0.018 (colts), 0.297 (geldings), and 0.191 (all horses). Overall medians indicate that cortisol (98.70%) is the predominant steroid, followed by aldosterone (0.37%), androstenedione (0.35%), 17-OH-progesterone (0.21%), estradiol (0.17%), progesterone (0.14%), and testosterone (0.06%). This information provides adrenal and gonadal steroid reference concentrations to assist in physiological characterization and diagnosis of endocrine disorders in domestic Mongolian horses.

  19. Terpenoids and steroids from Lappula anocarpa.

    PubMed

    Jin, Yuan-Peng; Shi, Yan-Ping

    2004-11-01

    A novel nor-terpenoid, named lappulanocarpine A and a known terpenoid derivative, nine known steroids and three known long chine esters were isolated from the alcoholic extract of the whole plant of Lappula anocarpa. The novel structure was characterized by means of spectral methods including 1D-, 2D-NMR and HR-ESIMS and the known compounds were identified on the basis of comparing their NMR data with those of the corresponding compounds in the literature.

  20. Steroidal Compounds in Commercial Parenteral Lipid Emulsions

    PubMed Central

    Xu, Zhidong; Harvey, Kevin A.; Pavlina, Thomas; Dutot, Guy; Hise, Mary; Zaloga, Gary P.; Siddiqui, Rafat A.

    2012-01-01

    Parenteral nutrition lipid emulsions made from various plant oils contain steroidal compounds, called phytosterols. During parenteral administration of lipid emulsions, phytosterols can reach levels in the blood that are many fold higher than during enteral administration. The elevated phytosterol levels have been associated with the development of liver dysfunction and the rare development of liver failure. There is limited information available in the literature related to phytosterol concentrations in lipid emulsions. The objective of the current study was to validate an assay for steroidal compounds found in lipid emulsions and to compare their concentrations in the most commonly used parenteral nutrition lipid emulsions: Liposyn® II, Liposyn® III, Lipofundin® MCT, Lipofundin® N, Structolipid®, Intralipid®, Ivelip® and ClinOleic®. Our data demonstrates that concentrations of the various steroidal compounds varied greatly between the eight lipid emulsions, with the olive oil-based lipid emulsion containing the lowest levels of phytosterols and cholesterol, and the highest concentration of squalene. The clinical impression of greater incidences of liver dysfunction with soybean versus MCT/LCT and olive/soy lipid emulsions may be reflective of the levels of phytosterols in these emulsions. This information may help guide future studies and clinical care of patients with lipid emulsion-associated liver dysfunction. PMID:23016123

  1. Anabolic steroids abuse and male infertility.

    PubMed

    El Osta, Rabih; Almont, Thierry; Diligent, Catherine; Hubert, Nicolas; Eschwège, Pascal; Hubert, Jacques

    2016-01-01

    For several decades, testosterone and its synthetic derivatives have been used with anabolic and androgenic purposes. These substances were first restricted to professional bodybuilders, but become more and more popular among recreational athletes. Up to date, 3,000,000 anabolic-androgenic steroids (AAS) users have been reported in the United States with an increasing prevalence, making AAS consumption a major public health growing concern. Infertility is defined by the WHO as the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse and a male factor is present in up to 50 % of all infertile couples. Several conditions may be related to male infertility. Substance abuse, including AAS, is commonly associated to transient or persistent impairment on male reproductive function, through different pathways. Herein, a brief overview on AAS is offered. Steroids biochemistry, patterns of use, physiological and clinical issues are enlightened. A further review about fertility outcomes among male AAS abusers is also presented, including the classic reports on transient anabolic steroid-induced hypogonadism (ASIH), and the more recent experimental reports on structural and genetic sperm damage.

  2. Anabolic steroids abuse and male infertility.

    PubMed

    El Osta, Rabih; Almont, Thierry; Diligent, Catherine; Hubert, Nicolas; Eschwège, Pascal; Hubert, Jacques

    2016-01-01

    For several decades, testosterone and its synthetic derivatives have been used with anabolic and androgenic purposes. These substances were first restricted to professional bodybuilders, but become more and more popular among recreational athletes. Up to date, 3,000,000 anabolic-androgenic steroids (AAS) users have been reported in the United States with an increasing prevalence, making AAS consumption a major public health growing concern. Infertility is defined by the WHO as the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse and a male factor is present in up to 50 % of all infertile couples. Several conditions may be related to male infertility. Substance abuse, including AAS, is commonly associated to transient or persistent impairment on male reproductive function, through different pathways. Herein, a brief overview on AAS is offered. Steroids biochemistry, patterns of use, physiological and clinical issues are enlightened. A further review about fertility outcomes among male AAS abusers is also presented, including the classic reports on transient anabolic steroid-induced hypogonadism (ASIH), and the more recent experimental reports on structural and genetic sperm damage. PMID:26855782

  3. Avoiding Complications in Endoscopic Third Ventriculostomy.

    PubMed

    Yadav, Yad Ram; Parihar, Vijay Singh; Ratre, Shailendra; Kher, Yatin

    2015-11-01

    Endoscopic neurosurgical techniques hold the potential for reducing morbidity. But they are also associated with limitations such as the initial learning curve, proximal blind spot, visual obscurity, difficulty in controlling bleeding, disorientation, and loss of stereoscopic image. Although some of the surgical techniques in neuroendoscopy and microsurgery are similar, endoscopy requires additional skills. A thorough understanding of endoscopic techniques and their limitations is required to get maximal benefit. Knowledge of possible complications and techniques to avoid such complications can improve results in endoscopic third ventriculostomy (ETV). The surgeon must be able to manage complications and have a second strategy such as a cerebrospinal fluid shunt if ETV fails. It is better to abandon the procedure if there is disorientation or a higher risk of complications such as bleeding or a thick and opaque floor without any clear visualization of anatomy. Attending live workshops, practice on models and simulators, simpler case selection in the initial learning curve, and hands-on cadaveric workshops can reduce complications. Proper case selection, good surgical technique, and better postoperative care are essential for a good outcome in ETV. Although it is difficult to make a preoperative diagnosis of complex hydrocephalus (combination of communicating and obstructive), improving methods to detect the exact type of hydrocephalus before surgery could increase the success rate of ETV and avoid an unnecessary ETV procedure in such cases. PMID:26140421

  4. Complications of tube thoracostomy in trauma

    PubMed Central

    Bailey, R

    2000-01-01

    Objective—To assess the complication rate of tube thoracostomy in trauma. To consider whether this rate is high enough to support a selective reduction in the indications for tube thoracostomy in trauma. Methods—A retrospective case series of all trauma patients who underwent tube thoracostomy during a 12 month period at a large UK teaching hospital with an accident and emergency (A&E) department seeing in excess of 125 000 new patients/year. These patients were identified using the hospital audit department computerised retrieval system supplemented by a hand search of both the data collected for the Major Trauma Outcome Study and the A&E admission unit log book. The notes were assessed with regard to the incidence of complications, which were divided into insertional, infective, and positional. Results—Fifty seven chest drains were placed in 47 patients over the 12 month period. Seven patients who died within 48 hours of drain insertion were excluded. The commonest indications for tube thoracostomy were pneumothorax (54%) and haemothorax (20%); 90% of tubes were placed as a result of blunt trauma. The overall complication rate of the procedure was 30%. There were no insertional complications and only one (2%) major complication, which was empyema thoracis. Conclusion—This study reveals no persuasive evidence to support a selective reduction in the indications for tube thoracostomy in trauma. A larger study to confirm or refute these findings must be performed before any change in established safe practice. PMID:10718232

  5. Standardizing the reporting of percutaneous nephrolithotomy complications

    PubMed Central

    Violette, Philippe D.; Denstedt, John D.

    2014-01-01

    Accurate reporting of complications is an essential component to critical appraisal and innovation in surgery and specifically with percutaneous nephrolithotomy (PCNL). We review the evolution of complication reporting for PCNL and suggest future directions for innovation. A selective review was carried out using Pubmed. Key search terms and their combinations included percutaneous, anatrophic, nephrolithotomy, PCNL, complications, Clavien, Martin score, bleeding, bowel injury, perforation, fever, sepsis. The references from relevant papers and reviews as well as AUA and EAU guidelines were also scanned for inclusion. PCNL has become the procedure of choice for large renal stones owing to decreased morbidity over alternative procedures. Both common and rare complications have been described in large case series, small randomized controlled trials, and case reports in an unstandardized form. Although these reports have provided an informative starting point, a standardized complication reporting methodology is necessary to enable appropriate comparisons between institutions, time periods, or innovations in technique. The Clavien-Dindo grading system has become widely accepted in urology and has facilitated the study of PCNL complications. Future research should focus on adaptions of this system to render it more comprehensive and applicable to PCNL. PMID:24497689

  6. The Interaction between Steroid Hormones and Lipid Monolayers on Water

    PubMed Central

    Gershfeld, N. L.; Muramatsu, M.

    1971-01-01

    The interaction of progesterone, testosterone, androsterone, and etiocholanolone with insoluble lipid films (cholesterol and saturated hydrocarbons containing either alcohol, ester, acetamide, phosphate, amine, or carboxyl groups) was studied. In addition to surface pressure and surface potential measurements of the surface films, radioactive tracers were used to measure the concentration of adsorbed steroid in the lipid films. In general, steroids form mixed films with the insoluble lipid films. Compression of the insoluble lipid films to their most condensed state leads to complete ejection of adsorbed steroid from the surface in all cases except with the amine, for which a small amount of steroid is still retained in the surface. Interactions between the steroids and insoluble lipids are primarily due to van der Waals or dispersion forces; there were no significant contributions from dipole-dipole interactions (except possibly with the amine). Specific interactions between cholesterol and the soluble steroids were not observed. Evidence suggests that low steroid concentrations influence structure of lipid films by altering the hydration layer in the surface film. In contrast to a specific site of action, it is proposed that steroid hormones initiate structural changes in a variety of biological sites; this model of steroid action is consistent with the ubiquity of many steroid hormones. PMID:5120392

  7. Philosophy on steroids: a reply.

    PubMed

    MacGregor, Oskar; McNamee, Mike

    2010-12-01

    Brent Kious has recently attacked several arguments generally adduced to support anti-doping in sports, which are widely supported by the sports medicine fraternity, international sports federations, and international governments. We show that his attack does not succeed for a variety of reasons. First, it uses an overly inclusive definition of doping at odds with the WADA definition, which has global, if somewhat contentious, currency. Second, it seriously misconstrues the position it attacks, rendering the attack without force against a more balanced construal of an anti-doping position. Third, it makes unwarranted appeals to matters Kious considers morally 'clear', while simultaneously attacking a position many others take to be equally morally 'clear', namely that of anti-doping. Such an inconsistency, attacking and appealing to the moral status quo as befits one's argument, is not acceptable without further qualification. Fourth, his position suffers from a general methodological flaw of over-reliance upon argumentation by analogy. Moreover, it is argued that the analogies, being poorly selected and developed, fail to justify his conclusion that the anti-doping lobby lacks philosophical and moral authority for its stance. These issues are symptomatic of a more fundamental problem: any attempt at providing a blanket solution to the question of whether doping is morally acceptable or not is bound to run up against problems when applied to highly specific contexts. Thus, rather than reaching any particular conclusion for or against doping products or processes in this article, we conclude that an increased context-sensitivity will result in a more evenhanded appraisal of arguments on the matter. PMID:20706791

  8. Philosophy on steroids: a reply.

    PubMed

    MacGregor, Oskar; McNamee, Mike

    2010-12-01

    Brent Kious has recently attacked several arguments generally adduced to support anti-doping in sports, which are widely supported by the sports medicine fraternity, international sports federations, and international governments. We show that his attack does not succeed for a variety of reasons. First, it uses an overly inclusive definition of doping at odds with the WADA definition, which has global, if somewhat contentious, currency. Second, it seriously misconstrues the position it attacks, rendering the attack without force against a more balanced construal of an anti-doping position. Third, it makes unwarranted appeals to matters Kious considers morally 'clear', while simultaneously attacking a position many others take to be equally morally 'clear', namely that of anti-doping. Such an inconsistency, attacking and appealing to the moral status quo as befits one's argument, is not acceptable without further qualification. Fourth, his position suffers from a general methodological flaw of over-reliance upon argumentation by analogy. Moreover, it is argued that the analogies, being poorly selected and developed, fail to justify his conclusion that the anti-doping lobby lacks philosophical and moral authority for its stance. These issues are symptomatic of a more fundamental problem: any attempt at providing a blanket solution to the question of whether doping is morally acceptable or not is bound to run up against problems when applied to highly specific contexts. Thus, rather than reaching any particular conclusion for or against doping products or processes in this article, we conclude that an increased context-sensitivity will result in a more evenhanded appraisal of arguments on the matter.

  9. Serum metabolite signatures of type 2 diabetes mellitus complications.

    PubMed

    Wu, Tao; Xie, Guoxiang; Ni, Yan; Liu, Tao; Yang, Ming; Wei, Huafeng; Jia, Wei; Ji, Guang

    2015-01-01

    A number of metabolic conditions, including hypoglycemia, high blood pressure (HBP), dyslipidemia, nerve damage and amputation, and vision problems, occur as a result of uncontrolled blood glucose levels over a prolonged period of time. The different components of diabetic complications are not independent but rather interdependent of each other, rendering the disease difficult to diagnose and control. The underlying pathogenesis of those components cannot be easily elucidated because of the heterogeneous, polygenic, and multifactorial nature of the disease. Metabonomics offers a snapshot of distinct biochemical variations that may reflect the unique metabolic phenotype under pathophysiological conditions. Here we report a mass-spectrometry-based metabonomic study designed to identify the distinct metabolic changes associated with several complications of type 2 diabetes mellitus (T2DM). The 292 patients recruited in the study were divided into five groups, including T2DM with HBP, T2DM with nonalcoholic fatty liver disease (NAFLD), T2DM with HBP and NAFLD, T2DM with HBP and coronary heart disease (CHD), and T2DM with HBP, NAFLD, and CHD. Serum differential metabolites were identified in each group of T2DM complication, mainly involving bile acid, fatty acid, amino acid, lipid, carbohydrate, steroids metabolism, and tricarboxylic acids cycle. These broad-spectrum metabolic changes emphasize the complex abnormalities present among these complications with elevated blood glucose levels, providing a novel strategy for stratifying patients with T2DM complications using blood-based metabolite markers.

  10. Cryptococcal meningitis complicating sarcoidosis

    PubMed Central

    Leonhard, Sonja E.; Fritz, Daan; van de Beek, Diederik; Brouwer, Matthijs C.

    2016-01-01

    Abstract Background: Cryptococcal meningitis is an uncommon but severe complication of sarcoidosis. Methods: We present 2 patients with cryptococcal meningitis complicating sarcoidosis and compared findings with 38 cases reported in the literature. Results: When analyzing our patients and 38 cases reported in the literature, we found that median age of sarcoidosis patients with cryptococcal meningitis was 39 years (range 30–48); 27 of 33 reported cases (82%) had a history of sarcoidosis. Only 16 of 40 patients (40%) received immunomodulating therapy at the time of diagnosis of cryptococcal meningitis. The diagnosis of cryptococcal meningitis was delayed in 17 of 40 patients (43%), mainly because of the initial suspicion of neurosarcoidosis. Cerebrospinal fluid (CSF) examination showed mildly elevated white blood cell count (range 23–129/mm3). Twenty-nine of 32 cases (91%) had a positive CSF culture for Cryptococcus neoformans and 25 of 27 cases (93%) had a positive CSF C neoformans antigen test. CD4 counts were low in all patients in whom counts were performed (84–228/mL). Twelve patients had an unfavorable outcome (32%), of which 7 died (19%) and 24 patients (65%) had a favorable outcome. The rate of unfavorable outcome in patients with a delayed diagnosis was 7 of 17 (41%) compared to 5 of 28 (21%) in patients in whom diagnosis was not delayed. Conclusion: Cryptococcal meningitis is a rare but life-threatening complication of sarcoidosis. Patients were often initially misdiagnosed as neurosarcoidosis, which resulted in considerable treatment delay and worse outcome. CSF cryptococcal antigen tests are advised in patients with sarcoidosis and meningitis. PMID:27583871

  11. Intraoperative anesthetic complications.

    PubMed

    Milam, S B

    1987-01-01

    Intraoperative anesthetic complications can be prevented or minimized if the anesthetist is able to anticipate such problems in the preanesthetic period. Therefore, an adequate preanesthetic medical history that includes previous anesthetic experiences and past and current drug therapy is extremely important. Furthermore, the anesthetist must be properly trained to anticipate undesirable reactions to anesthetic agents. The signs of an impending disaster are subtle and nonspecific in the anesthetized patient. Therefore, continuous vigilance of the patient's physiologic status coupled with a high index of suspicion are essential to safe anesthetic management of dental patients. PMID:3468015

  12. Complications of decorative tattoo.

    PubMed

    Shinohara, Michi M

    2016-01-01

    Decorative tattoo is a popular practice that is generally safe when performed in the professional setting but can be associated with a variety of inflammatory, infectious, and neoplastic complications, risks that may be increased with current trends in home tattooing. Modern tattoo inks contain azo dyes and are often of unknown composition and not currently regulated for content or purity. Biopsy of most (if not all) tattoo reactions presenting to the dermatologist is recommended, given recent clusters of nontuberculous mycobacterial infections occurring within tattoo, as well as associations between tattoo reactions and systemic diseases such as sarcoidosis. PMID:26903190

  13. [Complications of hemorrhoids].

    PubMed

    Slauf, P; Antoš, F; Marx, J

    2014-04-01

    The most common and serious complications of haemorrhoids include perianal thrombosis and incarcerated prolapsed internal haemorrhoids with subsequent thrombosis. They are characterised by severe pain in the perianal region possibly with bleeding. In a short history of the perianal thrombosis, acute surgical incision or excision is indicated, which can result in rapid relief of the painful symptoms. In incarcerated prolapsed internal haemorrhoids, emergency haemorrhoidectomy may also be indicated. Segmental haemorrhoidectomy in the most affected quadrants followed by further elective surgery for haemorrhoids in the next stage is preferred.

  14. Complicated Burn Resuscitation.

    PubMed

    Harrington, David T

    2016-10-01

    More than 4 decades after the creation of the Brooke and Parkland formulas, burn practitioners still argue about which formula is the best. So it is no surprise that there is no consensus about how to resuscitate a thermally injured patient with a significant comorbidity such as heart failure or cirrhosis or how to resuscitate a patient after an electrical or inhalation injury or a patient whose resuscitation is complicated by renal failure. All of these scenarios share a common theme in that the standard rule book does not apply. All will require highly individualized resuscitations. PMID:27600129

  15. [Acute complications of abortion].

    PubMed

    Obel, E

    1976-02-01

    The complications accompanying the various methods of abortion as studied in different surveys are reported. In studies of dilation and curettage (D and C) and vaccuum aspiration (VA), lethality ranges from .5 to 2.9 deaths/100,000 cases. Metrorrhagia occurred in 2.5-6% of the D and C cases studied and in 2.9-3.5% of the VA cases. The bleeding was accompanied by infection in most cases where abortive tissue remained in the uterus, which occured in .4-.8% of the D and C cases and in .6-.9% of the VA cases studied. Postabortive bleeding occurred through the 10th day in up to 25% of the patients and was related to the length of the gestation period before abortion. Pelvic infection, mostly of the endometrium, occurred in about 1.4% of the D and C patients and in .3-1.2% of the VA patients. 1.4% of the D and C patients and .6% of the VA patients experienced a rise in body temperature as the only complication of abortion. Perforation of the uterus occurred in about .8% of the D and C patients and in .1-.6% of VA patients. Lesions of the cervix had to be sutured in .1% of the D and C group and .3% of the VA group. Saline instillation, used for abortions in the second trimest er, had a mortality rate of about 20/100,000 cases. Since the success rate of saline instillation is 90-98%, complications are more frequent, often requiring treatment with oxytocin or curettage. Extensive bleeding occurred in 2.3-4%. Curettage of the placenta was required in about 2.1-16.9% of the cases. Pelvic inflammation occurred in about 2.5% and temperature elevation in 1-3.4%. Abdominal hysterotomies had a lethality of 208/100,000. Pelvic hemorrhage occurred in 31%, inflammation in 4.7%, temperature elevation in 13%, and febrile reactions in 31% of the abdominal hysterotomies studied. It is necessary to establish international definitions of abortion complications for better documentation, and postoperative observations should be recorded more conscientiously. PMID:1251502

  16. Lipases in green chemistry: acylation and alcoholysis on steroids and nucleosides.

    PubMed

    Baldessari, Alicia; Iglesias, Luis E

    2012-01-01

    In this article, we describe the application of lipases in acylation and alcoholysis reactions on steroids and nucleosides. In the field of steroids, a variety of acetyl and fatty acid derivatives of androstanes, pregnanes, and cholestanes have been prepared through lipase-catalyzed acylation and alcoholysis reactions taking advantage of the high regio- and stereoselectivity of these enzymes. The substrates as well as the products show a high degree of biological activity as neurosteroids, hormones, and glucocorticoids. The regioselective preparation of diacylated nucleosides by means of an enzymatic alcoholysis allowed the synthesis of nucleosides prodrugs or modified nucleosides. The quantitative full deacylation and dealkoxycarbonylation of nucleosides and steroids is a mild synthetic method for the deprotection of these labile compounds. Some of the reported steroid and nucleoside products are novel, and it is not possible to obtain them satisfactorily by following traditional synthetic procedures. The advantages presented by this methodology, such as selectivity, mild reaction conditions, and low environmental impact, make the lipases an important tool in the application of the principles of Green Chemistry, offering a convenient way to prepare derivatives of natural compounds with a great potential in the pharmaceutical industry. PMID:22426734

  17. Glucose-6-phosphate dehydrogenase is the target for the trypanocidal action of human steroids.

    PubMed

    Gupta, Shreedhara; Cordeiro, Artur T; Michels, Paul A M

    2011-04-01

    Steroids such as dehydroepiandrosterone (DHEA) and epiandrosterone (EA) exert multiple effects in mammals including the inhibition of glucose-6-phosphate dehydrogenase (G6PDH). Initially, the inhibition was considered specific for the mammalian enzyme. The beneficial effect of these steroids on infections by protists and nematodes was attributed to stimulation of the immune system. However, we showed previously that DHEA and EA also inhibit Trypanosoma brucei and T. cruzi G6PDH, with low micromolar K(i)' values, but not the enzyme from Leishmania species, and kill in vitro cultured trypanosomes. We report here that, contrary to wild-type trypanosomes, mutant bloodstream-form T. brucei cells expressing L. mexicana G6PDH are not susceptible to the steroids, proving that G6PDH is the in situ target. Moreover, bromo-derivatives of the steroids show 50-100 fold lower K(i)' values for the enzyme and display an increased potency to kill the parasites. Therefore, the compounds offer promise for use in development of parasite-selective drugs.

  18. Lipases in green chemistry: acylation and alcoholysis on steroids and nucleosides.

    PubMed

    Baldessari, Alicia; Iglesias, Luis E

    2012-01-01

    In this article, we describe the application of lipases in acylation and alcoholysis reactions on steroids and nucleosides. In the field of steroids, a variety of acetyl and fatty acid derivatives of androstanes, pregnanes, and cholestanes have been prepared through lipase-catalyzed acylation and alcoholysis reactions taking advantage of the high regio- and stereoselectivity of these enzymes. The substrates as well as the products show a high degree of biological activity as neurosteroids, hormones, and glucocorticoids. The regioselective preparation of diacylated nucleosides by means of an enzymatic alcoholysis allowed the synthesis of nucleosides prodrugs or modified nucleosides. The quantitative full deacylation and dealkoxycarbonylation of nucleosides and steroids is a mild synthetic method for the deprotection of these labile compounds. Some of the reported steroid and nucleoside products are novel, and it is not possible to obtain them satisfactorily by following traditional synthetic procedures. The advantages presented by this methodology, such as selectivity, mild reaction conditions, and low environmental impact, make the lipases an important tool in the application of the principles of Green Chemistry, offering a convenient way to prepare derivatives of natural compounds with a great potential in the pharmaceutical industry.

  19. Immunological features of idiopathic Addison's disease: an antibody to cells producing steroid hormones

    PubMed Central

    Anderson, J. R.; Goudie, R. B.; Gray, Kathleen; Stuart-Smith, D. A.

    1968-01-01

    Antibodies to adrenocortical cells, occurring in the serum of patients with idiopathic Addison's disease, were investigated by the indirect immunofluorescence technique. With selected human adrenal tissue obtained post mortem, staining was brightest in the innermost cells of the adrenal cortex. Strongly positive sera were observed to react with all thirty specimens of adrenal tissue examined, but lipid-depleted adrenocortical tissue provided the most suitable reagent for detecting weak antibody. Immunofluorescence tests upon twenty positive sera, using a wide range of human tissues, revealed in one serum an antibody, or antibodies, which reacted with all types of cells producing steroid hormones, namely testicular Leydig cells, hilus cells of the ovary and testis, theca interna and corpus luteal cells of the ovary, and placental trophoblast. A second, weaker example of `steroid-cell antibody' was detected among the twenty sera. The significance of steroid-cell antibody is discussed briefly in relation to steroid hormone biosynthesis and gonadal failure in idiopathic Addison's disease. PMID:4868174

  20. Neurologic Complications of Extracorporeal Membrane Oxygenation

    PubMed Central

    Rabinstein, Alejandro A

    2015-01-01

    Background and Purpose The rate and outcomes of neurologic complications of patients receiving extracorporeal membrane oxygenation (ECMO) are poorly understood. The purpose of this study was to identify these parameters in ECMO patients. Methods All patients receiving ECMO were selected from the Nationwide Inpatient Sample between 2001-2011. The rate and outcomes of neurologic complications [acute ischemic stroke, intracranial hemorrhage (ICH), and seizures] among these patients was determined. Discharge status, mortality, length of stay, and hospitalization costs were compared between patients with and without neurologic complications using chi-squared tests for categorical variables and Student's t-test for continuous variables. Results In total, 23,951 patients were included in this study, of which 2,604 (10.9%) suffered neurologic complications of seizure (4.1%), stroke (4.1%), or ICH (3.6%). When compared to patients without neurologic complications, acute ischemic stroke patients had significantly higher rates of discharge to a long-term facility (12.2% vs. 6.8%, p<0.0001) and a significantly longer mean length of stay (41.6 days vs. 31.9 days, p<0.0001). ICH patients had significantly higher rates of discharge to a long-term facility (9.5% vs. 6.8%, p=0.007), significantly higher mortality rates (59.7% vs. 50.0%, p<0.0001), and a significantly longer mean length of stay (41.8 days vs. 31.9 days) compared to patients without neurologic complications. These outcomes did not differ significantly between seizure patients and patients without neurologic complications. Conclusions Given the increasing utilization of ECMO and the high costs and poor outcomes associated with neurologic complications, more research is needed to help determine the best way to prevent these sequelae in this patient population. PMID:26320848

  1. The role of steroid hormones in the development of intrahepatic cholestasis of pregnancy.

    PubMed

    Pařízek, A; Dušková, M; Vítek, L; Šrámková, M; Hill, M; Adamcová, K; Šimják, P; Černý, A; Kordová, Z; Vráblíková, H; Boudová, B; Koucký, M; Malíčková, K; Stárka, L

    2015-01-01

    Intrahepatic cholestasis of pregnancy (ICP) is a disorder of liver function, commonly occurring in the third trimester but sometimes also as soon as the end of the second trimester of pregnancy. Symptoms of this disorder include pruritus, plus abnormal values of bile acids and hepatic transaminases. After birth, symptoms disappear and liver function returns to normal. Though ICP is relatively non-complicated and often symptomatically mild from the point-of-view of the mother, it presents a serious risk to the fetus, making this disease the subject of great interest. The etiology and pathogenesis of ICP is multifactorial and as yet not fully elucidated. Hormonal factors likely play a significant role, along with genetic as well as exogenous factors. Here we summarize the knowledge of changes in steroid hormones and their role in the development of intrahepatic cholestasis of pregnancy. In addition, we consider the role of exogenous factors as possible triggers of steroid hormone changes, the relationship between metabolic steroids and bile acids, as well as the combination of these factors in the development of ICP in predisposed pregnant women.

  2. Molecular Actions of Glucocorticoids in Cartilage and Bone During Health, Disease, and Steroid Therapy.

    PubMed

    Hartmann, Kerstin; Koenen, Mascha; Schauer, Sebastian; Wittig-Blaich, Stephanie; Ahmad, Mubashir; Baschant, Ulrike; Tuckermann, Jan P

    2016-04-01

    Cartilage and bone are severely affected by glucocorticoids (GCs), steroid hormones that are frequently used to treat inflammatory diseases. Major complications associated with long-term steroid therapy include impairment of cartilaginous bone growth and GC-induced osteoporosis. Particularly in arthritis, GC application can increase joint and bone damage. Contrarily, endogenous GC release supports cartilage and bone integrity. In the last decade, substantial progress in the understanding of the molecular mechanisms of GC action has been gained through genome-wide binding studies of the GC receptor. These genomic approaches have revolutionized our understanding of gene regulation by ligand-induced transcription factors in general. Furthermore, specific inactivation of GC signaling and the GC receptor in bone and cartilage cells of rodent models has enabled the cell-specific effects of GCs in normal tissue homeostasis, inflammatory bone diseases, and GC-induced osteoporosis to be dissected. In this review, we summarize the current view of GC action in cartilage and bone. We further discuss future research directions in the context of new concepts for optimized steroid therapies with less detrimental effects on bone.

  3. The role of steroid hormones in the development of intrahepatic cholestasis of pregnancy.

    PubMed

    Pařízek, A; Dušková, M; Vítek, L; Šrámková, M; Hill, M; Adamcová, K; Šimják, P; Černý, A; Kordová, Z; Vráblíková, H; Boudová, B; Koucký, M; Malíčková, K; Stárka, L

    2015-01-01

    Intrahepatic cholestasis of pregnancy (ICP) is a disorder of liver function, commonly occurring in the third trimester but sometimes also as soon as the end of the second trimester of pregnancy. Symptoms of this disorder include pruritus, plus abnormal values of bile acids and hepatic transaminases. After birth, symptoms disappear and liver function returns to normal. Though ICP is relatively non-complicated and often symptomatically mild from the point-of-view of the mother, it presents a serious risk to the fetus, making this disease the subject of great interest. The etiology and pathogenesis of ICP is multifactorial and as yet not fully elucidated. Hormonal factors likely play a significant role, along with genetic as well as exogenous factors. Here we summarize the knowledge of changes in steroid hormones and their role in the development of intrahepatic cholestasis of pregnancy. In addition, we consider the role of exogenous factors as possible triggers of steroid hormone changes, the relationship between metabolic steroids and bile acids, as well as the combination of these factors in the development of ICP in predisposed pregnant women. PMID:26680481

  4. Body Builder’s Nightmare: Black Market Steroid Injection Gone Wrong: a Case Report

    PubMed Central

    Arad, Ehud; Ben Amotz, Oded

    2016-01-01

    Summary: In the pursuit of success in sports, some athletes are not deterred by health risks associated with the (mis)use of black market preparations of dubious origin as performance-enhancing agents. Several studies published in the recent years demonstrated that anabolic-androgenic steroids, but also stimulants and growth hormones, are misused by numerous recreational athletes from all over the world. Trenbolone is an anabolic steroid routinely used in the finishing phase of beef production to improve animal performance and feed efficiency. A 35-year-old male patient presented to our plastic surgery clinic after self-intramuscular administration of Trenbolone to the superior gluteal area bilaterally, which led to a full-thickness defect in a cone-like distribution. The wounds underwent surgical debridement and were treated locally with mafenide acetate irrigation and wound dressings. Closure was achieved by secondary intention healing. In this report, we discuss the first documented case of full-thickness skin and subcutaneous tissue necrosis after black market anabolic steroid injection. This illustrates a plastic complication and resolution of a widespread but seldom reported problem. PMID:27757350

  5. Steroid-sparing properties of emollients in dermatology.

    PubMed

    Harcharik, Sara; Emer, Jason

    2014-01-01

    Topical corticosteroids (TCS) and topical calcineurin inhibitors (TCIs) are very effective treatments in inflammatory dermatoses, but carry risks with long-term use. TCS are associated with cutaneous atrophy and tachyphylaxis and TCIs can be irritating and contain a black box warning of an increased risk of cancers including lymphoma and non-melanomatous skin cancers. Nevertheless, they are appropriate treatments for inflammatory conditions such as psoriasis and atopic dermatitis (AD) and should be used more often with disease flares and less as maintenance therapy. Given the associated risks of long-term continuous use with these pharmacologic agents, alternatives are needed with similar anti-inflammatory and barrier repair properties that can be used indefinitely without risk. Some over-the-counter (OTC) ingredients such as colloidal oatmeal and petrolatum, as well as anti-inflammatory prescription moisturizers (medical device creams), have demonstrated efficacy with little complications in skin barrier repair and symptom relief in steroid-responsive conditions. With regimented application, these non-drug options are safe and effective and can limit the longterm continuous use of TCS or TCIs. PMID:24570291

  6. Steroid-sparing properties of emollients in dermatology.

    PubMed

    Harcharik, Sara; Emer, Jason

    2014-01-01

    Topical corticosteroids (TCS) and topical calcineurin inhibitors (TCIs) are very effective treatments in inflammatory dermatoses, but carry risks with long-term use. TCS are associated with cutaneous atrophy and tachyphylaxis and TCIs can be irritating and contain a black box warning of an increased risk of cancers including lymphoma and non-melanomatous skin cancers. Nevertheless, they are appropriate treatments for inflammatory conditions such as psoriasis and atopic dermatitis (AD) and should be used more often with disease flares and less as maintenance therapy. Given the associated risks of long-term continuous use with these pharmacologic agents, alternatives are needed with similar anti-inflammatory and barrier repair properties that can be used indefinitely without risk. Some over-the-counter (OTC) ingredients such as colloidal oatmeal and petrolatum, as well as anti-inflammatory prescription moisturizers (medical device creams), have demonstrated efficacy with little complications in skin barrier repair and symptom relief in steroid-responsive conditions. With regimented application, these non-drug options are safe and effective and can limit the longterm continuous use of TCS or TCIs.

  7. A complicated case of pachydermoperiostosis with spondyloarthritides: a case report

    PubMed Central

    2013-01-01

    Introduction Pachydermoperiostosis is a rare, hereditary disease commonly presenting with digital clubbing, pachydermia and periosteal hypertrophy. Therapeutic options for pachydermoperiostosis are few because of the unknown pathogenesis. Here, we report the complicated case of a patient with pachydermoperiostosis combined with spondyloarthritides, who was refractory to steroids and tumor necrosis factor alpha antagonists. We treated this patient with zoledronic acid and performed an arthroscopic synovectomy, with a satisfactory outcome. To the best of our knowledge, this is the first report in English on the combination of zoledronic acid administration and synovectomy for the treatment of a patient with pachydermoperiostosis and spondyloarthritides. Case presentation An 18-year-old Han Chinese man was diagnosed with pachydermoperiostosis in the presence of digital clubbing, periostitis and swollen limbs. Combined spondyloarthritides was also considered based on his lower back pain, lower limbs synovitis, bilateral sacroiliac sclerosis and a positive test for human leukocyte antigen B27, as well as immunoglobulin A nephropathy. He was refractory to steroids and tumor necrosis factor alpha antagonists, but treated with intravenous zoledronic acid and an arthroscopic synovectomy, with a satisfactory outcome. Conclusion This is a rare, complicated case of pachydermoperiostosis with spondyloarthritides. Combination therapy of zoledronic acid administration with synovectomy is a novel, convenient and effective option for patients with pachydermoperiostosis with remarkable synovitis. PMID:24330652

  8. Low-, medium- and high-dose steroids with or without aminocaproic acid in adult hematopoietic SCT patients with diffuse alveolar hemorrhage.

    PubMed

    Rathi, N K; Tanner, A R; Dinh, A; Dong, W; Feng, L; Ensor, J; Wallace, S K; Haque, S A; Rondon, G; Price, K J; Popat, U; Nates, J L

    2015-03-01

    Diffuse alveolar hemorrhage (DAH) is a poorly understood complication of transplantation carrying a high mortality. Patients commonly deteriorate and require intensive care unit (ICU) admission. Treatment with high-dose steroids and aminocaproic acid (ACA) has been suggested. The current study examined 119 critically ill adult hematopoietic transplant patients treated for DAH. Patients were subdivided into low-, medium- and high-dose steroid groups with or without ACA. All groups had similar baseline characteristics and severity of illness scores. Primary objectives were 30, 60, 100 day, ICU and hospital mortality. Overall mortality (n=119) on day 100 was high at 85%. In the steroids and ACA cohort (n=82), there were no significant differences in 30, 60, 100, day, ICU and hospital mortality between the dosing groups. In the steroids only cohort (n=37), the low-dose steroid group had a lower ICU and hospital mortality (P=0.02). Adjunctive treatment with ACA did not produce differences in outcomes. In the multivariate analysis, medium- and high-dose steroids were associated with a higher ICU mortality (P=0.01) as compared with the low-dose group. Our data suggest that treatment strategies may need to be reanalyzed to avoid potentially unnecessary and potentially harmful therapies.

  9. Complicated intestinal atresias.

    PubMed

    Miller, R C

    1979-05-01

    In this group of 45 intestinal atresia patients (duodenum, 16; jejunum, 24; ileum five) at the University of Mississippi Medical Center, individual hospitalizations ranged up to 245 days. Twelve patients required multiple operations, and the overall mortality rate was 22% (ten patients). While the patients with duodenal atresia had the greatest incidence of other congenital anomalies, including Down's syndrome, the patients with jejunal atresia presented with the most challenging surgical problems. Of the 24 jejunal atresia patients, only three had a single, simple area of obstruction. The remainder were complicated by other gastrointestinal lesions (five patients), by multiple areas of atresia (seven patients) including those in one surviving patient with 22 separate atretic segments, and by the Christmas tree deformity (nine patients). Intraoperative management of the complicated atresia should include: 1) grouping of multiple atresias during resection, 2) adequate resection of the dilated proximal atonic loop, 3) end-to-end anastomoses, 4) avoidance of intraluminal catheters, 5) additional resection of a segment of the distal loop in the Christmas tree deformity and 6) consideration of the shish kebab technique for multiple atretic webs. Postoperative management should involve early intravenous nutrition and repeated exploration for continued obstruction.

  10. 3D model of amphioxus steroid receptor complexed with estradiol

    SciTech Connect

    Baker, Michael E.; Chang, David J.

    2009-08-28

    The origins of signaling by vertebrate steroids are not fully understood. An important advance was the report that an estrogen-binding steroid receptor [SR] is present in amphioxus, a basal chordate with a similar body plan as vertebrates. To investigate the evolution of estrogen-binding to steroid receptors, we constructed a 3D model of amphioxus SR complexed with estradiol. This 3D model indicates that although the SR is activated by estradiol, some interactions between estradiol and human ER{alpha} are not conserved in the SR, which can explain the low affinity of estradiol for the SR. These differences between the SR and ER{alpha} in the steroid-binding domain are sufficient to suggest that another steroid is the physiological regulator of the SR. The 3D model predicts that mutation of Glu-346 to Gln will increase the affinity of testosterone for amphioxus SR and elucidate the evolution of steroid-binding to nuclear receptors.

  11. Anabolic-androgenic steroids: use and abuse in pediatric patients.

    PubMed

    Kerr, Julie M; Congeni, Joseph A

    2007-08-01

    The "win at all costs" mentality fuels athletes to seek performance-enhancing substances, such as anabolic-androgenic steroids, to gain an advantage over their opponents. Nonathletes espouse this same attitude to "win" the battle of attractiveness. An enhanced understanding of anabolic-androgenic steroids and the motivations behind their abuse will arm pediatricians with the ability to engage their patients in a balanced discussion of the benefits and costly risks of anabolic-androgenic steroids and successfully deter further use.

  12. Respiratory Complication in Liver Disease.

    PubMed

    Ramalingam, Vijaya S; Ansari, Sikandar; Fisher, Micah

    2016-07-01

    Cirrhosis, the twelfth leading cause of death, accounts for 1.1% of all deaths in the United States. Although there are multiple pulmonary complications associated with liver disease, the most important complications that cause significant morbidity and mortality are hepatopulmonary syndrome, hepatic hydrothorax, and portopulmonary hypertension. Patients with cirrhosis who complain of dyspnea should be evaluated for these complications. This article reviews these complications. PMID:27339676

  13. Metabolic complications in liver transplant recipients

    PubMed Central

    Jiménez-Pérez, Miguel; González-Grande, Rocío; Omonte Guzmán, Edith; Amo Trillo, Víctor; Rodrigo López, Juan Miguel

    2016-01-01

    The metabolic syndrome (MS), which includes obesity, dyslipidaemia, hypertension and hyperglycaemia according to the most widely accepted definitions now used, is one of the most common post-transplant complications, with a prevalence of 44%-58%. The MS, together with the immunosuppression, is considered the main risk factor for the development of cardiovascular disease (CVD) in transplant recipients, which in turn accounts for 19%-42% of all deaths unrelated to the graft. The presence of MS represents a relative risk for the development of CVD and death of 1.78. On the other hand, non-alcoholic fatty liver disease (NAFLD), considered as the manifestation of the MS in the liver, is now the second leading reason for liver transplantation in the United States after hepatitis C and alcohol. NAFLD has a high rate of recurrence in the liver graft and a direct relation with the worsening of other metabolic disorders, such as insulin resistance or diabetes mellitus. Consequently, it is vitally important to identify and treat as soon as possible such modifiable factors as hypertension, overweight, hyperlipidaemia or diabetes in transplanted patients to thus minimise the impact on patient survival. Additionally, steroid-free regimens are favoured, with minimal immunosuppression to limit the possible effects on the development of the MS. PMID:27605877

  14. Metabolic complications in liver transplant recipients

    PubMed Central

    Jiménez-Pérez, Miguel; González-Grande, Rocío; Omonte Guzmán, Edith; Amo Trillo, Víctor; Rodrigo López, Juan Miguel

    2016-01-01

    The metabolic syndrome (MS), which includes obesity, dyslipidaemia, hypertension and hyperglycaemia according to the most widely accepted definitions now used, is one of the most common post-transplant complications, with a prevalence of 44%-58%. The MS, together with the immunosuppression, is considered the main risk factor for the development of cardiovascular disease (CVD) in transplant recipients, which in turn accounts for 19%-42% of all deaths unrelated to the graft. The presence of MS represents a relative risk for the development of CVD and death of 1.78. On the other hand, non-alcoholic fatty liver disease (NAFLD), considered as the manifestation of the MS in the liver, is now the second leading reason for liver transplantation in the United States after hepatitis C and alcohol. NAFLD has a high rate of recurrence in the liver graft and a direct relation with the worsening of other metabolic disorders, such as insulin resistance or diabetes mellitus. Consequently, it is vitally important to identify and treat as soon as possible such modifiable factors as hypertension, overweight, hyperlipidaemia or diabetes in transplanted patients to thus minimise the impact on patient survival. Additionally, steroid-free regimens are favoured, with minimal immunosuppression to limit the possible effects on the development of the MS.

  15. Metabolic complications in liver transplant recipients.

    PubMed

    Jiménez-Pérez, Miguel; González-Grande, Rocío; Omonte Guzmán, Edith; Amo Trillo, Víctor; Rodrigo López, Juan Miguel

    2016-07-28

    The metabolic syndrome (MS), which includes obesity, dyslipidaemia, hypertension and hyperglycaemia according to the most widely accepted definitions now used, is one of the most common post-transplant complications, with a prevalence of 44%-58%. The MS, together with the immunosuppression, is considered the main risk factor for the development of cardiovascular disease (CVD) in transplant recipients, which in turn accounts for 19%-42% of all deaths unrelated to the graft. The presence of MS represents a relative risk for the development of CVD and death of 1.78. On the other hand, non-alcoholic fatty liver disease (NAFLD), considered as the manifestation of the MS in the liver, is now the second leading reason for liver transplantation in the United States after hepatitis C and alcohol. NAFLD has a high rate of recurrence in the liver graft and a direct relation with the worsening of other metabolic disorders, such as insulin resistance or diabetes mellitus. Consequently, it is vitally important to identify and treat as soon as possible such modifiable factors as hypertension, overweight, hyperlipidaemia or diabetes in transplanted patients to thus minimise the impact on patient survival. Additionally, steroid-free regimens are favoured, with minimal immunosuppression to limit the possible effects on the development of the MS. PMID:27605877

  16. Infectious complications in living related liver transplantation.

    PubMed

    Uemoto, S; Tanaka, K; Fujita, S; Sano, K; Shirahase, I; Kato, H; Yamamoto, E; Inomata, Y; Ozawa, K

    1994-04-01

    During the last 31 months, 50 children between 3 months and 15 years of age have undergone living related liver transplantation (LRLT) for end-stage liver diseases (39 biliary atresia, 2 Budd-Chiari syndrome, 2 progressive intrahepatic cholestasis, 3 liver cirrhosis, 1 Wilson disease, 1 protoporphyria, 1 tyrosinemia, and 1 fulminant hepatitis). Combined FK-506 and low-dose steroids were routinely used for immunosuppression. There were seven deaths, two of which were related to infection (Candida pneumonia and Epstein-Barr virus [EBV]-associated lymphoproliferative syndrome [LPS]). Five patients had a bacterial infection, all of which were associated with surgical complications. Three patients had Candida infection, all of which were malnourished, had biliary atresia, and had been managed with prolonged antibiotics against obstinate ascending cholangitis. There were 14 symptomatic viral infections (1 herpes simplex virus, 1 herpes zoster virus, 5 cytomegalovirus [CMV], 6 EBV, and 1 EBV-associated LPS). Three of the five CMV infections appeared in patients whose graft was ABO-incompatible, who were managed with prophylactic OKT-3. Most of the viral infections (except 1 EBV-associated LPS) were minor and were treated successfully. The low incidence and successful treatment of CMV infection are related to the high compatibility and low incidence of allograft rejection in LRLT. Bacterial and fungal infections can be decreased by greater refinement of surgical technique and more aggressive preoperative management. Treatment of EBV infection is still an unsolved problem.

  17. Complications of the external (combination) rhinoplasty approach.

    PubMed

    Burgess, L P; Everton, D M; Quilligan, J J; Charles, G; Lepore, M L; Van Sant, T E; Yim, D W

    1986-10-01

    More rhinoplastic surgeons are using the external (combination) rhinoplasty approach for selected patients. Although several large series report few complications, the initial experience of newcomers may be different. A series of 26 external rhinoplasty approaches was examined, representing the initial experience of supervised residents. The most common complication was incising the anterior margin of the lower lateral cartilage at the juncture of the lateral and medial crura. To prevent this problem, it is recommended that the skin be elevated off the lower lateral cartilages from both a medial direction up over the domes and a lateral direction downward. To repair this complication, a figure-of-eight suture is used to reapproximate the incision.

  18. Delineation of Steroid-Degrading Microorganisms through Comparative Genomic Analysis

    PubMed Central

    Bergstrand, Lee H.; Cardenas, Erick; Holert, Johannes; Van Hamme, Jonathan D.

    2016-01-01

    ABSTRACT Steroids are ubiquitous in natural environments and are a significant growth substrate for microorganisms. Microbial steroid metabolism is also important for some pathogens and for biotechnical applications. This study delineated the distribution of aerobic steroid catabolism pathways among over 8,000 microorganisms whose genomes are available in the NCBI RefSeq database. Combined analysis of bacterial, archaeal, and fungal genomes with both hidden Markov models and reciprocal BLAST identified 265 putative steroid degraders within only Actinobacteria and Proteobacteria, which mainly originated from soil, eukaryotic host, and aquatic environments. These bacteria include members of 17 genera not previously known to contain steroid degraders. A pathway for cholesterol degradation was conserved in many actinobacterial genera, particularly in members of the Corynebacterineae, and a pathway for cholate degradation was conserved in members of the genus Rhodococcus. A pathway for testosterone and, sometimes, cholate degradation had a patchy distribution among Proteobacteria. The steroid degradation genes tended to occur within large gene clusters. Growth experiments confirmed bioinformatic predictions of steroid metabolism capacity in nine bacterial strains. The results indicate there was a single ancestral 9,10-seco-steroid degradation pathway. Gene duplication, likely in a progenitor of Rhodococcus, later gave rise to a cholate degradation pathway. Proteobacteria and additional Actinobacteria subsequently obtained a cholate degradation pathway via horizontal gene transfer, in some cases facilitated by plasmids. Catabolism of steroids appears to be an important component of the ecological niches of broad groups of Actinobacteria and individual species of Proteobacteria. PMID:26956583

  19. Synthesis and antiproliferative activity of novel steroidal dendrimer conjugates.

    PubMed

    Magaña-Vergara, Nancy E; Rárová, Lucie; Soto-Castro, Delia; Farfán, Norberto; Strnad, Miroslav; Santillan, Rosa

    2013-12-11

    We describe the synthesis of steroidal dendrimer conjugates of first and second generation with tetramethylene core and 5-hydroxy-isophtalic acid dimethyl ester as branching unit modified to incorporate ethynylestradiol or 17α-estradiol as terminal units. The steroidal dendrimer conjugates, the free drug (steroids) and dendrimer were tested against a panel of cancer cell lines (CEM, MCF7, HeLa) and normal human fibroblast (BJ). The steroidal dendrimer conjugates of first generation exhibited cytotoxic activity and induced apoptosis in chronic leukemia (CEM) as resultant activation of caspase cascade which is mainly provoked in G2/M arrested cells.

  20. Neurological complications of transplantation.

    PubMed

    Pustavoitau, Aliaksei; Bhardwaj, Anish; Stevens, Robert

    2011-01-01

    Recipients of solid organ or hematopoietic cell transplants are at risk of life-threatening neurological disorders including encephalopathy, seizures, infections and tumors of the central nervous system, stroke, central pontine myelinolysis, and neuromuscular disorders-often requiring admission to, or occurring in, the intensive care unit (ICU). Many of these complications are linked directly or indirectly to immunosuppressive therapy. However, neurological disorders may also result from graft versus host disease, or be an expression of the underlying disease which prompted transplantation, as well as injury induced during radiation, chemotherapy, surgery, and ICU stay. In rare cases, neuroinfectious pathogens may be transmitted with the transplanted tissue or organ. Diagnosis may be a challenge because clinical symptoms and findings on neuroimaging lack specificity, and a biological specimen or tissue diagnosis is often needed for definitive diagnosis. Management is centered on preventing further neurological injury, etiology-targeted therapy, and balancing the benefits and toxicities of specific immunosuppressive agents. PMID:21764765

  1. Neuromuscular complications in cancer.

    PubMed

    Grisold, W; Grisold, A; Löscher, W N

    2016-08-15

    Cancer is becoming a treatable and even often curable disease. The neuromuscular system can be affected by direct tumor invasion or metastasis, neuroendocrine, metabolic, dysimmune/inflammatory, infections and toxic as well as paraneoplastic conditions. Due to the nature of cancer treatment, which frequently is based on a DNA damaging mechanism, treatment related toxic side effects are frequent and the correct identification of the causative mechanism is necessary to initiate the proper treatment. The peripheral nervous system is conventionally divided into nerve roots, the proximal nerves and plexus, the peripheral nerves (mono- and polyneuropathies), the site of neuromuscular transmission and muscle. This review is based on the anatomic distribution of the peripheral nervous system, divided into cranial nerves (CN), motor neuron (MND), nerve roots, plexus, peripheral nerve, the neuromuscular junction and muscle. The various etiologies of neuromuscular complications - neoplastic, surgical and mechanic, toxic, metabolic, endocrine, and paraneoplastic/immune - are discussed separately for each part of the peripheral nervous system. PMID:27423586

  2. Complicated bile duct stones

    PubMed Central

    Roy, Ashwin; Martin, Derrick

    2013-01-01

    Common bile duct stones (CBDSs) are solid deposits that can either form within the gallbladder or migrate to the common bile duct (CBD), or form de novo in the biliary tree. In the USA around 15% of the population have gallstones and of these, 3% present with symptoms annually. Because of this, there have been major advancements in the management of gallstones and related conditions. Management is based on the patient's risk profile; young and healthy patients are likely to be recommended for surgery and elderly patients with comorbidities are usually recommended for endoscopic procedures. Imaging of gallstones has advanced in the last 30 years with endoscopic retrograde cholangiopancreatography evolving from a diagnostic to a therapeutic procedure in removing CBDSs. We present a complicated case of a patient with a CBDS and periampullary diverticulum and discuss the techniques used to diagnose and remove the stone from the biliary system. PMID:23946532

  3. Cardiovascular complications in acromegaly.

    PubMed

    Vitale, G; Pivonello, R; Lombardi, G; Colao, A

    2004-09-01

    Cardiovascular morbidity and mortality are increased in acromegaly. In fact, GH and IGF-I excess induces a specific cardiomyopathy. The early stage of acromegaly is characterized by the hyperkinetic syndrome (high heart rate and increased systolic output). Frequently, concentric biventricular hypertrophy and diastolic dysfunction occur in acromegaly, leading to an impaired systolic function ending in heart failure if the disease is untreated or unsuccessfully untreated. Besides, abnormalities of cardiac rhythm and of valves have been also described in acromegaly. The coexistence of other complications, such as arterial hypertension and diabetes, aggravates the acromegalic cardiomyopathy. The suppression of GH/IGF-I following an efficacious therapy could decrease left ventricular mass and improve cardiac function. In conclusion, a careful evaluation of cardiac function, morphology and activity seems to be mandatory in acromegaly.

  4. Complications of collagenous colitis.

    PubMed

    Freeman, Hugh-James

    2008-03-21

    Microscopic forms of colitis have been described, including collagenous colitis. This disorder generally has an apparently benign clinical course. However, a number of gastric and intestinal complications, possibly coincidental, may develop with collagenous colitis. Distinctive inflammatory disorders of the gastric mucosa have been described, including lymphocytic gastritis and collagenous gastritis. Celiac disease and collagenous sprue (or collagenous enteritis) may occur. Colonic ulceration has been associated with use of nonsteroidal anti-inflammatory drugs, while other forms of inflammatory bowel disease, including ulcerative colitis and Crohn's disease, may evolve from collagenous colitis. Submucosal "dissection", colonic fractures or mucosal tears and perforation from air insufflation during colonoscopy may occur and has been hypothesized to be due to compromise of the colonic wall from submucosal collagen deposition. Similar changes may result from increased intraluminal pressure during barium enema contrast studies. Finally, malignant disorders have also been reported, including carcinoma and lymphoproliferative disease. PMID:18350593

  5. The potential use of complex derivatization procedures in comprehensive HPLC-MS/MS detection of anabolic steroids.

    PubMed

    Baranov, Pavel A; Appolonova, Svetlana A; Rodchenkov, Grigory M

    2010-10-01

    The use of two separate derivatization procedures with the formation of oxime (hydroxyl ammonium pretreatment) and picolinoyl (mixed anhydride method) derivates of anabolic steroids following HPLC-MS/MS analysis was proposed. The main product ions of obtained derivatives for 21 anabolic steroids were evaluated and fragmentation pathways were compared.The analysis of MS/MS spectra for underivatized steroids versus oxime or picolinoyl derivatives showed that in case of analytes containing conjugated double bonds in sterane core all of the observed MS/MS spectra contained abundant product ions of diagnostic value. The implementation of derivatization procedures to such compounds is useful for upgrading sensitivity or selectivity of the evaluated method. On the other hand, MS/MS spectra of underivatized and oxime analytes without conjugated double bonds in sterane core produce spectra with large amounts of low abundant product ions. Picolinoyl derivatives formation leads to highly specific spectra with product ions of diagnostic value coupled with sensitive and selective analysis at the same time. The intra- and inter-group comparison analysis revealed that fragmentation pathways for underivatized steroids and correspondent oxime derivatives are similar.The obtained oxime and picolinoyl derivatives provided 10-15 times higher ESI response in the HPLC-ESI-MS-selected reaction monitoring (SRM) when compared to those of underivatized molecules in positive HPLC-ESI-MS mode.Due to the laborious sample preparation we suggest to use the performed strategy for confirmation analysis purposes, metabolic studies or while the identification of new steroids or steroid-like substances.

  6. Flowers for Algernon: steroid dysgenesis, epigenetics and brain disorders.

    PubMed

    Sanders, Bryan K

    2012-01-01

    While a recent study has reported that early citalopram exposure alters cortical network function and produces autistic-like behaviors in male rats, when evaluating antidepressant animal models of autism spectrum disorder (ASD) it is important to note that some selective serotonin (5-HT) reuptake inhibitors alter 3α-hydroxysteroid dehydrogenase activity, and thus steroidogenesis. At least one study has examined the effect of repeated citalopram administration on the serum and brain concentration of testosterone (T) and its metabolites and shown that citalopram increases serum T. Several in vitro studies also suggest that sex steroid can alter 5-HT homeostasis. While research efforts have demonstrated that transgenic mice expressing the most common of multiple gain-of-function 5-HT reuptake transporter (SERT) coding variants, SERT Ala56, previously identified in children with ASD, exhibit autistic-like behaviors, elevated p38 MAPK-dependent transporter phosphorylation, enhanced 5-HT clearance rates and hyperserotonemia, a few studies provide some evidence that 5-HT may alter gonadal steroidogenesis. T, 17β-estradiol and synthetic estrogens are known inhibitors of AKR1C21 (BRENDA, E.C. 1.1.1.209), the epitestosterone (epiT) producing enzyme in rodents. EpiT is a naturally occurring steroid in mammals, including man. An analysis of the literature suggests that epiT may be the central mediator in the epigenetic regulation of gene expression. Over thirty years ago, it was shown that rat brain epiT production is higher in females than in males. A similar finding in humans could explain the sex differences in the incidence of autism and other brain disorders. Despite this, the role of epiT in brain development remains a long neglected area of research. PMID:23406739

  7. Ulcer bleeding and perforation: non-steroidal anti-inflammatory drugs or Helicobacter pylori.

    PubMed

    Svanes, C; Ovrebø, K; Søreide, O

    1996-01-01

    Non-steroidal anti-inflammatory drug (NSAID)-exposure increases the risk for ulcer perforation by a factor of 5-8. Recent data from Norway indicate that NSAID exposure is more common in gastric than in prepyloric, pyloric and duodenal perforation. Twenty to 40% of patients with gastric perforation have used NSAIDs; attributable risks are not published. The risk for ulcer bleeding is increased by a factor of 3-5 in NSAID users, with similar effects for stomach and duodenum. NSAID exposure accounts for 20-35% of ulcer bleedings. There is little knowledge about the role of Helicobacter pylori in ulcer complications, a limited importance of the bacteria is indicated in the etiology of both perforation and bleeding. Ulcer complications have a multifactorial origin. NSAIDs account for a limited part of the events. H. pylori infection may play a still undocumented role. Smoking, alcohol and aspirin are other important causal factors.

  8. Anabolic steroids abuse-induced cardiomyopathy and ischaemic stroke in a young male patient.

    PubMed

    Shamloul, Reham Mohammed; Aborayah, Ahmed Fathy; Hashad, Assem; Abd-Allah, Foad

    2014-02-26

    We report a case of a 37-year-old man presented with acute stroke and hepatorenal impairment which were associated with anabolic-androgenic steroids (AAS) abuse over 2 years. Despite the absence of apparent symptoms and signs of congestive heart failure at presentation, an AAS-induced dilated cardiomyopathy with multiple thrombi in the left ventricle was attributed to be the underlying cause of his condition. Awareness of the complications of AAS led to the prompt treatment of the initially unrecognised dilated cardiomyopathy, and improved the liver and kidney functions. However, the patient was exposed to a second severe ischaemic event, which led to his death. This unique and complex presentation of AAS complications opens for better recognition and treatment of their potentially fatal effects.

  9. Epidural steroid warning controversy still dogging FDA.

    PubMed

    Manchikanti, Laxmaiah; Candido, Kenneth D; Singh, Vijay; Gharibo, Christopher G; Boswell, Mark V; Benyamin, Ramsin M; Falco, Frank J E; Grider, Jay S; Diwan, Sudhir; Hirsch, Joshua A

    2014-01-01

    On April 23, 2014, the Food and Drug Administration (FDA) issued a letter of warning that injection of corticosteroids into the epidural space of the spine may result in rare, but serious adverse events, including "loss of vision, stroke, paralysis, and death." The advisory also advocated that patients should discuss the benefits and risks of epidural corticosteroid injections with their health care professionals, along with the benefits and risks associated with other possible treatments. In addition, the FDA stated that the effectiveness and safety of the corticosteroids for epidural use have not been established, and the FDA has not approved corticosteroids for such use. To raise awareness of the risks of epidural corticosteroid injections in the medical community, the FDA's Safe Use Initiative convened a panel of experts including pain management experts to help define the techniques for such injections with the aim of reducing preventable harm. The panel was unable to reach an agreement on 20 proposed items related to technical aspects of performing epidural injections. Subsequently, the FDA issued the above referenced warning and a notice that a panel will be convened in November 2014. This review assesses the inaccuracies of the warning and critically analyzes the available literature. The literature has been assessed in reference to alternate techniques and an understanding of the risk factors when performing transforaminal epidural injections in the cervical, thoracic, and lumbar regions, ultimately resulting in improved safety. The results of this review show the efficacy of epidural injections, with or without steroids, in a multitude of spinal ailments utilizing caudal, cervical, thoracic, and lumbar interlaminar approaches as well as lumbar transforaminal epidural injections . The evidence also shows the superiority of steroids in managing lumbar disc herniation utilizing caudal and lumbar interlaminar approaches without any significant difference as

  10. Treatment of severe steroid refractory ulcerative colitis

    PubMed Central

    Assche, Gert Van; Vermeire, Séverine; Rutgeerts, Paul

    2008-01-01

    Although systemic steroids are highly efficacious in ulcerative colitis (UC), failure to respond to steroids still poses an important challenge to the surgeon and physician alike. Even if the life time risk of a fulminant UC flare is only 20%, this condition is potentially life threatening and should be managed in hospital. If patients fail 3 to 5 d of intravenous corticosteroids and optimal supportive care, they should be considered for any of three options: intravenous cyclosporine (2 mg/kg for 7 d, and serum level controlled), infliximab (5 mg/kg IV, 0-2-6 wk) or total colectomy. The choice between these three options is a medical-surgical decision based on clinical signs, radiological and endoscopic findings and blood analysis (CRP, serum albumin). Between 65 and 85% of patients will initially respond to cyclosporine and avoid colectomy on the short term. Over 5 years only 50% of initial responders avoid colectomy and outcomes are better in patients naive to azathioprine (bridging strategy). The data on infliximab as a medical rescue in fulminant colitis are more limited although the efficacy of this anti tumor necrosis factor (TNF) monoclonal antibody has been demonstrated in a controlled trial. Controlled data on the comparative efficacy of cyclosporine and infliximab are not available at this moment. Both drugs are immunosuppressants and are used in combination with steroids and azathioprine, which infers a risk of serious, even fatal, opportunistic infections. Therefore, patients not responding to these agents within 5-7 d should be considered for colectomy and responders should be closely monitored for infections. PMID:18810767

  11. Separation of steroids using vegetable oils in microemulsion electrokinetic capillary chromatography.

    PubMed

    Sirén, Heli; Vesanen, Sari; Suomi, Johanna

    2014-01-15

    The steroids, hydrocortisone, androstenedione, 17-α-hydroxyprogesterone, testosterone, 17-α-methyltestosterone, and progesterone were separated with microemulsion electrokinetic chromatography (MEEKC) and detected with UV absorption. The microemulsion phases were prepared from both artificial and vegetable oils, from them the first was made of alkane and alcohol and the latter from colza, olive, linseed, and walnut oils. The electrolyte solutions were made to emulsions using sodium dodecyl sulfate and alkaline tetraborate. The solution mixtures made from ethyl acetate, sodium dodecyl sulfate, 1-butanol, acetonitrile, and sodium tetraborate were used as the reference solutions to evaluate the performance of the vegetable oil emulsions. Our study showed that the lipophilic organic phase in the microemulsion did provide resolution improvements but not selectivity changes. The results also correlate with real interactions of the steroids with the lipophilic organic microemulsion phase. The quality of the oils between the manufacturers did not have importance, which was noticed from the equal behavior of the steroids in the vegetable oil emulsions. Detection limits of the steroids in vegetable oil emulsions were at the level of 0.20-0.43μg/L. Thus, they were 2-10 times higher than the concentrations in the partial filling micellar electrokinetic chromatography (PF-MEKC), which we have obtained earlier. The repeatability (RSD%) of the electrophoretic mobilities of the steroids was between 0.50 and 3.70. The RSD% values between the inter-day separations were below 1%, but when walnut and olive oils were used the values exceeded even 10%.

  12. Evaluation of the skin blanching of topically applied steroids using a chroma meter in animals.

    PubMed

    Ishii, Hiroshi; Fujino, Konomi; Todo, Hiroaki; Sugibayashi, Kenji

    2012-01-01

    We evaluated the utility of animal skins for determining the skin blanching of steroids. A Chroma Meter was used to determine the skin blanching of steroids. Hydrophilic creams containing clobetasol propionate (CP) or prednisolone (PS) were selected as model steroid formulations. Skin blanching, a*, was determined using a Chroma Meter after the application of 0.005, 0.01, 0.1, or 1.0% CP or PS hydrophilic cream to the back skin of guinea pigs and hairless rats for 24 h. The relationships between Δa*(6h) and the skin concentrations of the steroids were determined at 6 h after removal of the cream. Δa*(6h) was markedly decreased after the application of CP hydrophilic cream to guinea pigs, and a good linear relationship was observed between Δa*(6h) and skin concentration (r=0.98). In contrast, no relationship was observed between these parameters after the application of CP cream to the hairless rats. Although skin blanching was observed after PS cream application in guinea pigs, no relationship was observed between Δa*(6h) and skin concentration of PS in each animal. These results suggest that the skin blanching effect of CP in guinea pigs is greater than that of PS and that its blanching effect in guinea pigs was stronger than that in hairless rats. Guinea pigs were found to be a good animal model for determining the skin blanching produced by steroid creams. In addition, Chroma Meters can be effectively used in skin vasoconstrictive tests in guinea pigs.

  13. Classification of two steroids, prostanozol and methasterone, as Schedule III anabolic steroids under the Controlled Substance Act. Final rule.

    PubMed

    2012-07-30

    With the issuance of this Final Rule, the Administrator of the DEA classifies the following two steroids as "anabolic steroids'' under the Controlled Substances Act (CSA): prostanozol (17[beta]-hydroxy-5[alpha]-androstano[3,2-c]pyrazole) and methasterone (2[alpha],17[alpha]-dimethyl-5[alpha]-androstan-17[beta]-ol-3-one). These steroids and their salts, esters, and ethers are Schedule III controlled substances subject to the regulatory control provisions of the CSA.

  14. Relationship between the Use of Inhaled Steroids for Chronic Respiratory Diseases and Early Outcomes in Community-Acquired Pneumonia

    PubMed Central

    Almirall, Jordi; Bolíbar, Ignasi; Serra-Prat, Mateu; Palomera, Elisabet; Roig, Jordi; Hospital, Imma; Carandell, Eugenia; Agustí, Mercè; Ayuso, Pilar; Estela, Andreu; Torres, Antoni

    2013-01-01

    Background The role of inhaled steroids in patients with chronic respiratory diseases is a matter of debate due to the potential effect on the development and prognosis of community-acquired pneumonia (CAP). We assessed whether treatment with inhaled steroids in patients with chronic bronchitis, COPD or asthma and CAP may affect early outcome of the acute pneumonic episode. Methods Over 1-year period, all population-based cases of CAP in patients with chronic bronchitis, COPD or asthma were registered. Use of inhaled steroids were registered and patients were followed up to 30 days after diagnosis to assess severity of CAP and clinical course (hospital admission, ICU admission and mortality). Results Of 473 patients who fulfilled the selection criteria, inhaled steroids were regularly used by 109 (23%). In the overall sample, inhaled steroids were associated with a higher risk of hospitalization (OR=1.96, p = 0.002) in the bivariate analysis, but this effect disappeared after adjusting by other severity-related factors (adjusted OR=1.08, p=0.787). This effect on hospitalization also disappeared when considering only patients with asthma (OR=1.38, p=0.542), with COPD alone (OR=4.68, p=0.194), but a protective effect was observed in CB patients (OR=0.15, p=0.027). Inhaled steroids showed no association with ICU admission, days to clinical recovery and mortality in the overall sample and in any disease subgroup. Conclusions Treatment with inhaled steroids is not a prognostic factor in COPD and asthmatic patients with CAP, but could prevent hospitalization for CAP in patients with clinical criteria of chronic bronchitis. PMID:24039899

  15. Steroids and genes related to steroid biosynthesis in the female giant freshwater prawn, Macrobrachium rosenbergii.

    PubMed

    Thongbuakaew, Tipsuda; Siangcham, Tanapan; Suwansa-ard, Saowaros; Elizur, Abigail; Cummins, Scott F; Sobhon, Prasert; Sretarugsa, Prapee

    2016-03-01

    The giant freshwater prawn, Macrobrachium rosenbergii, is important to many Asian countries due to its high economic value as an aquaculture product. With demand increasing, there is requirement for a better understanding of the biosynthetic components that regulate its growth and reproduction, including steroids, in order to help increase production. Vertebrate-type steroids and their receptors were identified in crustaceans and implicated in reproduction. In this study, we presented the sex steroids estradiol and progesterone by LC-MS/MS in female M. rosenbergii, and reveal steroidogenic-related genes by in silico analysis of de novo assembled transcriptomes. Comparative analysis with other species was performed to confirm their putative role, as well as tissue-specific and quantitative gene expression. We reveal 29 transcripts that encode for steroidogenic-related proteins, including steroidogenic enzymes, a nuclear steroid hormone receptors, and a steroidogenic factor. Moreover, we identified for the first time the presence of steroidogenic factor 1, StAR-related lipid transfer protein, estradiol receptor- and progesterone-like protein in M. rosenbergii. Those targeted for gene expression analysis (3 beta-hydroxysteroid dehydrogenase, 17 beta-hydroxysteroid dehydrogenase, estrogen sulfotransferase and progesterone receptor-like) showed widespread expression within many tissues, and at relatively high levels in the central nervous system (CNS) during ovarian maturation. In summary, we provide further evidence for the existence of steroidogenic pathways in crustaceans, which may be useful for advancing prawn aquaculture.

  16. Sex steroids imprinting and prostatic growth.

    PubMed

    Chung, L W; MacFadden, D K

    1980-01-01

    Sex steroids exposure to rats castrated at birth during the neonatal or prepubertal period permanently modified certain morphologic features of the accessory sex organs in adulthood. Similar treatment of intact rats failed to induce these changes. Hypophysectomy in adulthood did not abolish the neonatally androgen-induced imprinting of the growth response of the rat accessory sex organs in adulthood, which suggests that the effects of neonatal androgen administration are directly on the hormone-responsive target cells and are not mediated via the hypothalamic-pituitary axis.

  17. Steroid Resistant Nephrotic Syndrome-Genetic Consideration.

    PubMed

    Tasic, Velibor; Gucev, Zoran; Polenakovic, Momir

    2015-01-01

    Nephrotic syndrome is defined as the association of massive proteinuria, hypoalbuminaemia, edema, and hyperlipidemia. It is separated to steroid-sensitive or steroid-resistant (SRNS) forms in respect to the response to intensive steroid therapy. SRNS usually progresses to end-stage renal failure. According to the North American Pediatric Renal Trials and Collaborative Studies SRNS constitutes the second most frequent cause of ESRD in the first two decades of life. Unfortunately, there is no curative treatment for majority of patients. Majority of the SRNS patients have the histologic picture of focal segmental glomerulosclerosis. Interestingly, the risk of recurrence in the kidney graft in patients with hereditary SRNS is lower than in those who do not have genetic background. The etiology and pathogenesis of SRSN has remained enigma for decades. The discovery of 39 dominant or recessive SRNS genes enabled better understanding of the function of the glomerular podocytes and slit membrane. Hildebrandt's group has shown that 85% of the SRNS cases with onset by 3 months of age and 66% with onset by 1 year of age can be explained by recessive mutations in one of four genes only (NPHS1, NPHS2, LAMB2, or WT1). The same group used modern diagnostic techniques such as the next generation sequencing and tested a large international cohort of SRNS patients (n = 1783 families). The diagnostic panel included 21 genes with a recessive mode of inheritance and 6 genes with a dominant mode of inheritance. Single-gene cause was detected in 29.5% (526 of 1783) of the families with SRNS that manifested before 25 years of age. The identification of causative single-gene mutations may have important therapeutic consequences in some cases. This is very important for patients who carry mutations in a gene of coenzyme Q10 biosynthesis (COQ2, COQ6, ADCK4, or PDSS2). In these patients the treatment with coenzyme Q10 may be indicated. Also, patients with recessive mutations in PLCE1 may

  18. Ocular complications of diabetes mellitus

    PubMed Central

    Sayin, Nihat; Kara, Necip; Pekel, Gökhan

    2015-01-01

    Diabetes mellitus (DM) is a important health problem that induces ernestful complications and it causes significant morbidity owing to specific microvascular complications such as, retinopathy, nephropathy and neuropathy, and macrovascular complications such as, ischaemic heart disease, and peripheral vasculopathy. It can affect children, young people and adults and is becoming more common. Ocular complications associated with DM are progressive and rapidly becoming the world’s most significant cause of morbidity and are preventable with early detection and timely treatment. This review provides an overview of five main ocular complications associated with DM, diabetic retinopathy and papillopathy, cataract, glaucoma, and ocular surface diseases. PMID:25685281

  19. Cervical transforaminal epidural steroid injections: a proposal for optimizing the preprocedural evaluation with available imaging.

    PubMed

    Nishio, Isuta

    2014-01-01

    Cervical transforaminal epidural steroid injection (CTFESI) has been used to treat cervical radicular pain; however, rare but serious complications such as cerebellar or spinal cord infarction have been reported. The most probable causes of the serious complications include vertebral artery trauma, spasm, or accidental arterial injection of particulate steroid. Several recommendations have been made to improve the safety of CTFESI; however, evaluation and risk assessment of the patient's anatomy by the interventionist have not been sufficiently emphasized. Significant correlations between foraminal narrowing and proximity of the vertebral artery to the target of needle have been reported. This correlation is particularly problematic for interventionists because patients considered or referred for CTFESI are more likely to have foraminal narrowing at the level concerned. Without knowing the patient's anatomy, a common practice of rotating the C-arm obliquely to obtain a full view of the target foramen may carry significant risk of needle's encounter with the vertebral artery. Risk assessment through careful preprocedural review of the patient's magnetic resonance imaging by the interventionist is a worthwhile practice to optimize safety. Special attention should be paid to the vital structures such as the vertebral artery, neural foramen, and carotid artery. A preprocedural roadmap for the safest predicted needle trajectory can be created by simulation using the patient's available magnetic resonance imaging scans. These considerations may guide and help the interventionist to minimize the risk of inadvertent needle placement involving vital structures such as the vertebral artery or carotid artery.

  20. Complications of inflammatory bowel disease.

    PubMed

    Gasche, C

    2000-01-01

    Complications in inflammatory bowel disease determine the severity of disease as well as the complexities of medical or surgical treatment opportunities. Therefore, in known inflammatory bowel disease, the prevention, the early detection and the adequate therapeutic response to certain complications are important goals in the follow-up of inflammatory bowel disease patients. Disease complications are separated into intestinal and extraintestinal complications. Intestinal complications are somewhat disease specific, which means that they occur exclusively in either Crohn's disease or ulcerative colitis (e.g., enteric fistulas are particularly found in Crohn's disease and toxic megacolon in ulcerative colitis). Most extraintestinal complications occur in both forms of inflammatory bowel disease (e.g., anemia, thromboembolic events or osteoporosis). The current knowledge on pathogenesis, diagnostic tools, prevention and treatment of certain intestinal and extraintestinal complications is reviewed. PMID:10690585

  1. Dilated cardiomyopathy and acute liver injury associated with combined use of ephedra, gamma-hydroxybutyrate, and anabolic steroids.

    PubMed

    Clark, Brychan M; Schofield, Richard S

    2005-05-01

    Anabolic-androgenic steroids are synthetic derivatives of testosterone that some athletes have used to enhance muscle mass and improve their athletic performance. Ephedrine is a potent sympathomimetic agent that can lead to cardiomyopathy similar to that seen with catecholamine excess. Adverse cardiovascular events attributed to anabolic steroid and ephedra use, such as arrhythmias, myocardial infarction, cardiomyopathy, and sudden death, are rarely reported. Bodybuilders have used gamma-hydroxybutyrate, a potent secretagogue of growth hormone, to promote muscle development. Although dilated cardiomyopathy is a known complication of excess growth hormone levels, it has not been associated with use of gamma-hydroxybutyrate. A healthy 40-year-old man was admitted to our hospital for new-onset congestive heart failure and severe acute hepatitis that developed several months after he began using anabolic-androgenic steroids, ephedra, and gamma-hydroxybutyrate supplements. Analysis with an objective causality assessment scale revealed a probable adverse drug reaction between the patient's use of anabolic steroids, ephedra, and gamma-hydroxybutyrate and the development of his cardiomyopathy and acute liver injury. PMID:15899737

  2. Matrix metalloproteinases and their tissue inhibitors in preterm perinatal complications.

    PubMed

    Cockle, Julia V; Gopichandran, Nadia; Walker, James J; Levene, Malcolm I; Orsi, Nicolas M

    2007-10-01

    The objective of this article is to review the role of matrix metalloproteinases (MMPs) in fetomaternal/neonatal complications of preterm birth. The function of MMPs as proteolytic enzymes involved in tissue remodeling/destruction is reviewed in preterm labor, preeclampsia, premature rupture of membranes, intrauterine growth restriction, chronic lung disease, necrotizing enterocolitis, intraventricular hemorrhage, cystic periventricular leukomalacia, and retinopathy of prematurity. Cytokines, steroid hormones, and reactive oxygen species all regulate MMP labor and expression/activity. In labor, activation follows an inflammatory response, which results in fetal membrane rupture and cervical dilation/ripening, particularly when premature. Expression/activation is elevated during parturition, particularly when premature. While fetal membrane rupture is preceded by increases in tissue-specific MMPs, neonatal complications also ensue from an imbalance between MMPs and their tissue inhibitors. These e fects implicate environmental triggers and a genetic predisposition. MMPs are involved in the perinatal complications of prematurity and are potential targets for therapeutic intervention. Functional MMP genetic polymorphisms may assist in identifying patients at risk of complications.

  3. Rate of intraoperative complications during cataract surgery following intravitreal injections.

    PubMed

    Hahn, P; Jiramongkolchai, K; Stinnett, S; Daluvoy, M; Kim, T

    2016-08-01

    PurposeTo investigate the effect of prior intravitreal injections on intraoperative and postoperative complication rates associated with cataract surgery.MethodsA retrospective cohort analysis reviewed 10 105 cataract surgery procedures performed by experienced surgeons at the Duke Eye Center from 1 January 2005 to 10 December 2012. A group of 197 eyes with prior intravitreal injections was compared with an equal number of matched control eyes without prior injection using the Fisher's exact test of difference in proportions and the Wilcoxon rank-sum test of difference in means. Outcomes analyzed included baseline demographic information, preoperative clinical characteristics, prevalence of intraoperative complications, and postoperative intraocular pressure, glaucoma surgery, and glaucoma medication requirement through 1 year following cataract surgery.ResultsAn increased rate of intraoperative complications was identified during cataract surgery in eyes with prior intravitreal injections compared with control eyes (3 vs 0%, P=0.030). Injection eyes required more glaucoma medications at 1 year, but no difference was identified if steroid injections were excluded. No difference in postoperative IOP or glaucoma surgery was identified. No cases of endophthalmitis were reported.ConclusionsA history of intravitreal injections may be a risk factor for cataract surgery-related intraoperative complications. We hypothesize this may be due to unidentified iatrogenic lens trauma during intravitreal injections. Particular attention to the posterior capsule during preoperative assessment and intraoperatively is recommended in eyes undergoing cataract surgery with a prior history of intravitreal injections.

  4. Surgery on Fetus Reduces Complications of Spina Bifida

    MedlinePlus

    ... Spotlights Media Resources Interviews & Selected Staff Profiles Multimedia Video: Surgery on Fetus Reduces Complications of Spina Bifida ... opening in the spine. In a new Web video, study author Catherine Y. Spong, M.D., Chief ...

  5. Biocatalyst mediated production of 6β,11α-dihydroxy derivatives of 4-ene-3-one steroids.

    PubMed

    Kolet, Swati P; Niloferjahan, Siddiqui; Haldar, Saikat; Gonnade, Rajesh; Thulasiram, Hirekodathakallu V

    2013-11-01

    Biotransformation of steroids with 4-ene-3-one functionality such as progesterone (I), testosterone (II), 17α-methyltestosterone (III), 4-androstene-3,17-dione (IV) and 19-nortestosterone (V) were studied by using a fungal system belonging to the genera of Mucor (M881). The fungal system efficiently and quantitatively converted these steroids in regio- and stereo-selective manner into corresponding 6β,11α-dihydroxy compounds. Time course experiments suggested that the transformation was initiated by hydroxylation at 6β- or 11α-(10β-hydroxy in case of V) to form monohydroxy derivatives which upon prolonged incubation were converted into corresponding 6β,11α-dihydroxy derivatives. The fermentation studies carried out using 5L table-top fermentor with substrates (I and II) clearly indicates that 6β,11α-dihydroxy derivatives of steroids with 4-ene-3-one functionality can be produced in large scale by using M881.

  6. Sex steroid correlates of female-specific colouration, behaviour and reproductive state in Lake Eyre dragon lizards, Ctenophorus maculosus.

    PubMed

    Jessop, Tim S; Chan, Rita; Stuart-Fox, Devi

    2009-07-01

    In some species, females develop bright colouration to signal reproductive status and exhibit behavioural repertoires to incite male courtship and/or reduce male harassment and forced copulation. Sex steroids, including progesterone and testosterone, potentially mediate female reproductive colouration and reproductive behaviour. We measured associations among plasma profiles of testosterone and progesterone with variation in colour expression and reproductive behaviour, including unique courtship rejection behaviours, in female Lake Eyre dragon lizards, (Ctenophorus maculosus). At onset of breeding, progesterone and testosterone increased with vitellogenesis, coincident with colour intensification and sexual receptivity, indicated by acceptance of copulations. As steroid levels peaked around the inferred ovulation time, maximal colour development occurred and sexual receptivity declined. When females were gravid and exhibited maximal mate rejection behaviours, progesterone levels remained consistently high, while testosterone exhibited a discrete second peak. At oviposition, significant declines in plasma steroid levels, fading of colouration and a dramatic decrease in male rejection behaviours co-occurred. Our results indicate a generally concordant association among steroid levels, colouration, behaviour and reproductive events. However, the prolonged elevation in progesterone and a second peak of testosterone was unrelated to reproductive state or further colour change, possibly suggesting selection on females to retain high steroid levels for inducing rejection behaviours. PMID:19363614

  7. Sex steroid correlates of female-specific colouration, behaviour and reproductive state in Lake Eyre dragon lizards, Ctenophorus maculosus.

    PubMed

    Jessop, Tim S; Chan, Rita; Stuart-Fox, Devi

    2009-07-01

    In some species, females develop bright colouration to signal reproductive status and exhibit behavioural repertoires to incite male courtship and/or reduce male harassment and forced copulation. Sex steroids, including progesterone and testosterone, potentially mediate female reproductive colouration and reproductive behaviour. We measured associations among plasma profiles of testosterone and progesterone with variation in colour expression and reproductive behaviour, including unique courtship rejection behaviours, in female Lake Eyre dragon lizards, (Ctenophorus maculosus). At onset of breeding, progesterone and testosterone increased with vitellogenesis, coincident with colour intensification and sexual receptivity, indicated by acceptance of copulations. As steroid levels peaked around the inferred ovulation time, maximal colour development occurred and sexual receptivity declined. When females were gravid and exhibited maximal mate rejection behaviours, progesterone levels remained consistently high, while testosterone exhibited a discrete second peak. At oviposition, significant declines in plasma steroid levels, fading of colouration and a dramatic decrease in male rejection behaviours co-occurred. Our results indicate a generally concordant association among steroid levels, colouration, behaviour and reproductive events. However, the prolonged elevation in progesterone and a second peak of testosterone was unrelated to reproductive state or further colour change, possibly suggesting selection on females to retain high steroid levels for inducing rejection behaviours.

  8. Current concepts in anabolic-androgenic steroids.

    PubMed

    Evans, Nick A

    2004-03-01

    Anabolic-androgenic steroids (AAS) are synthetic derivatives of testosterone. According to surveys and media reports, the legal and illegal use of these drugs is gaining popularity. Testosterone restores sex drive and boosts muscle mass, making it central to 2 of society's rising preoccupations: perfecting the male body and sustaining the male libido. The anabolic effects of AAS have been questioned for decades, but recent scientific investigation of supraphysiologic doses supports the efficacy of these regimens. Testosterone has potent anabolic effects on the musculoskeletal system, including an increase in lean body mass, a dose-related hypertrophy of muscle fibers, and an increase in muscle strength. For athletes requiring speed and strength and men desiring a cosmetic muscle makeover, illegal steroids are a powerful lure, despite the risk of subjective side effects. Recent clinical studies have discovered novel therapeutic uses for physiologic doses of AAS, without any significant adverse effects in the short term. In the wake of important scientific advances during the past decade, the positive and negative effects of AAS warrant reevaluation. Guidelines for the clinical evaluation of AAS users will be presented for sports medicine practitioners.

  9. Complications of Anterior and Posterior Cervical Spine Surgery

    PubMed Central

    Cheung, Jason Pui Yin

    2016-01-01

    Cervical spine surgery performed for the correct indications yields good results. However, surgeons need to be mindful of the many possible pitfalls. Complications may occur starting from the anaesthestic procedure and patient positioning to dura exposure and instrumentation. This review examines specific complications related to anterior and posterior cervical spine surgery, discusses their causes and considers methods to prevent or treat them. In general, avoiding complications is best achieved with meticulous preoperative analysis of the pathology, good patient selection for a specific procedure and careful execution of the surgery. Cervical spine surgery is usually effective in treating most pathologies and only a reasonable complication rate exists. PMID:27114784

  10. Steroid binding to Autotaxin links bile salts and lysophosphatidic acid signalling.

    PubMed

    Keune, Willem-Jan; Hausmann, Jens; Bolier, Ruth; Tolenaars, Dagmar; Kremer, Andreas; Heidebrecht, Tatjana; Joosten, Robbie P; Sunkara, Manjula; Morris, Andrew J; Matas-Rico, Elisa; Moolenaar, Wouter H; Oude Elferink, Ronald P; Perrakis, Anastassis

    2016-01-01

    Autotaxin (ATX) generates the lipid mediator lysophosphatidic acid (LPA). ATX-LPA signalling is involved in multiple biological and pathophysiological processes, including vasculogenesis, fibrosis, cholestatic pruritus and tumour progression. ATX has a tripartite active site, combining a hydrophilic groove, a hydrophobic lipid-binding pocket and a tunnel of unclear function. We present crystal structures of rat ATX bound to 7α-hydroxycholesterol and the bile salt tauroursodeoxycholate (TUDCA), showing how the tunnel selectively binds steroids. A structure of ATX simultaneously harbouring TUDCA in the tunnel and LPA in the pocket, together with kinetic analysis, reveals that bile salts act as partial non-competitive inhibitors of ATX, thereby attenuating LPA receptor activation. This unexpected interplay between ATX-LPA signalling and select steroids, notably natural bile salts, provides a molecular basis for the emerging association of ATX with disorders associated with increased circulating levels of bile salts. Furthermore, our findings suggest potential clinical implications in the use of steroid drugs. PMID:27075612

  11. Study of osteoarthritis treatment with anti-inflammatory drugs: cyclooxygenase-2 inhibitor and steroids.

    PubMed

    Cho, Hongsik; Walker, Andrew; Williams, Jeb; Hasty, Karen A

    2015-01-01

    Patients with osteoarthritis (OA), a condition characterized by cartilage degradation, are often treated with steroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and cyclooxygenase-2 (COX-2) selective NSAIDs. Due to their inhibition of the inflammatory cascade, the drugs affect the balance of matrix metalloproteinases (MMPs) and inflammatory cytokines, resulting in preservation of extracellular matrix (ECM). To compare the effects of these treatments on chondrocyte metabolism, TNF-α was incubated with cultured chondrocytes to mimic a proinflammatory environment with increasing production of MMP-1 and prostaglandin E2 (PGE2). The chondrocytes were then treated with either a steroid (prednisone), a nonspecific COX inhibitor NSAID (piroxicam), or a COX-2 selective NSAID (celecoxib). Both prednisone and celecoxib decreased MMP-1 and PGE-2 production while the nonspecific piroxicam decreased only the latter. Both prednisone and celecoxib decreased gene expression of MMP-1 and increased expression of aggrecan. Increased gene expression of type II collagen was also noted with celecoxib. The nonspecific piroxicam did not show these effects. The efficacy of celecoxib in vivo was investigated using a posttraumatic OA (PTOA) mouse model. In vivo, celecoxib increases aggrecan synthesis and suppresses MMP-1. In conclusion, this study demonstrates that celecoxib and steroids exert similar effects on MMP-1 and PGE2 production in vitro and that celecoxib may demonstrate beneficial effects on anabolic metabolism in vivo.

  12. Steroid binding to Autotaxin links bile salts and lysophosphatidic acid signalling

    PubMed Central

    Keune, Willem-Jan; Hausmann, Jens; Bolier, Ruth; Tolenaars, Dagmar; Kremer, Andreas; Heidebrecht, Tatjana; Joosten, Robbie P.; Sunkara, Manjula; Morris, Andrew J.; Matas-Rico, Elisa; Moolenaar, Wouter H.; Oude Elferink, Ronald P.; Perrakis, Anastassis

    2016-01-01

    Autotaxin (ATX) generates the lipid mediator lysophosphatidic acid (LPA). ATX-LPA signalling is involved in multiple biological and pathophysiological processes, including vasculogenesis, fibrosis, cholestatic pruritus and tumour progression. ATX has a tripartite active site, combining a hydrophilic groove, a hydrophobic lipid-binding pocket and a tunnel of unclear function. We present crystal structures of rat ATX bound to 7α-hydroxycholesterol and the bile salt tauroursodeoxycholate (TUDCA), showing how the tunnel selectively binds steroids. A structure of ATX simultaneously harbouring TUDCA in the tunnel and LPA in the pocket, together with kinetic analysis, reveals that bile salts act as partial non-competitive inhibitors of ATX, thereby attenuating LPA receptor activation. This unexpected interplay between ATX-LPA signalling and select steroids, notably natural bile salts, provides a molecular basis for the emerging association of ATX with disorders associated with increased circulating levels of bile salts. Furthermore, our findings suggest potential clinical implications in the use of steroid drugs. PMID:27075612

  13. Steroids in teleost fishes: A functional point of view.

    PubMed

    Tokarz, Janina; Möller, Gabriele; Hrabě de Angelis, Martin; Adamski, Jerzy

    2015-11-01

    Steroid hormones are involved in the regulation of a variety of processes like embryonic development, sex differentiation, metabolism, immune responses, circadian rhythms, stress response, and reproduction in vertebrates. Teleost fishes and humans show a remarkable conservation in many developmental and physiological aspects, including the endocrine system in general and the steroid hormone related processes in particular. This review provides an overview of the current knowledge about steroid hormone biosynthesis and the steroid hormone receptors in teleost fishes and compares the findings to the human system. The impact of the duplicated genome in teleost fishes on steroid hormone biosynthesis and perception is addressed. Additionally, important processes in fish physiology regulated by steroid hormones, which are most dissimilar to humans, are described. We also give a short overview on the influence of anthropogenic endocrine disrupting compounds on steroid hormone signaling and the resulting adverse physiological effects for teleost fishes. By this approach, we show that the steroidogenesis, hormone receptors, and function of the steroid hormones are reasonably well understood when summarizing the available data of all teleost species analyzed to date. However, on the level of a single species or a certain fish-specific aspect of physiology, further research is needed.

  14. New cytotoxic steroids from the leaves of Clerodendrum trichotomum.

    PubMed

    Xu, Rui-Lan; Wang, Rui; Ding, Lan; Shi, Yan-Ping

    2013-07-01

    A phytochemical investigation of the leaves of Clerodendrum trichotomum led to the isolation of five new (2-6) and two known (1 and 7) steroids, whose structures and relative configurations were elucidated by comprehensive spectroscopic analysis and by comparison of their NMR data with those of related compounds. Steroids 2 and 5 exhibited moderate cytotoxicity in vitro against HeLa cell line.

  15. Total synthesis of steroids and heterosteroids from BISTRO.

    PubMed

    Ibrahim-Ouali, Malika

    2015-06-01

    Due to their high profile biological activity, the steroids are among the most important secondary metabolites. A review of literature on the total synthesis of steroids starting from BISTRO (1,8-bis(trimethylsilyl)-2,6-octadiene) is presented.

  16. Steroid hormones as biomarkers of endocrine disruption in wildlife

    SciTech Connect

    Guillette, L.J. Jr.; Rooney, A.A.; Crain, D.A.; Orlando, E.F.

    1999-07-01

    Xenobiotic compounds introduced into the environment by human activity have been shown to adversely affect the endocrine system of wildlife. Various species exhibit abnormalities of (1) plasma sex steroid hormones, (2) altered steroid synthesis form the gonad in vitro and (3) altered steroidogenic enzyme function. These endpoints are sensitive and relatively easy to measure quantitatively with reliability and precision. These observations have led to the conclusion that sex steroid hormones could be markers of exposure to, and altered function from, endocrine disrupting contaminants (EDCs). However, there are serious limitations in the use of steroid hormones as generalized markers of EDC exposure. Steroid hormones exhibit seasonal, ontogenetic, gender and species-specific variation. Moreover, the regulation of sex steroid plasma concentrations is a relatively complex phenomenon capable of short-term (minutes-hours) alteration due to environmental inputs, such as acute stress--an activational response. Alterations in steroids synthesis and degradation also can be a response to altered embryonic development due to EDC exposure--an organizational response. If steroid hormones are to be used as biomarkers, then closely controlled, well designed sampling has to be performed. Additionally, an appreciation of the variation possible in endocrine responses among the species to be studied must be obtained.

  17. The Regulation of Steroid Action by Sulfation and Desulfation

    PubMed Central

    Mueller, Jonathan W.; Gilligan, Lorna C.; Idkowiak, Jan; Arlt, Wiebke

    2015-01-01

    Steroid sulfation and desulfation are fundamental pathways vital for a functional vertebrate endocrine system. After biosynthesis, hydrophobic steroids are sulfated to expedite circulatory transit. Target cells express transmembrane organic anion-transporting polypeptides that facilitate cellular uptake of sulfated steroids. Once intracellular, sulfatases hydrolyze these steroid sulfate esters to their unconjugated, and usually active, forms. Because most steroids can be sulfated, including cholesterol, pregnenolone, dehydroepiandrosterone, and estrone, understanding the function, tissue distribution, and regulation of sulfation and desulfation processes provides significant insights into normal endocrine function. Not surprisingly, dysregulation of these pathways is associated with numerous pathologies, including steroid-dependent cancers, polycystic ovary syndrome, and X-linked ichthyosis. Here we provide a comprehensive examination of our current knowledge of endocrine-related sulfation and desulfation pathways. We describe the interplay between sulfatases and sulfotransferases, showing how their expression and regulation influences steroid action. Furthermore, we address the role that organic anion-transporting polypeptides play in regulating intracellular steroid concentrations and how their expression patterns influence many pathologies, especially cancer. Finally, the recent advances in pharmacologically targeting steroidogenic pathways will be examined. PMID:26213785

  18. Does Steroid Abuse Cause--Or Excuse--Violence?

    ERIC Educational Resources Information Center

    Lubell, Adele

    1989-01-01

    Use of anabolic steroids is believed to increase the odds of violent antisocial behavior, thus posing risks to consumers and the general public. Some research shows the danger of steroids in inducing severe adverse psychiatric effects. Certain lawyers use this abuse to plead insanity for their clients. (SM)

  19. New steps forward in the neuroactive steroid field.

    PubMed

    Giatti, Silvia; Garcia-Segura, Luis Miguel; Melcangi, Roberto Cosimo

    2015-09-01

    Evidence accumulated in recent years suggests that the systemic treatment with neuroactive steroids, or the pharmacological modulation of its production by brain cells, represent therapeutic options to promote neuroprotection. However, new findings, which are reviewed in this paper, suggest that the factors to be considered for the design of possible therapies based on neuroactive steroids are more complex than previously thought. Thus, although as recently reported, the nervous system regulates neuroactive steroid synthesis and metabolism in adaptation to modifications in peripheral steroidogenesis, the neuroactive steroid levels in the brain do not fully reflect its levels in plasma. Even, in some cases, neuroactive steroid level modifications occurring in the nervous tissues, under physiological and pathological conditions, are in the opposite direction than in the periphery. This suggests that the systemic treatment with these molecules may have unexpected outcomes on neural steroid levels. In addition, the multiple metabolic pathways and signaling mechanisms of neuroactive steroids, which may change from one brain region to another, together with the existence of regional and sex differences in its neural levels are additional sources of complexity that should be clarified. This complexity in the levels and actions of these molecules may explain why in some cases these molecules have detrimental rather than beneficial actions for the nervous system. This article is part of a Special Issue entitled 'Steroid Perspectives'.

  20. The Regulation of Steroid Action by Sulfation and Desulfation.

    PubMed

    Mueller, Jonathan W; Gilligan, Lorna C; Idkowiak, Jan; Arlt, Wiebke; Foster, Paul A

    2015-10-01

    Steroid sulfation and desulfation are fundamental pathways vital for a functional vertebrate endocrine system. After biosynthesis, hydrophobic steroids are sulfated to expedite circulatory transit. Target cells express transmembrane organic anion-transporting polypeptides that facilitate cellular uptake of sulfated steroids. Once intracellular, sulfatases hydrolyze these steroid sulfate esters to their unconjugated, and usually active, forms. Because most steroids can be sulfated, including cholesterol, pregnenolone, dehydroepiandrosterone, and estrone, understanding the function, tissue distribution, and regulation of sulfation and desulfation processes provides significant insights into normal endocrine function. Not surprisingly, dysregulation of these pathways is associated with numerous pathologies, including steroid-dependent cancers, polycystic ovary syndrome, and X-linked ichthyosis. Here we provide a comprehensive examination of our current knowledge of endocrine-related sulfation and desulfation pathways. We describe the interplay between sulfatases and sulfotransferases, showing how their expression and regulation influences steroid action. Furthermore, we address the role that organic anion-transporting polypeptides play in regulating intracellular steroid concentrations and how their expression patterns influence many pathologies, especially cancer. Finally, the recent advances in pharmacologically targeting steroidogenic pathways will be examined.

  1. Role of sex steroids and their receptors in human preterm infants: Impacts on future treatment strategies for cerebral development.

    PubMed

    Hübner, Stephanie; Reich, Bettina; Heckmann, Matthias

    2015-12-15

    Preterm birth is a major risk factor for cerebral complications, such as hemorrhage or periventricular leukomalacia, which lead to lifelong neurodevelopmental deficits. Hypoxia/ischemia, inflammation, hyperoxia, and prematurity itself contribute to the extent of impaired neurodevelopment. Preterm birth leads to disruption of the placental supply of estrogens and progesterone. Postnatally, the plasma levels of estrogens and progesterone drop 100-fold. Preterm infants are deprived of the placental supply of these hormones for up to sixteen weeks. Thus, supplementation of estradiol and progesterone to mimic intrauterine conditions may potentially improve a premature infant́s extrauterine development and help protect the brain against neurological complications. However, preliminary clinical studies did not find improved outcomes except for a trend towards less cerebral palsy. The decrease in estrogen and progesterone concentrations is accompanied by persistent, high postnatal production of fetal zone steroids, mainly dehydroepiandrosterone, which serve as precursors for maternal estrogen synthesis during pregnancy. This commentary will combine knowledge from endocrinology, pharmacology, and neonatology to explain the discrepancies between promising animal models and clinical findings. Most important targets will be classical and non-classical estrogen receptors, which interact differently-not only with estrogens but also with fetal zone steroids. The fetal zone is unique among humans and higher primates. Therefore, a clearly defined model is required to study the role of sex steroids and their receptors before further clinical studies begin. PMID:26300058

  2. Role of sex steroids and their receptors in human preterm infants: Impacts on future treatment strategies for cerebral development.

    PubMed

    Hübner, Stephanie; Reich, Bettina; Heckmann, Matthias

    2015-12-15

    Preterm birth is a major risk factor for cerebral complications, such as hemorrhage or periventricular leukomalacia, which lead to lifelong neurodevelopmental deficits. Hypoxia/ischemia, inflammation, hyperoxia, and prematurity itself contribute to the extent of impaired neurodevelopment. Preterm birth leads to disruption of the placental supply of estrogens and progesterone. Postnatally, the plasma levels of estrogens and progesterone drop 100-fold. Preterm infants are deprived of the placental supply of these hormones for up to sixteen weeks. Thus, supplementation of estradiol and progesterone to mimic intrauterine conditions may potentially improve a premature infant́s extrauterine development and help protect the brain against neurological complications. However, preliminary clinical studies did not find improved outcomes except for a trend towards less cerebral palsy. The decrease in estrogen and progesterone concentrations is accompanied by persistent, high postnatal production of fetal zone steroids, mainly dehydroepiandrosterone, which serve as precursors for maternal estrogen synthesis during pregnancy. This commentary will combine knowledge from endocrinology, pharmacology, and neonatology to explain the discrepancies between promising animal models and clinical findings. Most important targets will be classical and non-classical estrogen receptors, which interact differently-not only with estrogens but also with fetal zone steroids. The fetal zone is unique among humans and higher primates. Therefore, a clearly defined model is required to study the role of sex steroids and their receptors before further clinical studies begin.

  3. Derivatization of steroids in biological samples for GC-MS and LC-MS analyses.

    PubMed

    Marcos, Josep; Pozo, Oscar J

    2015-10-01

    The determination of steroids in biological samples is essential in different areas of knowledge. MS combined with either GC or LC is considered the best analytical technique for specific and sensitive determinations. However, due to the physicochemical properties of some steroids, and the low concentrations found in biological samples, the formation of a derivative prior to their analysis is required. In GC-MS determinations, derivatization is needed for generating volatile and thermally stable compounds. The improvement in terms of stability and chromatographic retention are the main reasons for selecting the derivatization agent. On the other hand, derivatization is not compulsory in LC-MS analyses and the derivatization is typically used for improving the ionization and therefore the overall sensitivity achieved.

  4. Ketoconazole inhibition of testicular secretion of testosterone and displacement of steroid hormones from serum transport proteins.

    PubMed Central

    Grosso, D S; Boyden, T W; Pamenter, R W; Johnson, D G; Stevens, D A; Galgiani, J N

    1983-01-01

    In vivo perfusion of canine testes with ketoconazole inhibited the stimulation of testosterone production by human chorionic gonadotropin in a dose-dependent manner. Ketoconazole also selectively displaced steroids from serum-binding globulins. Dihydrotestosterone and estradiol binding to sex hormone-binding globulin were inhibited by ketoconazole. Cortisol binding to corticosteroid-binding globulin was unaffected. The concentrations of ketoconazole that inhibited human chorionic gonadotropin stimulation of testicular androgen production and displaced sex steroids from sex hormone-binding globulin were in the range of blood levels found in patients on higher therapeutic dosage regimens. Suppression of testicular testosterone synthesis and displacement of estrogens from sex hormone-binding globulin may decrease the androgen/estrogen ratio of the blood and contribute to the development of gynecomastia that has been reported in some ketoconazole-treated patients. PMID:6301363

  5. Synthesis and acetylcholinesterase inhibitory activity of polyhydroxylated sulfated steroids: structure/activity studies.

    PubMed

    Richmond, Victoria; Murray, Ana P; Maier, Marta S

    2013-11-01

    Disulfated and trisulfated steroids have been synthesized from cholesterol and their acetylcholinesterase inhibitory activity has been evaluated. In our studies we have found that the activity was not only dependent on the location of the sulfate groups but on their configurations. 2β,3α,6α-trihydroxy-5α-cholestan-6-one trisulfate (18) was the most active steroid with an IC50 value of 15.48 μM comparable to that of 2β,3α-dihydroxy-5α-cholestan-6-one disulfate (1). Both compounds were found to be less active than the reference compound eserine. The butyrylcholinesterase activity of 1 and 18 was one magnitude lower than that against acetylcholinesterase revealing a selective inhibitor profile.

  6. Nongenomic Actions of Adrenal Steroids in the Central Nervous System

    PubMed Central

    Evanson, Nathan K.; Herman, James P.; Sakai, Randall R.; Krause, Eric G.

    2015-01-01

    Mineralocorticoids and glucocorticoids are steroid hormones that are released by the adrenal cortex in response to stress and hydromineral imbalance. Historically, adrenocorticosteroid actions are attributed to effects on gene transcription. More recently, however, it has become clear that genome-independent pathways represent an important facet of adrenal steroid actions. These hormones exert nongenomic effects throughout the body, but a significant portion of their actions are specific to the central nervous system. These actions are mediated by a variety of signalling pathways, and lead to physiologically meaningful events in vitro and in vivo. Here we review nongenomic effects of adrenal steroids in the central nervous system at the levels of behaviour, neural system activity, individual neurone activity, and subcellular signalling activity. A clearer understanding of adrenal steroid activity in the central nervous system will lead to a better ability both to treat human disease, and to reduce side-effects of steroid treatments already in use. PMID:20367759

  7. Infantile hemangiomas, complications and treatments.

    PubMed

    Cheng, Carol Erin; Friedlander, Sheila Fallon

    2016-03-01

    Infantile hemangiomas (IHs) are the most common vascular tumors of infancy. While the majority regress without the need for intervention, approximately 10%, often site dependent, can cause serious complications and require treatment. IH complications can be categorized as life threatening, obstructive, ulcerative or disfiguring. Life threatening complications include airway and hepatic IHs. Functional complications obstructing vital structures or impairing function include periocular, nasal, labial, parotid, auricular, and breast IHs. Local complications arise from ulceration or those in cosmetically sensitive areas. Therapeutic options for complicated IHs include pharmacologic (topical or systemic), surgical, or laser interventions. Topical agents are best employed for small, superficial, and localized IHs; while systemic therapy is reserved for larger IHs and those with more aggressive growth characteristics with propranolol as first-line therapy. PMID:27607318

  8. Steroid profiling in pregnancy: a focus on the human fetus.

    PubMed

    Hill, Martin; Pašková, Andrea; Kančeva, Radmila; Velíková, Marta; Kubátová, Jana; Kancheva, Lyudmila; Adamcová, Karolína; Mikešová, Michaela; Žižka, Zdeněk; Koucký, Michal; Šarapatková, Hana; Kačer, Viktor; Matucha, Petr; Meloun, Milan; Pařízek, Antonín

    2014-01-01

    In this review we focused on steroid metabolomics in human fetuses and newborns and its role in the physiology and pathophysiology of human pregnancy and subsequent stages of human life, and on the physiological relevance of steroids influencing the nervous systems with regards to their concentrations in the fetus. Steroid profiling provides valuable data for the diagnostics of diseases related to altered steroidogenesis in the fetal and maternal compartments and placenta. We outlined a potential use of steroid metabolomics for the prediction of reproductive disorders, misbalance of hypothalamic-pituitary-adrenal axis, and impaired insulin sensitivity in subsequent stages of human life. A possible role of steroids exhibiting a non-genomic effect in the development of gestational diabetes and in the neuroprotection via negative modulation of AMPA/kainate receptors was also indicated. Increasing progesterone synthesis and catabolism, declining production of tocolytic 5β-pregnane steroids, and rising activities of steroid sulfotransferases with the approaching term may be of importance in sustaining pregnancy. An increasing trend was demonstrated with advancing gestation toward the production of ketones (and 3β-hydroxyl groups in the case of 3α-hydroxy-steroids) was demonstrated in the fetus on the expense of 3α-hydroxy-, 17β-hydroxy-, and 20α-hydroxy-groups weakening in the sequence C17, C3, and C20. There was higher production of active progestogen but lower production of active estrogen and GABAergic steroids with the approaching term. Rising activities of placental CYP19A1 and oxidative isoforms of HSD17B, and of fetal CYP3A7 with advancing gestation may protect the fetus from hyperestrogenization. This article is part of a Special Issue entitled 'Pregnancy and Steroids'.

  9. Complications of hyaluronic acid fillers.

    PubMed

    Weinberg, Michael J; Solish, Nowell

    2009-12-01

    Hyaluronic acid filler use, user groups, and indications have expanded significantly in the past several years. This group of fillers is extremely safe in experienced hands. Complications are infrequent but can be devastating. There can be no substitution for recognized and specific training. Prompt recognition and proper treatment of serious complication can moderate and even prevent serious sequelae. This article describes the most frequent and serious complications, their prevention, and treatment.

  10. Steroid Injection and Nonsteroidal Anti-inflammatory Agents for Shoulder Pain: A PRISMA Systematic Review and Meta-Analysis of Randomized Controlled Trials.

    PubMed

    Sun, Yaying; Chen, Jiwu; Li, Hong; Jiang, Jia; Chen, Shiyi

    2015-12-01

    Advantages and possible risks associated with steroid injection compared with nonsteroidal anti-inflammatory drugs (NSAIDs) for shoulder pain are not fully understood. To compare the efficiency and safety of steroid injection versus NSAIDs for patients with shoulder pain. PubMed, Embase, and the Cochrane Library were searched through July 2015. Study eligibility criteria, participants, and interventions: randomized controlled trials (RCTs) that assessed steroid injection versus NSAIDs for patients with shoulder pain. Study appraisal and synthesis methods: predefined primary efficacy outcome was functional improvement; and secondary efficacy outcomes included pain relief and complications. Relative risks (RRs) and standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using a random-effects model accounting for clinical heterogeneity. Eight RCTs involving 465 participants were included in the meta-analysis. Five trials compared steroid injection with oral NSAIDs, and 3 compared steroids injection with NSAIDs injection. Compared with steroid injection, oral NSAIDs were less effective in 4 or 6 weeks for functional improvement (SMD 0.61; 95% CI, 0.08-1.14; P = 0.01), while there was no significant difference in pain relief (SMD 0.45; 95% CI, -0.50-1.40; P < 0.00001) or complication rate (RR 1.10; 95% CI, 0.26-4.58; P = 0.29). Meta-analysis was not performed for NSAIDs injection due to considerable heterogeneity. Conflicting results were observed in favor of either steroid or NSAIDs injection. Not all diseases that can lead to shoulder pain were included, detailed intervention protocols were inconsistent across studies, and some estimated data were input into comparison while some data were lost, which could exert an influence on pooled results. Steroid injection, compared with oral NSAIDs, provides slightly more improvement in shoulder function without superiority in pain relief or risk of complications at 4 to 6 weeks

  11. Effect of steroid use in anterior cervical discectomy and fusion: a randomized controlled trial.

    PubMed

    Jeyamohan, Shiveindra B; Kenning, Tyler J; Petronis, Karen A; Feustel, Paul J; Drazin, Doniel; DiRisio, Darryl J

    2015-08-01

    OBJECT Anterior cervical discectomy and fusion (ACDF) is an effective procedure for the treatment of cervical radiculopathy and/or myelopathy; however, postoperative dysphagia is a significant concern. Dexamethasone, although potentially protective against perioperative dysphagia and airway compromise, could inhibit fusion, a generally proinflammatory process. The authors conducted a prospective, randomized, double-blinded, controlled study of the effects of steroids on swallowing, the airway, and arthrodesis related to multilevel anterior cervical reconstruction in patients who were undergoing ACDF at Albany Medical Center between 2008 and 2012. The objective of this study was to determine if perioperative steroid use improves perioperative dysphagia and airway edema. METHODS A total of 112 patients were enrolled and randomly assigned to receive saline or dexamethasone. Data gathered included demographics, functional status (including modified Japanese Orthopaedic Association myelopathy score, neck disability index, 12-Item Short-Form Health Survey score, and patient-reported visual analog scale score of axial and radiating pain), functional outcome swallowing scale score, interval postoperative imaging, fusion status, and complications/reoperations. Follow-up was performed at 1, 3, 6, 12, and 24 months, and CT was performed 6, 12, and 24 months after surgery for fusion assessment. RESULTS Baseline demographics were not significantly different between the 2 groups, indicating adequate randomization. In terms of patient-reported functional and pain-related outcomes, there were no differences in the steroid and placebo groups. However, the severity of dysphagia in the postoperative period up to 1 month proved to be significantly lower in the steroid group than in the placebo group (p = 0.027). Furthermore, airway difficulty and a need for intubation trended toward significance in the placebo group (p = 0.057). Last, fusion rates at 6 months proved to be

  12. [Control measures for anabolic androgenic steroid medicines].

    PubMed

    Vázquez-Mourelle, Raquel; Carracedo-Martínez, Eduardo; Ces Gens, Eugenio; Cadórniga Valiño, Luis; Álvaro Esteban, Pilar; Pose Reino, José Manuel

    2015-01-01

    Anabolic androgenic steroids (AAS) can cause serious adverse effects when used without a therapeutic purpose. This article aims to show that the AAS are susceptible to being sold on the black market. We also aim to describe how certain limitations on the health inspection services of the Galician health service to pursue these illegal actions prompted a regulatory initiative demanding that additional actions be granted to community pharmacies when dispensing AAS. Four pharmacy inspections detected the diversion of a total of 3118 packages of AAS, which led to the opening of four disciplinary proceedings. In two of these, specialized police forces were called in as there was sufficient evidence of possible diversion to gymnasiums, resulting in a police operation called Operation Fitness. PMID:25778637

  13. Two new steroidal saponins from Tribulus terrestris.

    PubMed

    Su, Lan; Feng, Sheng-Guang; Qiao, Li; Zhou, Yu-Zhi; Yang, Rui-Ping; Pei, Yue-Hu

    2009-01-01

    Two new steroidal saponins and two known flavonoid glycosides were isolated from the fruits of Tribulus terrestris. Their structures were assigned by spectroscopic analysis and chemical reaction as 26-O-beta-D-glucopyranosyl-(25R)-5 alpha-furostan-12-one-3beta,22 alpha,26-triol-3-O-beta-D-glucopyranosyl (1 --> 2)-beta-D-glucopyranosyl(1 --> 4)-beta-D-galactopyranoside (1), 26-O-beta-D-glucopyranosyl-(25S)-5 alpha-furostan-22-methoxy-2 alpha,3beta,26-triol-3-O-beta-D-glucopyranosyl(1 --> 2)-beta-D-glucopyranosyl(1 --> 4)-beta-D-galactopyranoside (2), kaempferol-3-gentiobioside (3), and isorhamnetin-3-gentiobioside (4).

  14. New steroidal glycosides from Tribulus terrestris L.

    PubMed

    Chen, Gang; Liu, Tao; Lu, Xuan; Wang, Hai-Feng; Hua, Hui-Ming; Pei, Yue-Hu

    2012-01-01

    Two new steroidal glycosides were isolated from Tribulus terrestris L. Their structures were elucidated as 26-O-β-D-glucopyranosyl-5α-furostan-12-one-20(22)-ene-3β,23,26-triol-3-O-β-D-xylopyranosyl-(1 → 2)-[β-D-xylopyranosyl-(1 → 3)]-β-D-glucopyranosyl-(1 → 4)-[α-L-rhamnopyranosyl-(1 → 2)]-β-D-galactopyranoside (1) and 26-O-β-D-glucopyranosyl-5α-furostan-20(22)-ene-3β,23,26-triol-3-O-β-D-xylopyranosyl-(1 → 2)-[β-D-xylopyranosyl-(1 → 3)]-β-D-glucopyranosyl-(1 → 4)-[α-L-rhamnopyranosyl-(1 → 2)]-β-D-galactopyranoside (2) by spectroscopic methods including 1D and 2D NMR experiments.

  15. Cardiotonic Steroids as Modulators of Neuroinflammation

    PubMed Central

    Orellana, Ana Maria; Kinoshita, Paula Fernanda; Leite, Jacqueline Alves; Kawamoto, Elisa Mitiko; Scavone, Cristoforo

    2016-01-01

    Cardiotonic steroids (CTS) are a class of specific ligands of the Na+, K+- ATPase (NKA). NKA is a P-type ATPase that is ubiquitously expressed and although well known to be responsible for the maintenance of the cell electrochemical gradient through active transport, NKA can also act as a signal transducer in the presence of CTS. Inflammation, in addition to importantly driving organism defense and survival mechanisms, can also modulate NKA activity and memory formation, as well as being relevant to many chronic illnesses, neurodegenerative diseases, and mood disorders. The aim of the current review is to highlight the recent advances as to the role of CTS and NKA in inflammatory process, with a particular focus in the central nervous system. PMID:26909067

  16. Anabolic androgenic steroids abuse and liver toxicity.

    PubMed

    Neri, M; Bello, S; Bonsignore, A; Cantatore, S; Riezzo, I; Turillazzi, E; Fineschi, V

    2011-05-01

    In the athletes the wide use of Anabolic Androgenic Steroids (AAS) cause series damage in various organs, in particular, analyzing the liver, elevation on the levels of liver enzymes, cholestatic jaundice, liver tumors, both benign and malignant, and peliosis hepatis are described. A prolonged AAS administration provokes an increase in the activities of liver lysosomal hydrolases and a decrease in some components of the microsomal drug-metabolizing system and in the activity of the mitochondrial respiratory chain complexes without modifying classical serum indicators of hepatic function. Liver is a key organ actively involved in numerous metabolic and detoxifying functions. As a consequence, it is continuously exposed to high levels of endogenous and exogenous oxidants that are by-products of many biochemical pathways and, in fact, it has been demonstrated that intracellular oxidant production is more active in liver than in tissues, like the increase of inflammatory cytokines, apoptosis and the inhibitors of apoptosis NF- κB and Heat Shock Proteins.

  17. [Control measures for anabolic androgenic steroid medicines].

    PubMed

    Vázquez-Mourelle, Raquel; Carracedo-Martínez, Eduardo; Ces Gens, Eugenio; Cadórniga Valiño, Luis; Álvaro Esteban, Pilar; Pose Reino, José Manuel

    2015-01-01

    Anabolic androgenic steroids (AAS) can cause serious adverse effects when used without a therapeutic purpose. This article aims to show that the AAS are susceptible to being sold on the black market. We also aim to describe how certain limitations on the health inspection services of the Galician health service to pursue these illegal actions prompted a regulatory initiative demanding that additional actions be granted to community pharmacies when dispensing AAS. Four pharmacy inspections detected the diversion of a total of 3118 packages of AAS, which led to the opening of four disciplinary proceedings. In two of these, specialized police forces were called in as there was sufficient evidence of possible diversion to gymnasiums, resulting in a police operation called Operation Fitness.

  18. Anabolic androgenic steroid-induced hepatotoxicity.

    PubMed

    Bond, Peter; Llewellyn, William; Van Mol, Peter

    2016-08-01

    Anabolic androgenic steroids (AAS) have been abused for decades by both professional and amateur athletes in order to improve physical performance or muscle mass. AAS abuse can cause adverse effects, among which are hepatotoxic effects. These effects include cholestatic icterus and possibly peliosis hepatis and hepatocellular carcinoma or adenoma. In particular, 17α-alkylated AAS appear to be hepatotoxic, whereas nonalkylated AAS appear not to be. The 17α-alkyl substitution retards hepatic metabolism of the AAS rendering it orally bioavailable. The mechanism responsible for the hepatotoxicity induced by 17α-alkylated AAS remains poorly understood. However, oxidative stress has been repeatedly shown to be associated with it. In this manuscript we present a hypothesis which describes a potential mechanism responsible for AAS-induced hepatotoxicity, based on several observations from the literature which suggest oxidative stress being a causal factor. PMID:27372877

  19. [Rhabdomyolysis in a bodybuilder using steroids].

    PubMed

    Daniels, J M A; van Westerloo, D J; de Hon, O M; Frissen, P H J

    2006-05-13

    A 34-year-old bodybuilder presented at the emergency room with fever, vomiting and muscle cramps that had started during a bodybuilding session. Several days before he started training he had used tablets and intramuscular injections containing the anabolic steroids: dehydro-chloro-methyltestosterone, boldenone and trenbolone. In addition, he had taken clenbuterol tablets, liothyronine tablets and subcutaneous injections of phosphatidylcholine. Laboratory investigations revealed massive rhabdomyolysis. The patient was treated with intravenous fluid replacement and sodium bicarbonate to alkalinize the urine. He recovered quickly and his renal function remained unaffected. 'Doping' among amateur athletes in the Netherlands occurs frequently. Apart from long term side-effects, doping can also cause acute health problems. Therefore it is important to ask about doping use during history taking in amateur athletes.

  20. Anabolic androgenic steroid-induced hepatotoxicity.

    PubMed

    Bond, Peter; Llewellyn, William; Van Mol, Peter

    2016-08-01

    Anabolic androgenic steroids (AAS) have been abused for decades by both professional and amateur athletes in order to improve physical performance or muscle mass. AAS abuse can cause adverse effects, among which are hepatotoxic effects. These effects include cholestatic icterus and possibly peliosis hepatis and hepatocellular carcinoma or adenoma. In particular, 17α-alkylated AAS appear to be hepatotoxic, whereas nonalkylated AAS appear not to be. The 17α-alkyl substitution retards hepatic metabolism of the AAS rendering it orally bioavailable. The mechanism responsible for the hepatotoxicity induced by 17α-alkylated AAS remains poorly understood. However, oxidative stress has been repeatedly shown to be associated with it. In this manuscript we present a hypothesis which describes a potential mechanism responsible for AAS-induced hepatotoxicity, based on several observations from the literature which suggest oxidative stress being a causal factor.

  1. Mimicking postmenopausal steroid metabolism in breast cancer cell culture: Differences in response to DHEA or other steroids as hormone sources.

    PubMed

    Xu, Dan; Lin, Sheng-Xiang

    2016-07-01

    Following menopause virtually 100% of estrogens are synthesized in peripheral target tissues from precursor steroids of adrenal origin. These steroids are the unique source of sex steroids in these women. This positions some steroid metabolizing enzymes as primary targets for novel therapies for estrogen receptor-positive (ER+) breast cancer. However, previous research on the steroid-converting enzymes has been performed using their direct substrate as a hormone source, depending on the facility where studied and the robust signal obtained. These experiments may not always provide an accurate reflection of physiological and post-menopausal conditions. We suggest providing dehydroepiandrosterone (DHEA) as an intracrinological hormone source, and comparing the role of steroid-converting enzymes using DHEA and their direct substrates when an extensive mechanistic understanding is required. Here, we present a comparative study of these enzymes with the provision of DHEA and the direct substrates, estrone (E1) or dihydrotestosterone (DHT), or additional steroids as hormone sources, in breast cancer cells. Enzyme knockdown by respective specific siRNAs and observations on the resulting differences in biological function were carried out. Cell biology studies showed no difference in biological function for 17β-HSD1 and 17β-HSD7 when cultured with different steroid hormones: cell proliferation and estradiol levels decreased, whereas DHT accumulated; cyclinD1, PCNA, and pS2 were down-regulated after knocking down these two enzymes, although the quantitative results varied. However, culture medium supplementation was found to have a marked impact on the study of 3α-HSD3. We demonstrated that provision of different steroids as a substrate or hormone sources may promote modified biological effects: provision of DHEA is the preferred choice to mimic postmenopausal steroid metabolism in cell culture.

  2. Translational research on rapid steroid actions.

    PubMed

    Wendler, Alexandra; Wehling, Martin

    2010-01-01

    Translational research is a burgeoning science that shows potential to improve the transition of research from bench to bedside. This novel science explores all major aspects of preclinical and clinical issues which are relevant for the success of translational pharmaceutical or medical device/diagnostic innovations. This includes target risk assessment, biomarker evaluation and predictivity grading both for efficacy and toxicity, early human trial design adequate to guide stop/go decisions on grounds of biomarker panels, and biostatistical methods to analyze multiple readout situations and quantify risk projections. Representing a comparably novel science, rapid steroid actions have been recognized to carry potential clinical implications in various fields. Findings in this field have not yet been successfully translated into clinically relevant new medicines except for neurosteroids. A promising compound is the membrane estrogen receptor agonist STX, which may be applicable for estrogen withdrawal symptoms. Nongenomic vitamin D analogs may be useful as antiinflammatory, anticancer or diabetes preventing agents. Further the membrane thyroid receptor agonist tetrac may be useful in cancer treatment. Unfortunately lazaroids (membrane-only active glucocorticoids), which have been clinically tested as neuroprotective agents, had to be abandoned because of lacking clinical efficacy. Yet, the hierarchy of antirheumatic glucocorticoid action in regard to their clinical potency may better correlate with their membrane effects than their ability to bind to the classic glucocorticoid receptor. To improve the translational success of the rapid actions of steroids research, scientists should become familiar with major aspects of translational work and always seek for translational dimensions in their research. PMID:19782096

  3. The cardiovascular safety of triphasic contraceptive steroids.

    PubMed

    Shaarawy, M; Nafea, S; Abdel-Aziz, O; Rahseed, K; Sheiba, M

    1997-09-01

    It was hypothesized that estrogen-induced cardioprotection is mediated by up-regulation and down-regulation of expression of nitric oxide (NO) and P-selectin, respectively. Published data on circulating levels of the vasodilator NO, atherogenic glycoprotein P-selectin, and lipoprotein-a [Lp(a)] in users of triphasic contraceptive steroids are lacking. A total of 30 healthy women (nonusers, controls) and 82 women using oral triphasic contraceptive steroids (ethinyl estradiol and levonorgestrel: Triovlar, Schering AG) for 18 to 24 cycles participated in this study. Fasting blood samples were obtained from users and nonusers for the determination of P-selectin and Lp(a) by enzyme immunoassay and NO by a colorimetric method. The serum Lp(a) levels in OC users were significantly higher than those of nonusers. On the other hand, the serum NO levels in OC users were significantly elevated when compared to nonusers. Plasma P-selectin was significantly lowered in OC users p < 0.005. These results demonstrate the beneficial effects of ethinyl estradiol in the triphasic contraceptive regimen. Ethinyl estradiol may afford a degree of anti-atherogenic-cardioprotective effect by up-regulation of the expression of the vasodilator NO and down-regulation of the expression of the atherogenic P-selectin. This may outweigh the cardiovascular risk of the increased atherogenic Lp(a). This study may explain the very low rate of mortality from venous thromboembolism in OC users, which compares favorably with the risks that many people accept in daily life.

  4. Sensitivity of GC-EI/MS, GC-EI/MS/MS, LC-ESI/MS/MS, LC-Ag(+) CIS/MS/MS, and GC-ESI/MS/MS for analysis of anabolic steroids in doping control.

    PubMed

    Cha, Eunju; Kim, Sohee; Kim, Ho Jun; Lee, Kang Mi; Kim, Ki Hun; Kwon, Oh-Seung; Lee, Jaeick

    2015-01-01

    This study compared the sensitivity of various separation and ionization methods, including gas chromatography with an electron ionization source (GC-EI), liquid chromatography with an electrospray ionization source (LC-ESI), and liquid chromatography with a silver ion coordination ion spray source (LC-Ag(+) CIS), coupled to a mass spectrometer (MS) for steroid analysis. Chromatographic conditions, mass spectrometric transitions, and ion source parameters were optimized. The majority of steroids in GC-EI/MS/MS and LC-Ag(+) CIS/MS/MS analysis showed higher sensitivities than those obtained with other analytical methods. The limits of detection (LODs) of 65 steroids by GC-EI/MS/MS, 68 steroids by LC-Ag(+) CIS/MS/MS, 56 steroids by GC-EI/MS, 54 steroids by LC-ESI/MS/MS, and 27 steroids by GC-ESI/MS/MS were below cut-off value of 2.0 ng/mL. LODs of steroids that formed protonated ions in LC-ESI/MS/MS analysis were all lower than the cut-off value. Several steroids such as unconjugated C3-hydroxyl with C17-hydroxyl structure showed higher sensitivities in GC-EI/MS/MS analysis relative to those obtained using the LC-based methods. The steroids containing 4, 9, 11-triene structures showed relatively poor sensitivities in GC-EI/MS and GC-ESI/MS/MS analysis. The results of this study provide information that may be useful for selecting suitable analytical methods for confirmatory analysis of steroids.

  5. Sensitivity of GC-EI/MS, GC-EI/MS/MS, LC-ESI/MS/MS, LC-Ag(+) CIS/MS/MS, and GC-ESI/MS/MS for analysis of anabolic steroids in doping control.

    PubMed

    Cha, Eunju; Kim, Sohee; Kim, Ho Jun; Lee, Kang Mi; Kim, Ki Hun; Kwon, Oh-Seung; Lee, Jaeick

    2015-01-01

    This study compared the sensitivity of various separation and ionization methods, including gas chromatography with an electron ionization source (GC-EI), liquid chromatography with an electrospray ionization source (LC-ESI), and liquid chromatography with a silver ion coordination ion spray source (LC-Ag(+) CIS), coupled to a mass spectrometer (MS) for steroid analysis. Chromatographic conditions, mass spectrometric transitions, and ion source parameters were optimized. The majority of steroids in GC-EI/MS/MS and LC-Ag(+) CIS/MS/MS analysis showed higher sensitivities than those obtained with other analytical methods. The limits of detection (LODs) of 65 steroids by GC-EI/MS/MS, 68 steroids by LC-Ag(+) CIS/MS/MS, 56 steroids by GC-EI/MS, 54 steroids by LC-ESI/MS/MS, and 27 steroids by GC-ESI/MS/MS were below cut-off value of 2.0 ng/mL. LODs of steroids that formed protonated ions in LC-ESI/MS/MS analysis were all lower than the cut-off value. Several steroids such as unconjugated C3-hydroxyl with C17-hydroxyl structure showed higher sensitivities in GC-EI/MS/MS analysis relative to those obtained using the LC-based methods. The steroids containing 4, 9, 11-triene structures showed relatively poor sensitivities in GC-EI/MS and GC-ESI/MS/MS analysis. The results of this study provide information that may be useful for selecting suitable analytical methods for confirmatory analysis of steroids. PMID:26489966

  6. [Endoscopic third ventriculostomy: complications and failures].

    PubMed

    Massimi, L; Di Rocco, C; Tamburrini, G; Caldarelli, M; Iannelli, A

    2004-04-01

    Endoscopic third-ventriculostomy (ETV) became the treatment of choice for non-communicating hydrocephalus and its effectiveness is largely reported. On the contrary, specific articles on complications and failures of this technique are very rare and this review aims at supplying further information about it. Therefore, an analysis of the main and up-to-date series is made and exhaustive data about complications and failures of ETV and about their incidence are obtained. The overall frequency rate of complications is 6-20%. Their severity may vary either because of the length of the damage (transient or permanent) or the value of the involved structures (basilar artery, areas of the CNS, hypothalamus) or the importance of the injury (from subclinical sequelae to fatal complications). Moreover, this study showed both the risk that the endoscopic procedure must be suspended (intra-operative failure) and the risk of an early (before 1 month) or delayed (even some years after the intervention) narrowing of the ventriculostomy. The rate of and the reasons for failure have been analysed and the success of a second ETV has been estimated. The results of this analysis suggest that the children proposed for ETV are carefully selected and meticulously studied during the follow-up.

  7. Varicella complicated by scarlet fever.

    PubMed

    Yavuz, Taner; Parlak, Ali Haydar; Kocabay, Kenan

    2003-10-01

    We report a 3-year-old boy with varicella complicated by cellulitis and scarlet fever. He developed a typical rash of scarlet fever following the onset of varicella. Streptococcus pyogenes was isolated from the ulcers due to varicella. The present case suggests that scarlet fever may rarely develop following varicella and should be considered in children with complicated varicella.

  8. [Complications caused by intravenous therapy].

    PubMed

    Quirós Luque, José María; Gago Fornells, Manuel

    2005-11-01

    Nursing professionals must know everything related to complications caused by intravenous therapy including the ways to prevent and solve these complications. We need not forget that nurses are the ones mainly responsible for the insertion, manipulation, removal and care of catheters.

  9. Complications of Laparoscopic Gynecologic Surgery

    PubMed Central

    Fuentes, Mariña Naveiro; Naveiro Rilo, José Cesáreo; Paredes, Aida González; Aguilar Romero, María Teresa; Parra, Jorge Fernández

    2014-01-01

    Background and Objectives: To analyze the frequency of complications during laparoscopic gynecologic surgery and identify associated risk factors. Methods: A descriptive observational study was performed between January 2000 and December 2012 and included all gynecologic laparoscopies performed at our center. Variables were recorded for patient characteristics, indication for surgery, length of hospital stay (in days), major and minor complications, and conversions to laparotomy. To identify risk factors and variables associated with complications, crude and adjusted odds ratios were calculated with unconditional logistic regression. Results: Of all 2888 laparoscopies included, most were procedures of moderate difficulty (adnexal surgery) (54.2%). The overall frequency of major complications was 1.93%, and that of minor complications was 4.29%. The level of technical difficulty and existence of prior abdominal surgery were associated with a higher risk of major complications and conversions to laparotomy. Conclusion: Laparoscopic gynecologic surgery is associated with a low frequency of complications but is a procedure that is not without risk. Greater technical difficulty and prior surgery were factors associated with a higher frequency of complications. PMID:25392659

  10. Biliary Complications After Liver Transplantation.

    PubMed

    Jagannath, Sanjay; Kalloo, Anthony N.

    2002-04-01

    The incidence of biliary complications after liver transplant is estimated to be 8% to 20%. Post-liver transplant biliary complications may lead to acute and chronic liver injury. The early recognition and prompt treatment of such complications improves the long-term survival of the patient and graft. An understanding of the type of biliary reconstruction, the rationale for creating a particular anastomosis, and the technical difficulties in reconstructing the biliary tract are important in assessing and managing complications after liver transplant. Because the clinical presentation of these patients may be subtle, the physician must be aggressive and thoughtful in ordering and interpreting the diagnostic tests. Important points to remember are 1) that noninvasive examinations may fail to detect small obstructions or leaks, 2) a liver biopsy often is performed prior to cholangiography to exclude rejection and ischemia, and 3) the liver biopsy can miss an extrahepatic obstruction by misinterpreting portal inflammation as rejection. Biliary leaks and strictures are the most common biliary complications following liver transplant. Less common complications include ampullary dysfunction and stone/sludge formation. The effective management of biliary complications following a liver transplant depends on understanding the natural history, the prognosis, and the available therapeutic options for each type of complication.

  11. Embryonic modulation of maternal steroids in European starlings (Sturnus vulgaris)

    PubMed Central

    Paitz, Ryan T.; Bowden, Rachel M.; Casto, Joseph M.

    2011-01-01

    In birds, maternally derived yolk steroids are a proposed mechanism by which females can adjust individual offspring phenotype to prevailing conditions. However, when interests of mother and offspring differ, parent–offspring conflict will arise and embryonic interests, not those of the mother, should drive offspring response to maternal steroids in eggs. Because of this potential conflict, we investigated the ability of developing bird embryos to process maternally derived yolk steroids. We examined how progesterone, testosterone and oestradiol levels changed in both the yolk/albumen (YA) and the embryo of European starling eggs during the first 10 days of development. Next, we injected tritiated testosterone into eggs at oviposition to characterize potential metabolic pathways during development. Ether extractions separated organic and aqueous metabolites in both the embryo and YA homogenate, after which major steroid metabolites were identified. Results indicate that the concentrations of all three steroids declined during development in the YA homogenate. Exogenous testosterone was primarily metabolized to an aqueous form of etiocholanolone that remained in the YA. These results clearly demonstrate that embryos can modulate their local steroid environment, setting up the potential for parent–offspring conflict. Embryonic regulation must be considered when addressing the evolutionary consequences of maternal steroids in eggs. PMID:20667883

  12. Vocabularies of motive for illicit steroid use among bodybuilders.

    PubMed

    Monaghan, Lee F

    2002-09-01

    Illicit steroid use, for purposes of performance and physique enhancement, is widely deemed unnecessary, wrong and dangerous. Such activity would appear especially foolhardy when engaged in by non-professional athletes who otherwise adhere to 'healthy' exercise regimens. Here a gap exists between many illicit steroid users' actions and societal expectations. Using qualitative data generated in South Wales, this paper explores bodybuilders' vocabularies of motive for illicit steroid use. These accounts which justified, rather than excused, steroid use were predominant during question situations between the participant observer and the researched. In supporting the fundamental tenets of their drug subculture, and as part of the underlying negotiation of self-identity, respondents espoused three main justifications for their own and/or other bodybuilders' illicit steroid use; namely: self-fulfilment accounts, condemnation of condemners and a denial of injury. Here steroid use was rationalised as a legitimate means to an end, observers passing negative judgements were rejected and it was claimed steroids do not (seriously) harm the user's health or threaten society more generally. These vocabularies of motive, acquired and honoured within bodybuilding settings, comprise a complex of subjective meanings which seem to the actor to be an adequate ground for the conduct in question. Similar to other sociological studies, this paper states that it is imperative to explore the social meanings which illicit drug users attach to their 'risk' practices. Without these understandings, researchers and health promoters may struggle to appreciate fully why illicit drug users behave as they do.

  13. [The preparation and characterization of steroid antisera (author's transl)].

    PubMed

    Vadora, E; Dagradi, G; Bacchi-Modena, A; Salvarani, C; Coppola, F

    1976-01-01

    The steroids, as compounds of low molecular weight, are not immunogenic; however, certain small molecules (haptens) when covalently linked to proteins become antigenic i.e., they provoke the production of unique antibody. If a steroid were covalently copuled to a protein, an artifical antigen would be produced capable of eliciting the formation of antibody with specificity not only for the protein carrier but also for the particular haptenic steroid. The results would be an in vivo production of a tailor made binding sites for any steroid that can be attached as a hapten to a protein by covalent bonds and thus become antigenic. This procedure allow the preparation of steroid specific antisera suitable for clinical use in radioimmunoassay, methods. The Authors report the techniques of preparation of steroid-derivative antigens of Androstenedion, Testosteron, and Progesteron. The three derivative steroid antigens have shown a good antigenic property by eliciting the formation of specifical antisera in 5 out of 6 rabbits used for the immunization. After 10 weeks from the beginning of immunization antisera useful in radioimmunoassay at the diluition 1/300; 1/1600; 1/2000 respectively for Progesteron, Testosteron and Androstenedion were obtained. The standard curves show a good sensitivity suitable for clinical use.

  14. Embryonic modulation of maternal steroids in European starlings (Sturnus vulgaris).

    PubMed

    Paitz, Ryan T; Bowden, Rachel M; Casto, Joseph M

    2011-01-01

    In birds, maternally derived yolk steroids are a proposed mechanism by which females can adjust individual offspring phenotype to prevailing conditions. However, when interests of mother and offspring differ, parent-offspring conflict will arise and embryonic interests, not those of the mother, should drive offspring response to maternal steroids in eggs. Because of this potential conflict, we investigated the ability of developing bird embryos to process maternally derived yolk steroids. We examined how progesterone, testosterone and oestradiol levels changed in both the yolk/albumen (YA) and the embryo of European starling eggs during the first 10 days of development. Next, we injected tritiated testosterone into eggs at oviposition to characterize potential metabolic pathways during development. Ether extractions separated organic and aqueous metabolites in both the embryo and YA homogenate, after which major steroid metabolites were identified. Results indicate that the concentrations of all three steroids declined during development in the YA homogenate. Exogenous testosterone was primarily metabolized to an aqueous form of etiocholanolone that remained in the YA. These results clearly demonstrate that embryos can modulate their local steroid environment, setting up the potential for parent-offspring conflict. Embryonic regulation must be considered when addressing the evolutionary consequences of maternal steroids in eggs. PMID:20667883

  15. Metabolism of anabolic steroids by recombinant human cytochrome P450 enzymes. Gas chromatographic-mass spectrometric determination of metabolites.

    PubMed

    Rendic, S; Nolteernsting, E; Schänzer, W

    1999-11-26

    Metabolism of steroid hormones with anabolic properties was studied in vitro using human recombinant CYP3A4, CYP2C9 and 2B6 enzymes. The enzyme formats used for CYP3A4 and CYP2C9 were insect cell microsomes expressing human CYP enzymes and purified recombinant human CYP enzymes in a reconstituted system. CYP3A4 enzyme formats incubated with anabolic steroids, testosterone, 17alpha-methyltestosterone, metandienone, boldenone and 4-chloro-1,2-dehydro-17alpha-methyltestosterone, produced 6beta-hydroxyl metabolites identified as trimethylsilyl (TMS)-ethers by a gas chromatography-mass spectrometry (GC-MS) method. When the same formats of CYP2C9 were incubated with the anabolic steroids, no 6beta-hydroxyl metabolites were formed. Human lymphoblast cell microsomes expressing human CYP2B6 incubated with the steroids investigated produced traces of 6beta-hydroxyl metabolites with testosterone and 17alpha-methyltestosterone only. We suggest that the electronic effects of the 3-keto-4-ene structural moiety contribute to the selectivity within the active site of CYP3A4 enzyme resulting in selective 6beta-hydroxylation. PMID:10630892

  16. [Urinary complications after anorectal surgery].

    PubMed

    Iusuf, T; Sârbu, V; Cristache, C; Popescu, R; Botea, F; Panait, L

    2000-01-01

    The prevalence of urinary complications after various anorectal operations was studied in a group of 273 patients. The overall prevalence of urinary complications was 26.7%; most of these complications affected men between 41 and 50, mainly after hemorrhoidectomy. In 10.6% of patients, bladder catheterization was needed. These urinary complications result from nervous reflexes originating from the anus and determined by the operative trauma and/or rectal distinction. In the treatment of these urinary complications, the role of the muses is essential for reassuring the patients. Parasympathomimetic drugs are often efficient. Urinary catheterization must be delayed until the 18th hour. Fluid restriction may be useful to prevent urinary retention. PMID:14870531

  17. Neurological Complications of Bariatric Surgery.

    PubMed

    Goodman, Jerry Clay

    2015-12-01

    Obesity has attained pandemic proportions, and bariatric surgery is increasingly being employed resulting in turn to more neurological complications which must be recognized and managed. Neurological complications may result from mechanical or inflammatory mechanisms but primarily result from micro-nutritional deficiencies. Vitamin B12, thiamine, and copper constitute the most frequent deficiencies. Neurological complications may occur at reasonably predictable times after bariatric surgery and are associated with the type of surgery used. During the early post-operative period, compressive or stretch peripheral nerve injury, rhabdomyolysis, Wernicke's encephalopathy, and inflammatory polyradiculoneuropathy may occur. Late complications ensue after months to years and include combined system degeneration (vitamin B12 deficiency) and hypocupric myelopathy. Bariatric surgery patients require careful nutritional follow-up with routine monitoring of micronutrients at 6 weeks and 3, 6, and 12 months post-operatively and then annually after surgery and multivitamin supplementation for life. Sustained vigilance for common and rare neurological complications is essential.

  18. Complications of the Latarjet procedure.

    PubMed

    Gupta, Ashish; Delaney, Ruth; Petkin, Kalojan; Lafosse, Laurent

    2015-03-01

    The Latarjet procedure is an operation performed either arthroscopically or open for recurrent anterior shoulder instability, in the setting of glenoid bone loss; with good to excellent functional results. Despite excellent clinical results, the complication rates are reported between 15 and 30 %. Intraoperative complications such as graft malpositioning, neurovascular injury, and graft fracture can all be mitigated with meticulous surgical technique and understanding of the local anatomy. Nonunion and screw breakage are intermediate-term complications that occur in less than 5 % of patients. The long-term complications such as graft osteolysis are still an unsolved problem, and future research is required to understand the etiology and best treatment option. Recurrent instability after the Latarjet procedure can be managed with iliac crest bone graft reconstruction of the anterior glenoid. Shoulder arthritis is another complication reported after the Latarjet procedure, which poses additional challenges to both the surgeon and patient.

  19. Rate of steroid double-bond reduction catalysed by the human steroid 5β-reductase (AKR1D1) is sensitive to steroid structure: implications for steroid metabolism and bile acid synthesis.

    PubMed

    Jin, Yi; Chen, Mo; Penning, Trevor M

    2014-08-15

    Human AKR1D1 (steroid 5β-reductase/aldo-keto reductase 1D1) catalyses the stereospecific reduction of double bonds in Δ4-3-oxosteroids, a unique reaction that introduces a 90° bend at the A/B ring fusion to yield 5β-dihydrosteroids. AKR1D1 is the only enzyme capable of steroid 5β-reduction in humans and plays critical physiological roles. In steroid hormone metabolism, AKR1D1 serves mainly to inactivate the major classes of steroid hormones. AKR1D1 also catalyses key steps of the biosynthetic pathway of bile acids, which regulate lipid emulsification and cholesterol homoeostasis. Interestingly, AKR1D1 displayed a 20-fold variation in the kcat values, with steroid hormone substrates (e.g. aldosterone, testosterone and cortisone) having significantly higher kcat values than steroids with longer side chains (e.g. 7α-hydroxycholestenone, a bile acid precursor). Transient kinetic analysis revealed striking variations up to two orders of magnitude in the rate of the chemistry step (kchem), which resulted in different rate determining steps for the fast and slow substrates. By contrast, similar Kd values were observed for representative fast and slow substrates, suggesting similar rates of release for different steroid products. The release of NADP+ was shown to control the overall turnover for fast substrates, but not for slow substrates. Despite having high kchem values with steroid hormones, the kinetic control of AKR1D1 is consistent with the enzyme catalysing the slowest step in the catabolic sequence of steroid hormone transformation in the liver. The inherent slowness of the conversion of the bile acid precursor by AKR1D1 is also indicative of a regulatory role in bile acid synthesis.

  20. Intervention and prevention of steroid use in adolescents.

    PubMed

    Elliot, D; Goldberg, L

    1996-01-01

    Athletes with a higher intent to use anabolic steroids were similar to students who indicated no predisposition to use steroids on economic, academic, and physical measures. They had similar understandings of anabolic steroid effects, and their self-rated understandings of how to weight train and of sports nutrition were similar. In addition, the influence of the coaches and the media and the perceived prevalence of anabolic steroid use were not different between the higher- and lower-intent students. These results demonstrated several significant differences. Higher-intent students had higher levels of alcohol and marijuana use, which suggest that those items might be tackled concurrently. These athletes had higher hostility, impulsivity, and a win-at-all-costs attitude. Despite similar physical measures, they had a high body image, but were less satisfied with their current weight. These findings underscored the importance of using nutrition and appropriate training as effective alternatives to anabolic steroids. Higher-intent students had greater peer tolerance of drug use and less parental influence not to use drugs, which implies that a peer-led small group format might be important to dispel the perceived peer tolerance. Including a parent-based component, one that emphasizes a disapproval of drug use also could be effective. Higher-intent athletes had less ability to refuse an offer of steroids. The dynamics of turning down steroids may differ from that of other illicit substances so that training in refusal skills specific to steroids is needed. These differences provide a needs assessment to identify curricular components for an intervention to permit anabolic steroid use. The sports team may be a unique educational setting because it can capitalize on peer ties, the coach's influence, and an athletes' motivation to improve, to prevent drug use, and to promote healthy behaviors.