Sample records for glucocorticoid side effects

  1. Side Effects (United States)

    Side effects are problems that occur when cancer treatment affects healthy tissues or organs. Learn about side effects caused by cancer treatment. Know what signs and symptoms to call your doctor about. Learn about treatments for side effects.

  2. Glucocorticoids as mediators of developmental programming effects. (United States)

    Khulan, Batbayar; Drake, Amanda J


    Epidemiological evidence suggests that exposure to an adverse environment in early life is associated with an increased risk of cardio-metabolic and behavioral disorders in adulthood, a phenomenon termed 'early life programming'. One major hypothesis for early life programming is fetal glucocorticoid overexposure. In animal studies, prenatal glucocorticoid excess as a consequence of maternal stress or through exogenous administration to the mother or fetus is associated with programming effects on cardiovascular and metabolic systems and on the brain. These effects can be transmitted to subsequent generations. Studies in humans provide some evidence that prenatal glucocorticoid exposure may exert similar programming effects on glucose/insulin homeostasis, blood pressure and neurodevelopment. The mechanisms by which glucocorticoids mediate these effects are unclear but may include a role for epigenetic modifications. This review discusses the evidence for glucocorticoid programming in animal models and in humans. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Exogenous glucocorticoids and adverse cerebral effects in children

    DEFF Research Database (Denmark)

    Damsted, Sara K.; Born, A P; Paulson, Olaf B


    of the glucocorticoid receptor, which is associated with unfavorable cellular outcomes. Prenatal treatment with glucocorticoids can compromise brain growth and is associated with periventricular leukomalacia, attentions deficits and poorer cognitive performance. In the neonatal period exposure to glucocorticoids....... Glucocortioids affect several cellular structures and functions, which may explain the observed adverse effects. Glucocorticoids can impair neuronal glucose uptake, decrease excitability, cause atrophy of dendrites, compromise development of myelin-producing oligodendrocytes and disturb important cellular...

  4. Medications and Side Effects (United States)

    ... to fully work. You might feel some side effects of your medication before your feel the benefits – ... as sleepiness, anxiety or headache) is a side effect or a symptom of your illness. Many side ...

  5. Predicting the neurobehavioral side effects of dexamethasone in pediatric acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Warris, Lidewij T.; van den Akker, Erica L. T.; Aarsen, Femke K.; Bierings, Marc B.; van den Bos, Cor; Tissing, Wim J. E.; Sassen, Sebastiaan D. T.; Veening, Margreet A.; Zwaan, Christian M.; Pieters, Rob; van den Heuvel-Eibrink, Marry M.


    Although dexamethasone is an effective treatment for acute lymphoblastic leukemia (ALL), it can induce a variety of serious neurobehavioral side effects. We hypothesized that these side effects are influenced by glucocorticoid sensitivity at the tissue level. We therefore prospectively studied

  6. Exogenous glucocorticoids and adverse cerebral effects in children

    DEFF Research Database (Denmark)

    Damsted, Sara K.; Born, A P; Paulson, Olaf B


    of the glucocorticoid receptor, which is associated with unfavorable cellular outcomes. Prenatal treatment with glucocorticoids can compromise brain growth and is associated with periventricular leukomalacia, attentions deficits and poorer cognitive performance. In the neonatal period exposure to glucocorticoids...... reduces neurogenesis and cerebral volume, impairs memory and increases the incidence of cerebral palsy. Cerebral effects of glucocorticoids in later childhood have been less thoroughly studied, but apparent brain atrophy, reduced size of limbic structures and neuropsychiatric symptoms have been reported....... Glucocortioids affect several cellular structures and functions, which may explain the observed adverse effects. Glucocorticoids can impair neuronal glucose uptake, decrease excitability, cause atrophy of dendrites, compromise development of myelin-producing oligodendrocytes and disturb important cellular...

  7. Side Effects (Management) (United States)

    ... cancer care is relieving side effects, called symptom management, palliative care, or supportive care. It is important ... treat them. To learn about the symptoms and management of the long-term side effects of cancer ...

  8. Glucocorticoid-induced effects on the growth plate and the IGF system

    NARCIS (Netherlands)

    Smink, Jeske Johanna


    Glucocorticoids (GCs) are widely used as anti-inflammatory and immunosuppressive drugs. The use of these potent drugs, however, often results in side-effects, such as growth retardation in children. For already many years, this GC-induced growth retardation is suggested to involve impaired action of

  9. Radiation Therapy Side Effects (United States)

    Radiation therapy has side effects because it not only kills or slows the growth of cancer cells, it can also affect nearby healthy cells. Many people who get radiation therapy experience fatigue. Other side effects depend on the part of the body that is being treated. Learn more about possible side effects.

  10. Glucocorticoid receptor modulators. (United States)

    Meijer, Onno C; Koorneef, Lisa L; Kroon, Jan


    The glucocorticoid hormone cortisol acts throughout the body to support circadian processes and adaptation to stress. The glucocorticoid receptor is the target of cortisol and of synthetic glucocorticoids, which are used widely in the clinic. Both agonism and antagonism of the glucocorticoid receptor may be beneficial in disease, but given the wide expression of the receptor and involvement in various processes, beneficial effects are often accompanied by unwanted side effects. Selective glucocorticoid receptor modulators are ligands that induce a receptor conformation that allows activation of only a subset of downstream signaling pathways. Such molecules thereby combine agonistic and antagonistic properties. Here we discuss the mechanisms underlying selective receptor modulation and their promise in treating diseases in several organ systems where cortisol signaling plays a role. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  11. Side Effects: Sleep Problems (United States)

    Sleep problems are a common side effect during cancer treatment. Learn how a polysomnogram can assess sleep problems. Learn about the benefits of managing sleep disorders in men and women with cancer.

  12. Side Effects: Fatigue (United States)

    Fatigue is a common side effect of many cancer treatments such as chemotherapy, radiation therapy, immunotherapy, and surgery. Anemia and pain can also cause fatigue. Learn about symptoms and way to manage fatigue.

  13. Side Effects: Diarrhea (United States)

    Diarrhea, a side effect of cancer treatment, may cause symptoms such as loose, watery stools. Diarrhea can lead to dehydration and malnutrition in cancer patients. Learn about ways to treat and manage diarrhea during cancer treatment.

  14. Side Effects: Appetite Loss (United States)

    Cancer treatments may lower your appetite. Side effects such as nausea, fatigue, or mouth sores can also making eating difficult. Learn how to eat well to avoid losing weight or becoming dehydrated, so you stay strong during treatment.

  15. Side Effects: Pain (United States)

    Controlling pain is an important part of your cancer treatment plan. Learn how to track levels of pain. Find out how pain, a side effect of cancer treatment, is treated using acupuncture, biofeedback, and physical therapy.

  16. Side Effects: Anemia (United States)

    Anemia is a side effect of cancer treatments, including chemotherapy and radiation therapy. It can make women and men feel fatigued, dizzy, and short of breath. Learn how to manage fatigue caused by anemia during cancer treatment.

  17. Systematic review of the clinical effect of glucocorticoids on nonhematologic malignancy

    Directory of Open Access Journals (Sweden)

    Keith Bruce D


    Full Text Available Abstract Background Glucocorticoids are often used in the treatment of nonhematologic malignancy. This review summarizes the clinical evidence of the effect of glucocorticoid therapy on nonhematologic malignancy. Methods A systematic review of clinical studies of glucocorticoid therapy in patients with nonhematologic malignancy was undertaken. Only studies having endpoints of tumor response or tumor control or survival were included. PubMed, EMBASE, the Cochrane Register/Databases, conference proceedings (ASCO, AACR, ASTRO/ASTR, ESMO, ECCO and other resources were used. Data was extracted using a standard form. There was quality assessment of each study. There was a narrative synthesis of information, with presentation of results in tables. Where appropriate, meta-analyses were performed using data from published reports and a fixed effect model. Results Fifty four randomized controlled trials (RCTs, one meta-analysis, four phase l/ll trials and four case series met the eligibility criteria. Clinical trials of glucocorticoid monotherapy in breast and prostate cancer showed modest response rates. In advanced breast cancer meta-analyses, the addition of glucocorticoids to either chemotherapy or other endocrine therapy resulted in increased response rate, but not increased survival. In GI cancer, there was one RCT each of glucocorticoids vs. supportive care and chemotherapy +/- glucocorticoids; glucocorticoid effect was neutral. The only RCT found of chemotherapy +/- glucocorticoids, in which the glucocorticoid arm did worse, was in lung cancer. In glucocorticoid monotherapy, meta-analysis found that continuous high dose glucocorticoids had a detrimental effect on survival. The only other evidence, for a detrimental effect of glucocorticoid monotherapy, was in one of the two trials in lung cancer. Conclusion Glucocorticoid monotherapy has some benefit in breast and prostate cancer. In advanced breast cancer, the addition of glucocorticoids to other

  18. [Psychoanalysis and Side Effect]. (United States)

    Shirahase, Joichiro


    A study of psychoanalysis from the perspective of side effects reveals that its history was a succession of measures to deal with its own side effects. This, however, does not merely suggest that, as a treatment method, psychoanalysis is incomplete and weak: rather, its history is a record of the growth and development of psychoanalysis that discovered therapeutic significance from phenomena that were initially regarded as side effects, made use of these discoveries, and elaborated them as a treatment method. The approach of research seen during the course of these developments is linked to the basic therapeutic approach of psychoanalysis. A therapist therefore does not draw conclusions about a patient's words and behaviors from a single aspect, but continues to make efforts to actively discover a variety of meanings and values from them, and to make the patient's life richer and more productive. This therapeutic approach is undoubtedly one of the unique aspects of psychoanalysis. I discuss the issue of psychoanalysis and side effects with the aim of clarifying this unique characteristic of psychoanalysis. The phenomenon called resistance inevitably emerges during the process of psychoanalytic treatment. Resistance can not only obstruct the progress of therapy; it also carries the risk of causing a variety of disadvantages to the patient. It can therefore be seen as an adverse effect. However, if we re-examine this phenomenon from the perspective of transference, we find that resistance is in fact a crucial tool in psychoanalysis, and included in its main effect, rather than a side effect. From the perspective of minimizing the character of resistance as a side effect and maximizing its character as a main effect, I have reviewed logical organization, dynamic evaluation, the structuring of treatment, the therapist's attitudes, and the training of therapists. I conclude by stating that psychoanalysis has aspects that do not match the perspective known as a side

  19. The effect of early administration of glucocorticoids on learning and ...

    African Journals Online (AJOL)

    It has been observed that steroids administered postnatally may have transient retarding effect on learning and memory functions, and that animal age and sex may modify such effects. This study aims to illustrate the effect of early administration of glucocorticoids on learning and spatial memory. Wistar rat pups were ...

  20. Glucocorticoid effects on hippocampal protein synthesis

    International Nuclear Information System (INIS)

    Schlatter, L.K.


    Following subcutaneous injection of rats with 5 mg corticosterone, hippocampal slices in vitro show increased [ 35 S]-methionine labeling of a cytosolic protein with an apparent molecular weight (M r ) of 35,000 and an isoelectric point (IEP) of 6.6. This labeling is temporally consistent with a transcriptional event, and is steroid- and tissue-specific. The pear serum concentration of steroid occurs one hour or less following the injection. Maximal labeling of this protein is reached whenever serum corticosterone values are approximately 100 ng/ml. When endogenous corticosterone levels are elevated to 100 ng/ml through stressors or exogenous ACTH injections the same maximal increase in synthesis of the 35,000 M r protein is observed. Adrenalectomy prevents the observed response from occurring following stressor application or ACTH injections. Comparison of the increases observed after administration of the type 2 receptor agonist RU 28362 and aldosterone, which has a higher affinity for the type 1 receptor, shows a 50-fold greater sensitivity of the response to the type 2 receptor agonist. Synthesis of this protein following serum increases of steroid possibly correlates to the theorized function of the type 2 receptor feedback regulation. The similar protein in the liver has an IEP of 6.8 and a slightly higher M r . A second hippocampal protein with an M r of 46,000 and an IEP of 6.2 is also increased in labeling. Two additional liver proteins, one of Mr 53,000 (IEP of 6.2) and the other with an M r of 45,000 (IEP of 8.7-7.8) are increased in the liver following glucocorticoid administration

  1. Effects of Social Isolation on Glucocorticoid Regulation in Social Mammals (United States)

    Hawkley, Louise C.; Cole, Steve W.; Capitanio, John P.; Norman, Greg J.; Cacioppo, John T.


    The regulation and function of the hypothalamic-pituitary-adrenocortical (HPA) axis and glucocorticoids have been well conserved across vertebrate species. Glucocorticoids influence a wide range of physiological functions that include glucose regulation, metabolism, inflammatory control, as well as cardiovascular, reproductive, and neuronal effects. Some of these are relatively quick-acting non-genomic effects, but most are slower-acting genomic effects. Thus, any stimulus that affects HPA function has the potential to exert wide-ranging short-term and long-term effects on much of vertebrate physiology. Here, we review the effects of social isolation on the functioning of the HPA axis in social species, and on glucocorticoid physiology in social mammals in particular. Evidence indicates that objective and perceived social isolation alter HPA regulation, although the nature and direction of the HPA response differs among species and across age. The inconsistencies in the direction and nature of HPA effects have implications for drawing cross-species conclusions about the effects of social isolation, and are particularly problematic for understanding HPA-related physiological processes in humans. The animal and human data are incommensurate because, for example, animal studies of objective isolation have typically not been modeled on, or for comparability with, the subjective experience of isolation in humans. An animal model of human isolation must be taken more seriously if we want to advance our understanding of the mechanisms for the effects of objective and perceived isolation in humans. PMID:22663934

  2. Effect of glucocorticoids and gamma radiation on epidermal Langerhans cells

    International Nuclear Information System (INIS)

    Belsito, D.V.; Baer, R.L.; Thorbecke, G.J.; Gigli, I.


    The effect of 750 rads of gamma radiation on the rate of return of epidermal Langerhans cells (LC) following suppressive doses of topical glucorticoids was studied in guinea pigs. Gamma radiation alone had no effect on the LC as assessed by staining for cell membrane ATPase activity and Ia antigen. It did, however, delay the expected return of Ia but not ATPase surface markers on the LC after perturbation with glucocorticoids. The delayed return of surface Ia antigen is possibly related to a radiation-induced defect in the production of a required lymphokine and/or in intracellular Ia transport. Although our data do not rule out a cytolytic effect of steroids on the LC, they do strongly suggest that, at least in part, glucocorticoids act on the LC by altering cell surface characteristics

  3. Salivary cortisol day curves in assessing glucocorticoid replacement therapy in Addison's disease

    NARCIS (Netherlands)

    Smans, L.; Lentjes, E.G.W.M.; Hermus, A.R.; Zelissen, P.M.J.


    OBJECTIVE: Patients with Addison's disease require lifelong treatment with glucocorticoids. At present, no glucocorticoid replacement therapy (GRT) can exactly mimic normal physiology. As a consequence, under- and especially overtreatment can occur. Suboptimal GRT may lead to various side effects.

  4. Adverse consequences of glucocorticoid medication: psychological, cognitive, and behavioral effects

    NARCIS (Netherlands)

    Judd, L.L.; Schettler, P.J.; Brown, E.S.; Wolkowitz, O.M.; Sternberg, E.M.; Bender, B.G.; Bulloch, K.; Cidlowski, J.A.; Kloet, E.R. de; Fardet, L.; Joels, M.; Leung, D.Y.; McEwen, B.S.; Roozendaal, B.; Rossum, E.F. van; Ahn, J.; Brown, D.W.; Plitt, A.; Singh, G.


    Glucocorticoids are the most commonly prescribed anti-inflammatory/immunosuppressant medications worldwide. This article highlights the risk of clinically significant and sometimes severe psychological, cognitive, and behavioral disturbances that may be associated with glucocorticoid use, as well as

  5. Adverse Consequences of Glucocorticoid Medication : Psychological, Cognitive, and Behavioral Effects

    NARCIS (Netherlands)

    Judd, Lewis L.; Schettler, Pamela J.; Brown, E. Sherwood; Wolkowitz, Owen M.; Sternberg, Esther M.; Bender, Bruce G.; Bulloch, Karen; Cidlowski, John A.; de Kloet, E. Ronald; Fardet, Laurence; Joëls, Marian; Leung, Donald Y. M.; McEwen, Bruce S.; Roozendaal, Benno; Van Rossum, Elisabeth F. C.; Ahn, Junyoung; Brown, David W.; Plitt, Aaron; Singh, Gagandeep


    Glucocorticoids are the most commonly prescribed anti-inflammatory/immunosuppressant medications worldwide. This article highlights the risk of clinically significant and sometimes severe psychological, cognitive, and behavioral disturbances that may be associated with glucocorticoid use, as well as

  6. HIV Medicines and Side Effects (United States)

    ... medicines, talk to your health care provider about possible side effects. Tell your health care provider about your lifestyle and point out any possible side effects that would be especially hard for you to ...

  7. Probiotics: Safety and Side Effects (United States)

    ... of this page please turn JavaScript on. Feature: Probiotics Safety and Side Effects Past Issues / Winter 2016 ... Says About the Safety and Side Effects of Probiotics Whether probiotics are likely to be safe for ...

  8. The effects of glucocorticoids on the inhibition of emotional information: A dose-response study. (United States)

    Taylor, Véronique A; Ellenbogen, Mark A; Washburn, Dustin; Joober, Ridha


    There is evidence that cortisol influences cognitive and affective processes such as selective attention and memory for emotional events, yet the effects of glucocorticoids on attentional inhibition in humans remain unknown. Consequently, this double-blind study examined dose-dependent effects of exogenous glucocorticoids on the inhibition of emotional information. Sixty-three university students (14 male, 49 female) ingested either a placebo pill or hydrocortisone (10mg or 40mg), and completed a negative priming task assessing the inhibition of pictures depicting angry, sad, and happy faces. The 10mg, but not the 40mg hydrocortisone dose elicited increased inhibition for angry faces relative to placebo. Thus, moderate glucocorticoid elevations may have adaptive effects on emotional information processing, whereas high glucocorticoid elevations appear to attenuate this effect, consistent with the view that there are dose-dependent effects of glucocorticoids on cognition. Copyright © 2010 Elsevier B.V. All rights reserved.

  9. Effect of cAMP signaling on expression of glucocorticoid receptor, Bim and Bad in glucocorticoid-sensitive and resistant leukemic and multiple myeloma cells. (United States)

    Dong, Hongli; Carlton, Michael E; Lerner, Adam; Epstein, Paul M


    Stimulation of cAMP signaling induces apoptosis in glucocorticoid-sensitive and resistant CEM leukemic and MM.1 multiple myeloma cell lines, and this effect is enhanced by dexamethasone in both glucocorticoid-sensitive cell types and in glucocorticoid-resistant CEM cells. Expression of the mRNA for the glucocorticoid receptor alpha (GR) promoters 1A3, 1B and 1C, expression of mRNA and protein for GR, and the BH3-only proapoptotic proteins, Bim and Bad, and the phosphorylation state of Bad were examined following stimulation of the cAMP and glucocorticoid signaling pathways. Expression levels of GR promoters were increased by cAMP and glucocorticoid signaling, but GR protein expression was little changed in CEM and decreased in MM.1 cells. Stimulation of these two signaling pathways induced Bim in CEM cells, induced Bad in MM.1 cells, and activated Bad, as indicated by its dephosphorylation on ser112, in both cell types. This study shows that leukemic and multiple myeloma cells, including those resistant to glucocorticoids, can be induced to undergo apoptosis by stimulating the cAMP signaling pathway, with enhancement by glucocorticoids, and the mechanism by which this occurs may be related to changes in Bim and Bad expression, and in all cases, to activation of Bad.

  10. Glucocorticoids exert context-dependent effects on cells of the joint in vitro

    DEFF Research Database (Denmark)

    Madsen, Suzi H; Andreassen, Kim V; Christensen, Søren T


    Glucocorticoids are known to attenuate bone formation in vivo leading to decreased bone volume and increased risk of fractures, whereas effects on the joint tissue are less characterized. However, glucocorticoids appear to have a reducing effect on inflammation and pain in osteoarthritis. This st....... This study aimed at characterizing the effect of glucocorticoids on chondrocytes, osteoclasts, and osteoblasts....

  11. Glucocorticoid Effects on Memory Consolidation Depend on Functional Interactions between the Medial Prefrontal Cortex and Basolateral Amygdala

    NARCIS (Netherlands)

    Roozendaal, Benno; McReynolds, Jayme R.; Van der Zee, Eddy A.; Lee, Sangkwan; McGaugh, James L.; McIntyre, Christa K.


    Considerable evidence indicates that the basolateral complex of the amygdala (BLA) interacts with efferent brain regions in mediating glucocorticoid effects on memory consolidation. Here, we investigated whether glucocorticoid influences on the consolidation of memory for emotionally arousing

  12. Coping – Late Side Effects (United States)

    Cancer treatment can cause late side effects that may not show up for months or years after treatment. These late effects may include heart and lung problems, bone loss, eye and hearing changes, lymphedema, and other problems

  13. Expression and function of nuclear receptor coregulators in brain : understanding the cell-specific effects of glucocorticoids

    NARCIS (Netherlands)

    Laan, Siem van der


    Currently, the raising awareness of the role of glucocorticoids in the onset of numerous (neuro)-pathologies constitutes the increasing necessity of understanding the mechanisms of action of glucocorticoids in bodily processes and brain functioning. Glucocorticoids mediate their effects by binding

  14. The distorting effect of varying diets on fecal glucocorticoid measurements as indicators of stress

    DEFF Research Database (Denmark)

    Kalliokoski, Otto; Teilmann, A. Charlotte; Abelson, Klas S. P.


    The physiological stress response is frequently gauged in animals, non-invasively, through measuring glucocorticoids in excreta. A concern with this method is, however, the unknown effect of variations in diets on the measurements. With an energy dense diet, leading to reduced defecation, will low...... concentrations of glucocorticoids be artificially inflated? Can this effect be overcome by measuring the total output of glucocorticoids in excreta? In a controlled laboratory setting we explored the effect in mice. When standard mouse chow – high in dietary fiber – was replaced with a 17% more energy-dense diet...

  15. Side Effects and Their Management (United States)

    ... tumors. Donate Now Subscribe for e-updates Please leave this field empty ... tumors and their treatments bring an array of possible side effects in to a patient’s life. Fatigue, cognitive changes, and mood changes are ...

  16. Side Effects: Hair Loss (Alopecia) (United States)

    Hair loss, also called alopecia, is a side effect of cancer treatments, such as chemotherapy and radiation therapy. Learn how to cope with and manage hair loss. Listen to tips from others who have experienced hair loss.

  17. Side Effects: Nausea and Vomiting (United States)

    Types of nausea and vomiting caused by cancer treatment include: anticipatory, acute, and delayed. Controlling these side effects will help to prevent serious problems such as malnutrition and dehydration in people with cancer.

  18. The Pro-inflammatory Effects of Glucocorticoids in the Brain (United States)

    Duque, Erica de Almeida; Munhoz, Carolina Demarchi


    Glucocorticoids are a class of steroid hormones derived from cholesterol. Their actions are mediated by the glucocorticoid and mineralocorticoid receptors, members of the superfamily of nuclear receptors, which, once bound to their ligands, act as transcription factors that can directly modulate gene expression. Through protein–protein interactions with other transcription factors, they can also regulate the activity of many genes in a composite or tethering way. Rapid non-genomic signaling was also demonstrated since glucocorticoids can act through membrane receptors and activate signal transduction pathways, such as protein kinases cascades, to modulate other transcriptions factors and activate or repress various target genes. By all these different mechanisms, glucocorticoids regulate numerous important functions in a large variety of cells, not only in the peripheral organs but also in the central nervous system during development and adulthood. In general, glucocorticoids are considered anti-inflammatory and protective agents due to their ability to inhibit gene expression of pro-inflammatory mediators and other possible damaging molecules. Nonetheless, recent studies have uncovered situations in which these hormones can act as pro-inflammatory agents depending on the dose, chronicity of exposure, and the structure/organ analyzed. In this review, we will provide an overview of the conditions under which these phenomena occur, a discussion that will serve as a basis for exploring the mechanistic foundation of glucocorticoids pro-inflammatory gene regulation in the brain. PMID:27445981

  19. Experimental Study on the Effect of Calcitonin in Osteoporosis Induced by the Immobilization and Long-Term Glucocorticoid

    International Nuclear Information System (INIS)

    Park, Dong Jin; Lee, Sang Rae


    It is well known that the glucocorticoid induces osteoporosis by suppression of the osteoblast, but its effect on the osteoclast has some controversy whether it activates or suppresses the osteoclast. If the calcitonin, which is known to suppress the osteoclast, prevents the osteoporosis by glucocorticoid, then the suppression of the osteoclast by the glucocorticoid is not so significant. And if the calcitonin increases the osteoblastic activity, Tc-99m MDP uptake will be increased in spite of the glucocorticoid effect on the osteoblast. The immobilization operation was performed to the right leg of male Wistar rats weighing about 200 gm each. For 16 weeks after operation, rats were injected glucocorticoid alone or glucocorticoid and calcitonin. The bone density was measured by means of photodensitometry under reference aluminum step wedge and Tc-99m MDP uptake was available to the index of the osteoblastic activity. 1. The bone density of femoral head was markedly reduced than that of femoral shaft following ratio of cancellous and cortical components in both site. 2. glucocorticoid caused decrease in bone density of spine and femur, and there is significantly increase of it when medication of glucocorticoid and calcitonin injection simultaneously than that of glucocorticoid. 3. Tc-99m MDP uptake was revealed significant reduction in medication of glucocorticoid but increase in glucocorticoid and calcitonin injection simultaneously in later experimental period. 4. There was a slight reduction in plasma osteocalcin in medication of glucocorticoid through experimental periods and an increase in its value in case of giving glucocorticoid and calcitonin simultaneously in later experimental period. From these results, we suggest that osteoporosis by immobilization is more pronounced by glucocorticoid hormone and osteoporosis induced by immobilization and glucocorticoid use is prevented by calcitonin administration with increasing osteoblastic activity.

  20. Combined Effects of Glucocorticoid and Noradrenergic Activity on Loss Aversion. (United States)

    Margittai, Zsofia; Nave, Gideon; Van Wingerden, Marijn; Schnitzler, Alfons; Schwabe, Lars; Kalenscher, Tobias


    Loss aversion is a well-known behavioral regularity in financial decision making, describing humans' tendency to overweigh losses compared to gains of the same amount. Recent research indicates that stress and associated hormonal changes affect loss aversion, yet the underlying neuroendocrine mechanisms are still poorly understood. Here, we investigated the causal influence of two major stress neuromodulators, cortisol and noradrenaline, on loss aversion during financial decision making. In a double-blind, placebo-controlled between-subject design, we orally administered either the α2-adrenergic antagonist yohimbine (increasing noradrenergic stimulation), hydrocortisone, both substances, or a placebo to healthy young men. We tested the treatments' influence on a financial decision-making task measuring loss aversion and risk attitude. We found that both drugs combined, relative to either drug by itself, reduced loss aversion in the absence of an effect on risk attitude or choice consistency. Our data suggest that concurrent glucocorticoid and noradrenergic activity prompts an alignment of reward- with loss-sensitivity, and thus diminishes loss aversion. Our results have implications for the understanding of the susceptibility to biases in decision making.

  1. Fatal and non-fatal adverse events of glucocorticoid therapy for Graves' orbitopathy

    DEFF Research Database (Denmark)

    Marcocci, Claudio; Watt, Torquil; Altea, Maria Antonietta


    The objective of this study was to investigate the side effects of glucocorticoid (GC) therapy observed by European thyroidologists during the treatment of Graves' orbitopathy (GO).......The objective of this study was to investigate the side effects of glucocorticoid (GC) therapy observed by European thyroidologists during the treatment of Graves' orbitopathy (GO)....

  2. Glucocorticoids have state-dependent stimulant effects on the mesencephalic dopaminergic transmission.


    Piazza, P V; Rougé-Pont, F; Deroche, V; Maccari, S; Simon, H; Le Moal, M


    An increase in the activity of mesencephalic dopaminergic neurons has been implicated in the appearance of pathological behaviors such as psychosis and drug abuse. Several observations suggest that glucocorticoids might contribute to such an increase in dopaminergic activity. The present experiments therefore analyzed the effects of corticosterone, the major glucocorticoid in the rat, both on dopamine release in the nucleus accumbens of freely moving animals by means of microdialysis, and on ...

  3. Glucocorticoid effects on object recognition memory require training-associated emotional arousal


    Okuda, Shoki; Roozendaal, Benno; McGaugh, James L.


    Considerable evidence implicates glucocorticoid hormones in the regulation of memory consolidation and memory retrieval. The present experiments investigated whether the influence of these hormones on memory depends on the level of emotional arousal induced by the training experience. We investigated this issue in male Sprague–Dawley rats by examining the effects of immediate posttraining systemic injections of the glucocorticoid corticosterone on object recognition memory under two condition...

  4. Running away from side effects

    DEFF Research Database (Denmark)

    Casla, S; Hojman, P; Márquez-Rodas, I


    The number of breast cancer survivors increases every year, thanks to the development of new treatments and screening techniques. However, patients present with numerous side effects that may affect their quality of life. Exercise has been demonstrated to reduce some of these side effects...... be an integrative complementary intervention to improve physiological, physical and psychological factors that affect survival and quality of life of these patients. For that reason, the main objective of this review is to provide a general overview of exercise benefits in breast cancer patients and recommendations...

  5. The effects of glucocorticoid on microarchitecture, collagen, mineral and mechanical properties of sheep femur cortical bone

    DEFF Research Database (Denmark)

    Ding, Ming; Danielsen, Carl C; Overgaard, Søren


    The effects of glucocorticoid on microarchitecture, collagen, mineral and mechanical properties of sheep femur cortical bone – Validation of large animal model for tissue engineering and biomaterial research Ming Ding,1* Carl Christian Danielsen,2 Søren Overgaard1 1Orthopaedic Research Laboratory......, Department of Orthopaedics and Traumatology, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Odense C, Denmark 2Department of Connective Tissue Biology, Institute of Anatomy, University of Aarhus, Aarhus C, Denmark Osteopenia in sheep has been successfully induced...... by glucocorticoid treatment and the changes in properties of cancellous bone were comparable with those observed in humans after long-term glucocorticoid treatment. However, the influence on cortical bone has not been thoroughly elucidated. This study aimed to investigate the influence of glucocorticoid on sheep...

  6. Cytokine-induced loss of glucocorticoid function: effect of kinase inhibitors, long-acting β(2-adrenoceptor [corrected] agonist and glucocorticoid receptor ligands.

    Directory of Open Access Journals (Sweden)

    Christopher F Rider

    Full Text Available Acting on the glucocorticoid receptor (NR3C1, glucocorticoids are widely used to treat inflammatory diseases. However, glucocorticoid resistance often leads to suboptimal asthma control. Since glucocorticoid-induced gene expression contributes to glucocorticoid activity, the aim of this study was to use a 2 × glucocorticoid response element (GRE reporter and glucocorticoid-induced gene expression to investigate approaches to combat cytokine-induced glucocorticoid resistance. Pre-treatment with tumor necrosis factor-α (TNF or interleukin-1β inhibited dexamethasone-induced mRNA expression of the putative anti-inflammatory genes RGS2 and TSC22D3, or just TSC22D3, in primary human airway epithelial and smooth muscle cells, respectively. Dexamethasone-induced DUSP1 mRNA was unaffected. In human bronchial epithelial BEAS-2B cells, dexamethasone-induced TSC22D3 and CDKN1C expression (at 6 h was reduced by TNF pre-treatment, whereas DUSP1 and RGS2 mRNAs were unaffected. TNF pre-treatment also reduced dexamethasone-dependent 2×GRE reporter activation. This was partially reversed by PS-1145 and c-jun N-terminal kinase (JNK inhibitor VIII, inhibitors of IKK2 and JNK, respectively. However, neither inhibitor affected TNF-dependent loss of dexamethasone-induced CDKN1C or TSC22D3 mRNA. Similarly, inhibitors of the extracellular signal-regulated kinase, p38, phosphoinositide 3-kinase or protein kinase C pathways failed to attenuate TNF-dependent repression of the 2×GRE reporter. Fluticasone furoate, fluticasone propionate and budesonide were full agonists relative to dexamethasone, while GSK9027, RU24858, des-ciclesonide and GW870086X were partial agonists on the 2×GRE reporter. TNF reduced reporter activity in proportion with agonist efficacy. Full and partial agonists showed various degrees of agonism on RGS2 and TSC22D3 expression, but were equally effective at inducing CDKN1C and DUSP1, and did not affect the repression of CDKN1C or TSC22D3

  7. Effects of a single glucocorticoid injection on propylene glycol-treated cows with clinical ketosis. (United States)

    van der Drift, Saskia G A; Houweling, Martin; Bouman, Marina; Koets, Ad P; Tielens, Aloysius G M; Nielen, Mirjam; Jorritsma, Ruurd


    This study investigated the metabolic effects of glucocorticoids when administered to propylene glycol-treated cows with clinical ketosis. Clinical ketosis was defined by depressed feed intake and milk production, and a maximal score for acetoacetate in urine. All cows received 250 mL oral propylene glycol twice daily for 3 days and were randomly assigned to a single intramuscular injection with sterile isotonic saline solution (n = 14) or dexamethasone-21-isonicotinate (n = 17). Metabolic blood variables were monitored for 6 days and adipose tissue variables for 3 days. β-Hydroxybutyrate (BHBA) concentrations in blood decreased in all cows during treatment, but were lower in glucocorticoid-treated cows. Cows treated with glucocorticoids had higher plasma glucose and insulin concentrations, whereas concentrations of non-esterified fatty acids, 3-methylhistidine and growth hormone were unaffected. mRNA expression of hormone-sensitive lipase, BHBA receptor and peroxisome proliferator-activated receptor type γ in adipose tissue was not affected. This shows that lipolytic effects do not appear to be important in ketotic cows when glucocorticoids are combined with PG. Plasma 3-methyl histidine concentrations were similar in both groups, suggesting that glucocorticoids did not increase muscle breakdown and that the greater rise in plasma glucose in glucocorticoid-treated cows may not be due to increased supply of glucogenic amino acids from muscle. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. [Side Effects of Smoking Cessation]. (United States)

    Braun, Raffael; Huwiler, Bernhard


    Side Effects of Smoking Cessation Abstract. We present the case of a clozapine intoxication associated with aspiration pneumonia due to smoking cessation. Clozapine is mainly metabolized by CYP1A2. CYP1A2 is induced by cigarette smoking, which may change the plasma level of clozapine, especially if consuming habits change.

  9. Managing Chemotherapy Side Effects: Constipation (United States)

    N ational C ancer I nstitute Managing Chemotherapy Side Effects Constipation Take these steps: Eat high-fiber foods such as: ● ● Whole-grain breads and cereals ● ● Fruits and vegetables ● ● Nuts and seeds Turn this ...

  10. Finasteride and sexual side effects

    Directory of Open Access Journals (Sweden)

    Venkataram Mysore


    Full Text Available Finasteride, a 5-alpha reductase inhibitor, widely used in the medical management of male pattern hairloss, has been reported to cause sexual side effects. This article critically examines the evidence available and makes recommendations as to how a physician should counsel a patient while prescribing the drug.

  11. General effect of endotoxin on glucocorticoid receptors in mammalian tissues

    International Nuclear Information System (INIS)

    Stith, R.D.; McCallum, R.E.


    Considering the ubiquitous nature of glucocorticoid actions and the fact that endotoxin inhibits glucocorticoid action in the liver, we proposed to examine whether endotoxin affected extrahepatic actions of glucocorticoids. Fasted C57BL/6J mice were injected intraperitoneally with endotoxin (LD50) at 0800 and were killed 6 h later. Control mice were injected with an equal volume of saline. 3 H-dexamethasone binding, measured by a new cytosol exchange assay utilizing molybdate plus dithiothreitol, in liver, kidney, skeletal muscle, spleen, lung, and heart tissue was significantly lower in treated than in control mice. The equilibrium dissociation constants were not significantly different, but the number of available binding sites in each tissue was reduced by endotoxin treatment. Phosphoenolpyruvate carboxykinase activity was significantly reduced in liver but not in kidney. Endotoxin treatment lowered glycogen content in liver but not in skeletal muscle. The reduction observed in the a form of liver glycogen synthase due to endotoxin was not seen in skeletal muscle glycogen synthase a. These data support the proposal that endotoxin or a mediator of its action inhibits systemic glucocorticoid action. The results also emphasize the central role of the liver in the metabolic disturbances of the endotoxin-treated mouse

  12. Glucocorticoid receptor effects on the immune system and infl ammation

    NARCIS (Netherlands)

    E.L.T. van den Akker (Erica)


    textabstractThomas Addison’s discovery in the mid-1800s that the adrenal cortex was essential for survival preceded by nearly a century the demonstration that this gland produced at least two distinct hormones, each essential for normal life. How glucocorticoids sustained life remained a mystery for

  13. Warfarin Side Effects: Watch for Interactions (United States)

    Warfarin side effects: Watch for interactions Although commonly used to treat blood clots, warfarin (Coumadin, Jantoven) can have dangerous side effects or ... bleeding. Here are precautions to take to avoid warfarin side effects. By Mayo Clinic Staff If you' ...

  14. Metabolic Side Effects of Lithium

    Directory of Open Access Journals (Sweden)

    M. Cagdas Eker


    Full Text Available Lithium is an alkaline ion being used since 19th century. After its widespread use in psychiatric disorders, observed side effects caused skepticism about its therapeutic efficacy. Despite several disadvantages, lithium is one of the indispensible drugs used in affective disorders, especially in bipolar disorder. It became a necessity for physicians to recognize its side effects since lithium is still accepted as a gold standard in the treatment of bipolar disorder. Adverse effects of chronic administration of lithium on several organ systems are widely known. In this article metabolic effects of lithium on thyroid and parathyroid glands, body mass index and kidneys will be discussed along with their mechanisms, clinical findings, possible risk factors and treatment. One of the most common side effect of lithium is hypothyroidism. It has the same clinical and biochemical properties as primary hypothyroidism and observed as subclinical hypothyroidism in the first place. Hypothyroidism, even its subclinical form, may be associated with non-response or inadequate response and is indicated as a risk factor for development of rapid cycling bipolar disorder. Therefore, hypothyroidism should be screened no matter how severe it is and should be treated with thyroid hormone in the presence of clinical hypothyroidism. Weight gain due to lithium administration disturbs the compliance to treatment and negatively affects the course of the illness. Increased risk for diabetes, hypertension, ischemic heart disease and stroke because of weight gain constitute other centers of problem. Indeed, it is of importance to determine the risk factors before treatment, to follow up the weight, to re-organize nutritional habits and to schedule exercises. Another frequent problematic side effect of lithium treatment is renal dysfunction which clinically present as nephrogenic diabetes insipidus with the common symptoms of polyuria and polydipsia. Nephrogenic diabetes

  15. Effects of chronic mild stress on behavioral and neurobiological parameters - Role of glucocorticoid. (United States)

    Chen, Jiao; Wang, Zhen-zhen; Zuo, Wei; Zhang, Shuai; Chu, Shi-feng; Chen, Nai-hong


    Major depression is thought to originate from maladaptation to adverse events, particularly when impairments occur in mood-related brain regions. Hypothalamus-pituitary-adrenal (HPA) axis is one of the major systems involved in physiological stress response. HPA axis dysfunction and high glucocorticoid concentrations play an important role in the pathogenesis of depression. In addition, astrocytic disability and dysfunction of neurotrophin brain-derived neurotrophin factor (BDNF) greatly influence the development of depression and anxiety disorders. Therefore, we investigated whether depressive-like and anxiety-like behaviors manifest in the absence of glucocorticoid production and circulation in adrenalectomized (ADX) rats after chronic mild stress (CMS) exposure and its potential molecular mechanisms. The results demonstrate that glucocorticoid-controlled rats showed anxiety-like behaviors but not depression-like behaviors after CMS. Molecular and cellular changes included the decreased BDNF in the hippocampus, astrocytic dysfunction with connexin43 (cx43) decreasing and abnormality in gap junction in prefrontal cortex (PFC). Interestingly, we did not find any changes in glucocorticoid receptor (GR) or its chaperone protein FK506 binding protein 51 (FKBP5) expression in the hippocampus or PFC in ADX rats subjected to CMS. In conclusion, the production and circulation of glucocorticoids are one of the contributing factors in the development of depression-like behaviors in response to CMS. In contrast, the effects of CMS on anxiety-like behaviors are independent of the presence of circulating glucocorticoids. Meanwhile, stress decreased GR expression and enhanced FKBP5 expression via higher glucocorticoid exposure. Gap junction dysfunction and changes in BDNF may be associated with anxiety-like behaviors. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Neutrophils are not less sensitive than other blood leukocytes to the genomic effects of glucocorticoids.

    Directory of Open Access Journals (Sweden)

    Gaelle Hirsch

    Full Text Available Neutrophils are generally considered less responsive to glucocorticoids compared to other inflammatory cells. The reported increase in human neutrophil survival mediated by these drugs partly supports this assertion. However, it was recently shown that dexamethasone exerts potent anti-inflammatory effects in equine peripheral blood neutrophils. Few comparative studies of glucocorticoid effects in neutrophils and other leukocytes have been reported and a relative insensitivity of neutrophils to these drugs could not be ruled out.We assessed glucocorticoid-responsiveness in equine and human peripheral blood neutrophils and neutrophil-depleted leukocytes.Blood neutrophils and neutrophil-depleted leukocytes were isolated from 6 healthy horses and 4 human healthy subjects. Cells were incubated for 5 h with or without LPS (100 ng/mL alone or combined with hydrocortisone, prednisolone or dexamethasone (10(-8 M and 10(-6 M. IL-1β, TNF-α, IL-8, glutamine synthetase and GR-α mRNA expression was quantified by qPCR. Equine neutrophils were also incubated for 20 h with or without the three glucocorticoids and cell survival was assessed by flow cytometry and light microscopy on cytospin preparations.We found that glucocorticoids down-regulated LPS-induced pro-inflammatory mRNA expression in both cell populations and species. These drugs also significantly increased glutamine synthetase gene expression in both equine cell populations. The magnitude of glucocorticoid response between cell populations was generally similar in both species. We also showed that dexamethasone had a comparable inhibitory effect on pro-inflammatory gene expression in both human and equine neutrophils. As reported in other species, glucocorticoids significantly increase the survival in equine neutrophils.Glucocorticoids exert genomic effects of similar magnitude on neutrophils and on other blood leukocytes. We speculate that the poor response to glucocorticoids observed in some

  17. Neutrophils Are Not Less Sensitive Than Other Blood Leukocytes to the Genomic Effects of Glucocorticoids (United States)

    Hirsch, Gaelle; Lavoie-Lamoureux, Anouk; Beauchamp, Guy; Lavoie, Jean-Pierre


    Background Neutrophils are generally considered less responsive to glucocorticoids compared to other inflammatory cells. The reported increase in human neutrophil survival mediated by these drugs partly supports this assertion. However, it was recently shown that dexamethasone exerts potent anti-inflammatory effects in equine peripheral blood neutrophils. Few comparative studies of glucocorticoid effects in neutrophils and other leukocytes have been reported and a relative insensitivity of neutrophils to these drugs could not be ruled out. Objective We assessed glucocorticoid-responsiveness in equine and human peripheral blood neutrophils and neutrophil-depleted leukocytes. Methods Blood neutrophils and neutrophil-depleted leukocytes were isolated from 6 healthy horses and 4 human healthy subjects. Cells were incubated for 5 h with or without LPS (100 ng/mL) alone or combined with hydrocortisone, prednisolone or dexamethasone (10−8 M and 10−6 M). IL-1β, TNF-α, IL-8, glutamine synthetase and GR-α mRNA expression was quantified by qPCR. Equine neutrophils were also incubated for 20 h with or without the three glucocorticoids and cell survival was assessed by flow cytometry and light microscopy on cytospin preparations. Results We found that glucocorticoids down-regulated LPS-induced pro-inflammatory mRNA expression in both cell populations and species. These drugs also significantly increased glutamine synthetase gene expression in both equine cell populations. The magnitude of glucocorticoid response between cell populations was generally similar in both species. We also showed that dexamethasone had a comparable inhibitory effect on pro-inflammatory gene expression in both human and equine neutrophils. As reported in other species, glucocorticoids significantly increase the survival in equine neutrophils. Conclusions Glucocorticoids exert genomic effects of similar magnitude on neutrophils and on other blood leukocytes. We speculate that the poor response to

  18. Environmental Enrichment Effect on Fecal Glucocorticoid Metabolites and Captive Maned Wolf (Chrysocyon brachyurus) Behavior. (United States)

    Coelho, Carlyle Mendes; de Azevedo, Cristiano Schetini; Guimarães, Marcelo Alcino de Barros Vaz; Young, Robert John


    Environmental enrichment is a technique that may reduce the stress of nonhuman animals in captivity. Stress may interfere with normal behavioral expression and affect cognitive decision making. Noninvasive hormonal studies can provide important information about the stress statuses of animals. This study evaluated the effectiveness of different environmental enrichment treatments in the diminution of fecal glucocorticoid metabolites (stress indicators) of three captive maned wolves (Chrysocyon brachyurus). Correlations of the fecal glucocorticoid metabolite levels with expressed behaviors were also determined. Results showed that environmental enrichment reduced fecal glucocorticoid metabolite levels. Furthermore, interspecific and foraging enrichment items were most effective in reducing stress in two of the three wolves. No definite pattern was found between behavioral and physiological responses to stress. In conclusion, these behavioral and physiological data showed that maned wolves responded positively from an animal well being perspective to the enrichment items presented.

  19. Suppressive effect of glucocorticoids on TNF-alpha production is associated with their clinical effect in multiple sclerosis

    NARCIS (Netherlands)

    van Winsen, L.M.L.; Polman, C.H.; Dijkstra, C.D.; Tilders, F.J.H.; Uitdehaag, B.M.J.


    A reduced sensitivity to glucocorticoids can affect the clinical effect of treatment with high-dose intravenous methylprednisolone in multiple sclerosis. We prospectively studied 27 multiple sclerosis patients who were treated with intravenous methylprednisolone. Before and after treatment in vitro

  20. Divergent effects of endogenous and exogenous glucocorticoid-induced leucine zipper in animal models of inflammation and arthritis

    NARCIS (Netherlands)

    Ngo, Devi; Beaulieu, Elaine; Gu, Ran; Leaney, Alexandra; Santos, Leilani; Fan, Huapeng; Yang, Yuanhang; Kao, Wenping; Xu, Jiake; Escriou, Virginie; Loiler, Scott; Vervoordeldonk, Margriet J.; Morand, Eric F.


    Glucocorticoid-induced leucine zipper (GILZ) has effects on inflammatory pathways that suggest it to be a key inhibitory regulator of the immune system, and its expression is exquisitely sensitive to induction by glucocorticoids. We undertook this study to test our hypothesis that GILZ deficiency

  1. Topical glucocorticoid has no antinociceptive or anti-inflammatory effect in thermal injury

    DEFF Research Database (Denmark)

    Pedersen, J L; Møiniche, S; Kehlet, H


    We have studied the antinociceptive and anti-inflammatory effects of topical glucocorticoids in human thermal injury. The right and left legs of 12 healthy volunteers were allocated randomly to be treated with either 0.05% clobetasol propionate cream or placebo in a double-blind trial. Thermal...

  2. Effects of a single glucocorticoid injection on propylene glycol-treated cows with clinical ketosis

    NARCIS (Netherlands)

    van der Drift, Saskia G A; Houweling, Martin; Bouman, Marina; Koets, Ad P; Tielens, Aloysius G M; Nielen, Mirjam; Jorritsma, Ruurd


    This study investigated the metabolic effects of glucocorticoids when administered to propylene glycol-treated cows with clinical ketosis. Clinical ketosis was defined by depressed feed intake and milk production, and a maximal score for acetoacetate in urine. All cows received 250 mL oral propylene

  3. Early Life Stress Effects on the Glucocorticoid - BDNF interplay in the Hippocampus

    Directory of Open Access Journals (Sweden)

    Nikolaos P Daskalakis


    Full Text Available Early life stress (ELS is implicated in the etiology of multiple psychiatric disorders. Important biological effects of ELS are manifested in stress-susceptible regions of the hippocampus and are partially mediated by long-term effects on glucocorticoid and/or neurotrophin signaling pathways. Glucocorticoid (GC signaling mediates the regulation of the stress response to maintain homeostasis, while neurotrophin signaling plays a key role in neuronal outgrowth and is crucial for axonal guidance and synaptic integrity. The neurotrophin and glucocorticoid signaling pathways co-exist throughout the central nervous system (CNS, particularly in the hippocampus, which has high expression of glucocorticoid and mineralocorticoid receptors (GR and MR as well as brain-derived neurotrophic factor (BDNF and its receptor, tropomyosin-related kinase receptor B (TrkB. This review addresses the effects of ELS paradigms on GC- and BDNF- dependent mechanisms and their crosstalk in the hippocampus, including potential implications for the pathogenesis of common stress-related disorders.

  4. Fast effects of glucocorticoids on memory-related network oscillations in the mouse hippocampus. (United States)

    Weiss, E K; Krupka, N; Bähner, F; Both, M; Draguhn, A


    Transient or lasting increases in glucocorticoids accompany deficits in hippocampus-dependent memory formation. Recent data indicate that the formation and consolidation of declarative and spatial memory are mechanistically related to different patterns of hippocampal network oscillations. These include gamma oscillations during memory acquisition and the faster ripple oscillations (approximately 200 Hz) during subsequent memory consolidation. We therefore analysed the effects of acutely applied glucocorticoids on network activity in mouse hippocampal slices. Evoked field population spikes and paired-pulse responses were largely unaltered by corticosterone or cortisol, respectively, despite a slight increase in maximal population spike amplitude by 10 microm corticosterone. Several characteristics of sharp waves and superimposed ripple oscillations were affected by glucocorticoids, most prominently the frequency of spontaneously occurring sharp waves. At 0.1 microm, corticosterone increased this frequency, whereas maximal (10 microm) concentrations led to a reduction. In addition, gamma oscillations became slightly faster and less regular in the presence of high doses of corticosteroids. The present study describes acute effects of glucocorticoids on sharp wave-ripple complexes and gamma oscillations in mouse hippocampal slices, revealing a potential background for memory deficits in the presence of elevated levels of these hormones.

  5. Long-term safety, efficacy, and patient acceptability of teriparatide in the management of glucocorticoid-induced osteoporosis

    Directory of Open Access Journals (Sweden)

    Dore RK


    Full Text Available Robin K DoreDavid Geffen School of Medicine, University of California, Los Angeles, CA, USAAbstract: Glucocorticoids are commonly prescribed medications to treat multiple diseases across many medical specialties. One of the most common yet largely unappreciated side effect of glucocorticoid use is increased risk of fracture. Many different therapies are indicated to prevent and treat this condition; many guidelines exist that suggest appropriate use of both glucocorticoids and the medications approved to prevent this common side effect of glucocorticoid therapy. Nevertheless, 30%–50% of patients on long-term glucocorticoid therapy sustain a fracture. Teriparatide, recombinant human parathyroid hormone (1–34, is a daily self-injectable therapy for 24 months approved for use in patients taking long-term glucocorticoids. Teriparatide has been shown to increase bone mineral density and reduce vertebral fracture risk in glucocorticoid-treated patients. Glucocorticoids have many adverse effects on bone that teriparatide has been shown to prevent or negate. Given the fact that preventive therapy for glucocorticoid-induced osteoporosis is often not prescribed, one wonders whether a daily self-injectable therapy for this condition would be prescribed by physicians and accepted by patients. This article reviews the epidemiology, pathophysiology, treatment, guidelines, and persistence data (when available for patients with glucocorticoid-induced osteoporosis treated with teriparatide.Keywords: glucocorticoid-induced osteoporosis, teriparatide, anabolic, PTH, parathyroid hormone

  6. Hormones, stress, and cognition: The effects of glucocorticoids and oxytocin on memory (United States)

    Wirth, Michelle M.


    Hormones have nuanced effects on learning and memory processes. The degree and direction of the effect (e.g., is memory impaired or enhanced?) depends on the dose, type and stage of memory, and type of material being learned, among other factors. This review will focus on two specific topics within the realm of effects of hormones on memory: (1) How glucocorticoids (the output hormones of the hypothalamic-pituitary-adrenal axis) affect long-term memory consolidation, retrieval, and working memory, with a focus on neural mechanisms and effects of emotion; and (2) How oxytocin affects memory, with emphasis on a speculative hypothesis that oxytocin might exert its myriad effects on human social cognition and behavior via impacts on more general cognitive processes. Oxytocin-glucocorticoid interactions will be briefly addressed. These effects of hormones on memory will also be considered from an evolutionary perspective. PMID:25893159

  7. [Glucocorticoid induced osteoporosis]. (United States)

    Anić, Branimir; Mayer, Miroslav


    Secondary osteoporosis most often develops due to glucocorticoid therapy. Glucocorticoids affect all stages of the bone remodeling cycle, its formation and resorption. Osteoblasts are primarily affected, decreasing their activity and enhancing apoptosis. Patients treated with glucocorticoids have lower bone mineral density and increased fracture risk. Glucocorticoid-induced osteoporosis can be prevented by administering the minimal effective dose of glucocorticoids, calcium and vitamin D supplementation or, if possible, by hormone replace- ment therapy. Moreover, appropriate physical activity should be encouraged. Patients who are at higher risk for low-energy fractures (for example post-menopausal women) have to be actively treated, usually with antiresorptive drugs among which bisphosphonates are currently the first line therapy.

  8. Sexual side effects induced by psychotropic drugs

    DEFF Research Database (Denmark)

    Kristensen, Ellids


    The majority of psychotropic drugs entail sexual side effects. The sexual side effects may reduce quality of life and may give rise to non-compliance. For example, 30-60 per cent of patients treated with antidepressants are known to develop a sexual dysfunction. However, some psychotropic drugs...... with no or very few sexual side effects have begun to emerge. The treatment of sexual side effects induced by psychotropic drugs may consist of: modified sexual habits, reduction in dosage, switching to another medication, possibly in combination with different psychotropic agents, other varieties...

  9. Glucocorticoid effects on object recognition memory require training-associated emotional arousal. (United States)

    Okuda, Shoki; Roozendaal, Benno; McGaugh, James L


    Considerable evidence implicates glucocorticoid hormones in the regulation of memory consolidation and memory retrieval. The present experiments investigated whether the influence of these hormones on memory depends on the level of emotional arousal induced by the training experience. We investigated this issue in male Sprague-Dawley rats by examining the effects of immediate posttraining systemic injections of the glucocorticoid corticosterone on object recognition memory under two conditions that differed in their training-associated emotional arousal. In rats that were not previously habituated to the experimental context, corticosterone (0.3, 1.0, or 3.0 mg/kg, s.c.) administered immediately after a 3-min training trial enhanced 24-hr retention performance in an inverted-U shaped dose-response relationship. In contrast, corticosterone did not affect 24-hr retention of rats that received extensive prior habituation to the experimental context and, thus, had decreased novelty-induced emotional arousal during training. Additionally, immediate posttraining administration of corticosterone to nonhabituated rats, in doses that enhanced 24-hr retention, impaired object recognition performance at a 1-hr retention interval whereas corticosterone administered after training to well-habituated rats did not impair 1-hr retention. Thus, the present findings suggest that training-induced emotional arousal may be essential for glucocorticoid effects on object recognition memory.

  10. Transcriptional effects of glucocorticoid receptors in the dentate gyrus increase anxiety-related behaviors.

    Directory of Open Access Journals (Sweden)

    Nadège Sarrazin

    Full Text Available The Glucocorticoid Receptor (GR is a transcription factor ubiquitously expressed in the brain. Activation of brain GRs by high levels of glucocorticoid (GC hormones modifies a large variety of physiological and pathological-related behaviors. Unfortunately the specific cellular targets of GR-mediated behavioral effects of GC are still largely unknown. To address this issue, we generated a mutated form of the GR called DeltaGR. DeltaGR is a constitutively transcriptionally active form of the GR that is localized in the nuclei and activates transcription without binding to glucocorticoids. Using the tetracycline-regulated system (Tet-OFF, we developed an inducible transgenic approach that allows the expression of the DeltaGR in specific brain areas. We focused our study on a mouse line that expressed DeltaGR almost selectively in the glutamatergic neurons of the dentate gyrus (DG of the hippocampus. This restricted expression of the DeltaGR increased anxiety-related behaviors without affecting other behaviors that could indirectly influence performance in anxiety-related tests. This behavioral phenotype was also associated with an up-regulation of the MAPK signaling pathway and Egr-1 protein in the DG. These findings identify glutamatergic neurons in the DG as one of the cellular substrate of stress-related pathologies.

  11. Effect of insulin and glucocorticoids on glucose transporters in rat adipocytes

    International Nuclear Information System (INIS)

    Carter-Su, C.; Okamoto, K.


    The ability of glucocorticoids to modify the effect of insulin on glucose (L-1- 3 H(N)]glucose and D-[ 14 C-U]glucose) transport was investigated in both intact isolated rat adipocytes and in membranes isolated from hormone-treated adipocytes. In intact adipocytes, dexamethasone, a potent synthetic glucocorticoid, inhibited insulin-stimulated 3-O-methylglucose transport at all concentrations of insulin tested. Insulin sensitivity, as well as the maximal response to insulin, was decreased by dexamethasone in the absence of a change in 125 I insulin binding. The inhibition was observed regardless of which hormone acted first, was blocked by actinomycin D, and resulted from a decrease in V/sub max/ rather than an increase in K/sub t/ of transport. In plasma membranes isolated from insulin-treated adipocytes, glucose transport activity and the amount of glucose transporter covalently labeled with [ 3 H]cytochalasin B were increased in parallel in a dose-dependent fashion. The amount of labeled transporter in a low-density microsomal fraction (LDMF) was decreased in a reciprocal fashion. In contrast, addition of dexamethasone to insulin-stimulated cells caused decreases in both transport activity and amount of labeled transporter in the plasma membranes. This was accompanied by a small increase in the amount of [ 3 H]cytochalasin B incorporated into the glucose transporter in the LDMF. These results are consistent with both insulin and glucocorticoids altering the distribution of glucose transporters between the plasma membrane and LDMF, in opposite directions

  12. Effect of glucocorticoid therapy upon glucose metabolism in COPD patients with acute exacerbation

    International Nuclear Information System (INIS)

    Wu Sihai; Wei Zhenggan; Huang Ming'an; Yao Jianguo; Li Hongsheng


    Objective: To study the effect of glucocorticoids therapy upon glucose metabolism in COPD patients with acute exacerbation. Methods: Plasma glucose and insulin levels in COPD patients after intravenous administration of 10 mg dexamethasone daily for 5 days were determined oral with glucose tolerance test (OGTT) and insulin release test (IRT). Results: 1) The levels of basal plasma glucose and insulin were significantly higher in severe hypoxemic group than those in moderate hypoxemic group (p 2 (r = -0.5242, p < 0.05). 2) The levels of plasma glucose in intermediate and severe hypoxemic groups were remarkable higher (p < 0.05) than those in mild group. The two peak times of glucose curve were observed at one and two hour after oral glucose load. 3) After the administration of glucocorticoids, at half an hour and one hour plasma glucose levels were significantly higher than those before, the peak time of glucose levels appeared earlier and the insulin release levels were higher than they were before therapy (p < 0.05). Conclusion: COPD patients with acute exacerbation complicated with hypoxemia had problems of impaired glucose tolerance. The administration of glucocorticoids made the impairment worse

  13. Oxidative stress in the developing brain: effects of postnatal glucocorticoid therapy and antioxidants in the rat.

    Directory of Open Access Journals (Sweden)

    Emily J Camm

    Full Text Available In premature infants, glucocorticoids ameliorate chronic lung disease, but have adverse effects on long-term neurological function. Glucocorticoid excess promotes free radical overproduction. We hypothesised that the adverse effects of postnatal glucocorticoid therapy on the developing brain are secondary to oxidative stress and that antioxidant treatment would diminish unwanted effects. Male rat pups received a clinically-relevant tapering course of dexamethasone (DEX; 0.5, 0.3, and 0.1 mg x kg(-1 x day(-1, with or without antioxidant vitamins C and E (DEXCE; 200 mg x kg(-1 x day(-1 and 100 mg x kg(-1 x day(-1, respectively, on postnatal days 1-6 (P1-6. Controls received saline or saline with vitamins. At weaning, relative to controls, DEX decreased total brain volume (704.4±34.7 mm(3 vs. 564.0±20.0 mm(3, the soma volume of neurons in the CA1 (1172.6±30.4 µm(3 vs. 1002.4±11.8 µm(3 and in the dentate gyrus (525.9±27.2 µm(3 vs. 421.5±24.6 µm(3 of the hippocampus, and induced oxidative stress in the cortex (protein expression: heat shock protein 70 [Hsp70]: +68%; 4-hydroxynonenal [4-HNE]: +118% and nitrotyrosine [NT]: +20%. Dexamethasone in combination with vitamins resulted in improvements in total brain volume (637.5±43.1 mm(3, and soma volume of neurons in the CA1 (1157.5±42.4 µm(3 and the dentate gyrus (536.1±27.2 µm(3. Hsp70 protein expression was unaltered in the cortex (+9%, however, 4-HNE (+95% and NT (+24% protein expression remained upregulated. Treatment of neonates with vitamins alone induced oxidative stress in the cortex (Hsp70: +67%; 4-HNE: +73%; NT: +22% and in the hippocampus (NT: +35%. Combined glucocorticoid and antioxidant therapy in premature infants may be safer for the developing brain than glucocorticoids alone in the treatment of chronic lung disease. However, antioxidant therapy in healthy offspring is not recommended.

  14. RGD(F/S/V-Dex: towards the development of novel, effective, and safe glucocorticoids

    Directory of Open Access Journals (Sweden)

    Jiang X


    Full Text Available Xueyun Jiang,1 Ming Zhao,1,2 Yuji Wang,1 Haimei Zhu,1 Shurui Zhao,1 Jianhui Wu,1 Yuanbo Song,3 Shiqi Peng1 1Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People’s Republic of China; 2Faculty of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Guangxi Pusen Biotechnology Co. Ltd., Nanning, Guangxi, People’s Republic of China Abstract: Dexamethasone (Dex is an effective glucocorticoid in treating inflammation and preventing rejection reaction. However, the side effects limit its clinical application. To improve its druggable profile, the conjugates of RGD-peptide-modified Dex were presented and their enhanced anti-inflammation activity, minimized osteoporotic action, and nanoscaled assembly were explored. (RGD stands for Arg-Gly-Asp. Standard single letter biochemical abbreviations for amino acids have been used throughout this paper. In respect of the rejection reaction, the survival time of the implanted myocardium of the mice treated with 1.43 µmol/kg/d of the conjugates for 15 consecutive days was significantly longer than that of the mice treated with 2.5 µmol/kg/d of Dex, and the conjugates, but not Dex, exhibited no toxic action. At a single dose of 14.3 µmol/kg (100 times minimal effective dose, 0.143 µmol/kg, the conjugates induced no liver, kidney, or systemic toxicity. At the dose of 1.43 µmol/kg, the conjugates, but not Dex, prolonged the bleeding time of the mice, and inhibited the thrombosis of the rats. In water and rat plasma, the conjugates formed nanoparticles of 14–250 and 101–166 nm in diameter, respectively. Since the nanoparticles of ~100 nm in size cannot be entrapped by macrophages in the circulation, RGDF-Dex would particularly be worthy

  15. Lymphedema as a Cancer Treatment Side Effect (United States)

    ... Considerations How Cancer is Treated Side Effects Dating, Sex, and Reproduction Advanced Cancer For Children For Teens For Young Adults For Older Adults Prevention and Healthy Living Cancer.Net Videos Coping With Cancer Research and Advocacy Survivorship Blog ...

  16. Managing Chemotherapy Side Effects: Bleeding Problems (United States)

    ... C ancer I nstitute Managing Chemotherapy Side Effects Bleeding Problems “My nurse said that chemotherapy could make ... with a clean cloth. Keep pressing until the bleeding stops. If you bruise: Put ice on the ...

  17. Managing Chemotherapy Side Effects: Hair Loss (Alopecia) (United States)

    ... C ancer I nstitute Managing Chemotherapy Side Effects Hair Loss (Alopecia) “Losing my hair was hard at first. ... and anywhere on your body may fall out. Hair loss is called alopecia. When will my hair start ...

  18. Managing Chemotherapy Side Effects: Nausea and Vomiting (United States)

    N ational C ancer I nstitute Managing Chemotherapy Side Effects U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Nausea and Vomiting “I take medicine so I won’t feel sick ...

  19. Managing Chemotherapy Side Effects: Swelling (Fluid Retention) (United States)

    N ational C ancer I nstitute Managing Chemotherapy Side Effects Swelling (Fluid retention) “My hands and feet were swollen and puffy. My nurse helped me understand why I had to stop eating salty ...

  20. Uncommon vancomycin: induced side effects

    Directory of Open Access Journals (Sweden)

    Rocha Jaime Luís Lopes


    Full Text Available Vancomycin has been used with increased frequency during the past 15 years and the most common toxicity with this drug is the "red man syndrome". Other adverse effects include neutropenia, fever, phlebitis, nephrotoxicity, ototoxicity, thrombocytopenia, interstitial nephritis, lacrimation, linear IgA bullous dermatosis, necrotizing cutaneous vasculitis and toxic epidermal necrolysis. Only two cases of vancomycin-induced Stevens-Johnson syndrome and one case of pancytopenia have been reported in the medical literature. The treatment for both situations is based on cessation of the vancomycin therapy; in cases of Stevens-Johnson syndrome, antihistamine and/or steroid agents can be used. This article reports a case of pancytopenia and a case of erythema major associated with neutropenia.

  1. Effect of a topical glucocorticoid, budesonide, on nasal mucosal blood flow as measured with 133Xe wash-out technique

    International Nuclear Information System (INIS)

    Bende, M.; Lindqvist, N.; Pipkorn, U.


    The ''vasoconstrictor'' effect of dermally applicated steroids is a widely used parameter when determining the potency of glucocorticoids. A similar effect on the nasal mucosa has been suggested as providing an explanation for the clinical effect of topically administered glucocorticoids in the treatment of nasal disorders such as allergic and vasomotor rhinitis. The recently described 133 Xe wash-out method was used for the purpose of blood flow determination in 11 healthy subjects. In a randomized double-blind cross-over study, the effect of topically administered budesonide, a non-halogenated glucocorticoid, for 1 week was compared with that of placebo. No difference was found to occur in the mucosal blood flow after the administration of budesonide, as compared with placebo. It seems likely that a more complex activity than vasoconstriction is responsible for the clinical effect in the treatment of nasal disorders, and further research is required in order to clarify this issue. (author)

  2. Adverse effects of perioperative paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations

    DEFF Research Database (Denmark)

    Mathiesen, O; Wetterslev, Jørn; Kontinen, V K


    with the most common perioperative non-opioid analgesics: paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids (GCCs), gabapentinoids and their combinations. The review is based on data from systematic reviews with meta-analyses of analgesic efficacy and/or adverse effects...... of perioperative non-opioid analgesics, and randomised trials and cohort/retrospective studies. Generally, data on AE are sparse and related to the immediate post-operative period. For paracetamol, the incidence of AEs appears trivial. Data are inconclusive regarding an association of NSAIDs with mortality...

  3. Glucocorticoid control of gene transcription in neural tissue

    NARCIS (Netherlands)

    Morsink, Maarten Christian


    Glucocorticoid hormones exert modulatory effects on neural function in a delayed genomic fashion. The two receptor types that can bind glucocorticoids, the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR), are ligand-inducible transcription factors. Therefore, changes in gene

  4. Glucocorticoid-related bone changes from endogenous or exogenous glucocorticoids. (United States)

    Warriner, Amy H; Saag, Kenneth G


    Glucocorticoids have a negative impact on bone through direct effects on bone cells and indirect effects on calcium absorption. Here, recent findings regarding glucocorticoid-induced osteoporosis, bone changes in patients with endogenous glucocorticoid derangements, and treatment of steroid-induced bone disease are reviewed. Although the majority of our understanding arises from the outcomes of patients treated with exogenous steroids, endogenous overproduction appears to be similarly destructive to bone, but these effects are reversible with cure of the underlying disease process. Additionally, there are bone changes that occur in diseases that interrupt adrenal glucocorticoid production, both in response to our inability to perfectly match glucocorticoid replacement and also related to the underlying disease process. More investigation is required to understand which patients with endogenous overproduction or underproduction of glucocorticoid would benefit from osteoporosis treatment. Better understood is the benefit that can be achieved with currently approved treatments for glucocorticoid-induced osteoporosis from exogenous steroids. With growing concern of long-term use of bisphosphonates, however, further investigation into the duration of use and use in certain populations, such as children and premenopausal women, is essential. Glucocorticoid-induced osteoporosis is a complex disease that is becoming better understood through advances in the study of exogenous and endogenous glucocorticoid exposure. Further advancement of proper treatment and prevention is on the horizon.

  5. Timing is critical for effective glucocorticoid receptor mediated repression of the cAMP-induced CRH gene.

    Directory of Open Access Journals (Sweden)

    Siem van der Laan

    Full Text Available Glucocorticoid negative feedback of the hypothalamus-pituitary-adrenal axis is mediated in part by direct repression of gene transcription in glucocorticoid receptor (GR expressing cells. We have investigated the cross talk between the two main signaling pathways involved in activation and repression of corticotrophin releasing hormone (CRH mRNA expression: cyclic AMP (cAMP and GR. We report that in the At-T20 cell-line the glucocorticoid-mediated repression of the cAMP-induced human CRH proximal promoter activity depends on the relative timing of activation of both signaling pathways. Activation of the GR prior to or in conjunction with cAMP signaling results in an effective repression of the cAMP-induced transcription of the CRH gene. In contrast, activation of the GR 10 minutes after onset of cAMP treatment, results in a significant loss of GR-mediated repression. In addition, translocation of ligand-activated GR to the nucleus was found as early as 10 minutes after glucocorticoid treatment. Interestingly, while both signaling cascades counteract each other on the CRH proximal promoter, they synergize on a synthetic promoter containing 'positive' response elements. Since the order of activation of both signaling pathways may vary considerably in vivo, we conclude that a critical time-window exists for effective repression of the CRH gene by glucocorticoids.

  6. The Metabolic Implications of Glucocorticoids in a High-Fat Diet Setting and the Counter-Effects of Exercise

    Directory of Open Access Journals (Sweden)

    Emily C. Dunford


    Full Text Available Glucocorticoids (GCs are steroid hormones, naturally produced by activation of the hypothalamic-pituitary-adrenal (HPA axis, that mediate the immune and metabolic systems. Synthetic GCs are used to treat a number of inflammatory conditions and diseases including lupus and rheumatoid arthritis. Generally, chronic or high dose GC administration is associated with side effects such as steroid-induced skeletal muscle loss, visceral adiposity, and diabetes development. Patients who are taking exogenous GCs could also be more susceptible to poor food choices, but the effect that increasing fat consumption in combination with elevated exogenous GCs has only recently been investigated. Overall, these studies show that the damaging metabolic effects initiated through exogenous GC treatment are significantly amplified when combined with a high fat diet (HFD. Rodent studies of a HFD and elevated GCs demonstrate more glucose intolerance, hyperinsulinemia, visceral adiposity, and skeletal muscle lipid deposition when compared to rodents subjected to either treatment on its own. Exercise has recently been shown to be a viable therapeutic option for GC-treated, high-fat fed rodents, with the potential mechanisms still being examined. Clinically, these mechanistic studies underscore the importance of a low fat diet and increased physical activity levels when individuals are given a course of GC treatment.

  7. Glucocorticoid Signaling and Bone Biology. (United States)

    Komori, T


    Since glucocorticoids remain an effective therapeutic option for the treatment of many inflammatory and autoimmune diseases, glucocorticoid-induced osteoporosis is the most common form of secondary osteoporosis. Fractures may occur in as many as 30-50% of patients receiving chronic glucocorticoid therapy. Under physiological conditions, glucocorticoids are required for normal bone development due to their regulation of osteoblast differentiation, possibly via the Wnt/β-catenin pathway and TSC22D3. However, serum levels of endogenous corticosterone are elevated in aged mice and glucocorticoids exert negative effects on the survival of osteoblasts and osteocytes as well as angiogenesis. Glucocorticoid treatments impair bone formation and enhance bone resorption. Excess glucocorticoids induce osteoblast and osteocyte apoptosis by increasing pro-apoptotic molecules, reactive oxygen species, and endoplasmic reticulum stress and suppressing the Wnt/β-catenin pathway. Autophagy protects osteocytes from glucocorticoid-induced apoptosis, but passed some threshold, the process of autophagy leads the cells to apoptosis. Excess glucocorticoids impair osteoblastogenesis by inducing Wnt antagonists, including Dkk1, Sost, and sFRP-1. However, the findings are controversial and the involvement of Wnt antagonists requires further study. Excess glucocorticoids reduce the phosphorylation of Akt and GSK3β, which enhances the degradation of β-catenin. Excess glucocorticoids have been shown to modulate the expression of miRNAs, including miR-29a, miR-34a-5p, and miR-199a-5p, which regulate the proliferation and differentiation of osteoblast lineage cells. Excess glucocorticoids also enhance bone resorption by reducing OPG expression, increasing Rankl expression and reactive oxygen species, and prolonging the life span of osteoclasts; however, they also suppress the bone-degrading capacity of osteoclasts by disturbing the organization of the cytoskeleton. © Georg Thieme Verlag KG

  8. Effects of glucocorticoid hormones on radiation induced and 12-O-tetradecanoylphorbol-13-acetate enhanced radiation transformation in vitro

    International Nuclear Information System (INIS)

    Kennedy, A.R.; Umans, R.S.


    We have studied the interactions of glucocorticoid hormones with radiation in the induction of transformation in vitro in C3AH10T1/2 cells. We have observed that cortisone has its primary enhancing effect on radiation transformation when present after the radiation exposure during the ''expression period'', or the time after carcinogen exposure during which promoting agents have been shown to enhance radiation transformation in vitro, and that two different glucocorticoid hormones, dexamethasone and cortisone, have a suppressive effect on the 12-O-tetradecanoylphorbol-13-acetate (TPA) enhancement of radiation transformation in vitro

  9. The effects of glucocorticoid on microarchitecture, collagen, mineral and mechanical properties of sheep femur cortical bone

    DEFF Research Database (Denmark)

    Ding, Ming; Danielsen, Carl Christian; Overgaard, Søren


    of 3 months without treatment. Group 3 was left untreated and served as controls. All sheep received a restricted diet with low calcium and phosphorus. At sacrifice, cortical bone samples from the femur midshaft of each sheep were harvested, micro-CT scanned and subjected to three-point bending...... and tensile strength testing. Bone collagen and mineral were determined. Cortical porosity was significantly increased in the glucocorticoid-2 compared with the glucocorticoid-1 and control groups. Apparent density was significantly decreased in the glucocorticoid-2 compared with the glucocorticoid-1 group....... Collagen content was significantly increased in the glucocorticoid-2 compared with the glucocorticoid-1 and control groups. Bone mineral content did not differ between the groups. Neither the three-point bending mechanical properties nor the tensile mechanical properties differed significantly between...

  10. Phase 1 trial of vamorolone, a first-in-class steroid, shows improvements in side effects via biomarkers bridged to clinical outcomes. (United States)

    Hoffman, Eric P; Riddle, Valerie; Siegler, Maxime A; Dickerson, Daniel; Backonja, Miroslav; Kramer, William G; Nagaraju, Kanneboyina; Gordish-Dressman, Heather; Damsker, Jesse M; McCall, John M


    Glucocorticoid drugs are highly effective anti-inflammatory agents, but chronic use is associated with extensive pharmacodynamic safety concerns that have a considerable negative impact on patient quality of life. Vamorolone (VBP15) is a first-in-class steroidal multi-functional drug that shows potent inhibition of pro-inflammatory NFkB pathways via high-affinity binding to the glucocorticoid receptor, high affinity antagonism for the mineralocorticoid receptor, and membrane stabilization properties. Pre-clinical data in multiple mouse models of inflammation showed retention of anti-inflammatory efficacy, but loss of most or all side effects. We report first-in-human Phase 1 clinical trials (86 healthy adult males), with single ascending doses (0.1-20.0 mg/kg), and multiple ascending doses (1.0-20 mg/kg/day; 14 days treatment). Vamorolone was well-tolerated at all dose levels. Vamorolone showed pharmacokinetic and metabolism profiles similar to prednisone. Biomarker studies showed loss of side effects of traditional glucocorticoid drugs (bone fragility, metabolic disturbance, immune suppression). Suppression of the adrenal axis was 10-fold less than prednisone. The crystallographic structure of vamorolone was solved, and compared to prednisone and dexamethasone. There was overlap in structure, but differences in conformation at the C-ring where glucocorticoids interact with Asn564 of the glucocorticoid receptor. The predicted loss of Asn564 binding to vamorolone may underlie the loss of gene transcriptional activity. Vamorolone is a dissociative steroid that retains high affinity binding and nuclear translocation of both glucocorticoid (agonist) and mineralocorticoid (antagonist) receptors, but does not show pharmacodynamic safety concerns of existing glucocorticoid drugs at up to 20 mg/kg/day. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  11. The Social Side Effects of Acetaminophen (United States)

    Mischkowski, Dominik

    About 23% of all adults in the US take acetaminophen during an average week (Kaufman, Kelly, Rosenberg, Anderson, & Mitchell, 2002) because acetaminophen is an effective physical painkiller and easily accessible over the counter. The physiological side effects of acetaminophen are well documented and generally mild when acetaminophen is consumed in the appropriate dosage. In contrast, the psychological and social side effects of acetaminophen are largely unknown. Recent functional neuroimaging research suggests that the experience of physical pain is fundamentally related to the experience of empathy for the pain of other people, indicating that pharmacologically reducing responsiveness to physical pain also reduces cognitive, affective, and behavioral responsiveness to the pain of others. I tested this hypothesis across three double-blind between-subjects drug intervention studies. Two experiments showed that acetaminophen had moderate effects on empathic affect, specifically personal distress and empathic concern, and a small effect on empathic cognition, specifically perceived pain, when facing physical and social pain of others. The same two experiments and a third experiment also showed that acetaminophen can increase the willingness to inflict pain on other people, i.e., actual aggressive behavior. This effect was especially pronounced among people low in dispositional empathic concern. Together, these findings suggest that the physical pain system is more involved in the regulation of social cognition, affect, and behavior than previously assumed and that the experience of physical pain and responsiveness to the pain of others share a common neurochemical basis. Furthermore, these findings suggest that acetaminophen has unappreciated but serious social side effects, and that these side effects may depend on psychological characteristics of the drug consumer. This idea is consistent with recent theory and research on the context-dependency of neurochemical

  12. The role of glucocorticoid, interleukin-1β, and antioxidants in prenatal stress effects on embryonic microglia. (United States)

    Bittle, Jada; Stevens, Hanna E


    Maternal stress during pregnancy is associated with an increased risk of psychopathology in offspring. Resident immune cells of the brain, microglia, may be mediators of prenatal stress and altered neurodevelopment. Here, we demonstrate that neither the exogenous pro-inflammatory cytokine, interleukin-1β (IL-1β), nor the glucocorticoid hormone, corticosterone, recapitulated the full effects of prenatal stress on the morphology of microglial cells in the cortical plate of embryonic mice; IL-1β effects showed greater similarity to prenatal stress effects on microglia. Unexpectedly, oil vehicle alone, which has antioxidant properties, moderated the effects of prenatal stress on microglia. Microglia changes with prenatal stress were also sensitive to the antioxidant, N-acetylcysteine, suggesting redox dysregulation as a mechanism of prenatal stress.

  13. Post-operative analgesic effects of paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations

    DEFF Research Database (Denmark)

    Dahl, Jørgen Berg; Nielsen, Rasmus; Wetterslev, Jørn


    , and no well-documented 'gold standards' exist. The aim of the present topical, narrative review is to provide an update of the evidence for post-operative analgesic efficacy with the most commonly used, systemic non-opioid drugs, paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs)/COX-2 antagonists......, glucocorticoids, gabapentinoids, and combinations of these. The review is based on data from previous systematic reviews with meta-analyses, investigating effects of non-opioid analgesics on pain, opioid-requirements, and opioid-related adverse effects. Paracetamol, NSAIDs, COX-2 antagonists, and gabapentin....... Trials of pregabalin > 300 mg/day indicated a morphine-sparing effect of 13.4 (4, 22.8) mg morphine/24 h. Notably, though, the available evidence for additive or synergistic effects of most combination regimens was sparse or lacking. Paracetamol, NSAIDs, selective COX-2 antagonists, and gabapentin all...

  14. Effect of single x-irradiation on glucocorticoid function of adrenal glands of adult and old rats

    International Nuclear Information System (INIS)

    Gorban', Je.M.; Topol'nyikova, N.V.


    The peculiarities of short-term (1 h, 1 day) adrenal glucocorticoid function in adult and old rats after single x-irradiation at different doses was studied. changes in the glucocorticoid function of the adrenal glands at studied terms after single x-irradiation at used doses were observed in adult but not in old animals. This testifies to an age-related decrease in the range of adaptive possibilities of this link of the organism adaptive system to x-irradiation effects

  15. Side effects of creatine supplementation in athletes.


    Francaux, Marc; Poortmans, Jacques R


    Context: Allegations about side effects of creatine supplementation by athletes have been published in the popular media and scientific publications. Purpose: To examine the experimental evidence relating to the physiological effects of creatine supplementation. Results: One of the purported effects of oral creatine supplementation is increased muscle mass. A review of the literature reveals a 1.0% to 2.3% increase in body mass, which is attributed to fat-free mass and, more specifically, to ...

  16. Factors effecting paint performance on wood siding (United States)

    Christopher G. Hunt; R. Sam Williams; Mark Knaebe; Peter Sotos; Steven Lacher


    Several different studies are compared to assess the effectiveness of commercial water repellent preservatives (WRP’s) in the late 1990’s on vertical and horizontal siding. Besides WRP, variables included wood species, exposure location (Wisconsin or Mississippi), and solid color stain vs. primer + paint. Data on substrate checking and paint flaking are presented....

  17. Side effects of ambulatory blood pressure monitoring.

    NARCIS (Netherlands)

    Steen, M.S. van der; Lenders, J.W.M.; Thien, Th.


    OBJECTIVE: To study the experiences and complaints of patients who underwent 24 h blood pressure monitoring. METHODS: Two groups of hypertensive patients of a tertiary outpatient clinic were asked to fill in a nine-item questionnaire about the side effects of ambulatory blood pressure monitoring

  18. Neglected Side Effects After Radical Prostatectomy

    DEFF Research Database (Denmark)

    Frey, Anders Ullmann; Sønksen, Jens; Fode, Mikkel


    INTRODUCTION: A series of previously neglected sexually related side effects to radical prostatectomy (RP) has been identified over the recent years. These include orgasm-associated incontinence (OAI), urinary incontinence in relation to sexual stimulation (UISS), altered perception of orgasm, or...

  19. Hallucinatory Side Effects of ADHD Drugs

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap


    Full Text Available Clinical trial and postmarketing surveillance data for drugs used in treatment of attention deficit hyperactivity disorder were analyzed to determine the frequency of hallucinations and other psychotic side effects, in a study at the US Food and Drug Administration, and Department of Health and Human Services, Maryland.

  20. Cancer treatment: fertility and sexual side effects in women (United States)

    ... Cancer treatment: fertility and sexual side effects in women To use the sharing features on this page, ... Bladder cancer Types of Sexual Side Effects For women, the most common sexual side effects include: Loss ...

  1. [Effect of glucocorticoides on the release of amino acids in the perfused rat hindquarter (author's transl)]. (United States)

    Thienhaus, R; Tharandt, L; Zais, U; Staib, W


    The release of amino acids by skeletal muscle was studied in the isolated perfused rat hindquarter. Adrenalectomy depressed the formation of glutamine and alanine as well as the efflux of all other amino acids measured. Betamethasone--a synthetic glucocorticoid--caused a significant increase in the efflux of nearly all amino acids up to the level of normal controls. The release of amino acids was also increased in perfused hindquarters of diabetic rats. On the other hand, insulin exhibited a depressing effect on the release of amino acids by hindquarters of normal rats. The metabolic integrity of the muscle tissue was proved by measuring creatine phosphate, ATP, ADP and water content as well as by the significant insulin effect on glucose uptake and on [14C]leucine incorporation into muscle proteins.

  2. Programming Effects of Prenatal Glucocorticoid Exposure with a Postnatal High-Fat Diet in Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Jiunn-Ming Sheen


    Full Text Available Increasing evidence has shown that many chronic diseases originate from early life, even before birth, through what are termed as fetal programming effects. Glucocorticoids are frequently used prenatally to accelerate the maturation of the lungs of premature infants. High-fat diets are associated with insulin resistance, but the effects of prenatal glucocorticoid exposure plus a postnatal high-fat diet in diabetes mellitus remain unclear. We administered pregnant Sprague-Dawley rats’ intraperitoneal dexamethasone (0.1 mg/kg body weight or vehicle at gestational days 14–20. Male offspring were administered a normal or high-fat diet starting from weaning. We assessed the effects of prenatal steroid exposure plus postnatal high-fat diet on the liver, pancreas, muscle and fat at postnatal day 120. At 15 and 30 min, sugar levels were higher in the dexamethasone plus high-fat diet (DHF group than the vehicle plus high-fat diet (VHF group in the intraperitoneal glucose tolerance test (IPGTT. Serum insulin levels at 15, 30 and 60 min were significantly higher in the VHF group than in the vehicle and normal diet group. Liver insulin receptor and adenosine monophosphate-activated protein kinase mRNA expressions and protein levels were lower in the DHF group. Insulin receptor and insulin receptor substrate-1 mRNA expressions were lower in the epididymal adipose tissue in the VHF and DHF groups. “Programming” of liver or epididymal adipose tissue resulted from prenatal events. Prenatal steroid exposure worsened insulin resistance in animals fed a high-fat diet.

  3. Programming Effects of Prenatal Glucocorticoid Exposure with a Postnatal High-Fat Diet in Diabetes Mellitus. (United States)

    Sheen, Jiunn-Ming; Hsieh, Chih-Sung; Tain, You-Lin; Li, Shih-Wen; Yu, Hong-Ren; Chen, Chih-Cheng; Tiao, Miao-Meng; Chen, Yu-Chieh; Huang, Li-Tung


    Increasing evidence has shown that many chronic diseases originate from early life, even before birth, through what are termed as fetal programming effects. Glucocorticoids are frequently used prenatally to accelerate the maturation of the lungs of premature infants. High-fat diets are associated with insulin resistance, but the effects of prenatal glucocorticoid exposure plus a postnatal high-fat diet in diabetes mellitus remain unclear. We administered pregnant Sprague-Dawley rats' intraperitoneal dexamethasone (0.1 mg/kg body weight) or vehicle at gestational days 14-20. Male offspring were administered a normal or high-fat diet starting from weaning. We assessed the effects of prenatal steroid exposure plus postnatal high-fat diet on the liver, pancreas, muscle and fat at postnatal day 120. At 15 and 30 min, sugar levels were higher in the dexamethasone plus high-fat diet (DHF) group than the vehicle plus high-fat diet (VHF) group in the intraperitoneal glucose tolerance test (IPGTT). Serum insulin levels at 15, 30 and 60 min were significantly higher in the VHF group than in the vehicle and normal diet group. Liver insulin receptor and adenosine monophosphate-activated protein kinase mRNA expressions and protein levels were lower in the DHF group. Insulin receptor and insulin receptor substrate-1 mRNA expressions were lower in the epididymal adipose tissue in the VHF and DHF groups. "Programming" of liver or epididymal adipose tissue resulted from prenatal events. Prenatal steroid exposure worsened insulin resistance in animals fed a high-fat diet.

  4. Glucocorticoid control of rat growth hormone gene expression: Effect on cytoplasmic messenger ribonucleic acid production and degradation

    International Nuclear Information System (INIS)

    Gertz, B.J.; Gardner, D.G.; Baxter, J.D.


    The effect of the glucocorticoid dexamethasone on the production and degradation of rat GH (rGH) cytoplasmic mRNA was studied in cultured rat pituitary tumor (GC) cells. The incorporation of [3H]uridine into both rGH cytoplasmic mRNA and the pyrimidine nucleotide precursor pool was determined in hormone-treated and control cells. From these measurements glucocorticoid effects on absolute production rates of rGH cytoplasmic mRNA were determined and compared to effects on rGH mRNA accumulation. Rat GH mRNA half-life was then calculated based on a first-order decay model. Rat GH mRNA half-life was also directly assayed by: (1) pulse-chase studies and (2) measuring the kinetics of decay of rGH mRNA in cells after transfer from serum-containing to hormone-deficient media. From these independent analyses rGH mRNA half-life estimates ranged from 28-55 h in different experiments. Within individual experiments there was little variability of rGH mRNA decay rates; glucocorticoids were found not to alter the stability of rGH cytoplasmic mRNA. Glucocorticoid induction of rGH cytoplasmic mRNA accumulation was accounted for solely on the basis of increased mRNA production

  5. An in vitro approach for prioritization and evaluation of chemical effects on glucocorticoid receptor mediated adipogenesis. (United States)

    Hartman, Jessica K; Beames, Tyler; Parks, Bethany; Doheny, Daniel; Song, Gina; Efremenko, Alina; Yoon, Miyoung; Foley, Briana; Deisenroth, Chad; McMullen, Patrick D; Clewell, Rebecca A


    Rising obesity rates worldwide have socio-economic ramifications. While genetics, diet, and lack of exercise are major contributors to obesity, environmental factors may enhance susceptibility through disruption of hormone homeostasis and metabolic processes. The obesogen hypothesis contends that chemical exposure early in development may enhance adipocyte differentiation, thereby increasing the number of adipocytes and predisposing for obesity and metabolic disease. We previously developed a primary human adipose stem cell (hASC) assay to evaluate the effect of environmental chemicals on PPARG-dependent adipogenesis. Here, the assay was modified to determine the effects of chemicals on the glucocorticoid receptor (GR) pathway. In differentiation cocktail lacking the glucocorticoid agonist dexamethasone (DEX), hASCs do not differentiate into adipocytes. In the presence of GR agonists, adipocyte maturation was observed using phenotypic makers for lipid accumulation, adipokine secretion, and expression of key genes. To evaluate the role of environmental compounds on adipocyte differentiation, progenitor cells were treated with 19 prioritized compounds previously identified by ToxPi as having GR-dependent bioactivity, and multiplexed assays were used to confirm a GR-dependent mode of action. Five chemicals were found to be strong agonists. The assay was also modified to evaluate GR-antagonists, and 8/10 of the hypothesized antagonists inhibited adipogenesis. The in vitro bioactivity data was put into context with extrapolated human steady state concentrations (Css) and clinical exposure data (Cmax). These data support using a human adipose-derived stem cell differentiation assay to test the potential of chemicals to alter human GR-dependent adipogenesis. Copyright © 2017. Published by Elsevier Inc.

  6. Effects of supplemental feeding and aggregation on fecal glucocorticoid metabolite concentrations in elk (United States)

    Forristal, Victoria E.; Creel, Scott; Taper, Mark L.; Scurlock, Brandon M.; Cross, Paul C.


    Habitat modifications and supplemental feeding artificially aggregate some wildlife populations, with potential impacts upon contact and parasite transmission rates. Less well recognized, however, is how increased aggregation may affect wildlife physiology. Crowding has been shown to induce stress responses, and increased glucocorticoid (GC) concentrations can reduce immune function and increase disease susceptibility. We investigated the effects of supplemental feeding and the aggregation that it induces on behavior and fecal glucocorticoid metabolite concentrations (fGCM) in elk (Cervus elaphus) using observational and experimental approaches. We first compared fGCM levels of elk on supplemental feedgrounds to neighboring elk populations wintering in native habitats using data from 2003 to 2008. We then experimentally manipulated the distribution of supplemental food on feedgrounds to investigate whether more widely distributed food would result in lower rates of aggression and stress hormone levels. Contrary to some expectations that fed elk may be less stressed than unfed elk during the winter, we found that elk on feedgrounds had fecal GC levels at least 31% higher than non-feedground populations. Within feedgrounds, fGCM levels were strongly correlated with local measures of elk density (r2 = 0.81). Dispersing feed more broadly, however, did not have a detectable effect on fGCM levels or aggression rates. Our results suggest that increases in aggregation associated with winter feedgrounds affects elk physiology, and the resulting increases in fGCM levels are not likely to be mitigated by management efforts that distribute the feed more widely. Additional research is needed to assess whether these increases in fGCMs directly alter parasite transmission and disease dynamics.

  7. The Ups and Downs of Glucocorticoid Signaling | Center for Cancer Research (United States)

    Glucocorticoids are steroids that react to stress by regulating inflammation and controlling metabolism. Because of their anti-inflammatory and immunosuppressive properties, corticosteroids are among the most frequently prescribed drugs. Glucocorticoids are often used to treat arthritis and autoimmune diseases and are also given in combination with other drugs to treat cancers—such as leukemias and lymphomas—or to alleviate side effects from chemotherapy and radiation. In humans, a glucocorticoid called cortisol is released from the adrenal gland approximately every hour to send signals to cells throughout the body. This pulsed release of hormone is called ultradian secretion.  

  8. Side effects after ambulatory lumbar iohexol myelography

    International Nuclear Information System (INIS)

    Sand, T.; Myhr, G.; Stovner, L.J.; Dale, L.G.; Tangerud, A.


    Side effect incidences after ambulatory (22G needle and two h bed rest) and after non-ambulatory (22 and 20G needles and 20 h bed rest) lumbar iohexol myelography have been estimated and compared. Headache incidence was significantly greater in ambulatory (50%, n=107) as compared to nonambulatory myelography (26%, n=58). Headaches in the ambulatory group tended to be of shorter duration and the difference between severe headaches in ambulatory and non-ambulatory groups was not significant. Serious adverse reactions did not occur and none of the ambulatory patients required readmission because of side effects. The headache was predominantly postural and occurred significantly earlier in the ambulatory group. Headache incidence was significantly greater after 20G needle myelography (44%, n=97) as compared to 22G needle iohexol myelography (26%, n=58). The results support the hypothesis that CSF leakage is a major cause of headache after lumbar iohexol myelography. (orig.)

  9. Side effects of external tooth bleaching

    DEFF Research Database (Denmark)

    Bruzell, E.M.; Pallesen, Ulla; Thoresen, N.R.


    Objective The study was performed to assess the risk of at-home and in-office bleaching procedures, and to recognise potential predictors for side effects. Design Multi-centre, questionnaire-based prospective study with follow-ups at around 14 days and around one year post-treatment. Setting...... General practices and university clinics during the years 2007‑2009 in Scandinavia. Subjects Patients with tooth bleaching as part of the treatment plan. Results The prevalence of experienced tooth sensitivity at first follow-up was independent of bleaching procedure (at-home = 50.3% [n = 143]; in...... attributed to the bleaching treatment in the at-home and in-office groups, respectively. Predictors for side effects were tooth sensitivity, surface loss and gingivitis when observed at inclusion. Treatment-related predictors were bleaching concentration and contact between tray and gingiva. Conclusions...

  10. Side effects after lumbar iohexol myelography

    International Nuclear Information System (INIS)

    Sand, T.; Stovner, L.J.; Myhr, G.; Dale, L.G.


    Side effects of iohexol lumbar myelography have been analyzed with respect to the influence of the type of radiological abnormality, sex and age in a group of 200 patients. Headache, postural headache, nausea and back/leg pain were significantly more frequent in patients without definite radiological abnormalities. Postural headache, nausea, dizziness and mental symptoms were more frequent in women, while headache, postural headache, nausea, dizziness, minor mental symptoms (i.e. anxiety or depression) and pain became less frequent with age. This pattern is similar to that reported after lumbar puncture. Young women without definite clinical signs of nerve root lesions probably have the greatest risk of experiencing side effects after iohexol lumbar myelography. (orig.)

  11. Effects and side effects of inspections and accountability in education

    NARCIS (Netherlands)

    de Wolff, I.; Janssens, F.


    This paper presents an overview of studies into effects and side effects of control mechanisms in education. We focus on effects and side effects of inspection visits and public performance indicators. A first conclusion is that the studies do not provide us with a clear answer to the question of

  12. The effects of irradiation on the cytosol glucocorticoid receptor and concentrations of corticosterone and cyclic nucleotides in the rat liver

    International Nuclear Information System (INIS)

    Teshima, Teruki; Mori, Masaki; Honke, Yoshifumi


    The effects of irradiation on both the cytosol glucocorticoid receptor and concentrations of corticosterone and cyclic nucleotides in the rat liver were investigated. The liver concentrations of corticosterone and cyclic nucleotides were measured by radioimmunoassay before and after the irradiation of 1,000 rad/l fraction. The glucocorticoid receptor in the liver cytosol was determined by the measurement of the cytosol binding to 3 H-dexamethasone. The cytosol and nuclear corticosterone levels reached a peak 1 day after the irradiation of the rat liver and declined to the control levels after 2 days. The increase in corticosterone levels may be due to the direct stimulation of the right adrenal gland and/ or the stress induced by the irradiation. The binding capacity of the glucocorticoid receptor in rat liver cytosol decreased to the minimum 1 day after the irradiation, and the recovery occurred at 4 days. The Kd value of the glucocorticoid receptor remained unchanged from 1 hour until 4 days but was high at 4 and 7 days. The distinctly increased levels of cyclic GMP in the rat liver were found from 1 hour through 7 days after the irradiation, while cyclic AMP did not change. The inversed relationship between the cytosol glucocorticoid receptor and corticosterone levels in cytosol and the nuclei indicates that the receptor-bound corticosterone in cytosol can be transferred to a nucleus and remain there in the presence of appropriate amounts of corticosterone in cytosol, after which the receptor is released from the nucleus into cytosol. The high Kd values observed 4 -- 7 days after the irradiation may be either due to the direct effect of irradiation or to the replenishment of the receptor with a low affinity. (author)

  13. Side effects of AAS abuse: an overview. (United States)

    Turillazzi, E; Perilli, G; Di Paolo, M; Neri, M; Riezzo, I; Fineschi, V


    Anabolic - androgenic steroids (AAS) were originally developed to promote growth of skeletal muscle. AAS abuse is commonly associated with bodybuilders, weightlifters, and other athletes. The issue of AAS toxicity is not yet completely understood since the adverse effects outline a varied scenario with side effects reported affecting many organs and systems in humans. The true incidence of AAS related medical problems is not known, due to several drawbacks in human studies. The entity of side effects depends on the sex, the dose, the duration of treatment, whether they are taken during exercise training or under sedentary conditions, and the susceptibility of the individuals themselves to androgen exposure partly depending on genetic factors. Both the acute and the chronic effects can lead to toxicity, but generally the serious and even fatal effects depend on the time and the duration of AAS administration. A limitation of human studies is represented by the fact that information about the intake of steroids are, generally, self reported and it is hardly possible to assess the exact dosage. AAS are often used in combination with other dugs or substances, so it is difficult to separate their toxic effects from those caused by the other drugs abused. Hence experimental studies conducted on animal models are mandatory to investigate the mechanisms underlying to AAS toxicity and the organ alterations due to these substances. Finally, clinicians should be aware of the complex and varied pattern of toxicity so as to be able to perform correct diagnoses and treatments.

  14. Membrane-Associated Effects of Glucocorticoid on BACE1 Upregulation and Aβ Generation: Involvement of Lipid Raft-Mediated CREB Activation. (United States)

    Choi, Gee Euhn; Lee, Sei-Jung; Lee, Hyun Jik; Ko, So Hee; Chae, Chang Woo; Han, Ho Jae


    Glucocorticoid has been widely accepted to induce Alzheimer's disease, but the nongenomic effect of glucocorticoid on amyloid β (Aβ) generation has yet to be studied. Here, we investigated the effect of the nongenomic pathway induced by glucocorticoid on amyloid precursor protein processing enzymes as well as Aβ production using male ICR mice and human neuroblastoma SK-N-MC cells. Mice groups exposed to restraint stress or intracerebroventricular injection of Aβ showed impaired cognition, decreased intracellular glucocorticoid receptor (GR) level, but elevated level of membrane GR (mGR). In this respect, we identified the mGR-dependent pathway evoked by glucocorticoid using impermeable cortisol conjugated to BSA (cortisol-BSA) on SK-N-MC cells. Cortisol-BSA augmented the expression of β-site amyloid precursor protein cleaving enzyme 1 (BACE1), the level of C-terminal fragment β of amyloid precursor protein (C99) and Aβ production, which were maintained even after blocking intracellular GR. We also found that cortisol-BSA enhanced the interaction between mGR and Gαs, which colocalized in the lipid raft. The subsequently activated CREB by cortisol-BSA bound to the CRE site of the BACE1 promoter increasing its expression, which was downregulated by inhibiting CBP. Consistently, blocking CBP attenuated cognitive impairment and Aβ production induced by corticosterone treatment or intracerebroventricular injection of Aβ more efficiently than inhibiting intracellular GR in mice. In conclusion, glucocorticoid couples mGR with Gαs and triggers cAMP-PKA-CREB axis dependent on the lipid raft to stimulate BACE1 upregulation and Aβ generation. SIGNIFICANCE STATEMENT Patients with Alzheimer's disease (AD) have been growing sharply and stress is considered as the major environment factor of AD. Glucocorticoid is the primarily responsive factor to stress and is widely known to induce AD. However, most AD patients usually have impaired genomic pathway of glucocorticoid

  15. Glucocorticoid effect on melphalan cytotoxicity, cell-cycle position, cell size, and [3H]uridine incorporation in one of three human melanoma cell lines

    International Nuclear Information System (INIS)

    Benckhuijsen, C.; Osman, A.M.; Hillebrand, M.J.; Smets, L.A.


    Three human melanoma cell lines of known content of specific glucocorticoid-binding sites were studied for colony formation after a microM dose of glucocorticoid combined with melphalan. In one of the three cell lines, M-5A, subcloned from M-5 (formerly designated RPMI 8322), the effect of combined treatment was markedly increased compared to that of melphalan even if the glucocorticoid was applied for 1 h only, 10 h before the melphalan. Semilogarithmic dose-effect plots for a reduction of final plating efficiency by glucocorticoid were curvilinear, according to a receptor-mediated process. The effects of glucocorticoid, melphalan, and their combination were linearized by bilogarithmic median-effect plotting which allowed the quantitation of a synergism which was more marked in case of glucocorticoid pretreatment, for 1 or 24 h, than on simultaneous exposure. According to sequential DNA per cell cytophotometry, melphalan abolished in M-5A a glucocorticoid-induced arrest in the G1 phase of the cell cycle. The cytotoxic synergism correlated with an apparent stimulation by glucocorticoid of the rate of acid-insoluble incorporation of [ 3 H]uridine and [ 14 C]leucine and an increase in cell size and protein content in M-5A cells but not in the other two cell lines. The way in which glucocorticoids induce an enhanced susceptibility to melphalan is not clear. Our results appear compatible with a hypothesis that chromatin in a transcriptionally activated state is more vulnerable to cytotoxic attack by an alkylating agent than under average conditions

  16. The effect of exogenous glucocorticoids on plasma catecholamines and metanephrines in patients without phaeochromocytomas. (United States)

    Druce, M R; Walker, D; Maher, K T; Dodzo, K; Perry, L; Ball, S; Peaston, R; Chew, S L; Drake, W M; Akker, S A; Grossman, A B


    The aim of the study was to evaluate the effects of steroid administration under standardised conditions in a range of patients both normal and with adrenal pathologies and to review the impact on plasma catecholamines and metanephrines. Corticosteroid administration has been linked to the development of hypertensive crises in patients with phaeochromocytoma, however a mechanism for this is not fully understood. We aimed to add useful information about the effect of steroids on levels of these hormones under usual circumstances. A prospective, observational cohort study of 50 patients undergoing the low-dose dexamethasone suppression test (LDDST) was undertaken. Additional blood samples were taken at the start and end of the standard LDDST. Biochemical analysis was carried out for plasma catecholamines and plasma free metanephrines. Demographic and hormonal data were acquired from review of the notes or measured at baseline. No significant changes in plasma catecholamines or metanephrines were seen at the end of the LDDST compared to baseline. This was also true of subgroup analysis, divided by age, gender, or type of underlying pathology. Our results suggest that hypertensive reaction responses, rare as they are, are unlikely to be related to normal adrenal physiology. Thus LDDST is likely to be safe under most circumstances, however caution should be exercised in patients with adrenal masses with imaging characteristics compatible with phaeochromocytoma. It may be prudent to defer glucocorticoid administration until functioning phaeochromocytoma has been excluded biochemically. © Georg Thieme Verlag KG Stuttgart · New York.

  17. Xenobiotics and the Glucocorticoid Receptor

    International Nuclear Information System (INIS)

    Gulliver, Linda S M


    Glucocorticoid Receptor (GR) is present in virtually every human cell type. Representing a nuclear receptor superfamily, GR has several different isoforms essentially acting as ligand-dependent transcription factors, regulating glucocorticoid-responsive gene expression in both a positive and a negative manner. Although the natural ligand of the Glucocorticoid Receptor, glucocorticoids (GC) represent only some of the multiple ligands for GR. Xenobiotics, ubiquitous in the environment, bind to GR and are also capable of activating or repressing GR gene expression, thereby modulating GR cell and tissue-specific downstream effects in a multitude of ways that include responses to inflammatory, allergic, metabolic, neoplastic and autoimmune processes. Many xenobiotics, if inadequately metabolized by xenobiotic metabolizing enzymes and not wholly eliminated, could have deleterious toxic effects with potentially lethal consequences. This review examines GR, the genomic and non-genomic actions of natural and synthetic GC and the body's handling of xenobiotic compounds, before reviewing what is presently known about GR's interactions with many of the more commonly encountered and some of the less well known GR-associated xenobiotics. GR promiscuity and crosstalk with other signaling pathways is discussed, alongside novel roles for GR that include mood disorder and addiction. A knowledge of GR interactions with xenobiotics is increasingly relevant when considering aging populations and the related prevalence of neoplastic disease, together with growing concerns around human exposure to mixtures of chemicals in the environment. Furthermore, escalating rates of obesity, Type 2 diabetes; autoimmune, allergy, addiction and mood disorder-related pathologies, require novel targeted interventions and GR appears a promising pharmacological candidate. - Highlights: • Biological impact of xenobiotics acting through Glucocorticoid Receptor. • Promiscuity of Glucocorticoid

  18. Xenobiotics and the Glucocorticoid Receptor

    Energy Technology Data Exchange (ETDEWEB)

    Gulliver, Linda S M, E-mail:


    Glucocorticoid Receptor (GR) is present in virtually every human cell type. Representing a nuclear receptor superfamily, GR has several different isoforms essentially acting as ligand-dependent transcription factors, regulating glucocorticoid-responsive gene expression in both a positive and a negative manner. Although the natural ligand of the Glucocorticoid Receptor, glucocorticoids (GC) represent only some of the multiple ligands for GR. Xenobiotics, ubiquitous in the environment, bind to GR and are also capable of activating or repressing GR gene expression, thereby modulating GR cell and tissue-specific downstream effects in a multitude of ways that include responses to inflammatory, allergic, metabolic, neoplastic and autoimmune processes. Many xenobiotics, if inadequately metabolized by xenobiotic metabolizing enzymes and not wholly eliminated, could have deleterious toxic effects with potentially lethal consequences. This review examines GR, the genomic and non-genomic actions of natural and synthetic GC and the body's handling of xenobiotic compounds, before reviewing what is presently known about GR's interactions with many of the more commonly encountered and some of the less well known GR-associated xenobiotics. GR promiscuity and crosstalk with other signaling pathways is discussed, alongside novel roles for GR that include mood disorder and addiction. A knowledge of GR interactions with xenobiotics is increasingly relevant when considering aging populations and the related prevalence of neoplastic disease, together with growing concerns around human exposure to mixtures of chemicals in the environment. Furthermore, escalating rates of obesity, Type 2 diabetes; autoimmune, allergy, addiction and mood disorder-related pathologies, require novel targeted interventions and GR appears a promising pharmacological candidate. - Highlights: • Biological impact of xenobiotics acting through Glucocorticoid Receptor. • Promiscuity of Glucocorticoid

  19. Vitamin K2 Ameliorates Damage of Blood Vessels by Glucocorticoid: a Potential Mechanism for Its Protective Effects in Glucocorticoid-induced Osteonecrosis of the Femoral Head in a Rat Model. (United States)

    Zhang, Yuelei; Yin, Junhui; Ding, Hao; Zhang, Changqing; Gao, You-Shui


    Glucocorticoid has been reported to decrease blood vessel number and harm the blood supply in the femoral head, which is recognized to be an important mechanism of glucocorticoid-induced osteonecrosis of the femoral head (ONFH). To prevent glucocorticoid-induced ONFH, medication that promotes both bone formation and angiogenesis would be ideal. Vitamin K2 has been revealed to play an important role in bone metabolism; however, few studies have focused on the effect of Vitamin K2 on new vascular formation. Thus, this study aimed to investigate whether Vitamin K2 promoted new blood vessel formation in the presence of glucocorticoids, both in vitro and in vivo. The effect of Vitamin K2 on viability, migration, in vitro tube formation, and VEGF, vWF, CD31, KDR, Flt and PDGFB in EAhy926 incubated with or without dexamethasone were elucidated. VEGF, TGF-β and BMP-2, angiogenesis-related proteins secreted by osteoblasts, were also detected in the osteoblast-like cell line of MG63. In addition, blood vessels of the femoral head in rats administered with or without methylprednisolone and Vitamin K2 were evaluated using angiography and CD31 staining. In vitro studies showed that Vitamin K2 significantly protected endothelial cells from dexamethasone-induced apoptosis, promoted endothelial cell migration and in vitro tube formation. Angiogenesis-related proteins both in EAhy926 and MG63 were also upregulated by Vitamin K2 when cotreated with dexamethasone. In vivo studies showed enhanced blood vessel volume and CD31-positive staining cells in rats cotreated with VK2 and methylprednisolone compared to rats treated with methylprednisolone only. Collectively, Vitamin K2 has the ability to promote angiogenesis in vitro and to ameliorate vessels of the femoral head in glucocorticoid-treated rats in vivo, indicating that Vitamin K2 is a promising drug that may be used to prevent steroid-induced ONFH.

  20. Effects of ACTH, capture, and short term confinement on glucocorticoid concentrations in harlequin ducks (Histrionicus histrionicus) (United States)

    Nilsson, P.B.; Hollmén, Tuula E.; Atkinson, S.; Mashburn, K.L.; Tuomi, P.A.; Esler, Daniel N.; Mulcahy, D.M.; Rizzolo, D.J.


    Little is known about baseline concentrations of adrenal hormones and hormonal responses to stress in sea ducks, although significant population declines documented in several species suggest that sea ducks are exposed to increased levels of environmental stress. Such declines have been observed in geographically distinct harlequin duck populations. We performed an adrenocorticotropic hormone (ACTH) challenge to evaluate adrenal function and characterize corticosterone concentrations in captive harlequin ducks and investigated the effects of capture, surgery, and short term confinement on corticosterone concentrations in wild harlequin ducks. Harlequin ducks responded to the ACTH challenge with an average three-fold increase in serum corticosterone concentration approximately 90 min post injection, and a four- to five-fold increase in fecal glucocorticoid concentration 2 to 4 h post injection. Serum corticosterone concentrations in wild harlequin ducks increased within min of capture and elevated levels were found for several hours post capture, indicating that surgery and confinement maintain elevated corticosterone concentrations in this species. Mean corticosterone concentrations in wild harlequin ducks held in temporary captivity were similar to the maximum response levels during the ACTH challenge in captive birds. However, large variation among individuals was observed in responses of wild birds, and we found additional evidence suggesting that corticosterone responses varied between hatch year and after hatch year birds.

  1. [Side effects of biologic therapies in psoriasis]. (United States)

    Altenburg, A; Augustin, M; Zouboulis, C C


    The introduction of biologics has revolutionized the treatment of moderate to severe plaque psoriasis. Due to the continuous expansion of biological therapies for psoriasis, it is particularly important to acknowledge efficacy and safety of the compounds not only in clinical trials but also in long-term registry-based observational studies. Typical side effects and significant risks of antipsoriatic biologic therapies considering psoriatic control groups are presented. A selective literature search was conducted in PubMed and long-term safety studies of the psoriasis registries PsoBest, PSOLAR and BADBIR were evaluated. To assess the long-term safety of biologics, the evaluation of the course of large patient cohorts in long-term registries is of particular medical importance. Newer biologic drugs seem to exhibit a better safety profile than older ones.

  2. Side effects from intense pulsed light

    DEFF Research Database (Denmark)

    Thaysen-Petersen, Daniel; Erlendsson, Andres M; Nash, J F


    BACKGROUND AND OBJECTIVE: Intense pulsed light (IPL) is a mainstream treatment for hair removal. Side effects after IPL are known, but risk factors remain to be investigated. The objective of this study was to assess the contribution of skin pigmentation, fluence level, and ultraviolet radiation...... stacking of 46 J/cm2. Areas were subsequently randomized to no UVR or single solar-simulated UVR exposure of 3 Standard Erythema Dose at 30 minutes or 24 hours after IPL. Each area had a corresponding control, resulting in 15 treatment sites. Follow-up visits were scheduled up to 4 weeks after IPL. Outcome...... measures were: (i) blinded clinical skin reactions; (ii) objectively measured erythema and pigmentation; (iii) pain measured by visual analog scale (VAS); (iv) histology (H&E, Fontana-Masson); and (v) mRNA-expression of p53. RESULTS: Fifteen subjects with FST II-IV completed the protocol. IPL induced...

  3. Not all side effects associated with tricyclic antidepressant therapy are true side effects. (United States)

    Thiwan, Syed; Drossman, Douglas A; Morris, Carolyn B; Dalton, Chris; Toner, Brenda B; Diamant, Nicholas E; Hu, J B; Whitehead, William E; Leserman, Jane; Bangdiwala, Shrikant I


    Patients with functional gastrointestinal disorders treated with tricyclic antidepressants sometimes report nongastrointestinal symptoms; it is unclear whether these are drug side effects or reflect a behavioral tendency to report symptoms. We evaluated whether symptoms reported before treatment with a tricyclic antidepressant (desipramine) increased in number or worsened in severity after 2 weeks of treatment and assessed the baseline factors that predispose patients to report symptoms. Female patients in a multicenter National Institutes of Health trial for functional bowel disorders completed a 15-item symptom questionnaire at baseline (before randomization), 2 weeks after they were given desipramine (n = 81) or placebo (n = 40), and at study completion (12 weeks). Patients were asked about the severity and frequency of 15 symptoms. Results were analyzed from 57 patients given desipramine who completed the questionnaires. Symptoms reported as side effects to have occurred more frequently and also worsened at week 2 in the group given desipramine included dizziness, dry mouth/thirstiness, lightheadedness, jittery feelings/tremors, and flushing. Symptoms that did not change in severity or showed improvement at week 2 in the group given desipramine included morning tiredness, nausea, blurred vision, headaches, appetite reduction, and trouble sleeping. Psychologic distress but not desipramine blood level correlated with symptom reporting. Most symptoms often attributed to side effects of desipramine were present before treatment; only a few, related to anticholinergic effects, worsened 2 weeks after treatment, suggesting that most so-called side effects were not associated specifically with desipramine use. Such symptoms might instead be associated with psychologic distress.

  4. Functional interaction between the glucocorticoid receptor and GANP/MCM3AP

    International Nuclear Information System (INIS)

    Osman, Waffa; Laine, Sanna; Zilliacus, Johanna


    Glucocorticoids are widely used to treat inflammatory diseases but have a number of side effects that partly are connected to inhibition of cell proliferation. Glucocorticoids mediated their action by binding to the glucocorticoid receptor. In the present study, we have identified by two-hybrid screens the germinal center-associated protein (GANP) and MCM3-associated protein (MCM3AP), a splicing variant of GANP, as glucocorticoid receptor interacting proteins. GANP and MCM3AP can bind to the MCM3 protein involved in initiation of DNA replication. Glutathione-S-transferase-pull-down and co-immunoprecipitation assays showed that the C-terminal domain of GANP, encompassing MCM3AP, interacts with the ligand-binding domain of the glucocorticoid receptor. Characterization of the intracellular localization of GANP revealed that GANP is shuttling between the nucleus and the cytoplasm. Furthermore, we show that glucocorticoids are unable to inhibit DNA replication in HeLa cells overexpressing MCM3AP suggesting a role for both glucocorticoid receptor and GANP/MCM3AP in regulating cell proliferation

  5. Side Effects of Chemotherapy and Radiation (For Parents) (United States)

    ... Safe Videos for Educators Search English Español Side Effects of Chemotherapy and Radiation KidsHealth / For Parents / Side Effects of Chemotherapy and Radiation What's in this article? What to ...

  6. Chemotherapy Side Effects: A Cause of Heart Disease? (United States)

    ... Can chemotherapy side effects increase the risk of heart disease? Answers from Timothy J. Moynihan, M.D. Chemotherapy side effects may increase the risk of heart disease, including weakening of the heart muscle (cardiomyopathy) and ...

  7. Effect of lipopolysaccharide and antidepressant drugs on glucocorticoid receptor-mediated gene transcription

    Czech Academy of Sciences Publication Activity Database

    Budziszewska, B.; Basta-Kaim, A.; Kubera, M.; Jaworska, L.; Leskiewicz, M.; Tetich, M.; Otczyk, M.; Zajícová, Alena; Holáň, Vladimír; Lasoń, W.


    Roč. 57, č. 4 (2005), s. 540-544 ISSN 1734-1140 Grant - others:State Committee for Scientific Research (KBN)(PL) 6P05A076 Institutional research plan: CEZ:AV0Z5052915 Keywords : glucocorticoid receptor * antidepressant drugs * interleukin-6 Subject RIV: EB - Genetics ; Molecular Biology

  8. Involvement of the insular cortex in regulating glucocorticoid effects on memory consolidation of inhibitory avoidance training

    NARCIS (Netherlands)

    Fornari, Raquel V.; Wichmann, Romy; Atucha, Erika; Desprez, Tifany; Eggens-Meijer, Ellie; Roozendaal, Benno


    Glucocorticoids are known to enhance the consolidation of memory of emotionally arousing experiences by acting upon a network of interconnected brain regions. Although animal studies typically do not consider the insular cortex (IC) to be part of this network, the present findings indicate that the

  9. Suppression of autophagy in osteocytes does not modify the adverse effects of glucocorticoids on cortical bone. (United States)

    Piemontese, Marilina; Onal, Melda; Xiong, Jinhu; Wang, Yiying; Almeida, Maria; Thostenson, Jeff D; Weinstein, Robert S; Manolagas, Stavros C; O'Brien, Charles A


    Glucocorticoid excess decreases bone mass and strength in part by acting directly on osteoblasts and osteocytes, but the mechanisms remain unclear. Macroautophagy (herein referred to as autophagy) is a lysosome-based recycling pathway that promotes the turnover of intracellular components and can promote cell function and survival under stressful conditions. Recent studies have shown that glucocorticoids stimulate autophagy in osteocytes, suggesting that autophagy may oppose the negative actions of glucocorticoids on this cell type. To address this possibility, we compared the impact of prednisolone administration on the skeletons of adult mice in which autophagy was suppressed in osteocytes, via deletion of Atg7 with a Dmp1-Cre transgene, to their control littermates. In control mice, prednisolone increased autophagic flux in osteocyte-enriched bone as measured by LC3 conversion, but this change did not occur in the mice lacking Atg7 in osteocytes. Nonetheless, prednisolone reduced femoral cortical thickness, increased cortical porosity, and reduced bone strength to similar extents in mice with and without autophagy in osteocytes. Prednisolone also suppressed osteoblast number and bone formation in the cancellous bone of control mice. As shown previously, Atg7 deletion in osteocytes reduced osteoblast number and bone formation in cancellous bone, but these parameters were not further reduced by prednisolone administration. In cortical bone, prednisolone elevated osteoclast number to a similar extent in both genotypes. Taken together, these results demonstrate that although glucocorticoids stimulate autophagy in osteocytes, suppression of autophagy in this cell type does not worsen the negative impact of glucocorticoids on the skeleton. Published by Elsevier Inc.

  10. Side effects of endobronchial laser treatment

    Energy Technology Data Exchange (ETDEWEB)

    Dierkesmann, R.; Huzly, A.


    Side effects that have occurred in over 250 endobronchial laser treatments are reported. The laser has been used in severe tracheal and in bronchial obstructions. In two cases significant bleeding had to be treated with tamponade. In one patient an emphysema of the mediastinum developed, in 2 further patients a small pneumothorax. Perforation of the airway was not detected and no special treatment was necessary. Three patients with life-threatening tracheal stenoses and one patient with severe stenosis of both the mainstem bronchi due to metastasis in the bifurcation lymph node had a large defect in the tracheal or bronchial wall with a deep necrosis five to twelve weeks after laser treatment; all these patients had extensive radiotherapy in addition. One patient died due to severe respiratory insufficiency, probably caused by smoke intoxication. After the laser treatment, rubber-like fibrin-rich plaques may develop, which can lead to life-threatening obstructions of the airway. It is recommended that laser bronchoscopy should be performed with the rigid bronchoscope. After treatment of tracheal lesion an endoscopic check must be performed within 24 hours. The combination of laser treatment and radiotherapy seems to involve a certain risk of large defects in the bronchial wall due to necrosis of the tumor.

  11. Effects of environmental conditions, human activity, reproduction, antler cycle and grouping on fecal glucocorticoids of free-ranging Pampas deer stags (Ozotoceros bezoarticus bezoarticus). (United States)

    Garcia Pereira, Ricardo José; Barbanti Duarte, José Maurício; Negrão, João Alberto


    In this study, a commercial enzyme immunoassay (EIA) was validated in detecting glucocorticoids in Pampas deer feces, in order to investigate the influence of several factors on the adrenocortical function. Fecal samples, behavioral data and information concerning male grouping and antlers status were collected at a monthly basis during a 1 year period from free-ranging stags living at Emas National Park, Brazil (18 degrees S/52 degrees W). The results revealed that concentrations of fecal glucocorticoids in winter were significantly higher than those corresponding to spring and summer. In addition, dry season data presented higher levels than during the wet season. Significant difference was found between fecal levels of breeding stags in summer and nonbreeding stags, whereas no difference was observed between breeding stags in winter and nonbreeding stags. On the other hand, males from areas with frequent human disturbance exhibited higher glucocorticoid concentrations and flight distances than individuals from areas of lower human activity. Males with antlers in velvet had elevated levels compared with animals in hard antler or antler casting. Also, we found that glucocorticoid levels were higher in groups with three or more males than in groups with only one male. The flight distances showed positive correlation with fecal glucocorticoid. These data indicate that fecal glucocorticoid provides a useful approach in the evaluation of physiological effects of environment, inter-individuals relationship and human-induced stressors on free-ranging Pampas deer stags.

  12. Comparison of side effects in myelography with iopamidol and metrizamide

    International Nuclear Information System (INIS)

    Lee, Yong; Kang, Heung Sik; Chang, Kee Hyun; Han, Seoul Heui; Kwon, Oh Sung; Myung, Ho Gin


    The study was conducted to compare the side effects in myelography of the two non-ionic water-soluble contrast medias, lopamidol (Niopam) and Metrizamide (Amipaque). A total of 111 patients were examined, 64 with lopamidol and 47 with Metrizamide. Side effects consisted of headache, nausea, vomiting, dizziness, urinary difficulty, muscular pain, seizure, neurobehavioral disturbance, neurological sign change, vital sign change and etc. The common side effects were headache, nausea, vomiting and dizziness in order of frequency. Most of the side effects were subsided within 24 hours following myelography. lopamidol myelography caused fewer and milder side effects than Metrizamide study. The side effects were more commonly observed in cervical, thoracic or total myelography than in lumbar myelography with either lopamidol or Metrizamide. There was no significant correlation between incidence of the side effects and premedication with phenobarbital or valium injection before myelography and CSF sampling during the procedure.

  13. Comparison of side effects in myelography with iopamidol and metrizamide

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yong; Kang, Heung Sik; Chang, Kee Hyun; Han, Seoul Heui; Kwon, Oh Sung; Myung, Ho Gin [Seoul National University College of Medicine, Seoul (Korea, Republic of)


    The study was conducted to compare the side effects in myelography of the two non-ionic water-soluble contrast medias, lopamidol (Niopam) and Metrizamide (Amipaque). A total of 111 patients were examined, 64 with lopamidol and 47 with Metrizamide. Side effects consisted of headache, nausea, vomiting, dizziness, urinary difficulty, muscular pain, seizure, neurobehavioral disturbance, neurological sign change, vital sign change and etc. The common side effects were headache, nausea, vomiting and dizziness in order of frequency. Most of the side effects were subsided within 24 hours following myelography. lopamidol myelography caused fewer and milder side effects than Metrizamide study. The side effects were more commonly observed in cervical, thoracic or total myelography than in lumbar myelography with either lopamidol or Metrizamide. There was no significant correlation between incidence of the side effects and premedication with phenobarbital or valium injection before myelography and CSF sampling during the procedure.

  14. Elevated glucocorticoid receptor binding in cultured human lymphoblasts following hydroxyurea treatment: lack of effect on steroid responsiveness

    International Nuclear Information System (INIS)

    Littlefield, B.A.; Hoagland, H.C.; Greipp, P.R.


    While studying the effects of chemotherapy on glucocorticoid receptor (GR) binding levels in hematological malignancies, we observed a sizable increase in nuclear GR binding of [ 3 H]dexamethasone in peripheral leukocytes from a chronic basophilic leukemia patient following treatment with hydroxyurea plus prednisone, but not after prednisone alone. This apparent clinical effect of hydroxyurea led to an examination of hydroxyurea effects on GR binding and sensitivity in the glucocorticoid-sensitive human lymphoblast cell line GM4672A. GR binding levels in GM4672A cells were measured following a 3-day exposure to 50 microM hydroxyurea, a concentration chosen to have a minimal but measurable effect on cellular growth rates with little or no effect on cellular viability. Under these conditions, nuclear [ 3 H]dexamethasone receptor binding measured by Scatchard analysis using a whole-cell assay was elevated 2.4-fold over control values (P less than 0.05), while cytosolic residual receptor binding (measured at 37 0 C) remained unchanged. Thus, the total cellular content of measurable GR was increased, and this increase was totally accounted for by GR capable of nuclear binding. Hydroxyurea treatment of GM4672A cells had no effect on the affinity of nuclear or cytosolic GR for [ 3 H]dexamethasone. The increase in measurable nuclear-bound receptors occurred in a time-dependent manner over a period of 3 days and was fully reversible within 3 days following removal of hydroxyurea. The increase in receptor binding could not be explained by the slight alterations in cell cycle kinetics which occur at this low level of hydroxyurea. Despite increased receptor binding, cellular glucocorticoid responsiveness was unaltered as assessed by dexamethasone inhibition of cell growth and dexamethasone inhibition of a urokinase-like plasminogen activator

  15. Side effects of retinoid therapy on the quality of vision

    Directory of Open Access Journals (Sweden)

    Bergler-Czop Beata


    Full Text Available Retinoids are compounds chemically related to vitamin A, which are frequently used in dermatological practice (1. They are characterized by numerous mechanisms of action leading to normalization of keratinocyte proliferation and maturation. They have anti-seborrhoeic, immunomodulatory and anti-inflammatory effects (1, 2. A number of side effects to retinoid treatment have been recorded; one group of such side effects relates to eyes and vision. Dry eye syndrome and blepharoconjunctivitis are the most common side effects, appearing in 20-50 % of patients treated with retinoids. They often contribute to the occurrence of other side-effects such as eye discomfort and contact lens intolerance. Due to the widespread use in clinical practice, the adverse effects, including ocular side effects, should be studied. To confirm the variety of adverse effects of retinoids, several case reports of rare side-effects are presented.

  16. Pathophysiology of Glucocorticoid Signaling. (United States)

    Vitellius, Géraldine; Trabado, Séverine; Bouligand, Jérôme; Delemer, Brigitte; Lombès, Marc


    Glucocorticoids (GC), such as cortisol or dexamethasone, control various physiological functions, notably those involved in development, metabolism, inflammatory processes and stress, and exert most of their effects upon binding to the glucocorticoid receptor (GR, encoded by NR3C1 gene). GC signaling follows several consecutive steps leading to target gene transactivation, including ligand binding, nuclear translocation of ligand-activated GR complexes, DNA binding, coactivator interaction and recruitment of functional transcriptional machinery. Any step may be impaired and may account for altered GC signaling. Partial or generalized glucocorticoid resistance syndrome may result in a reduced level of functional GR, a decreased hormone affinity and binding, a defect in nuclear GR translocation, a decrease or lack of DNA binding and/or post-transcriptional GR modifications. To date, 26 loss-of-function NR3C1 mutations have been reported in the context of hypertension, hirsutism, adrenal hyperplasia or metabolic disorders. These clinical signs are generally associated with biological features including hypercortisolism without negative regulatory feedback loop on the hypothalamic-pituitary-adrenal axis. Patients had often low plasma aldosterone and renin levels despite hypertension. Only one GR gain-of-function mutation has been described associating Cushing's syndrome phenotype with normal urinary-free cortisol. Some GR polymorphisms (ER22/23EK, GR-9β) have been linked to glucocorticoid resistance and a healthier metabolic profile whereas some others seemed to be associated with GC hypersensitivity (N363S, BclI), increasing cardiovascular risk (diabetes type 2, visceral obesity). This review focuses on the earlier findings on the pathophysiology of GR signaling and presents criteria facilitating identification of novel NR3C1 mutations in selected patients. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  17. Side Effects of Leukotriene Receptor Antagonists in Asthmatic Children. (United States)

    Erdem, Semiha Bahceci; Nacaroglu, Hikmet Tekin; Unsal Karkiner, Canan Sule; Gunay, Ilker; Can, Demet


    Leukotriene receptor antagonists (LTRAs) are drugs which have been widely used more than ten years. As the use of LTRAs increases, our knowledge with respect to their side effects increases as well. The objective of our study was to evaluat the observed side effects of LTRAs used in patients with astma. 1024 patients treated only with LTRAs owing to asthma or early wheezing were included in the study for a five-year period. The observed side effects of LTRAs in these patients were retrospectively investigated. The side effects were divided into two parts as psychiatric and non-psychiatric. Among the 1024 cases included in the study, 67.5% of the patients out of 41 with side effects were male, 32.5% were female and the average age was 6.5 years. The rate of patients with asthma was 63.41% and 36.58% of the patients had early wheezing. It was determined that sex, age and diagnosis (early wheezing or asthma) of the patients were ineffective in the emergence of side effects. The average period for the emergence of side effects was the first month. It was observed that hyperactivity was the most frequently observed psychiatric side effect and that abdominal pain was the non-psychiatric side effect. The side effects of LTRAs were common in children. Therefore, patients must be informed at the beginning of the treatment and they must be evaluated at certain intervals.

  18. Local metabolism of glucocorticoids in Prague hereditary hypertriglyceridemic rats – Effect of hypertriglyceridemia and gender

    Czech Academy of Sciences Publication Activity Database

    Klusoňová, Petra; Pátková, Lenka; Ergang, Peter; Mikšík, Ivan; Zicha, Josef; Kuneš, Jaroslav; Pácha, Jiří


    Roč. 76, č. 12 (2011), s. 1252-1259 ISSN 0039-128X R&D Projects: GA ČR(CZ) GA305/08/0139; GA AV ČR(CZ) KJB500110703 Institutional research plan: CEZ:AV0Z50110509 Keywords : 11beta-hydroxysteroid dehydrogenase * glucocorticoids * hypertriglyceridemia Subject RIV: ED - Physiology Impact factor: 2.829, year: 2011

  19. A systematic review of the effect of oral glucocorticoids on energy intake, appetite, and body weight in humans. (United States)

    Berthon, Bronwyn S; MacDonald-Wicks, Lesley K; Wood, Lisa G


    Obesity is a serious risk factor for chronic disease, and commonly prescribed oral glucocorticoids (OCS) may be contributing to the prevalence of obesity. The objective of this review was to assess the impact of OCS on obesity in humans through effects on body weight (BW), energy intake, appetite, and body composition. An electronic search of English language peer-reviewed studies from 1973 up to March 2012 was conducted using Medline, CINAHL, EMBASE, and Cochrane databases. Original studies that addressed the effects of OCS on appetite, energy intake, BW, or body composition in adults were considered eligible. Data from 21 studies with objectively measured outcomes were extracted and assessed for quality using standardized tools. The publication year varied from 1986 to 2013, and the sample size, from 6 to 189. Energy intake was measured in 6 studies; BW, in 19 studies; energy expenditure, in 3 studies; body composition, in 6 studies; and appetite was evaluated in 3 studies. Short-term oral glucocorticoid therapy may result in small increases in energy intake but does not appear to result in increased BW, possibly due to an increase in energy expenditure. Long-term therapy may result in clinically significant weight gain. Within-subject variation due to metabolism and physical activity levels confounds the relationship. A dose-response relationship of oral glucocorticoid therapy on energy intake, appetite, BW, or body composition was not found. Additional well-designed, double-blind, placebo-controlled clinical trials that use standardized doses of OCS and assess the effects on appetite, energy intake, BW, and composition are strongly justified to confirm the findings of this review. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Glucocorticoid effects on the programming of AT1b angiotensin receptor gene methylation and expression in the rat.

    Directory of Open Access Journals (Sweden)

    Irina Bogdarina


    Full Text Available Adverse events in pregnancy may 'programme' offspring for the later development of cardiovascular disease and hypertension. Previously, using a rodent model of programmed hypertension we have demonstrated the role of the renin-angiotensin system in this process. More recently we showed that a maternal low protein diet resulted in undermethylation of the At1b angiotensin receptor promoter and the early overexpression of this gene in the adrenal of offspring. Here, we investigate the hypothesis that maternal glucocorticoid modulates this effect on fetal DNA methylation and gene expression. We investigated whether treatment of rat dams with the 11beta-hydroxylase inhibitor metyrapone, could prevent the epigenetic and gene expression changes we observed. Offspring of mothers subjected to a low protein diet in pregnancy showed reduced adrenal Agtr1b methylation and increased adrenal gene expression as we observed previously. Treatment of mothers with metyrapone for the first 14 days of pregnancy reversed these changes and prevented the appearance of hypertension in the offspring at 4 weeks of age. As a control for non-specific effects of programmed hypertension we studied offspring of mothers treated with dexamethasone from day 15 of pregnancy and showed that, whilst they had raised blood pressure, they failed to show any evidence of Agtr1b methylation or increase in gene expression. We conclude that maternal glucocorticoid in early pregnancy may induce changes in methylation and expression of the Agtr1b gene as these are clearly reversed by an 11 beta-hydroxylase inhibitor. However in later pregnancy a converse effect with dexamethasone could not be demonstrated and this may reflect either an alternative mechanism of this glucocorticoid or a stage-specific influence.

  1. Target Essentiality and Centrality Characterize Drug Side Effects


    Wang, Xiujuan; Thijssen, Bram; Yu, Haiyuan


    Author Summary The ultimate goal of medical research is to develop effective treatments for disease with minimal side effects. Currently, about 20% of drug candidates failed at clinical trial phases II and III due to safety issues. Therefore, understanding the determining factors of drug side effects is of paramount importance to human health and the pharmaceutical industry. Here, we present the first systematic study to uncover key factors leading to drug side effects within the framework of...

  2. Effects of proportions of dietary macronutrients on glucocorticoid metabolism in diet-induced obesity in rats.

    Directory of Open Access Journals (Sweden)

    Roland H Stimson


    Full Text Available Tissue glucocorticoid levels in the liver and adipose tissue are regulated by regeneration of inactive glucocorticoid by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1 and inactivation by 5alpha- and 5beta-reductases. A low carbohydrate diet increases hepatic 11beta-HSD1 and reduces glucocorticoid metabolism during weight loss in obese humans. We hypothesized that similar variations in macronutrient proportions regulate glucocorticoid metabolism in obese rats. Male Lister Hooded rats were fed an obesity-inducing ad libitum 'Western' diet (37% fat, n = 36 for 22 weeks, then randomised to continue this diet (n = 12 or to switch to either a low carbohydrate (n = 12 or a moderate carbohydrate (n = 12 diet for the final 8 weeks. A parallel lean control group were fed an ad libitum control diet (10% fat, n = 12 throughout. The low and moderate carbohydrate diets decreased hepatic 11beta-HSD1 mRNA compared with the Western diet (both 0.7+/-0.0 vs 0.9+/-0.1 AU; p<0.01, but did not alter 11beta-HSD1 in adipose tissue. 5Alpha-reductase mRNA was increased on the low carbohydrate compared with the moderate carbohydrate diet. Compared with lean controls, the Western diet decreased 11beta-HSD1 activity (1.6+/-0.1 vs 2.8+/-0.1 nmol/mcg protein/hr; p<0.001 and increased 5alpha-reductase and 5beta-reductase mRNAs (1.9+/-0.3 vs 1.0+/-0.2 and 1.6+/-0.1 vs 1.0+/-0.1 AU respectively; p<0.01 in the liver, and reduced 11beta-HSD1 mRNA and activity (both p<0.01 in adipose tissue. Although an obesity-inducing high fat diet in rats recapitulates the abnormal glucocorticoid metabolism associated with human obesity in liver (but not in adipose tissue, a low carbohydrate diet does not increase hepatic 11beta-HSD1 in obese rats as occurs in humans.

  3. Side-effects of topical steroids: A long overdue revisit. (United States)

    Coondoo, Arijit; Phiske, Meghana; Verma, Shyam; Lahiri, Koushik


    The introduction of topical steroids (TS) of varying potency have rendered the therapy of inflammatory cutaneous disorders more effective and less time-consuming. However the usefulness of these has become a double edged sword with constantly rising instances of abuse and misuse leading to serious local, systemic and psychological side effects. These side effects occur more with TS of higher potency and on particular areas of the body like face and genitalia. The article reviews the side effects of TS with special mention about peadiatric age group, also includes the measures for preventing the side effects.

  4. Side-effects of topical steroids: A long overdue revisit

    Directory of Open Access Journals (Sweden)

    Arijit Coondoo


    Full Text Available The introduction of topical steroids (TS of varying potency have rendered the therapy of inflammatory cutaneous disorders more effective and less time-consuming. However the usefulness of these has become a double edged sword with constantly rising instances of abuse and misuse leading to serious local, systemic and psychological side effects. These side effects occur more with TS of higher potency and on particular areas of the body like face and genitalia.The article reviews the side effects of TS with special mention about peadiatric age group, also includes the measures for preventing the side effects.

  5. Early life stress determines the effects of glucocorticoids and stress on hippocampal function: Electrophysiological and behavioral evidence respectively. (United States)

    Pillai, Anup G; Arp, Marit; Velzing, Els; Lesuis, Sylvie L; Schmidt, Mathias V; Holsboer, Florian; Joëls, Marian; Krugers, Harm J


    Exposure to early-life adversity may program brain function to prepare individuals for adaptation to matching environmental contexts. In this study we tested this hypothesis in more detail by examining the effects of early-life stress - induced by raising offspring with limited nesting and bedding material from postnatal days 2-9 - in various behavioral tasks and on synaptic function in adult mice. Early-life stress impaired adult performance in the hippocampal dependent low-arousing object-in-context recognition memory task. This effect was absent when animals were exposed to a single stressor before training. Early-life stress did not alter high-arousing context and auditory fear conditioning. Early-life stress-induced behavioral modifications were not associated with alterations in the dendritic architecture of hippocampal CA1 pyramidal neurons or principal neurons of the basolateral amygdala. However, early-life stress reduced the ratio of NMDA to AMPA receptor-mediated excitatory postsynaptic currents and glutamate release probability specifically in hippocampal CA1 neurons, but not in the basolateral amygdala. These ex vivo effects in the hippocampus were abolished by acute glucocorticoid treatment. Our findings support that early-life stress can hamper object-in-context learning via pre- and postsynaptic mechanisms that affect hippocampal function but these effects are counteracted by acute stress or elevated glucocorticoid levels. Copyright © 2018. Published by Elsevier Ltd.

  6. Side-effects of topical steroids: A long overdue revisit


    Coondoo, Arijit; Phiske, Meghana; Verma, Shyam; Lahiri, Koushik


    The introduction of topical steroids (TS) of varying potency have rendered the therapy of inflammatory cutaneous disorders more effective and less time-consuming. However the usefulness of these has become a double edged sword with constantly rising instances of abuse and misuse leading to serious local, systemic and psychological side effects. These side effects occur more with TS of higher potency and on particular areas of the body like face and genitalia. The article reviews the side effe...

  7. A side effect resource to capture phenotypic effects of drugs

    DEFF Research Database (Denmark)

    Kuhn, Michael; Campillos, Monica; Letunic, Ivica


    The molecular understanding of phenotypes caused by drugs in humans is essential for elucidating mechanisms of action and for developing personalized medicines. Side effects of drugs (also known as adverse drug reactions) are an important source of human phenotypic information, but so far research...

  8. Differential effects of the new glucocorticoid receptor antagonist ORG 34517 and RU486 (mifepristone) on glucocorticoid receptor nuclear translocation in the AtT20 cell line. (United States)

    Peeters, B W M M; Ruigt, G S F; Craighead, M; Kitchener, P


    Glucocorticoid agonists bind to cytoplasmic glucocorticoid receptors (GRs) and subsequently translocate as an agonist-GR complex into the nucleus. In the nucleus the complex regulates the transcription of target genes. A number of GR antagonists (RU486, progesterone, RU40555) have also been shown to induce receptor translocation. These compounds should be regarded as partial agonists. For the nonselective progesterone receptor antagonists, RTI3021-012 and RTI3021-022, it was shown that GR antagonism is possible without the induction of GR translocation. In the present studies, the new GR antagonist, ORG 34517, was investigated for its potential to induce GR translocation and to antagonize corticosterone-induced GR translocation in the AtT20 (mouse pituitary) cell line. ORG 34517 was compared to RU486. In contrast to RU486, ORG 34517 (at doses up to 3 x 10(-7) M) did not induce GR translocation, but was able to block corticosterone (3 x 10(-8) M) induced GR translocation. ORG 34517 can be regarded as a true competitive GR antagonist without partial agonistic activities.

  9. Glucocorticoid-induced hyperglycaemia

    NARCIS (Netherlands)

    Gerards, M.C.


    This thesis contains studies on current practice, clinical implications and treatment of excess glucocorticoid receptor (GCR) stimulation, with a focus on glucocorticoid-induced hyperglycaemia (GCIH). Chapter 1 is a general introduction to the glucocorticoid hormone. In chapter 2 , we have

  10. Islet-cell dysfunction induced by glucocorticoid treatment

    DEFF Research Database (Denmark)

    van Raalte, Daniël H; Kwa, Kelly A A; van Genugten, Renate E


    Glucocorticoids impair glucose tolerance by inducing insulin resistance. We investigated the dose-dependent effects of glucocorticoid treatment on islet-cell function in healthy males and studied the role of the autonomic nervous system.......Glucocorticoids impair glucose tolerance by inducing insulin resistance. We investigated the dose-dependent effects of glucocorticoid treatment on islet-cell function in healthy males and studied the role of the autonomic nervous system....

  11. Effects of side lying on lung function in older individuals. (United States)

    Manning, F; Dean, E; Ross, J; Abboud, R T


    Body positioning exerts a strong effect on pulmonary function, but its effect on other components of the oxygen transport pathway are less well understood, especially the effects of side-lying positions. This study investigated the interrelationships between side-lying positions and indexes of lung function such as spirometry, alveolar diffusing capacity, and inhomogeneity of ventilation in older individuals. Nineteen nonsmoking subjects (mean age=62.8 years, SD=6.8, range=50-74) with no history of cardiac or pulmonary disease were tested over 2 sessions. The test positions were sitting and left side lying in one session and sitting and right side lying in the other session. In each of the positions, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), single-breath pulmonary diffusing capacity (DLCO/VA), and the slope of phase III (DN2%/L) of the single-breath nitrogen washout test to determine inhomogeneity of ventilation were measured. Compared with measurements obtained in the sitting position, FVC and FEV1 were decreased equally in the side-lying positions, but no change was observed in DLCO/VA or DN2%/L. Side-lying positions resulted in decreases in FVC and FEV1, which is consistent with the well-documented effects of the supine position. These findings further support the need for prescriptive rather than routine body positioning of patients with risks of cardiopulmonary compromise and the need to use upright positions in which lung volumes and capacities are maximized.

  12. Glucocorticoid programming of neuroimmune function. (United States)

    Walker, David J; Spencer, Karen A


    Throughout life physiological systems strive to maintain homeostasis and these systems are susceptible to exposure to maternal or environmental perturbations, particularly during embryonic development. In some cases, these perturbations may influence genetic and physiological processes that permanently alter the functioning of these physiological systems; a process known as developmental programming. In recent years, the neuroimmune system has garnered attention for its fundamental interactions with key hormonal systems, such as the hypothalamic pituitary adrenal (HPA) axis. The ultimate product of this axis, the glucocorticoid hormones, play a key role in modulating immune responses within the periphery and the CNS as part of the physiological stress response. It is well-established that elevated glucocorticoids induced by developmental stress exert profound short and long-term physiological effects, yet there is relatively little information of how these effects are manifested within the neuroimmune system. Pre and post-natal periods are prime candidates for manipulation in order to uncover the physiological mechanisms that underlie glucocorticoid programming of neuroimmune responses. Understanding the potential programming role of glucocorticoids may be key in uncovering vulnerable windows of CNS susceptibility to stressful experiences during embryonic development and improve our use of glucocorticoids as therapeutics in the treatment of neurodegenerative diseases. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  13. Are peripheral opioid antagonists the solution to opioid side effects?

    LENUS (Irish Health Repository)

    Bates, John J


    Opioid medication is the mainstay of therapy for severe acute and chronic pain. Unfortunately, the side effects of these medications can affect patient comfort and safety, thus limiting their proven therapeutic potential. Whereas the main analgesic effects of opioids are centrally mediated, many of the common side effects are mediated via peripheral receptors. Novel peripheral opioid antagonists have been recently introduced that can block the peripheral actions of opioids without affecting centrally mediated analgesia. We review the clinical and experimental evidence of their efficacy in ameliorating opioid side effects and consider what further information might be useful in defining their role. IMPLICATIONS: The major analgesic effects of opioid medication are mediated within the brain and spinal cord. Many of the side effects of opioids are caused by activation of receptors outside these areas. Recently developed peripherally restricted opioid antagonists have the ability to block many opioid side effects without affecting analgesia.

  14. Effects of glucocorticoid hormones on cell proliferation in dimethylhydrazine-induced tumours in rat colon. (United States)

    Tutton, P J; Barkla, D H


    Adrenocortical hormones have previously been shown to influence cell proliferation in many tissues. In this report, their influence on cell proliferation in the colonic crypt epithelium and in colonic adenocarcinomata is compared. Colonic tumour cell proliferation was found to be retarded following adrenalectomy and this retardation was reversible by administration of hydrocortisone, or by administration of synthetic steroids with predominantly glucocorticoid activity. Tumour cell proliferation in adrenalectomized rats was not promoted by the mineralocorticoid hormone aldosterone. Neither adrenalectomy, nor adrenocortical hormone treatment, significantly influenced colonic crypt cell proliferation.

  15. Inhibitory effects of glucocorticoid on apoptosis and activation of NF-κB in P388 cells induced by radiation

    International Nuclear Information System (INIS)

    Shi Jianhui; Niu Yuhong; Ge Junbo; Xu Xiaoping; Cheng Wenying; Feng Xiao; Zhang Zongliang


    Objective: To explore effects of glucocorticoid on apoptosis and activation of NF-κB in P388 cells induced by radiation. Methods: Apoptosis in P388 cells induced by radiation treatment was detected by TUNEL assay. EMSA was used to detect the activation of NF-κB . Results: The apoptosis and activation of NF-κB in P388 cells could be induced by radiation. Dexamethasone (DXM) which could suppress activation of NF-κB of P388 cells increased significantly the apoptosis induced by radiation. Apoptosis rates in DXM-treated P388 cells after 2, 4, 6 and 8 Gy exposure increased by 60%, 100%, 129% and 67%, respectively. Activation rates of NF-κB in DXM-treated P388 cells after 2, 4, 6 and 8 Gy exposure decreased by 25%, 45%, 52% and 40%, respectively. Conclusion: Radiation induces apoptosis and activation of NF-κB in P388 cells simultaneously. Glucocorticoid enhances apoptosis in leukemic cells, which may be by means of suppressing activation of NF-κB

  16. Side effects of vagus nerve stimulation during physical exercise

    NARCIS (Netherlands)

    Mulders, D.M.; de Vos, Cecilia Cecilia Clementine; Vosman, I.; Driesse, M.J.; van Putten, Michel Johannes Antonius Maria


    RATIONALE: Vagus nerve stimulation (VNS) is a treatment option in the case of refractory epilepsy. However, several side effects have been reported, including dyspnea, coughing and bradycardias [JCA 2010: 22;213-222]. Although some patients experience hardly any side effects from the stimulation

  17. Side Effects and Interactions of the Xanthine Oxidase Inhibitor Febuxostat. (United States)

    Jordan, Andreas; Gresser, Ursula


    The paper addresses the safety of febuxostat and summarizes reports on side effects and interactions of febuxostat published by the cut-off date (last day of literature search) of 20 March 2018. Publications on side effects and the interactions of febuxostat were considered. Information concerning the occurrence of side effects and interactions in association with the treatment with febuxostat was collected and summarized in the review. The incidence of severe side effects was much less frequent than mild side effects (1.2⁻3.8% to 20.1⁻38.7%). The rate and range of febuxostat side effects are low at doses of up to 120 mg and only increase with a daily dose of over 120 mg. The publications reveal no age-dependent increase in side effects for febuxostat. In patients with impaired renal function, no increase in adverse events is described with a dose of up to 120 mg of febuxostat per day. Patients with impaired liver function had no elevated risk for severe side effects. A known allopurinol intolerance increases the risk of skin reactions during treatment with febuxostat by a factor of 3.6. No correlation between treatment with febuxostat and agranulocytosis has been confirmed. Possible interactions with very few medications (principally azathioprine) are known for febuxostat. Febuxostat is well tolerated and a modern and safe alternative to allopurinol therapy.

  18. NALP3 inflammasome up-regulation and CASP1 cleavage of the glucocorticoid receptor causes glucocorticoid resistance in leukemia cells (United States)

    Paugh, Steven W.; Bonten, Erik J.; Savic, Daniel; Ramsey, Laura B.; Thierfelder, William E.; Gurung, Prajwal; Malireddi, R. K. Subbarao; Actis, Marcelo; Mayasundari, Anand; Min, Jaeki; Coss, David R.; Laudermilk, Lucas T.; Panetta, John C.; McCorkle, J. Robert; Fan, Yiping; Crews, Kristine R.; Stocco, Gabriele; Wilkinson, Mark R.; Ferreira, Antonio M.; Cheng, Cheng; Yang, Wenjian; Karol, Seth E.; Fernandez, Christian A.; Diouf, Barthelemy; Smith, Colton; Hicks, J. Kevin; Zanut, Alessandra; Giordanengo, Audrey; Crona, Daniel; Bianchi, Joy J.; Holmfeldt, Linda; Mullighan, Charles G.; den Boer, Monique L.; Pieters, Rob; Jeha, Sima; Dunwell, Thomas L.; Latif, Farida; Bhojwani, Deepa; Carroll, William L.; Pui, Ching-Hon; Myers, Richard M.; Guy, R. Kiplin; Kanneganti, Thirumala-Devi; Relling, Mary V.; Evans, William E.


    Glucocorticoids are universally used in the treatment of acute lymphoblastic leukemia (ALL), and leukemia cell resistant to glucocorticoids confers a poor prognosis. To elucidate mechanisms of glucocorticoid resistance, we determined the sensitivity to prednisolone of primary leukemia cells from 444 newly diagnosed ALL patients, revealing significantly higher expression of caspase 1 (CASP1) and its activator NLRP3 in glucocorticoid resistant leukemia cells, due to significantly lower somatic methylation of CASP1 and NLRP3 promoters. Over-expression of CASP1 resulted in cleavage of the glucocorticoid receptor, diminished glucocorticoid-induced transcriptional response and increased glucocorticoid resistance. Knockdown or inhibition of CASP1 significantly increased glucocorticoid receptor levels and mitigated glucocorticoid resistance in CASP1 overexpressing ALL. Our findings establish a new mechanism by which the NLRP3/CASP1 inflammasome modulates cellular levels of the glucocorticoid receptor and diminishes cell sensitivity to glucocorticoids. The broad impact on glucocorticoid transcriptional response suggests this mechanism could also modify glucocorticoid effects in other diseases. PMID:25938942

  19. Central nervous system side effects associated with zolpidem treatment. (United States)

    Toner, L C; Tsambiras, B M; Catalano, G; Catalano, M C; Cooper, D S


    Zolpidem is one of the newer medications developed for the treatment of insomnia. It is an imidazopyridine agent that is an alternative to the typical sedative-hypnotic agents. Zolpidem use is gaining favor because of its efficacy and its side effect profile, which is milder and less problematic than that of the benzodiazepines and barbiturates used to treat insomnia. Still, side effects are not uncommon with zolpidem use. We report a series of cases in which the patients developed delirium, nightmares and hallucinations during treatment with zolpidem. We will review its pharmacology, discuss previous reports of central nervous system side effects, examine the impact of drug interactions with concurrent use of antidepressants, examine gender differences in susceptibility to side effects, and explore the significance of protein binding in producing side effects.

  20. Systematic identification of proteins that elicit drug side effects

    DEFF Research Database (Denmark)

    Kuhn, Michael; Al Banchaabouchi, Mumna; Campillos, Monica


    Side effect similarities of drugs have recently been employed to predict new drug targets, and networks of side effects and targets have been used to better understand the mechanism of action of drugs. Here, we report a large-scale analysis to systematically predict and characterize proteins...... that cause drug side effects. We integrated phenotypic data obtained during clinical trials with known drug-target relations to identify overrepresented protein-side effect combinations. Using independent data, we confirm that most of these overrepresentations point to proteins which, when perturbed, cause......) is responsible for hyperesthesia in mice, which, in turn, can be prevented by a drug that selectively inhibits HTR7. Taken together, we show that a large fraction of complex drug side effects are mediated by individual proteins and create a reference for such relations....

  1. Effects of short-term glucocorticoid deprivation on growth hormone (GH) response to GH-releasing peptide-6: Studies in normal men and in patients with adrenal insufficiency


    Pinto, Ana Claudia de Assis Rocha [UNIFESP; Dias-da-Silva, Magnus Régios [UNIFESP; Martins, Manoel R. [UNIFESP; Brunner, Elisa [UNIFESP; Lengyel, Ana Maria Judith [UNIFESP


    There are no data in the literature about the effects of glucocorticoid deprivation on GH-releasing peptide-g (GHRP-6)-induced GH release. the aims of this study were to evaluate GH responsiveness to GHRP-6 1) after metyrapone administration in normal men, and 2) in patients with chronic hypocortisolism after glucocorticoid withdrawal for 72 h. in normal subjects, metyrapone ingestion did not alter significantly GH responsiveness to GHRP-6 [n = 8; peak, 39.3 +/- 7.1 mu g/L; area under the cur...

  2. Measuring side effects after radiotherapy for pharynx cancer

    DEFF Research Database (Denmark)

    Jensen, Kenneth


    Data on side effects after radiotherapy is needed to establish the benefits and drawbacks of new treatments, but side effects are not quantified as easily as survival or local control. Side effects may be quantified using physical measures. Unfortunately, only few endpoints exist where a physical...... measure is obtainable, and the case of a patient-relevant measure is even rarer. Radiotherapy is often followed by complex symptoms not easily quantifiable by the observer. Quantitative patient reported side effects can be retrieved using validated questionnaires, but this kind of data is often difficult...... to interpret and the correlation with clinically observable or measurable changes not straightforward. The exploitation of the possibilities of highly conformal radiotherapy and multimodality treatment depends on a better understanding of the correlation between dose, volume, modifying factors, and side...

  3. Differential effect of glucocorticoids on tumour necrosis factor production in mice: up-regulation by early pretreatment with dexamethasone. (United States)

    Fantuzzi, G; Demitri, M T; Ghezzi, P


    Glucocorticoids (GC) are well known inhibitors of tumour necrosis factor (TNF) production. We investigated the role of endogenous GC in the regulation of TNF production in mice treated with lipopolysaccharide (LPS) using a pretreatment with dexamethasone (DEX) to down-regulate the hypothalamus-pituitary-adrenal axis (HPA). Short-term DEX pretreatment (up to 12 h before LPS) inhibited TNF production, but earlier (24-48 h) pretreatments potentiated it. This up-regulating effect was not observed in adrenalectomized mice or when GC synthesis was inhibited with cyanoketone (CK). This effect could not be explained only by the suppression of LPS-induced corticosterone (CS) levels induced by DEX, since a 48-h pretreatment potentiated TNF production without affecting LPS-induced CS levels. On the other hand, mice chronically pretreated with DEX were still responsive to its inhibitory effect on TNF production, thus ruling out the possibility of a decreased responsiveness to GC.

  4. Side Flow Effect on Surface Generation in Nano Cutting. (United States)

    Xu, Feifei; Fang, Fengzhou; Zhang, Xiaodong


    The side flow of material in nano cutting is one of the most important factors that deteriorate the machined surface quality. The effects of the crystallographic orientation, feed, and the cutting tool geometry, including tool edge radius, rake angle and inclination angle, on the side flow are investigated employing molecular dynamics simulation. The results show that the stagnation region is formed in front of tool edge and it is characterized by the stagnation radius R s and stagnation height h s . The side flow is formed because the material at or under the stagnation region is extruded by the tool edge to flow to the side of the tool edge. Higher stagnation height would increase the size of the side flow. The anisotropic nature of the material which partly determines the stagnation region also influences the side flow due to the different deformation mechanism under the action of the tool edge. At different cutting directions, the size of the side flow has a great difference which would finally affect the machined surface quality. The cutting directions of {100} , {110} , and {110}  are beneficial to obtain a better surface quality with small side flow. Besides that, the side flow could be suppressed by reducing the feed and optimizing the cutting tool geometry. Cutting tool with small edge radius, large positive rake angle, and inclination angle would decrease the side flow and consequently improve the machined surface quality.

  5. In vivo assessment of antiretroviral therapy-associated side effects

    Directory of Open Access Journals (Sweden)

    Eduardo Milton Ramos-Sanchez


    Full Text Available Antiretroviral therapy has been associated with side effects, either from the drug itself or in conjunction with the effects of human immunodeficiency virus infection. Here, we evaluated the side effects of the protease inhibitor (PI indinavir in hamsters consuming a normal or high-fat diet. Indinavir treatment increased the hamster death rate and resulted in an increase in triglyceride, cholesterol and glucose serum levels and a reduction in anti-oxLDL auto-antibodies. The treatment led to histopathological alterations of the kidney and the heart. These results suggest that hamsters are an interesting model for the study of the side effects of antiretroviral drugs, such as PIs.

  6. Developmental neurotoxicity targeting hepatic and cardiac sympathetic innervation: effects of organophosphates are distinct from those of glucocorticoids. (United States)

    Seidler, Frederic J; Slotkin, Theodore A


    Early-life exposure to organophosphate pesticides leads to subsequent hyperresponsiveness of β-adrenergic receptor-mediated cell signaling that regulates hepatic gluconeogenesis, culminating in metabolic abnormalities resembling prediabetes. In the current study, we evaluated the effects of chlorpyrifos or parathion on presynaptic sympathetic innervation to determine whether the postsynaptic signaling effects are accompanied by defects in neuronal input. We administered either chlorpyrifos or parathion to newborn rats using exposure paradigms known to elicit the later metabolic changes but found no alterations in either hepatic or cardiac norepinephrine levels in adolescence or adulthood. However, shifting chlorpyrifos exposure to the prenatal period did evoke changes: exposure early in gestation produced subsequent elevations in norepinephrine, whereas later gestational exposure produced significant deficits. We also distinguished the organophosphate effects from those of the glucocorticoid, dexamethasone, a known endocrine disruptor that leads to later-life metabolic and cardiovascular disruption. Postnatal exposure to dexamethasone elicited deficits in peripheral norepinephrine levels but prenatal exposure did not. Our results indicate that early-life exposure to organophosphates leads to subsequent abnormalities of peripheral sympathetic innervation through mechanisms entirely distinct from those of glucocorticoids, ruling out the possibility that the organophosphate effects are secondary to stress or disruption of the HPA axis. Further, the effects on innervation were separable from those on postsynaptic signaling, differing in critical period as well as tissue- and sex-selectivity. Organophosphate targeting of both presynaptic and postsynaptic β-adrenergic sites, each with different critical periods of vulnerability, thus sets the stage for compounding of hepatic and cardiac functional abnormalities. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Optimal glucocorticoid replacement in adrenal insufficiency. (United States)

    Øksnes, Marianne; Ross, Richard; Løvås, Kristian


    Adrenal insufficiency (glucocorticoid deficiency) comprises a group of rare diseases, including primary adrenal insufficiency, secondary adrenal insufficiency and congenital adrenal hyperplasia. Lifesaving glucocorticoid therapy was introduced over 60 years ago, but since then a number of advances in treatment have taken place. Specifically, little is known about short- and long-term treatment effects, and morbidity and mortality. Over the past decade, systematic cohort and registry studies have described reduced health-related quality of life, an unfavourable metabolic profile and increased mortality in patients with adrenal insufficiency, which may relate to unphysiological glucocorticoid replacement. This has led to the development of new modes of replacement that aim to mimic normal glucocorticoid physiology. Here, evidence for the inadequacy of conventional glucocorticoid therapy and recent developments in treatment are reviewed, with an emphasis on primary adrenal insufficiency. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Reported Sildenafil Side Effects in Pediatric Pulmonary Hypertension Patients

    Directory of Open Access Journals (Sweden)

    Stephanie Leigh Siehr


    Full Text Available Background: Sildenafil, a phosphodiestase type 5 inhibitor, was approved in 2005 for the treatment of pulmonary arterial hypertension (PAH in adults, and is commonly used off-label for pediatric patients. Little is known, however, about sildenafil’s side effects in this population.Methods: Single institution, longitudinal survey-based study performed in an outpatient pediatric cardiology clinic. Pediatric patients on sildenafil (alone or in combination with other PH therapies completed questionnaires regarding frequency of vascular, gastrointestinal, neurologic and hematologic side effects. Results: Between January 2011 and May 2014, 66 pediatric patients with PH on sildenafil filled out 214 surveys, 32 patients (96 surveys on monotherapy, and 43 patients (118 surveys on sildenafil plus an endothelin receptor antagonist (bosentan or ambrisentan and/or a prostacyclin (epoprostenol or treprostinil. Overall, 30% of respondents identified at least one side effect. For all patients on sildenafil, incidence of side effects by system was 37% gastrointestinal, 35% vascular and 22% neurologic. For patients on sildenafil monotherapy, incidence of side effects by system was 24% gastrointestinal, 21% vascular and 18% neurologic compared to patients on combination therapy who reported an incidence of 48% gastrointestinal, 45% vascular and 25% neurologic.Conclusion: Incidence of vascular, gastrointestinal and neurologic side effect in pediatric patients on sildenafil therapy for pulmonary arterial hypertension was 30%. Side effects were more common in patients on combination therapy with an endothelin receptor antagonist and/or prostacyclin than in patients on sildenafil monotherapy.

  9. Effect of glucocorticoids on melatonin receptor expression under T-cell activated immune response

    International Nuclear Information System (INIS)

    Tauschanova, P.; Georgiev, G.; Manchev, S.; Konakchieva, R.


    The present study was aimed to explore the stress response in rats under conditions of T-cell antigen-activated immune function and to investigate the specific melatonin (MEL) receptor binding in primary and secondary immune tissue of rats employing 2-( 125 I)-iodo melatonin autoradiography and in vitro ligand binding assay. The study revealed that melatonin receptor binding was specifically expressed in discrete areas of the lymphoid sheath of the spleen and in a network of interdigitating cells of the experimental rats. Demonstration of the modulation of MEL receptor binding in the course of a primary immune response under hypercorticalemic conditions indicate that the pineal hormone might interfere in the processes of glucocorticoid-dependent immune competency. (authors)

  10. Cancer cell-selective promoter recognition accompanies antitumor effect by glucocorticoid receptor-targeted gold nanoparticle (United States)

    Sau, Samaresh; Agarwalla, Pritha; Mukherjee, Sudip; Bag, Indira; Sreedhar, Bojja; Pal-Bhadra, Manika; Patra, Chitta Ranjan; Banerjee, Rajkumar


    Nanoparticles, such as gold nanoparticles (GNP), upon convenient modifications perform multi tasks catering to many biomedical applications. However, GNP or any other type of nanoparticles is yet to achieve the feat of intracellular regulation of endogenous genes of choice such as through manipulation of a gene-promoter in a chromosome. As for gene modulation and delivery, GNP (or other nanoparticles) showed only limited gene therapy potential, which relied on the delivery of `exogenous' genes invoking gene knockdown or replacement. Practically, there are no instances for the nanoparticle-mediated promoter regulation of `endogenous' genes, more so, as a cancer selective phenomenon. In this regard, we report the development of a simple, easily modifiable GNP-formulation, which promoted/up-regulated the expression of a specific category of `endogenous' genes, the glucocorticoid responsive genes. This genetic up-regulation was induced in only cancer cells by modified GNP-mediated transcriptional activation of its cytoplasmic receptor, glucocorticoid receptor (GR). Normal cells and their GR remained primarily unperturbed by this GNP-formulation. The most potent gene up-regulating GNP-formulation down-regulated a cancer-specific proliferative signal, phospho-Akt in cancer cells, which accompanied retardation of tumor growth in the murine melanoma model. We show that GR-targeted GNPs may find potential use in the targeting and modulation of genetic information in cancer towards developing novel anticancer therapeutics.Nanoparticles, such as gold nanoparticles (GNP), upon convenient modifications perform multi tasks catering to many biomedical applications. However, GNP or any other type of nanoparticles is yet to achieve the feat of intracellular regulation of endogenous genes of choice such as through manipulation of a gene-promoter in a chromosome. As for gene modulation and delivery, GNP (or other nanoparticles) showed only limited gene therapy potential, which relied

  11. Network analysis of quantitative proteomics on asthmatic bronchi: effects of inhaled glucocorticoid treatment

    Directory of Open Access Journals (Sweden)

    Sihlbom Carina


    Full Text Available Abstract Background Proteomic studies of respiratory disorders have the potential to identify protein biomarkers for diagnosis and disease monitoring. Utilisation of sensitive quantitative proteomic methods creates opportunities to determine individual patient proteomes. The aim of the current study was to determine if quantitative proteomics of bronchial biopsies from asthmatics can distinguish relevant biological functions and whether inhaled glucocorticoid treatment affects these functions. Methods Endobronchial biopsies were taken from untreated asthmatic patients (n = 12 and healthy controls (n = 3. Asthmatic patients were randomised to double blind treatment with either placebo or budesonide (800 μg daily for 3 months and new biopsies were obtained. Proteins extracted from the biopsies were digested and analysed using isobaric tags for relative and absolute quantitation combined with a nanoLC-LTQ Orbitrap mass spectrometer. Spectra obtained were used to identify and quantify proteins. Pathways analysis was performed using Ingenuity Pathway Analysis to identify significant biological pathways in asthma and determine how the expression of these pathways was changed by treatment. Results More than 1800 proteins were identified and quantified in the bronchial biopsies of subjects. The pathway analysis revealed acute phase response signalling, cell-to-cell signalling and tissue development associations with proteins expressed in asthmatics compared to controls. The functions and pathways associated with placebo and budesonide treatment showed distinct differences, including the decreased association with acute phase proteins as a result of budesonide treatment compared to placebo. Conclusions Proteomic analysis of bronchial biopsy material can be used to identify and quantify proteins using highly sensitive technologies, without the need for pooling of samples from several patients. Distinct pathophysiological features of asthma can be

  12. Paediatric radiotherapy: Management and side effects

    International Nuclear Information System (INIS)

    Barare, C.


    This paper presents the general overview of management of children undergoing or who have undergone radiation therapy, and the associated effects. since the safe use of ionizing radiation in treatment of some children conditions is inevitable, the immediate and future effects need to be known and better understood for precise and accurate forecasting to benefit verses risk indicators. this is not withstanding the psychological trauma inflicted as some of the manifestations are visibly evident as the children grow

  13. What side effects are problematic for patients prescribed antipsychotic medication? The Maudsley Side Effects (MSE) measure for antipsychotic medication. (United States)

    Wykes, T; Evans, J; Paton, C; Barnes, T R E; Taylor, D; Bentall, R; Dalton, B; Ruffell, T; Rose, D; Vitoratou, S


    Capturing service users' perspectives can highlight additional and different concerns to those of clinicians, but there are no up to date, self-report psychometrically sound measures of side effects of antipsychotic medications. Aim To develop a psychometrically sound measure to identify antipsychotic side effects important to service users, the Maudsley Side Effects (MSE) measure. An initial item bank was subjected to a Delphi exercise (n = 9) with psychiatrists and pharmacists, followed by service user focus groups and expert panels (n = 15) to determine item relevance and language. Feasibility and comprehensive psychometric properties were established in two samples (N43 and N50). We investigated whether we could predict the three most important side effects for individuals from their frequency, severity and life impact. MSE is a 53-item measure with good reliability and validity. Poorer mental and physical health, but not psychotic symptoms, was related to side-effect burden. Seventy-nine percent of items were chosen as one of the three most important effects. Severity, impact and distress only predicted 'putting on weight' which was more distressing, more severe and had more life impact in those for whom it was most important. MSE is a self-report questionnaire that identifies reliably the side-effect burden as experienced by patients. Identifying key side effects important to patients can act as a starting point for joint decision making on the type and the dose of medication.

  14. Effects of a new glucocorticoid, oxazacort, on some variables connected with bone metabolism in man: a comparison with prednisone. (United States)

    Caniggia, A; Marchetti, M; Gennari, C; Vattimo, A; Nicolis, F B


    The urinary elimination of calcium, other electrolytes, and hydroxyproline and the oral absorption of 47Ca have been evaluated in three groups of 8 patients before and during a 15-day treatment with prednisone at daily doses of 25 and 50 mg and with oxazacort, a new glucocorticoid, at a daily dose of 50 mg. The results obtained demonstrate that oxazacort in short-term teatment with a high dose has no significant effect on the urinary elimination of calcium and hydroxypyroline in experimental conditions in which prednisone produces statistically significant and clinically relevant increase, both when given at the same dose and when given at half that dose. On the other hand, the oral absorption of 47Ca is decreased by oxazacort, but less than by prednisone at the same dose. As the antirheumatic activity of oxazacort appears to be only slightly lower than that of prednisone (activity ratio of about 0.84: 1), these findings may have interesting therapeutic implications.

  15. Membrane Transporters as Mediators of Cisplatin Effects and Side Effects

    Directory of Open Access Journals (Sweden)

    Giuliano Ciarimboli


    Full Text Available Transporters are important mediators of specific cellular uptake and thus, not only for effects, but also for side effects, metabolism, and excretion of many drugs such as cisplatin. Cisplatin is a potent cytostatic drug, whose use is limited by its severe acute and chronic nephro-, oto-, and peripheral neurotoxicity. For this reason, other platinum derivatives, such as carboplatin and oxaliplatin, with less toxicity but still with antitumoral action have been developed. Several transporters, which are expressed on the cell membranes, have been associated with cisplatin transport across the plasma membrane and across the cell: the copper transporter 1 (Ctr1, the copper transporter 2 (Ctr2, the P-type copper-transporting ATPases ATP7A and ATP7B, the organic cation transporter 2 (OCT2, and the multidrug extrusion transporter 1 (MATE1. Some of these transporters are also able to accept other platinum derivatives as substrate. Since membrane transporters display a specific tissue distribution, they can be important molecules that mediate the entry of platinum derivatives in target and also nontarget cells possibly mediating specific effects and side effects of the chemotherapeutic drug. This paper summarizes the literature on toxicities of cisplatin compared to that of carboplatin and oxaliplatin and the interaction of these platinum derivatives with membrane transporters.

  16. Managing Chemotherapy Side Effects: Sexual and Fertility Changes in Men (United States)

    ... I nstitute Managing Chemotherapy Side Effects Sexual and Fertility Changes in Men “I talked with my doctor ... learn what sexual changes or changes to your fertility you may have. The changes you may have ...

  17. Managing Chemotherapy Side Effects: Sexual and Fertility Changes in Women (United States)

    N ational C ancer I nstitute Managing Chemotherapy Side Effects Sexual and Fertility Changes in Women “Talk with your doctor before you start treatment. Ask how chemotherapy could affect your ability to have ...

  18. Effect of long-term inhalation of glucocorticoids on the level of leptin, IL-13 and IL-2 in bronchial asthmatic children

    International Nuclear Information System (INIS)

    Pan Jiongwei


    Objective: To determine the effect of long-term inhalation of glucocorticoids on the level of leptin, IL-13, and IL-2 in bronchial asthmatic patient. Methods: Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum IL-13 and IL-2 level in 60 healthy persons (normal control group) and 70 bronchial asthma patients untreated and 3, 6, 12 months post-treatment, meanwhile leptin was determined by radio immunoassay. Results: The serum levels of leptin, Il-13, and IL-2 in were significantly increased in patient with bronchial asthma compared with that in the normal control group. The serum levels of leptin, IL-13, and IL-2 in children with asthma were decreased gradually after inhaling glucocorticoids for 3 months (P<0.05). The treatment of inhaled glucocorticoids for 6 and 12 months can attenuate the elevation of leptin, IL-13, and IL-2 compared with that before the treatment. Conclusion: Long-term inhaled glucocorticoid is an important means for asthma, and the effects are related to the decrease of level of leptin, IL-13, and IL-2. (authors)

  19. Soy and phytoestrogens: possible side effects

    Directory of Open Access Journals (Sweden)

    Jargin, Sergei V.


    Full Text Available [english] Phytoestrogens are present in certain edible plants being most abundant in soy; they are structurally and functionally analogous to the estrogens. Phytoestrogens have been applied for compensation of hormone deficiency in the menopause. At the same time, soy products are used in infant food and other foodstuffs. Furthermore, soy is applied as animal fodder, so that residual phytoestrogens and their active metabolites such as equol can remain in meat and influence the hormonal balance of the consumers. There have been only singular reports on modified gender-related behavior or feminization in humans in consequence of soy consumption. In animals, the intake of phytoestrogens was reported to impact fertility, sexual development and behavior. Feminizing effects in humans can be subtle and identifiable only statistically in large populations.

  20. Beyond the technological fix. [Detrimental and unforeseen side effects

    Energy Technology Data Exchange (ETDEWEB)

    Weinberg, A.M.


    Both technological and social fixes are likely to bring with them deterimental and unforeseen side effects. Although the perceived side effects of nuclear energy can undoubtedly be ameliorated by improved technology, a permanent institutional infrastructure will probably also be required. It is pointed out that confinement of nuclear energy to relatively few large sites rather than many small sites may be a first step toward creating this permanent institutional infrastructure.

  1. Elementary affine $lambda$-calculus with multithreading and side effects


    Madet, Antoine; Amadio, Roberto M.


    Linear logic provides a framework to control the complexity of higher-order functional programs. We present an extension of this framework to programs with multithreading and side effects focusing on the case of elementary time. Our main contributions are as follows. First, we provide a new combinatorial proof of termination in elementary time for the functional case. Second, we develop an extension of the approach to a call-by-value $lambda$-calculus with multithreading and side effects. Thi...

  2. Side effects during subcutaneous immunotherapy in children with allergic diseases. (United States)

    Tophof, Max A; Hermanns, Anne; Adelt, Thomas; Eberle, Peter; Gronke, Christine; Friedrichs, Frank; Knecht, Roland; Mönter, Ernst; Schöpfer, Helmut; Schwerk, Nicolaus; Steinbach, Jörg; Umpfenbach, Hans-Ulrich; Weißhaar, Christian; Wilmsmeyer, Brigitte; Bufe, Albrecht


    Allergen-specific immunotherapy is the only causal form of therapy for IgE-mediated allergic diseases. Subcutaneous immunotherapy (SCIT) is considered safe and well tolerated in adults, yet there is less evidence of safety in the pediatric population. A non-interventional prospective observing longitudinal study was carried out to determine the incidence of local and systemic side effects by SCIT, routinely performed in pediatric patients. A total of 581 pediatric patients were observed in 18 study centers between March 2012 and October 2014, recording 8640 treatments and 10 015 injections. A total of 54.6% of the patients experienced immediate local side effects at least once; delayed local side effects were seen in 56.1%. Immediate systemic adverse reactions occurred in 2.2% of patients; 7.4% experienced delayed systemic side effects. However, severe systemic side effects (grade III in the classification of Ring and Messmer) were seen in 0.03% of all treatments, all appearing within 30 minutes after the injections. No grade IV reactions were observed. In addition, many potential risk factors were investigated, yet only a few were found to be associated with the occurrence of side effects. Subcutaneous immunotherapy is a safe form of therapy in pediatric patients, with similar rates of local side effects compared to adult patients and low rates of severe systemic side effects. However, local and systemic reactions occurring later than 30 minutes after injection were observed more often than expected, which makes it essential to be attentive on behalf of pediatricians, patients, and parents. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  3. CHECKPOINT INHIBITOR IMMUNE THERAPY: Systemic Indications and Ophthalmic Side Effects. (United States)

    Dalvin, Lauren A; Shields, Carol L; Orloff, Marlana; Sato, Takami; Shields, Jerry A


    To review immune checkpoint inhibitor indications and ophthalmic side effects. A literature review was performed using a PubMed search for publications between 1990 and 2017. Immune checkpoint inhibitors are designed to treat system malignancies by targeting one of three ligands, leading to T-cell activation for attack against malignant cells. These ligands (and targeted drug) include cytotoxic T-lymphocyte antigen-4 (CTLA-4, ipilimumab), programmed death protein 1 (PD-1, pembrolizumab, nivolumab), and programmed death ligand-1 (PD-L1, atezolizumab, avelumab, durvalumab). These medications upregulate the immune system and cause autoimmune-like side effects. Ophthalmic side effects most frequently manifest as uveitis (1%) and dry eye (1-24%). Other side effects include myasthenia gravis (n = 19 reports), inflammatory orbitopathy (n = 11), keratitis (n = 3), cranial nerve palsy (n = 3), optic neuropathy (n = 2), serous retinal detachment (n = 2), extraocular muscle myopathy (n = 1), atypical chorioretinal lesions (n = 1), immune retinopathy (n = 1), and neuroretinitis (n = 1). Most inflammatory side effects are managed with topical or periocular corticosteroids, but advanced cases require systemic corticosteroids and cessation of checkpoint inhibitor therapy. Checkpoint inhibitors enhance the immune system by releasing inhibition on T cells, with risk of autoimmune-like side effects. Ophthalmologists should include immune-related adverse events in their differential when examining cancer patients with new ocular symptoms.

  4. Effect of Bungee-carcass enrichment on behavior and fecal glucocorticoid metabolites in two species of zoo-housed Felids. (United States)

    Ruskell, Amber D; Meiers, Susan T; Jenkins, Sean E; Santymire, Rachel M


    Enrichment can improve animal physiological and psychological well-being. This study sought to promote more natural felid behavior and prevent development or incidence of stereotypies through the use of a feeding enrichment. Our objectives are to use fecal glucocorticoid metabolites values and behavioral observations to quantify the effectiveness of the enrichment device for two species of large cats, Bengal tiger (Panthera tigris tigris; n = 2) and cougar (Felis concolor; n = 2). The feeding enrichment, a white-tailed deer carcass flank securely attached to an AussieDog Products(©) Felid 120-cm bungee, was implemented twice for each individual separated by 1 month. Fecal samples were obtained from each felid and analyzed for pre- and post-enrichment fecal glucocorticoid metabolites (FGM) concentrations using a cortisol enzyme immunoassay. An ethogram with 12 mutual exclusive behavioral categories was utilized to record behavioral responses to the enrichment. Results demonstrate that: 1) there were no differences (P > 0.05) in FGMs for either species between pre- and post-enrichment; 2) pacing decreased (P = 0.025) and walking increased (P = 0.017) after exposure to enrichment in both cougars; and 3) tigers reduced (P = 0.025) 'other' behavioral category after the first enrichment exposure and laid down more (P = 0.025) after the second enrichment exposure. The neutral hormonal impact on the animals coupled with the behavioral changes indicates that this enrichment is successful at altering the animals' behavior without adding physiological stress to their environments. These findings, combined with the low cost and versatility of the enrichment, promote the use of this enrichment to enhance large felid enclosures. © 2014 Wiley Periodicals, Inc.

  5. Side effects after diagnostic lumbar puncture and lumbar iohexol myelography

    International Nuclear Information System (INIS)

    Sand, T.; Stovner, L.J.; Salvesen, R.; Dale, L.


    A prospective, controlled study was performed to compare side effect incidences after lumbar iohexol myelography (n=97) and diagnostic lumbar puncture (n=85). No significant side effect incidence differences (iohexol vs. controls) were found regarding number of patients with any side effect (63 vs. 73%), headache (44 vs. 54%), nausea, dizziness, visual, auditory, or psychic symptoms. Early-onset headache occurred significantly more often in the iohexol group (16 vs 5%), while postural headache occurred most frequently after lumbar puncture (25 vs. 41%). These results suggest that apart from the slight early-onset headache, most side effets after lumbar iohexol myelography are related to the puncture per se, not to the contrast agent. (orig.)

  6. Effect of the systemic versus inhalatory administration of synthetic glucocorticoids on the urinary steroid profile as studied by gas chromatography-mass spectrometry

    International Nuclear Information System (INIS)

    Mazzarino, Monica; Rossi, Francesca; Giacomelli, Laura; Botre, Francesco


    This paper presents a gas chromatography-mass spectrometry (GC-MS) study carried out on human urine to verify whether the administration of glucocorticoids can affect the urinary steroid profile, and especially the levels of endogenous glucocorticoids, androgens and their main metabolites. Betamethasone and beclomethasone, administered either systemically (per os or i.m.) or locally (by inhalation) have been studied. The determination of the urinary levels of endogenous glucocorticoids and androgens was carried out by GC-MS in electron impact ionization mode. Data were evaluated taking into account the baseline individual variability, and compared with values obtained on a control group. Detectable differences were recorded in the steroids metabolites excretion profiles between men and women. The circadian variability of the steroid profile was the same for both sexes, showing a maximum during the morning hours. After systemic treatment with synthetic glucocorticoids, the relative urinary concentrations of corticosteroids, androgens and of their metabolites were significantly altered, recording a transient decrease of the concentration of cortisol and tetrahydrocortisol and a parallel, although less pronounced, increase of the concentration of testosterone, epitestosterone and related androgenic steroids; while no effects were recorded if the administration was by inhalation

  7. Piper sarmentosum Effects on 11β-Hydroxysteroid Dehydrogenase Type 1 Enzyme in Serum and Bone in Rat Model of Glucocorticoid-Induced Osteoporosis. (United States)

    Mohamad Asri, Siti Fadziyah; Mohd Ramli, Elvy Suhana; Soelaiman, Ima Nirwana; Mat Noh, Muhamad Alfakry; Abdul Rashid, Abdul Hamid; Suhaimi, Farihah


    Glucocorticoid-induced osteoporosis is one of the common causes of secondary osteoporosis. Piper sarmentosum ( Ps ) extract possesses antioxidant and anti-inflammatory activities. In this study, we determined the correlation between the effects of Ps leaf water extract with the regulation of 11β-hydroxysteroid dehydrogenase (HSD) type 1 enzyme activity in serum and bone of glucocorticoid-induced osteoporotic rats. Twenty-four Sprague-Dawley rats were grouped into following: G1: sham-operated group administered with intramuscular vehicle olive oil and vehicle normal saline orally; G2: adrenalectomized (adrx) control group given intramuscular dexamethasone (120 μg/kg/day) and vehicle normal saline orally; G3: adrx group given intramuscular dexamethasone (120 μg/kg/day) and water extract of Piper sarmentosum (125 mg/kg/day) orally. After two months, the femur and serum were taken for ELISA analysis. Results showed that Ps leaf water extract significantly reduced the femur corticosterone concentration ( p < 0.05). This suggests that Ps leaf water extract was able to prevent bone loss due to long-term glucocorticoid therapy by acting locally on the bone cells by increasing the dehydrogenase action of 11β-HSD type 1. Thus, Ps may have the potential to be used as an alternative medicine against osteoporosis and osteoporotic fracture in patients on long-term glucocorticoid treatment.

  8. Effect of the systemic versus inhalatory administration of synthetic glucocorticoids on the urinary steroid profile as studied by gas chromatography-mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Mazzarino, Monica [Laboratorio Antidoping, Federazione Medico Sportiva Italiana, Largo Giulio Onesti 1, 00197 Rome (Italy); Rossi, Francesca [Laboratorio Antidoping, Federazione Medico Sportiva Italiana, Largo Giulio Onesti 1, 00197 Rome (Italy); Giacomelli, Laura [Dipartimento di Scienze Chirurgiche, Universita La Sapienza, Viale Regina Elena 324, 00161 Rome (Italy); Botre, Francesco [Laboratorio Antidoping, Federazione Medico Sportiva Italiana, Largo Giulio Onesti 1, 00197 Rome (Italy) and Dipartimento CGMIA, Universita La Sapienza, Via del Castro Laurenziano 9, 00161 Rome (Italy)]. E-mail:


    This paper presents a gas chromatography-mass spectrometry (GC-MS) study carried out on human urine to verify whether the administration of glucocorticoids can affect the urinary steroid profile, and especially the levels of endogenous glucocorticoids, androgens and their main metabolites. Betamethasone and beclomethasone, administered either systemically (per os or i.m.) or locally (by inhalation) have been studied. The determination of the urinary levels of endogenous glucocorticoids and androgens was carried out by GC-MS in electron impact ionization mode. Data were evaluated taking into account the baseline individual variability, and compared with values obtained on a control group. Detectable differences were recorded in the steroids metabolites excretion profiles between men and women. The circadian variability of the steroid profile was the same for both sexes, showing a maximum during the morning hours. After systemic treatment with synthetic glucocorticoids, the relative urinary concentrations of corticosteroids, androgens and of their metabolites were significantly altered, recording a transient decrease of the concentration of cortisol and tetrahydrocortisol and a parallel, although less pronounced, increase of the concentration of testosterone, epitestosterone and related androgenic steroids; while no effects were recorded if the administration was by inhalation.

  9. The Effect and Side Effect of Dipyridamole in Myocardial SPECT

    International Nuclear Information System (INIS)

    Yang, Hyung In; Lee, Dong Soo; Yeo, Jeong Suk; Bae, Sang Kyun; Choi, Chang Woon; Chung, June Key; Lee, Myung Chul; Koh, Chang Soon


    Dipyridamole is an agent that may be used to noninvasively evaluate coronary artery disease. The effect of dipyridamole infusion its generally related to its induced peripheral vasodilatory effect. In normal person, heart rate is generally increased slightly while blood pressure decrease, but the achieved double product and related myocardial oxygen consumption have no significant change. The purpose of this study is to examine the effect and side effect of dipyridamole, and to compare different response to dipyridamole among the patients. We evaluated 847 patients who underwent dipyridamole stress myocardial SPECT. 93.6% of them had induced hypotension 0.9% showed no change of blood pressure, 5.5% had increased blood pressure 8.3% had no change of pulse rate more than 10% of basal pulse rate. Among diabetes, 16.9% was not change of pulse rate, 6.7% in non-diabetes. There was no significant correlation between age and rate pressure product rest(RPPr), in patients without perfusion defects on SPECT(y=7.1x+48.4r=0.13 p>0.01). As increasing age, RPPs/RPPr was declined(y=-11.6x+68.9 r=0.17 p<0.01), similar results were obtained in patients with perfusion defect. The size of perfusion defect on myocardial SPECT have no correlation between RPPr and RPPs/RPPr. The side effects of dipyridamole included chest pain and chest tightness, headache, abdominal pain, dizziness, nausea, and dyspnea. As increasing age, dipyridamole-induced cardiac work at rest was increased, cardiac response to dipyridamole was decreased.

  10. Chronic anthropogenic noise disrupts glucocorticoid signaling and has multiple effects on fitness in an avian community. (United States)

    Kleist, Nathan J; Guralnick, Robert P; Cruz, Alexander; Lowry, Christopher A; Francis, Clinton D


    Anthropogenic noise is a pervasive pollutant that decreases environmental quality by disrupting a suite of behaviors vital to perception and communication. However, even within populations of noise-sensitive species, individuals still select breeding sites located within areas exposed to high noise levels, with largely unknown physiological and fitness consequences. We use a study system in the natural gas fields of northern New Mexico to test the prediction that exposure to noise causes glucocorticoid-signaling dysfunction and decreases fitness in a community of secondary cavity-nesting birds. In accordance with these predictions, and across all species, we find strong support for noise exposure decreasing baseline corticosterone in adults and nestlings and, conversely, increasing acute stressor-induced corticosterone in nestlings. We also document fitness consequences with increased noise in the form of reduced hatching success in the western bluebird ( Sialia mexicana ), the species most likely to nest in noisiest environments. Nestlings of all three species exhibited accelerated growth of both feathers and body size at intermediate noise amplitudes compared with lower or higher amplitudes. Our results are consistent with recent experimental laboratory studies and show that noise functions as a chronic, inescapable stressor. Anthropogenic noise likely impairs environmental risk perception by species relying on acoustic cues and ultimately leads to impacts on fitness. Our work, when taken together with recent efforts to document noise across the landscape, implies potential widespread, noise-induced chronic stress coupled with reduced fitness for many species reliant on acoustic cues.

  11. Glucocorticoids and hemopoietic stem cells

    International Nuclear Information System (INIS)

    Romashko, O.O.; Berin, G.I.


    Analyzing the data of home and foreign investigators the problems of the glucocorticoid effect on blood and bone marrow of experimental (including irradiated ones) animals are discussed. Considered are a character and mechanism of the adrenal cortex hormones effect on blood formation, as well as the effect of pharmacological doses of corticosteroids on CFU, their erythropoietic effect in physiological doses on a morphological picture of bone marrow after irradiation and subsequent introduction of hormones and the hormone effect on intensity of erythropoiesis recovery in irradiated mice. Presented are the experimental data on studying the effect of endogenic hypercorticoidism and a reduced level of endogenic corticosteroids on blood-forming stem cells in the irradiated mice and the data on the ACTH injection effect on CFU migration after irradiation. Evaluated are already available data and further investigations to ground advisability and conditions of using corticosteroids as well as determining rational therapeutic effects on secretion of endogenic glucocorticoids when treating blood system diseases

  12. Glucocorticoid programming of intrauterine development. (United States)

    Fowden, A L; Valenzuela, O A; Vaughan, O R; Jellyman, J K; Forhead, A J


    Glucocorticoids (GCs) are important environmental and maturational signals during intrauterine development. Toward term, the maturational rise in fetal glucocorticoid receptor concentrations decreases fetal growth and induces differentiation of key tissues essential for neonatal survival. When cortisol levels rise earlier in gestation as a result of suboptimal conditions for fetal growth, the switch from tissue accretion to differentiation is initiated prematurely, which alters the phenotype that develops from the genotype inherited at conception. Although this improves the chances of survival should delivery occur, it also has functional consequences for the offspring long after birth. Glucocorticoids are, therefore, also programming signals that permanently alter tissue structure and function during intrauterine development to optimize offspring fitness. However, if the postnatal environmental conditions differ from those signaled in utero, the phenotypical outcome of early-life glucocorticoid receptor overexposure may become maladaptive and lead to physiological dysfunction in the adult. This review focuses on the role of GCs in developmental programming, primarily in farm species. It examines the factors influencing GC bioavailability in utero and the effects that GCs have on the development of fetal tissues and organ systems, both at term and earlier in gestation. It also discusses the windows of susceptibility to GC overexposure in early life together with the molecular mechanisms and long-term consequences of GC programming with particular emphasis on the cardiovascular, metabolic, and endocrine phenotype of the offspring. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Ex vivo stimulation of whole blood as a means to determine glucocorticoid sensitivity

    Directory of Open Access Journals (Sweden)

    Burnsides C


    Full Text Available Christopher Burnsides,1,* Jacqueline Corry,1,* Jacob Alexander,1 Catherine Balint,1 David Cosmar,1 Gary Phillips,2 Jeanette I Webster Marketon1,31Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Internal Medicine, 2Center for Biostatistics, 3Institute for Behavioral Medicine Research, Wexner Medical Center at The Ohio State University, Columbus, OH, USA*JC and CB have equally contributed to this workPurpose: Glucocorticoids are commonly prescribed to treat a number of diseases including the majority of inflammatory diseases. Despite considerable interpersonal variability in response to glucocorticoids, an insensitivity rate of about 30%, and the risk of adverse side effects of glucocorticoid therapy, currently no assay is performed to determine sensitivity.Patients and methods: Here we propose a whole blood ex vivo stimulation assay to interrogate known glucocorticoid receptor (GR up- and downregulated genes to indicate glucocorticoid sensitivity. We have chosen to employ real-time PCR in order to provide a relatively fast and inexpensive assay.Results: We show that the GR-regulated genes, GILZ and FKBP51, are upregulated in whole blood by treatment with dexamethasone and that LPS-induction of cytokines (IL-6 and TNFα are repressed by dexamethasone in a dose responsive manner. There is considerable interpersonal variability in the maximum induction of these genes but little variation in the EC50 and IC50 concentrations. The regulation of the GR-induced genes differs throughout the day whereas the suppression of LPS-induced cytokines is not as sensitive to time of day.Conclusion: In all, this assay would provide a method to determine glucocorticoid receptor responsiveness in whole blood.Keywords: glucocorticoid responsiveness, gene regulation, nuclear receptor, GILZ, FKBP51, cytokines

  14. Early and Late Side Effects Associated with Photo(chemotherapy

    Directory of Open Access Journals (Sweden)

    Günseli Öztürk


    Full Text Available Phototherapy (PUVA ve UVB is a widely used and effective treatment method for a variety of dermatological diseases. Adverse effects associated with phototherapy can be classified as acute and chronic side effects. Acute side effects are mostly related with UV doses and drug intolerance, and include itching, nausea, erythema, edema and phototoxic reactions that sometimes blister formation is seen. Acute side effects are usually moderate and transient. Chronic side effects of phototherapy are early aging of skin, pigmentary changes and increased risk of skin carcinogenesis. The major concern is development of skin cancer. This risk is especially related to long-term exposure and high cumulative doses of PUVA, increase in time and is persistent. Therefore, risk/advantage ratio of phototherapy should be carefully evaluated in each patient, and treatment protocols with minimal UV exposure should be chosen according to the phototherapy guides. Follow-up of the patients for long terms is important in prevention or in reduction of this risk by detecting and treating any premalignant or malignant lesion early. In this article, acute and chronic side effects of phototherapy are reviewed with recent literature findings.

  15. Effects of habituation, research and ecotourism on faecal glucocorticoid metabolites in wild western lowland gorillas: Implications for conservation management

    Czech Academy of Sciences Publication Activity Database

    Shutt, K.; Heistermann, M.; Kasim, A.; Kalousová, B.; Profousová, I.; Petrželková, Klára Judita; Fuh, T.; Dicky, J.-F.; Bopalanzognako, J.-B.; Setchell, J. M.


    Roč. 172, April (2014), s. 72-79 ISSN 0006-3207 Institutional support: RVO:68081766 Keywords : Conservation * Ecotourism * Faecal-glucocorticoids * Habituation * Primate * Stress * Wildlife Subject RIV: EG - Zoology Impact factor: 3.762, year: 2014

  16. Long-term effects of glucocorticoids on function, quality of life, and survival in patients with Duchenne muscular dystrophy: a prospective cohort study. (United States)

    McDonald, Craig M; Henricson, Erik K; Abresch, Richard T; Duong, Tina; Joyce, Nanette C; Hu, Fengming; Clemens, Paula R; Hoffman, Eric P; Cnaan, Avital; Gordish-Dressman, Heather


    Glucocorticoid treatment is recommended as a standard of care in Duchenne muscular dystrophy; however, few studies have assessed the long-term benefits of this treatment. We examined the long-term effects of glucocorticoids on milestone-related disease progression across the lifespan and survival in patients with Duchenne muscular dystrophy. For this prospective cohort study, we enrolled male patients aged 2-28 years with Duchenne muscular dystrophy at 20 centres in nine countries. Patients were followed up for 10 years. We compared no glucocorticoid treatment or cumulative treatment duration of less than 1 month versus treatment of 1 year or longer with regard to progression of nine disease-related and clinically meaningful mobility and upper limb milestones. We used Kaplan-Meier analyses to compare glucocorticoid treatment groups for time to stand from supine of 5 s or longer and 10 s or longer, and loss of stand from supine, four-stair climb, ambulation, full overhead reach, hand-to-mouth function, and hand function. Risk of death was also assessed. This study is registered with, number NCT00468832. 440 patients were enrolled during two recruitment periods (2006-09 and 2012-16). Time to all disease progression milestone events was significantly longer in patients treated with glucocorticoids for 1 year or longer than in patients treated for less than 1 month or never treated (log-rank p<0·0001). Glucocorticoid treatment for 1 year or longer was associated with increased median age at loss of mobility milestones by 2·1-4·4 years and upper limb milestones by 2·8-8·0 years compared with treatment for less than 1 month. Deflazacort was associated with increased median age at loss of three milestones by 2·1-2·7 years in comparison with prednisone or prednisolone (log-rank p<0·012). 45 patients died during the 10-year follow-up. 39 (87%) of these deaths were attributable to Duchenne-related causes in patients with known duration of

  17. Side effects associated with current and prospective antimigraine pharmacotherapies. (United States)

    González-Hernández, Abimael; Marichal-Cancino, Bruno A; MaassenVanDenBrink, Antoinette; Villalón, Carlos M


    Migraine is a neurovascular disorder. Current acute specific antimigraine pharmacotherapies target trigeminovascular 5-HT 1B/1D , 5-HT 1F and CGRP receptors but, unfortunately, they induce some cardiovascular and central side effects that lead to poor treatment adherence/compliance. Therefore, new antimigraine drugs are being explored. Areas covered: This review considers the adverse (or potential) side effects produced by current and prospective antimigraine drugs, including medication overuse headache (MOH) produced by ergots and triptans, the side effects observed in clinical trials for the new gepants and CGRP antibodies, and a section discussing the potential effects resulting from disruption of the cardiovascular CGRPergic neurotransmission. Expert opinion: The last decades have witnessed remarkable developments in antimigraine therapy, which includes acute (e.g. triptans) and prophylactic (e.g. β-adrenoceptor blockers) antimigraine drugs. Indeed, the triptans represent a considerable advance, but their side effects (including nausea, dizziness and coronary vasoconstriction) preclude some patients from using triptans. This has led to the development of the ditans (5-HT 1F receptor agonists), the gepants (CGRP receptor antagonists) and the monoclonal antibodies against CGRP or its receptor. The latter drugs represent a new hope in the antimigraine armamentarium, but as CGRP plays a role in cardiovascular homeostasis, the potential for adverse cardiovascular side effects remains latent.

  18. Personal coping strategies for managing the side effects of ...

    African Journals Online (AJOL)

    This study describes the burden of side effects from ARV treatment as experienced by a sample of HIV/AIDS patients and identifies the personal strategies they used to cope with ... The most common adverse effects reported were tiredness, nightmares, mood swings, nausea, poor appetite, insomnia, vomiting and dizziness.

  19. Side effects of curative radiotherapy of the prostatic cancer

    International Nuclear Information System (INIS)

    Ziegler, F.; Metzger, H.; Huebener, K.H.; Kurtz, B.


    The side effects of primary percutaneous radiotherapy in 100 patients with prostatic cancer were evaluated and classified into different degrees of gravity. It was shown that especially chronic side effects are benign in most of all cases. Severe - but not vitally dangerous - complications in bladder and intestine are rare (3%); their percentage corresponds roughly to the average mortality rate of surgical intervention (radical prostatectomy). Contrary to operation, troubles of the sexual function appear only in one third of the patients. Taking into consideration the similar therapeutic results of intervention and radiotherapy, radiotherapy is more favorable with respect to side effects. This essential aspects should be considered when making a decision whether to apply a surgical or radiotherapeutic treatment. (orig.) [de

  20. Glucocorticoids are ineffective in alcoholic hepatitis

    DEFF Research Database (Denmark)

    Christensen, E; Gluud, C


    The aim of this study was to perform a meta-analysis of controlled clinical trials of glucocorticoid treatment in clinical alcoholic hepatitis, adjusting for prognostic variables and their possible interaction with therapy, because these trials have given appreciably different results. Weighted...... logistic regression analysis was applied using the summarised descriptive data (for example, % with encephalopathy, mean bilirubin value) of the treatment and control groups of 12 controlled trials that gave this information. Despite evidence of publication bias favouring glucocorticoid treatment, its...... overall effect on mortality was not statistically significant (p = 0.20)--the relative risk (steroid/control) was 0.78 (95% confidence intervals 0.51, 1.18). There was indication of interaction between glucocorticoid therapy and gender, but not encephalopathy. Thus, the effect of glucocorticoid treatment...

  1. Chronic stress effects on hippocampal structure and synaptic function: relevance for depression and normalization by anti-glucocorticoid treatment

    Directory of Open Access Journals (Sweden)

    Harmen J Krugers


    Full Text Available Exposure of an organism to environmental challenges activates two hormonal systems that help the organism to adapt. As part of this adaptational process, brain processes are changed such that appropriate behavioral strategies are selected that allow optimal performance at the short term, while relevant information is stored for the future. Over the past years it has become evident that chronic uncontrollable and unpredictable stress also exerts profound effects on structure and function of limbic neurons, but the impact of chronic stress is not a mere accumulation of repeated episodes of acute stress exposure. Dendritic trees are reduced in some regions but expanded in others, and cells are generally exposed to a higher calcium load upon depolarization. Synaptic strengthening is largely impaired. Neurotransmitter responses are also changed, e.g. responses to serotonin. We here discuss: a the main cellular effects after chronic stress with emphasis on the hippocampus, b how such effects could contribute to the development of psychopathology in genetically vulnerable individuals, and c their normalization by brief treatment with anti-glucocorticoids.

  2. The SIDER database of drugs and side effects

    DEFF Research Database (Denmark)

    Kuhn, Michael; Letunic, Ivica; Jensen, Lars Juhl


    , targets and side effects into a more complete picture of the therapeutic mechanism of actions of drugs and the ways in which they cause adverse reactions. To this end, we have created the SIDER ('Side Effect Resource', database of drugs and ADRs. The current release, SIDER 4......% of which can be compared to the frequency under placebo treatment. SIDER furthermore contains a data set of drug indications, extracted from the package inserts using Natural Language Processing. These drug indications are used to reduce the rate of false positives by identifying medical terms that do...

  3. The timeliness of patients reporting the side effects of chemotherapy. (United States)

    Olver, Ian; Carey, Mariko; Boyes, Allison; Hall, Alix; Noble, Natasha; Bryant, Jamie; Walsh, Justin; Sanson-Fisher, Rob


    To explore the actions cancer patients reported they would take in response to a range of common side effects of chemotherapy and whether these were considered appropriate based on current guidelines and evidence; and to explore the sociodemographic and cancer-related variables associated with patients selecting the appropriate action (immediate medical attention or reporting) for two potentially life-threatening side effects: fever, and unusual bleeding and bruising. Four hundred thirty-six medical oncology and haematology patients receiving chemotherapy completed two surveys to provide demographic, disease and treatment characteristics, and details on how they would respond if they experienced a range of specified side effects of chemotherapy (for example, nausea and vomiting, fatigue, and skin rash or nail changes). The proportion of patients reporting the appropriate action for each side effect was calculated. Multiple logistic regressions examined the patient demographic and cancer characteristics associated with selecting the appropriate action (seeking immediate medical attention) for two potentially life-threatening side effects of chemotherapy: high fever of 38 °C or more, and unusual bleeding or bruising. Two thirds of patients indicated that they would seek immediate medical attention for high fever (67%), but only 41% would seek immediate attention for bleeding or bruising. Cancer type and time since diagnosis were significantly associated with patients indicating that they would seek immediate medical attention for high fever; while time since diagnosis was the only variable significantly associated with patients reporting that they would seek immediate medical attention for unusual bleeding or bruising. For chronic side effects, like skin rash or nail changes, and tingling or numbness, which usually do not require urgent reporting, only between 12 and 16% would report them immediately. A significant proportion of patients reported that they would

  4. A glucocorticoid education group meeting: an effective strategy for improving self-management to prevent adrenal crisis. (United States)

    Repping-Wuts, Han J W J; Stikkelbroeck, Nike M M L; Noordzij, Alida; Kerstens, Mies; Hermus, Ad R M M


    To assess self-management in patients receiving glucocorticoid replacement therapy for primary or secondary adrenal failure before and 6 months after a glucocorticoid education group meeting. All patients with primary or secondary adrenal insufficiency, treated at the Department of Medicine, Division of Endocrinology, were invited by their endocrinologist to participate in a 3-h glucocorticoid education group meeting, consisting of a lecture about the disease and glucocorticoid doses adjustments in case of stress, followed by an instruction on how to inject hydrocortisone i.m. Finally, all participants could practise the i.m. injection and discuss their experience with (imminent) adrenal crises with other patients and the health care providers. Two weeks before the meeting and 6 months after the meeting, patients were asked to fill out a questionnaire about how they would act in six different conditions (e.g. febrile illness or vomiting). Of the 405 patients who were invited, 246 patients (61%) participated. At baseline the response by the participants on the questionnaire was 100% (n=246) and at follow-up 74% (n=183). At follow-up, significantly more participants (P≤0.005) gave the correct answers to how to act in different situations (e.g. self-administration of a glucocorticoid injection and phone contact in case of vomiting/diarrhoea without fever). Moreover, the use of self-management tools, such as having a 'medicine passport (travel document with information about disease and medication) (P=0.007) or SOS medallion (P=0.0007)', increased. A glucocorticoid education group meeting for patients with adrenal failure seems helpful to improve self-management and proper use of stress-related glucocorticoid dose adjustment.

  5. Molecular mechanisms of glucocorticoid receptor signaling

    Directory of Open Access Journals (Sweden)

    Marta Labeur


    Full Text Available This review highlights the most recent findings on the molecular mechanisms of the glucocorticoid receptor (GR. Most effects of glucocorticoids are mediated by the intracellular GR which is present in almost every tissue and controls transcriptional activation via direct and indirect mechanisms. Nevertheless the glucocorticoid responses are tissue -and gene- specific. GR associates selectively with corticosteroid ligands produced in the adrenal gland in response to changes of humoral homeostasis. Ligand interaction with GR promotes either GR binding to genomic glucocorticoid response elements, in turn modulating gene transcription, or interaction of GR monomers with other transcription factors activated by other signalling pathways leading to transrepression. The GR regulates a broad spectrum of physiological functions, including cell differentiation, metabolism and inflammatory responses. Thus, disruption or dysregulation of GR function will result in severe impairments in the maintenance of homeostasis and the control of adaptation to stress.


    Institute of Scientific and Technical Information of China (English)



    In the present study, the effect of electroecupuncture (EA) of acupoints of Ren, Spleen and Stomach Meridians on artificial abortion-induced side effects was observed in 100 artificial abortion women. In comparison with 45 artificial abortion women in the control group (who had not accepted EA treatment), EA possessed significant effects in relieving abdominal pain, reducing vaginal bleeding duration, lowering infection rate and infertility rate after artificial abortion operation.

  7. Statistical Significance and Effect Size: Two Sides of a Coin. (United States)

    Fan, Xitao

    This paper suggests that statistical significance testing and effect size are two sides of the same coin; they complement each other, but do not substitute for one another. Good research practice requires that both should be taken into consideration to make sound quantitative decisions. A Monte Carlo simulation experiment was conducted, and a…

  8. Patients knowledge about side effects of orthodontic treatment

    Directory of Open Access Journals (Sweden)

    Mia Amalia


    Full Text Available Disharmonious of dental arrangement can possibly create problems for the patient, such as the masticatory function, esthetical, psychosocial, and also the increased risk of trauma and periodontal disease. These are reasons for a patient to seek orthodontic treatment. The aim of this study was to know the patient’s knowledge about the side effects possibility that they receive during orthodontic treatment. The side effects include pain experience during orthodontic treatment, the possibility of soft tissue damage, email demineralization, loss of tooth vitality, periodontal problem, root resorption, temporomandibular joint disorders, and relapse. A cross-sectional study was conducted in patients who registered at Orthodontic Department, Faculty of Dentistry, Universitas Indonesia on March-June 2009. The participants of this study were 100 patients, consist of 86 women and 14 men respectively. Twenty-seven questions about the side-effects of orthodontic treatment were used to obtain the patient’s knowledge and the result was categorized into 3 groups, good, average and poor. The result of the study showed that patient’s knowledge about the side effect of pain experience during orthodontic treatment was average and the patient’s knowledge about the possibility of soft tissue damage due to orthodontic treatment was good. However, the patient’s knowledge about the possibility of email demineralization, loss of tooth vitality, periodontal problem, root resorption, temporomandibular joint disorders and relapse due to orthodontic treatment was low.

  9. Capecitabine induced hypertriglyceridaemia: An underreported and potentially severe side effect


    Tabchi S; Joseph K


    A 57 year-old-woman, with no previous history of dyslipedemia, developed severe hypertriglyceridemia while being treated with capecitabine for metastatic breast cancer. Capecitabine was not discontinued and serum triglyceride levels were normalized after 4 weeks of treatment with fenofibrate. Capecitabine induced hypertriglyceridemia, as a rare drug-related side effect, seems to be often overlooked by clinicians.

  10. Capecitabine induced hypertriglyceridaemia: An underreported and potentially severe side effect

    Directory of Open Access Journals (Sweden)

    Tabchi S


    Full Text Available A 57 year-old-woman, with no previous history of dyslipedemia, developed severe hypertriglyceridemia while being treated with capecitabine for metastatic breast cancer. Capecitabine was not discontinued and serum triglyceride levels were normalized after 4 weeks of treatment with fenofibrate. Capecitabine induced hypertriglyceridemia, as a rare drug-related side effect, seems to be often overlooked by clinicians.

  11. Tamoxifen treatment and gynecologic side effects : A review

    NARCIS (Netherlands)

    Mourits, MJE; De Vries, EGE; Willemse, PHB; Ten Hoor, KA; Hollema, H; Van der Zee, AGJ

    Objective: To review the literature on tamoxifen side effects on the female genital tract and psychosexual function in premenopausal and postmenopausal women. Data Sources: We used the English-language literature in MEDLINE and reference lists from selected articles. Search terms included:

  12. Safety and side effects of cannabidiol, a Cannabis sativa constituent. (United States)

    Bergamaschi, Mateus Machado; Queiroz, Regina Helena Costa; Zuardi, Antonio Waldo; Crippa, José Alexandre S


    Cannabidiol (CBD), a major nonpsychotropic constituent of Cannabis, has multiple pharmacological actions, including anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties. However, little is known about its safety and side effect profile in animals and humans. This review describes in vivo and in vitro reports of CBD administration across a wide range of concentrations, based on reports retrieved from Web of Science, Scielo and Medline. The keywords searched were "cannabinoids", "cannabidiol" and "side effects". Several studies suggest that CBD is non-toxic in non-transformed cells and does not induce changes on food intake, does not induce catalepsy, does not affect physiological parameters (heart rate, blood pressure and body temperature), does not affect gastrointestinal transit and does not alter psychomotor or psychological functions. Also, chronic use and high doses up to 1,500 mg/day of CBD are reportedly well tolerated in humans. Conversely, some studies reported that this cannabinoid can induce some side effects, including inhibition of hepatic drug metabolism, alterations of in vitro cell viability, decreased fertilization capacity, and decreased activities of p-glycoprotein and other drug transporters. Based on recent advances in cannabinoid administration in humans, controlled CBD may be safe in humans and animals. However, further studies are needed to clarify these reported in vitro and in vivo side effects.

  13. Glucocorticoids and fetal programming part 2: Mechanisms. (United States)

    Moisiadis, Vasilis G; Matthews, Stephen G


    The lifelong health of an individual is shaped during critical periods of development. The fetus is particularly susceptible to internal and external stimuli, many of which can alter developmental trajectories and subsequent susceptibility to disease. Glucocorticoids are critical in normal development of the fetus, as they are involved in the growth and maturation of many organ systems. The surge in fetal glucocorticoid levels that occurs in most mammalian species over the last few days of pregnancy is an important developmental switch leading to fundamental changes in gene regulation in many organs, including the brain. These changes are important for the transition to postnatal life. Exposure of the fetus to increased levels of glucocorticoids, resulting from maternal stress or treatment with synthetic glucocorticoids, can lead to long-term 'programming' of hypothalamic-pituitary-adrenal function and behaviours. Glucocorticoids act at multiple levels within the fetal brain. Growing evidence indicates that they can exert powerful effects on the epigenome, including on DNA methylation, histone acetylation and microRNA, to influence gene expression. Such influences probably represent a critical component of the 'programming' process, and might be partly responsible for the transgenerational effects of antenatal glucocorticoid exposure on neurologic, cardiovascular and metabolic function.

  14. The Role of MKP-1 in the Anti-Proliferative Effects of Glucocorticoids in Primary Rat Pre-Osteoblasts.

    Directory of Open Access Journals (Sweden)

    Micheline Sanderson

    Full Text Available Glucocorticoid (GC-induced osteoporosis has been attributed to a GC-induced suppression of pre-osteoblast proliferation. Our previous work identified a critical role for mitogen-activated protein kinase (MAPK phosphatase-1 (MKP-1 in mediating the anti-proliferative effects of GCs in immortalized pre-osteoblasts, but we subsequently found that MKP-1 null mice were not protected against the pathological effects of GCs on bone. In order to reconcile this discrepancy, we have assessed the effects of GCs on proliferation, activation of the MAPK ERK1/2 and MKP-1 expression in primary adipose-derived stromal cells (ADSCs and ADSC-derived pre-osteoblasts (ADSC-OBs. ADSCs were isolated by means of collagenase digestion from adipose tissue biopsies harvested from adult male Wistar rats. ADSC-OBs were prepared by treating ADSCs with osteoblast differentiation media for 7 days. The effects of increasing concentrations of the GC dexamethasone on basal and mitogen-stimulated cell proliferation were quantified by tritiated thymidine incorporation. ERK1/2 activity was measured by Western blotting, while MKP-1 expression was quantified on both RNA and protein levels, using semi-quantitative real-time PCR and Western blotting, respectively. GCs were strongly anti-proliferative in both naïve ADSCs and ADSC-OBs, but had very little effect on mitogen-induced ERK1/2 activation and did not upregulate MKP-1 protein expression. These findings suggest that the anti-proliferative effects of GCs in primary ADSCs and ADSC-OBs in vitro do not require the inhibition of ERK1/2 activation by MKP-1, which is consistent with our in vivo findings in MKP-1 null mice.

  15. Side effects of sugammadex use in pediatric patients

    Directory of Open Access Journals (Sweden)

    Sinem Sarı


    Full Text Available Objective: It is accepted that sugammadex show its effectsmore rapidly than the other neuromuscular block antagonistsin many studies, however especially in pediatriccases, it is seen that about its reliability and side effectsare limited in some studies. In our retrospective study,we aimed to present our experiences on sugammadexin terms of its side effects in the pediatric cases in ourhospital for a 1-year period.Methods: The patient files and intraoperative anesthesiarecords, postoperative 24th hour and after postoperative24th hour of the cases that underwent the application ofsugammadex under general anesthesia in pediatric surgeryoperating room in a 1-year period were analyzed.Results: Totally 46 patients received sugammadex; infants(28 days-23 months (n=24, children (2 years-11years (n=16 and adolescent (11-17 years (n=6. Noneof the patients showed hypersensitivity and statisticallysignificant side effects correlated to sugammadex.Conclusion: We think that sugammadex may open newdoors in pediatric patient group with its features. However,more documentation is needed about the safety inpediatric patient group, particularly in infants. J Clin ExpInvest 2013; 4 (3: 265-268Key words: Sugammadex, pediatric patient, side effect

  16. Effects of glucocorticoid combined with antibiotics on serum infection indexes, acute phase proteins and stress hormones in patients with severe pneumonia

    Directory of Open Access Journals (Sweden)

    Yang Yu


    Full Text Available Objective: To study the effects of glucocorticoid combined with antibiotics on serum infection indexes, acute phase proteins and stress hormones in patients with severe pneumonia. Methods: a total of 80 patients with severe pneumonia who were hospitalized between August 2014 and January 2017 were retrospectively analyzed and divided into the routine treatment group (n=46 who received conventional antibiotic therapy and the combined treatment group (n=34 who received glucocorticoid combined with antibiotic therapy, and the differences in infection indexes, acute proteins and stress hormones were compared between the two groups of patients before and after treatment. Results: The differences in serum levels of infection indexes, acute phase proteins and stress hormones were not statistically significant between the two groups before treatment. After 1 week of treatment, serum infection indexes CRP and PCT levels of observation group were lower than those of control group; serum acute phase proteins α1-AT, α1-AG and CER levels were lower than those of control group; serum stress hormones Cor, AngⅠ and AngⅡ levels were lower than those of control group. Conclusion: Glucocorticoid combined with antibiotics can effectively inhibit systemic infection and stress and optimize the illness in patients with severe pneumonia.

  17. Developmental programming of adult adrenal structure and steroidogenesis: effects of fetal glucocorticoid excess and postnatal dietary omega-3 fatty acids. (United States)

    Waddell, Brendan J; Bollen, Maike; Wyrwoll, Caitlin S; Mori, Trevor A; Mark, Peter J


    Fetal glucocorticoid excess programs a range of detrimental outcomes in the adult phenotype, at least some of which may be due to altered adult adrenocortical function. In this study, we determined the effects of maternal dexamethasone treatment on offspring adrenal morphology and function, as well as the interactive effects of postnatal dietary omega-3 (n-3) fatty acids. This postnatal dietary intervention has been shown to alleviate many of the programming outcomes in this model, but whether this is via the effects on adrenal function is unknown. Dexamethasone acetate was administered to pregnant rats (0.75 microg/ml drinking water) from day 13 to term. Cross-fostered offspring were raised on either a standard or high-n-3 diet. Adrenal weight (relative to body weight) at 6 months of age was unaffected by prenatal dexamethasone, regardless of postnatal diet, and stereological analysis showed no effect of dexamethasone on the volumes of adrenal components (zona glomerulosa, zona fasciculata/reticularis or adrenal medulla). Expression of key steroidogenic genes (Cyp11a1 and Star) was unaffected by either prenatal dexamethasone or postnatal diet. In contrast, adrenal expression of Mc2r mRNA, which encodes the ACTH receptor, was higher in offspring of dexamethasone-treated mothers, an effect partially attenuated by the Hn3 diet. Moreover, stress-induced levels of plasma and urinary corticosterone and urinary aldosterone were elevated in offspring of dexamethasone-treated mothers, indicative of enhanced adrenal responsiveness. In conclusion, this study shows that prenatal exposure to dexamethasone does not increase basal adrenocortical activity but does result in a more stress-responsive adrenal phenotype, possibly via increased Mc2r expression.

  18. Adrenal gland hypofunction in active polymyalgia rheumatica. effect of glucocorticoid treatment on adrenal hormones and interleukin 6. (United States)

    Cutolo, Maurizio; Straub, Rainer H; Foppiani, Luca; Prete, Camilla; Pulsatelli, Lia; Sulli, Alberto; Boiardi, Luigi; Macchioni, Pierluigi; Giusti, Massimo; Pizzorni, Carmen; Seriolo, Bruno; Salvarani, Carlo


    To evaluate hypothalamic-pituitary-adrenal (HPA) axis function in patients with recent onset polymyalgia rheumatica (PMR) not previously treated with glucocorticoids; and to detect possible correlations between adrenal hormone levels, interleukin 6 (IL-6), and other acute phase reactants at baseline and during 12 months of glucocorticoid treatment. Forty-one PMR patients of both sexes with recent onset disease and healthy sex and age matched controls were enrolled into a longitudinal study. Patients were monitored for serum cortisol, dehydroepiandrosterone sulfate (DHEAS), androstenedione (ASD), and clinical and laboratory measures of disease activity such as C-reactive protein and IL-6 concentrations at baseline and after 1, 3, 6, 9 and 12 months of glucocorticoid treatment. To assess dynamic HPA axis function, serum cortisol and plasma adrenocorticotropic hormone (ACTH) levels were evaluated in another 8 patients with recent onset PMR not treated with glucocorticoid in comparison to controls after challenge with ovine corticotropin releasing hormone (oCRH) test. In addition, serum cortisol and 17-hydroxyprogesterone (17-OHP) levels were evaluated after stimulation with low dose (1 microg) intravenous ACTH. Serum cortisol and ASD levels of all PMR patients at baseline did not differ from controls. During followup, cortisol levels dipped at one and 3 months. Serum DHEAS levels in all patients were significantly lower than in controls at baseline. In female PMR patients a significant correlation was found at baseline between cortisol levels and duration of disease. Serum concentrations of IL-6 at baseline were significantly higher in PMR patients than in controls. During 12 months of glucocorticoid treatment IL-6 levels dropped significantly at one month; thereafter they remained stable and did not increase again despite tapering of the glucocorticoid dose. After oCRH stimulation, a similar cortisol response was found in patients and controls. After ACTH

  19. The Economic Side Effects of Dangerous Drug Announcements.


    Dranove, David; Olsen, Chris


    Immediately prior to the passage of the 1962 Food and Drug Administration Amendments, there were a number of drugs recalled from markets worldwide. Announcements about the dangerous side effects of these drugs were associated with lower-share prices for their manufacturers and the industry as a whole. We perform several analyses to sort out alternative explanations for the observed declines. We find that dangerous drug announcements had no effect on the sales of other drugs and didn't affect ...

  20. Side effects due to irradiation of patients with mammary carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Hohenberg, G [Vienna Univ. (Austria). Strahlentherapeutische Klinik; Vienna Univ. (Austria). Inst. fuer Klinische Strahlenbiologie)


    The essay gives a brief survey of possible side effects occurring in irradiating patients with carinomas of the breast. Special attention is paid to difficulties concerning differential diagnosis and occurring in differentiating radiation reactions from secondary blastomas in the skeleton system. The problems concerning lymphatic oedema in the arm, and changes in the lungs and the effects of radiotherapy on the haematopoictic system are dealt with.

  1. Polyglycerol-opioid conjugate produces analgesia devoid of side effects. (United States)

    González-Rodríguez, Sara; Quadir, Mohiuddin A; Gupta, Shilpi; Walker, Karolina A; Zhang, Xuejiao; Spahn, Viola; Labuz, Dominika; Rodriguez-Gaztelumendi, Antonio; Schmelz, Martin; Joseph, Jan; Parr, Maria K; Machelska, Halina; Haag, Rainer; Stein, Christoph


    Novel painkillers are urgently needed. The activation of opioid receptors in peripheral inflamed tissue can reduce pain without central adverse effects such as sedation, apnoea, or addiction. Here, we use an unprecedented strategy and report the synthesis and analgesic efficacy of the standard opioid morphine covalently attached to hyperbranched polyglycerol (PG-M) by a cleavable linker. With its high-molecular weight and hydrophilicity, this conjugate is designed to selectively release morphine in injured tissue and to prevent blood-brain barrier permeation. In contrast to conventional morphine, intravenous PG-M exclusively activated peripheral opioid receptors to produce analgesia in inflamed rat paws without major side effects such as sedation or constipation. Concentrations of morphine in the brain, blood, paw tissue, and in vitro confirmed the selective release of morphine in the inflamed milieu. Thus, PG-M may serve as prototype of a peripherally restricted opioid formulation designed to forego central and intestinal side effects.

  2. Intranasal corticosteroids topical characteristics: side effects, formulation, and volume. (United States)

    Petty, David A; Blaiss, Michael S


    Guidelines from throughout the world recommend intranasal corticosteroids (INSs) as first-line treatment for most patients with moderate to severe allergic rhinitis. In general, limited comparative studies between different INSs have not indicated that one particular steroid moiety is more effective than another in controlling symptoms of allergic rhinitis. However, there are numerous formulations available with different ingredients that may influence a patient's adherence to treatment. This article looks at topical features with these agents, specifically, formulations, vehicles (aqueous vs aerosol), and side effects such as epistaxis and nasal septal perforation. Topical side effects are minimal with INSs with the exception of epistaxis. There are major differences in formulations, volumes, and vehicles between INSs, which could affect adherence. Physicians need to be aware of the different INS attributes to try to match patients' preferences in order to achieve better adherence and improve outcomes in sufferers of allergic rhinitis.

  3. Glucocorticoid actions on L6 muscle cells in culture

    International Nuclear Information System (INIS)

    Max, S.R.; Konagaya, M.; Konagaya, Y.


    Glucocorticoids exert striking catabolic effects on skeletal muscle. The mechanism of these effects remains poorly understood. They employed L6 muscle cells in culture to ascertain whether intracellular glucocorticoid receptors are involved. Studies in vitro permit exploration of glucocorticoid effects in the absence of other hormonal influences. L6 myoblasts were induced to form differentiated myotubes by growth in 1% serum. L6 myotubes were found to possess a high-affinity, limited capacity intracellular glucocorticoid receptor (apparent K/sub D/ = 5 x 10 -10 M; B/sub max/ = 711 pmols/g protein) with ligand specificity similar to that of glucocorticoid receptors from classical glucocorticoid target tissues. Further, [ 3 H] triamcinolone acetonide specific binding to L6 cell homogenates was blocked by a glucocorticoid antagonist, RU38486 (11β-(4-dimethyl-aminophenyl)-17β-hydroxy-17α-(prop-l-ynyl)-estra-4,9-dien-3-one). Dexamethasone (10 -5 M) caused a 10-fold increase in the activity of gluatmine synthetase in L6 myotubes; this increase was prevented by RU38486. Similarly, dexamethasone (10 -5 M) caused a 20% decrease in [ 12 C] leucine incorporation into protein. This effect also was blocked by RU38486. Thus, induction of glutamine synthetase and diminution of protein synthesis by dexamethasone require intracellular glucocorticoid receptors. L6 cells should prove particularly valuable for further studies of glucocorticoid actions on skeletal muscle

  4. Cutaneous side-effects during therapy of melanoma by vemurafenib

    Directory of Open Access Journals (Sweden)

    Anna Ankudowicz


    Full Text Available Introduction. Vemurafenib is a selective inhibitor of serine-threonine kinase BRAF used in the treatment of advanced melanoma with BRAF mutation. Effectiveness of this drug was confirmed in a large clinical trial, which led to the increase of its usage. During treatment with vemurafenib, particular attention should be paid to the numerous side effects, including those concerning the skin. Vemurafenib is highly toxic to the skin. Skin lesions occurring during the treatment of melanoma with this medicament can be divided into: early (observed 3 to 6 weeks after beginning treatment, late (observed 6 weeks after beginning treatment and hypersensitivity reactions to vemurafenib. Objective. Presentation of vemurafenib toxic effects on the skin and side effects that can be caused by this drug. Case report. We present a 58-year-old woman with metastatic melanoma who was treated with vemurafenib. During the course of therapy, numerous adverse reactions, including inflammatory tumors, emergence of a number of melanocytic naevi, skin horns, alopecia, hyperkeratosis of the palms and soles, and palmar erythrodysesthesia were observed. She was treated with anti-inflammatory drugs, an antibiotic, circulation-improving preparations and local moisturizing and keratolytic treatment. The patient remains under the care of oncologists and dermatologists. Conclusions. The new generation anti-cancer drugs bring hope for a cure or prolongation of life, but can also significantly reduce the quality of life by inducing both general and local adverse side effects. Oncological patients should also be taken care of by dermatologists.

  5. Ketamine for Pain Management-Side Effects & Potential Adverse Events. (United States)

    Allen, Cheryl A; Ivester, Julius R


    An old anesthetic agent, ketamine is finding new use in lower doses for analgesic purposes. There are concerns stemming from its potential side effects-specifically psychomimetic effects. These side effects are directly related to dose amount. The doses used for analgesic purposes are much lower than those used for anesthesia purposes. A literature review was performed to ascertain potential side effects and/or adverse events when using ketamine for analgesia purposes. The search included CINAHL, PubMed, and Ovid using the search terms "ketamine," "ketamine infusion," "pain," "adverse events," "practice guideline," and "randomized controlled trial." Searches were limited to full-text, peer-reviewed articles and systematic reviews. Initially 1,068 articles were retrieved. The search was then narrowed by using the Boolean connector AND with various search term combinations. After adjusting for duplication, article titles and abstracts were reviewed, leaving 25 articles for an in-depth analysis. Specific exclusion criteria were then applied. The literature supports the use of ketamine for analgesic purposes, and ketamine offers a nonopioid option for the management of some pain conditions. Because ketamine is still classified as an anesthetic agent, health care institutions should develop their own set of policies and protocols for the administration of ketamine. By using forethought and understanding of the properties of ketamine, appropriate care may be planned to mitigate potential side effects and adverse events so that patients are appropriately cared for and their pain effectively managed. Copyright © 2017 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

  6. Late side effects of Ruthenium 106 therapy for uveal melanomas

    International Nuclear Information System (INIS)

    Langmann, G.; Faulborn, J.; Poier, E.


    When effectiveness is evaluated in brachytherapy with Ruthenium 106 special emphasis has to be put on tumor destruction and late side effects responsible for the definite functional results. We evaluated the late side effects of 22 uveal melanomas, which had been treated with 106 Ruthenium plaques. The tumor prominences ranged from 3 to 10 mm, the diameter from 4 to 9 disc diameters. In 4 patients the tumor involved the posterior pole, 14 melanomas were located in the midperiphery of the fundus, 4 tumors were ciliary body melanomas. The total radiation dose of the apex ranged from 100 to 240 Gy with a corresponding dose to the sclera between 540 to 1000 Gy. Because of the short half life of the plaque we have been using different dose rates (1.6-11 Gy/h). In 17/22 eyes adequate regression could be achieved by Ruthenium therapy alone. In one case additional laser treatment of the macular part of the melanoma had to be performed, Gamma Knife therapy was necessary in another melanoma with 10 mm tumor prominence. 3 recurrences led to enucleation. The mean follow up was 4.8 years ranging from 1 to 7 years. In 2/22 patients opticopathy caused severe visual impairment, in another 2 patients radiation maculopathy and opticopathy was observed. 7/22 developed vasculopathy with neovascularization treated by photocoagulation. In one case of focal radiation maculopathy laser treatment could prevent further visual impairment. The following factors are responsible for a higher incidence of late side effects: 1. High dose rate of the plaques in combination with a high radiation dose to the sclera 2. Location of the tumor within a minimum distance of 2 disc diameters to the optic nerve or macula 3. Tumor location at the ciliary body Laser treatment in case of neovascularization and focal radiation maculopathy is the only effective treatment with regard to late side effects. Ischemic maculopathy and radiation opticopathy are responsible for late visual impairment. (authors)

  7. Nanomedicinal products: a survey on specific toxicity and side effects

    Directory of Open Access Journals (Sweden)

    Brand W


    Full Text Available Walter Brand,1,* Cornelle W Noorlander,1,* Christina Giannakou,2,3 Wim H De Jong,2 Myrna W Kooi,1 Margriet VDZ Park,2 Rob J Vandebriel,2 Irene EM Bosselaers,4 Joep HG Scholl,5 Robert E Geertsma2 1Centre for Safety of Substances and Products, 2Centre for Health Protection, National Institute for Public Health and the Environment (RIVM, Bilthoven, 3Department of Toxicogenomics, Maastricht University, Maastricht, 4Section Pharmacology, Toxicology and Pharmacokinetics, Medicines Evaluation Board (CBG-MEB, Utrecht, 5Research & Analysis Department, Netherlands Pharmacovigilance Centre Lareb, ‘s-Hertogenbosch, the Netherlands *These authors contributed equally to this work Abstract: Due to their specific properties and pharmacokinetics, nanomedicinal products (NMPs may present different toxicity and side effects compared to non-nanoformulated, conventional medicines. To facilitate the safety assessment of NMPs, we aimed to gain insight into toxic effects specific for NMPs by systematically analyzing the available toxicity data on approved NMPs in the European Union. In addition, by comparing five sets of products with the same active pharmaceutical ingredient (API in a conventional formulation versus a nanoformulation, we aimed to identify any side effects specific for the nano aspect of NMPs. The objective was to investigate whether specific toxicity could be related to certain structural types of NMPs and whether a nanoformulation of an API altered the nature of side effects of the product in humans compared to a conventional formulation. The survey of toxicity data did not reveal nanospecific toxicity that could be related to certain types of structures of NMPs, other than those reported previously in relation to accumulation of iron nanoparticles (NPs. However, given the limited data for some of the product groups or toxicological end points in the analysis, conclusions with regard to (a lack of potential nanomedicine-specific effects need to be

  8. Atenolol versus pindolol: side-effects in hypertension. (United States)

    Foerster, E C; Greminger, P; Siegenthaler, W; Vetter, H; Vetter, W


    This randomized crossover out-patient study was designed to compare the antihypertensive effects of atenolol and pindolol. After a wash-out period of two weeks in pretreated cases, 107 patients with essential hypertension were given either atenolol 100 mg once-daily or pindolol 20 mg slow release (SR) once-daily. Both atenolol and pindolol lowered blood pressure over the 24 week period. The diastolic blood pressure reduction was significantly greater (p less than 0.01) with atenolol than with pindolol. Before beta-blocker therapy, many patients had already experienced side-effects such as fatigue, sleep disturbances and dreams. This probably relates to the high sensitivity of the analogue scale used to assess side-effects, and to the high incidence of such symptoms in untreated patients. As the study progressed there was a reduction in the frequency of fatigue (p less than 0.03) and dreams (p less than 0.05) in both groups, whereas sleep disturbances significantly increased under pindolol (p less than 0.05) but decreased under atenolol (p less than 0.05). The only important side-effect difference between the two beta-blockers was the higher incidence of sleep disturbances with pindolol which may be due to the higher lipophilicity of this beta-blocker.

  9. Effects of histamine H1 receptor signaling on glucocorticoid receptor activity. Role of canonical and non-canonical pathways

    NARCIS (Netherlands)

    Zappia, C.D.; Granja-Galeano, G.; Fernández, N.; Shayo, C.; Davio, C.; Fitzsimons, C.P.; Monczor, F.


    Histamine H1 receptor (H1R) antagonists and glucocorticoid receptor (GR) agonists are used to treat inflammatory conditions such as allergic rhinitis, atopic dermatitis and asthma. Consistent with the high morbidity levels of such inflammatory conditions, these receptors are the targets of a vast

  10. Drug target identification using side-effect similarity

    DEFF Research Database (Denmark)

    Campillos, Monica; Kuhn, Michael; Gavin, Anne-Claude


    Targets for drugs have so far been predicted on the basis of molecular or cellular features, for example, by exploiting similarity in chemical structure or in activity across cell lines. We used phenotypic side-effect similarities to infer whether two drugs share a target. Applied to 746 marketed...... drugs, a network of 1018 side effect-driven drug-drug relations became apparent, 261 of which are formed by chemically dissimilar drugs from different therapeutic indications. We experimentally tested 20 of these unexpected drug-drug relations and validated 13 implied drug-target relations by in vitro...... binding assays, of which 11 reveal inhibition constants equal to less than 10 micromolar. Nine of these were tested and confirmed in cell assays, documenting the feasibility of using phenotypic information to infer molecular interactions and hinting at new uses of marketed drugs....

  11. May disordered protein cause serious drug side effect? (United States)

    Tou, Weng Ieong; Chen, Calvin Yu-Chian


    Insomnia is a self-reported disease where patients lose their ability to initiate and maintain sleep, leading to daytime performance impairment. Several drug targets to ameliorate insomnia symptoms have been discovered; however, these drug targets lead to serious side effects. Thus, we characterize the structural properties of these sleep-related receptors and the clock complex and discuss a possible drug design that will reduce side effects. Computational prediction shows that disordered property is shared. Over 30% of the structure of CLOCK, PER1/2/3, BMAL-1, muscarinic acetylcholine receptor-M1, melatonin receptor and casein kinase I are structurally disordered (the remaining proteins represent insomnia drugs might be closely related to the protein architecture. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Side effects of cancer therapies. International classification and documentation systems

    International Nuclear Information System (INIS)

    Seegenschmiedt, M.H.


    The publication presents and explains verified, international classification and documentation systems for side effects induced by cancer treatments, applicable in general and clinical practice and clinical research, and covers in a clearly arranged manner the whole range of treatments, including acute and chronic side effects of chemotherapy and radiotherapy, surgery, or combined therapies. The book fills a long-felt need in tumor documentation and is a major contribution to quality assurance in clinical oncology in German-speaking countries. As most parts of the book are bilingual, presenting German and English texts and terminology, it satisfies the principles of interdisciplinarity and internationality. The tabulated form chosen for presentation of classification systems and criteria facilitate the user's approach as well as application in daily work. (orig./CB) [de

  13. Linezolid induced black hairy tongue: a rare side effect. (United States)

    Aijazi, Ishma; Abdulla, Fadhil M


    Linezolid induced black hairy tongue is a rare benign reversible side effect of linezolid therapy. We report a case of a 61 year old diabetic lady who developed thrombocytopenia and black hairy discoloration of the tongue after being prescribed linezolid for foot osteomyelitis by the orthopaedic surgeon. Patient was encouraged to practice good oral dental hygiene, advised to use a soft tooth brush, regular mouth wash and baking soda containing tooth paste. The condition resolved four weeks after cessation of the antibiotic therapy.

  14. [Rare side effects in management of hyperthyroidism. Case report]. (United States)

    Sohár, Gábor; Kovács, Mónika; Györkös, Andrea; Gasztonyi, Beáta


    The authors present the case history of a patient suffering from hyperthyroidism. The diagnostic procedures revealed the presence of propylthiouracyl induced vasculitis with renal involvement, that recovered completely after the withdrawal of propylthiouracyl and corticosteroid treatment. Thereafter, the patient was treated with thiamasol, that caused agranulocytosis with fever. After transient litium carbonate therapy a succesful thyreoidectomy was performed. Cumulative serious side effects of antithyroid drugs are rare. This case highlights some of the challenges and complications encountered in the management of hyperthyroidism.

  15. Treatment of frozen shoulder with subcutaneous TNF-alpha blockade compared with local glucocorticoid injection

    DEFF Research Database (Denmark)

    Schydlowsky, Pierre; Szkudlarek, Marcin; Madsen, Ole Rintek


    We compared the effect of subcutaneous adalimumab injections with intraarticular glucocorticoid injections on frozen shoulder of 18 patients with unilateral joint involvement. Ten patients were randomised to subcutaneous injections with adalimumab and eight to intraarticular glucocorticoid inject...

  16. Anti-Inflammatory Modulation of Microglia via CD163-Targeted Glucocorticoids Protects Dopaminergic Neurons in the 6-OHDA Parkinson's Disease Model

    DEFF Research Database (Denmark)

    Tentillier, Noemie; Etzerodt, Anders; Olesen, Mads N


    intravenous CD163-targeted liposomes with Dexa for 3 weeks exhibited better motor performance than the control groups and had minimal glucocorticoid-driven side effects. Furthermore, these animals showed better survival of dopaminergic neurons in substantia nigra and an increased number of microglia...

  17. The Anabolic Effect of PTH on Bone is Attenuated by Simultaneous Glucocorticoid Treatment

    DEFF Research Database (Denmark)

    Oxlund, Hans; Ørtoft, Gitte; Thomsen, Jesper Skovhus


    . The pronounced anabolic effect of PTH injections on the endocortical and trabecular bone surfaces and less pronounced anabolic effect on periosteal surfaces were partially inhibited, but not prevented, by simultaneous GC treatment in old rats. Both cortical and cancellous bone possessed full mechanical...

  18. Cutaneous Side-effects of Immunomodulators in MS. (United States)

    Lebrun, C; Bertagna, M; Cohen, M


    Local skin reactions to subcutaneous injections of interferon beta (IFNB) or glatiramer acetate (GA) in multiple sclerosis (MS) are frequent, while severe cutaneous toxicity is rare. Both IFNB and GA are immunomodulatory drugs that have excellent safety profiles and are currently used for treatment of MS. They are administered by SC injection every other day for IFNB-1b, three times a week for IFNB-1a or daily for 20 mg for GA. The most common adverse effects, which occur in approximately 20-60% of patients, include pain, inflammation and induration at the injection sites. Another adverse effect is frank panniculitis followed by localized lipoatrophy at the injection sites, which has been described in half of the patients receiving GA injections but is also described with Subcutaneous IFNB-1b. No guidelines have yet been established for the treatment of skin reactions, which is a frequent point for discussion between neurologists and dermatologists. In addition, no treatment has been found for established lipoatrophy. The prevention and management of cutaneous side-effects include patient education, regular examination and manual palpation of all injection sites. Non-steroid antiinflammatory gels, local corticosteroids or endermology can help patients to resolve side-effects and to continue immunomodulatory treatment.

  19. Foreknowledge, Caring, and the Side-Effect Effect in Young Children (United States)

    Pellizzoni, Sandra; Siegal, Michael; Surian, Luca


    Children and adults often judge that the side effects of the actions of an uncaring story agent have been intentional if the effects are harmful but not if these are beneficial, creating an asymmetrical "side-effect" effect. The authors report 3 experiments involving 4- and 5-year-olds (N = 188) designed to clarify the role of foreknowledge and…

  20. Effects and side effects of inspections and accountability in education: an overview of empirical studies

    NARCIS (Netherlands)

    de Wolf, Inge F.; Janssens, F.J.G.

    This paper presents an overview of studies into effects and side effects of control mechanisms in education. We focus on effects and side effects of inspection visits and public performance indicators. A first conclusion is that the studies do not provide us with a clear answer to the question of

  1. Major side-effect of metrizamide. A case report

    Energy Technology Data Exchange (ETDEWEB)

    Sonoda, Hiroshi; Yoshida, Akimasa; Ohtsuka, Tadahiro; Takaki, Shuichi; Matsukado, Yasuhiko


    We have presented a case showing a major side-effect following metrizamide CT cisternography. The patient was a 68-year-old woman who developed anaphylactic shock and a disturbance of consciousness 6 hours after metrizamide CT cisternography with a dose of 850 mg of iodine. In spite of vigorous therapy, she died 60 hours after the shock. Examples of anaphylactic shock by metrizamide administered intrathecally have been reported very rarely. The pathogenesis of this case was presumably due to anaphylactic shock, but other etiological factors, such as a hypothalamic dysfunction due to a disturbed glucose metabolism of the brain, may also be suspected.

  2. Framing effects on expectations, decisions, and side effects experienced: the case of influenza immunization. (United States)

    O'Connor, A M; Pennie, R A; Dales, R E


    To examine the effects of using positive or negative frames to describe influenza vaccine benefits and side effects on patients' expectations, decisions, decisional conflict, and reported side effects. 292 previously unimmunized patients with chronic respiratory or cardiac disease were randomly assigned to receive benefit/risk information that was framed: (1) positively as the percentage who remain free of influenza and have no vaccine side effects, or (2) negatively as the percentage who acquire influenza and have vaccine side effects. Questionnaires elicited expectations, decisions, and decisional conflict. Vaccines were telephoned 3 days later for a self-report of local and systemic side effects and work absenteeism. Both groups had similar immunization rates and decisional conflict scores. The positive frame group had lower and more realistic expectations of vaccine side effects, fewer systemic side effects, and less work absenteeism (p framing did not influence patients' decisions, possibly due to the patients' awareness of their higher risk of influenza complications and greater desire to follow recommendations. The common practice of using negative frames when describing probabilities of side effects may need to be reexamined, considering its deleterious influence on self-reported side effects and work absenteeism.

  3. Effects of glucocorticoids on memory retrieval and reconsolidation of recent and remote memories in mice

    Directory of Open Access Journals (Sweden)

    Mansoreh Najjar


    Full Text Available Introduction: Previous studies demonstrated that the systemic injection of corticosterone impairs both retrieval and reconsolidation of fear memory in experimental animals. Here, we investigated whether these disrupting effects of corticosterone depend on the age (recent or remote of the memory in mice. Materials and Methods: Mice were trained and tested in an inhibitory avoidance task (50 Hz, 1mA for 3 S. Corticosterone (1, 3 and 10mg/kg injected 30 min before of retrieval test of either a two-day recent or 36-day remote memory. Memory retrieval tested during 10 min. For memory reconsolidation experiments immediately after memory reactivation of two-day recent or 36-day remote memories, mice received corticosterone (1, 3 and 10mg/kg or vehicle. Two, five, seven and nine days after memory reactivation, mice were returned to the context for 10 min, and step-through latency was recorded.Results: For memory retrieval, corticosterone impaired subsequent expression of both recent and remote memories. Similar effect was found on the reconsolidation of both memories. Additionally, a higher dose of corticosterone was needed to impair retrieval and reconsolidation of remote memory. No significant differences were found on the amount of memory deficit induced by corticosterone among memories with different age. Conclusion: Our data indicate that the efficacy of corticosterone in impairing retrieval and reconsolidation of fear memory is not limited to the age of memory

  4. Glucocorticoid-Induced Osteoporosis (United States)

    ... nervosa Cigarette smoking Alcohol abuse Low calcium and vitamin D, by low dietary intake or poor absorption in your gut Sedentary (inactive) lifestyle or immobility Certain medications besides glucocorticoids, including the following: excess thyroid hormone replacement the blood thinner heparin some ...

  5. Glucocorticoids and fetal programming part 1: Outcomes. (United States)

    Moisiadis, Vasilis G; Matthews, Stephen G


    Fetal development is a critical period for shaping the lifelong health of an individual. However, the fetus is susceptible to internal and external stimuli that can lead to adverse long-term health consequences. Glucocorticoids are an important developmental switch, driving changes in gene regulation that are necessary for normal growth and maturation. The fetal hypothalamic-pituitary-adrenal (HPA) axis is particularly susceptible to long-term programming by glucocorticoids; these effects can persist throughout the life of an organism. Dysfunction of the HPA axis as a result of fetal programming has been associated with impaired brain growth, altered behaviour and increased susceptibility to chronic disease (such as metabolic and cardiovascular disease). Moreover, the effects of glucocorticoid-mediated programming are evident in subsequent generations, and transmission of these changes can occur through both maternal and paternal lineages.

  6. Unintended Side Effects of Digital Transition: Perspectives of Japanese Experts

    Directory of Open Access Journals (Sweden)

    Masahiro Sugiyama


    Full Text Available The core of the digital transition is the representation of all kinds of real-world entities and processes and an increasing number of cognitive processes by digital information and algorithms on computers. These allow for seemingly unlimited storage, operation, retrieval, and transmission capacities that make digital tools economically available for all domains of society and empower human action, particularly combined with real-world interfaces such as displays, robots, sensors, 3D printers, etc. Digital technologies are general-purpose technologies providing unprecedented potential benefits for sustainability. However, they will bring about a multitude of potential unintended side effects, and this demands a transdisciplinary discussion on unwanted societal changes as well as a shift in science from analog to digital modeling and structure. Although social discourse has begun, the topical scope and regional coverage have been limited. Here, we report on an expert roundtable on digital transition held in February 2017 in Tokyo, Japan. Drawing on a variety of disciplinary backgrounds, our discussions highlight the importance of cultural contexts and the need to bridge local and global conversations. Although Japanese experts did mention side effects, their focus was on how to ensure that AI and robots could coexist with humans. Such a perspective is not well appreciated everywhere outside Japan. Stakeholder dialogues have already begun in Japan, but greater efforts are needed to engage a broader collection of experts in addition to stakeholders to broaden the social debate.

  7. Local Side Effects of Sublingual and Oral Immunotherapy. (United States)

    Passalacqua, Giovanni; Nowak-Węgrzyn, Anna; Canonica, Giorgio Walter

    Sublingual immunotherapy (SLIT) is increasingly used worldwide, and several products have been recently registered as drugs for respiratory allergy by the European Medicine Agency and the Food and Drug Administration. Concerning inhalant allergens, the safety of SLIT is overall superior to that of subcutaneous immunotherapy in terms of systemic adverse events. No fatality has been ever reported, and episodes of anaphylaxis were described only exceptionally. Looking at the historical and recent trials, most (>90%) adverse events are "local" and confined to the site of administration. For this reason, a specific grading system has been developed by the World Allergy Organization to classify and describe local adverse events. There is an increasing amount of literature concerning oral desensitization for food allergens, referred to as oral immunotherapy. Also, in this case, local side effects are predominant, although systemic adverse events are more frequent than with inhalant allergens. We review herein the description of local side effects due to SLIT, with a special focus on large trials having a declared sample size calculation. The use of the Medical Dictionary for Regulatory Activities nomenclature for adverse events is mentioned in this context, as recommended by regulatory agencies. It is expected that a uniform classification/grading of local adverse events will improve and harmonize the surveillance and reporting on the safety of SLIT. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  8. Glucocorticoids for the treatment of post-traumatic stress disorder and phobias: a novel therapeutic approach. (United States)

    de Quervain, Dominique J-F; Margraf, Jürgen


    Post-traumatic stress disorder (PTSD) and phobias belong to the most common anxiety disorders and to the most common psychiatric illnesses in general. In both disorders, aversive memories are thought to play an important role in the pathogenesis and symptomatology. Previously, we have reported that elevated glucocorticoid levels inhibit memory retrieval in animals and healthy humans. We therefore hypothesized that the administration of glucocorticoids might also inhibit the retrieval of aversive memory, thereby reducing symptoms in patients with PTSD and phobias. In recent clinical studies, we found first evidence to support this hypothesis. In patients with PTSD, low-dose cortisol treatment for one month reduced symptoms of traumatic memories without causing adverse side effects. Furthermore, we found evidence for a prolonged effect of the cortisol treatment. Persistent retrieval and reconsolidation of traumatic memories is a process that keeps these memories vivid and thereby the disorder alive. By inhibiting memory retrieval, cortisol may weaken the traumatic memory trace, and thus reduce symptoms even beyond the treatment period. In patients with social phobia, we found that a single oral administration of cortisone 1 h before a socio-evaluative stressor significantly reduced self-reported fear during the anticipation-, exposure-, and recovery phase of the stressor. In subjects with spider phobia, repeated oral administration of cortisol 1 h before exposure to a spider photograph induced a progressive reduction of stimulus-induced fear. This effect was maintained when subjects were exposed to the stimulus again two days after the last cortisol administration, indicating that cortisol facilitated the extinction of phobic fear. In conclusion, by a common mechanism of reducing the retrieval of aversive memories, glucocorticoids may be suited for the treatment of PTSD as well as phobias. More studies are needed to further evaluate the therapeutic efficacy of

  9. The Regulation of Muscle Mass by Endogenous Glucocorticoids

    Directory of Open Access Journals (Sweden)

    Daniel L Marks


    Full Text Available Glucocorticoids are highly conserved fundamental regulators of energy homeostasis. In response to stress in the form of perceived danger or acute inflammation, glucocorticoids are released from the adrenal gland, rapidly mobilizing energy from carbohydrate, fat and protein stores. In the case of inflammation, mobilized protein is critical for the rapid synthesis of acute phase reactants and an efficient immune response to infection. While adaptive in response to infection, chronic mobilization can lead to a p rofound depletion of energy stores. Skeletal muscle represents the major body store of protein, and can become substantially atrophied under conditions of chronic inflammation. Glucocorticoids elicit the atrophy of muscle by increasing the rate of protein degradation by the ubiquitin-proteasome system and autophagy lysosome system. Protein synthesis is also suppressed at the level of translational initiation, preventing the production of new myofibrillar protein. Glucocorticoids also antagonize the action of anabolic regulators such as insulin further exacerbating the loss of protein and muscle mass. The loss of muscle mass in the context of chronic disease is a key feature of cachexia and contributes substantially to morbidity and mortality. A growing body of evidence demonstrates that glucocorticoid signaling is a common mediator of wasting, irrespective of the underlying initiator or disease state. This review will highlight fundamental mechanisms of glucocorticoid signaling and detail the mechanisms of glucocorticoid-induced muscle atrophy. Additionally, the evidence for glucocorticoids as a driver of muscle wasting in numerous disease states will be discussed. Given the burden of wasting diseases and the nodal nature of glucocorticoid signaling, effective anti-glucocorticoid therapy would be a valuable clinical tool. Therefore, the progress and potential pitfalls in the development of glucocorticoid antagonists for muscle wasting will

  10. Contribution of glucocorticoids and glucocorticoid receptors to the regulation of neurodegenerative processes. (United States)

    Vyas, Sheela; Maatouk, Layal


    Isolation of glucocorticoids (GCs) from adrenal glands followed by synthesis led rapidly to their first clinical application, about 70 years ago, for treatment of rheumatoid arthritis. To this day GCs are used in diseases that have an inflammatory component. However, their use is carefully monitored because of harmful side effects. GCs are also synonymous with stress and adaptation. In CNS, GC binds and activates high affinity mineralocorticoid receptor (MR) and low affinity glucocorticoid receptor (GR). GR, whose expression is ubiquitous, is only activated when GC levels rise as during circadian peak and in response to stress. Numerous recent studies have yielded important and new insights on the mechanisms concerning pulsatile secretory pattern of GCs as well as various processes that tightly control their synthesis via hypothalamic-pituitary-adrenal (HPA) axis involving regulated release of corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) from hypothalamus and pituitary, respectively. GR modulates neuronal functions and viability through both genomic and non-genomic actions, and importantly its transcriptional regulatory activity is tightly locked with GC secretory pattern. There is increasing evidence pointing to involvement of GC-GR in neurodegenerative disorders. Patients with Alzheimer's or Parkinson's or Huntington's disease show chronically high cortisol levels suggesting changes occurring in controls of HPA axis. In experimental models of these diseases, chronic stress or GC treatment was found to exacerbate both the clinical symptoms and neurodegenerative processes. However, recent evidence also shows that GC-GR can exert neuroprotective effects. Thus, for any potential therapeutic strategies in these neurodegenerative diseases we need to understand the precise modifications both in HPA axis and in GR activity and find ways to harness their protective actions.

  11. Ocular side effect of tinidazole: A rare case report

    Directory of Open Access Journals (Sweden)

    Hina Kauser


    Full Text Available Ocular side effects in the form of punctate epithelial erosions with the use of tinidazole - a 5-nitroimidazole group of drugs is very rare. A 32-year-old male was prescribed tablet tinidazole for the treatment of amoebiasis but developed adverse effects in the form of blisters on both upper and lower lips with itching and burning sensation, itching and burning on penile and anal area associated with punctate epithelial erosions of cornea of both the eyes. All these are rare manifestations but punctate epithelial erosions of cornea has never been reported in the literature so far. Punctate epithelial erosions of cornea have not previously been reported and should be added to the list of complications of tinidazole. Hence, this case is being reported .

  12. Efectos del tratamiento con glucocorticoides durante el embarazo. A propósito de un caso

    Directory of Open Access Journals (Sweden)

    Diana Machado Ramírez


    Full Text Available The use of anti-inflammatory glucocorticoids may be necessary during pregnancy to treat some maternal conditions. Its effects in pregnant women are virtually the same as those described in the general adult population. Avascular necrosis is the death of bone tissue due to the interruption of the blood supply, and is mainly associated with the use of high-dose corticosteroids for long periods. We present the case of a 21-year-old patient at 34 weeks’ gestation admitted to the Intensive Care Unit of the Enrique Cabrera Hospital because of decompensated hypertension, obesity and congenital adrenal hyperplasia treated with suppressive doses of steroids. Subsequently, she was diagnosed with an avascular necrosis of both femoral heads. Iatrogenic Cushing’s syndrome resulting from all these factors was found. The newborn developed a seborrheic dermatitis of the scalp. The purpose of this presentation is to describe the side effects of the chronic use of glucocorticoids in pregnant women.

  13. Sex-specific effects of daily gavage with a mixed progesterone and glucocorticoid receptor antagonist on hypoxic ventilatory response in newborn rats. (United States)

    Fournier, Stéphanie; Doan, Van Diep; Joseph, Vincent


    We tested the hypothesis that daily gavage with mifepristone, a mixed progesterone/glucocorticoid receptor antagonist would alter hypoxic ventilatory response (HVR) in newborn male and female rats. Rats were treated with mifepristone (40µg/g/day), or vehicle between postnatal days 3-12, and used at 10-12 days of age to record baseline ventilatory and metabolic values using whole body plethysmography. HVR was tested by exposing the animals to 14% and 12% O(2) for 20 minutes each. HVR was enhanced by mifepristone treatment, mainly due to an effect on tidal volume that remained higher in mifepristone treated rats during both levels of hypoxic exposure. This effect was sex-specific being apparent only in male rats. In Vehicle treated rats, HVR was higher in females than in males, which was also due to a higher tidal volume in hypoxia (at 14 and 12% O(2)). We conclude that the activity of the progesterone and/or glucocorticoid receptors modulates respiratory control in rat pups, and that these effects are different in males and females.

  14. Gastrointestinal Side Effects of Antiarrhythmic Medications: A Review of Current Literature. (United States)

    Amjad, Waseem; Qureshi, Waqas; Farooq, Ali; Sohail, Umair; Khatoon, Salma; Pervaiz, Sarah; Narra, Pratyusha; Hasan, Syeda M; Ali, Farman; Ullah, Aman; Guttmann, Steven


    Antiarrhythmic drugs are commonly prescribed cardiac drugs. Due to their receptor mimicry with several of the gastrointestinal tract receptors, they can frequently lead to gastrointestinal side effects. These side effects are the most common reasons for discontinuation of these drugs by the patients. Knowledge of these side effects is important for clinicians that manage antiarrhythmic drugs. This review focuses on the gastrointestinal side effects of these drugs and provides a detailed up-to-date literature review of the side effects of these drugs. The review provides case reports reported in the literature as well as possible mechanisms that lead to gastrointestinal side effects.

  15. Using fecal glucocorticoids for stress assessment in Mourning Doves (United States)

    Washburn, Brian E.; Millspaugh, Joshua J.; Schulz, John H.; Jones, Susan B.; Mong, T.


    Fecal glucocorticoid assays provide a potentially useful, noninvasive means to study physiological responses of wildlife to various stressors. The objective of our study was to validate a method for measuring glucocorticoid metabolites in Mourning Dove (Zenaida macroura) feces. We validated the assay using standard procedures (e.g., parallelism, recovery of exogenous corticosterone) to demonstrate that the assay accurately and precisely measured glucocorticoid metabolites in Mourning Dove fecal extracts. We conducted adrenocorticotropin (ACTH) challenge experiments to validate the assay's ability to determine biologically important changes in fecal glucocorticoids. Fecal glucocorticoid levels increased significantly approximately 2-3 hr after administration of ACTH at 50 IU per kg body mass to wild Mourning Doves held in captivity. In contrast, fecal glucocorticoid metabolites did not increase in control birds, birds that received saline injections, or a lower dose of ACTH (1 IU per kg body mass). Variation in overall fecal glucocorticoid metabolite levels may have been influenced by season and the length of time birds were held in captivity. Non-invasive fecal glucocorticoid metabolite analyses, in combination with demographic information, may have considerable utility for monitoring the effects of natural and anthropogenic disturbances on Mourning Dove populations.

  16. Side-effects of improving CERN's spam filter

    CERN Multimedia


    To further improve the fight against spam (unsolicited email), CERN implemented in June a mechanism that returns electronic mail messages to the sender if the originating server is wrongly configured. This "reverse DNS lookup" is an increasingly widespread technique to identify whether the sending e-mail server is legitimate and has a valid host name. This change has nearly doubled the spam rejection efficiency at CERN. However, it has a known side-effect. A small number of correspondents are sending legitimate electronic mail to CERN from mail servers that are incorrectly configured (in technical terms, they do not have a reverse DNS registration). These persons will have their messages returned to them with an error message, provided their sender address is valid. The typical error message that the correspondent receives in such cases is "Relaying denied. No reverse DNS configured for IP". If a correspondent complains to you that emails they are sending you at CERN are being returned with...

  17. Measles Vaccine : A Study On Seroconversion And Side Effects

    Directory of Open Access Journals (Sweden)

    Malik Abida


    Full Text Available Research Question: 1. What is the extent of immune response of Edmonston Zagreb Strain in children? 2. What are the side effects of this vaccine? Objectives: 1. To follow up children after Edmonston Zagreb strain vaccination for evaluation of seroconverstion. Study: Cross sectional Setting: Well Baby Clinic of pediatrics OPD at J.N. Medical College, A.M.U., Aigarh (U.P participants: Children between 9-15 months. Sample Size: 100 consecutive children coming for routine immunization. Study variable: Malnourished and poor socio-economic status Outcome variable: Extent of seroconversion with no statistical significant difference between malnourished and socio-economically poor children. 26% showed minor self-limiting post vaccination reactions in all age groups. Recommendations: Edmonston Zagreb measles vaccine is recommended since it has very good immunogenic activity and post vaccination reactions.

  18. Price Competition in Two-Sided Markets with Heterogeneous Consumers and Network Effects

    NARCIS (Netherlands)

    Filistrucchi, L.; Klein, T.J.

    We model a two-sided market with heterogeneous customers and two heterogeneous network effects. In our model, customers on each market side care differently about both the number and the type of customers on the other side. Examples of two-sided markets are online platforms or daily newspapers. In

  19. Tripeptide tyroserleutide plus doxorubicin: therapeutic synergy and side effect attenuation

    International Nuclear Information System (INIS)

    Zhu, Zhi-feng; Yao, Zhi; Chen, Li-juan; Lu, Rong; Jia, Jing; Liang, Yu; Xu, Qiong; Zhou, Chun-lei; Wang, Li; Wang, Song


    Tripeptide tyroserleutide (YSL) is a novel small molecule anti-tumor polypeptide that has been shown to inhibit the growth of human liver cancer cells. In this study, we investigated the effects of YSL plus doxorubicin on the growth of human hepatocellular carcinoma BEL-7402 cells that had been transplanted into nude mice. Nude mice bearing human hepatocellular carcinoma BEL-7402 tumors were treated with successive intraperitoneal injections of saline; low-, mid-, or high-dose doxorubicin; or low-, mid-, or high-dose doxorubicin plus YSL. Effects on the weight and volume of the tumors were evaluated. Co-administration of YSL and high-dose doxorubicin (6 mg/kg every other day) prolonged the survival time of tumor-bearing mice as compared to high-dose doxorubicin alone. As well, the anti-tumor effects of mid- and low-dose doxorubicin (2 and 0.7 mg/kg every other day, respectively) were enhanced when supplemented with YSL; the tumor growth inhibition rates for YSL plus doxorubicin were greater than the inhibition rates for the same dosages of doxorubicin alone. The combination of YSL and doxorubicin decreased chemotherapy-associated weight loss, leukocyte depression, and heart, liver, and kidney damage as compared to doxorubicin alone. The combination of YSL plus doxorubicin enhances the anti-tumor effect and reduces the side effects associated with doxorubicin chemotherapy

  20. Minoxidil use in dermatology, side effects and recent patents. (United States)

    Rossi, Alfredo; Cantisani, Carmen; Melis, Luca; Iorio, Alessandra; Scali, Elisabetta; Calvieri, Stefano


    Minoxidil, a vasodilator medication known for its ability to slow or stop hair loss and promote hair regrowth, was first introduced, exclusively as an oral drug, to treat high blood pressure. It was however discovered to have the important side-effect of increasing growth or darkening of fine body hairs; this led to the development of a topical formulation as a 2% concentration solution for the treatment of female androgenic alopecia or 5% for treating male androgenic alopecia. Measurable changes disappear within months after discontinuation of treatment. The mechanism by which it promotes hair growth is not fully understood. Minoxidil is a potassium channel opener, causing hyperpolarization of cell membranes and it is also a vasodilator, it is speculated that, by widening blood vessels and opening potassium channels, it allows more oxygen, blood and nutrients to the follicle. This can also cause follicles in the telogen phase to shed, usually soon to be replaced by new, thicker hairs in a new anagen phase. It needs to be applied regularly, once or twice daily, for hair gained to be maintained, and side effects are common. The most common adverse reactions of the topical formulation are limited to irritant and allergic contact dermatitis on the scalp. There have been cases of allergic reactions to the nonactive ingredient propylene glycol, which is found in some topical solution especially if they are galenic. Increased hair loss which can occur during Minoxidil use, is due to the synchronization of the hair cycle that the treatment induces. In this review, we described its mechanism of action, use in dermatology and some patents related to alternative treatment of allergic reactions due to its use.

  1. Side effects of ionizing radiation on healthy tissues and organs at risk

    International Nuclear Information System (INIS)

    Cosset, J.M.


    Ionizing radiations induce cell death, causing deterministic or stochastic side-effects. This paper briefly summarizes the biological mechanisms of early and late side-effects of ionizing radiations on healthy tissue. (author)

  2. Systems Biology of Glucocorticoids in Muscle Disease (United States)


    Introduction Duchenne muscular dystrophy (DMD) is the most common and incurable muscular dystrophy of childhood. Muscle regeneration fails with...SUBJECT TERMS Duchenne Muscular dystrophy , Glucocorticoids, Systems biology, Drug mechanism 16. SECURITY CLASSIFICATION OF: U 17. LIMITATION...better targeted and more effective therapies for Duchenne muscular dystrophy dynamically. This MDA grant proposal is led by Dr. Eric Hoffman, and it

  3. Drug side effect extraction from clinical narratives of psychiatry and psychology patients. (United States)

    Sohn, Sunghwan; Kocher, Jean-Pierre A; Chute, Christopher G; Savova, Guergana K


    To extract physician-asserted drug side effects from electronic medical record clinical narratives. Pattern matching rules were manually developed through examining keywords and expression patterns of side effects to discover an individual side effect and causative drug relationship. A combination of machine learning (C4.5) using side effect keyword features and pattern matching rules was used to extract sentences that contain side effect and causative drug pairs, enabling the system to discover most side effect occurrences. Our system was implemented as a module within the clinical Text Analysis and Knowledge Extraction System. The system was tested in the domain of psychiatry and psychology. The rule-based system extracting side effects and causative drugs produced an F score of 0.80 (0.55 excluding allergy section). The hybrid system identifying side effect sentences had an F score of 0.75 (0.56 excluding allergy section) but covered more side effect and causative drug pairs than individual side effect extraction. The rule-based system was able to identify most side effects expressed by clear indication words. More sophisticated semantic processing is required to handle complex side effect descriptions in the narrative. We demonstrated that our system can be trained to identify sentences with complex side effect descriptions that can be submitted to a human expert for further abstraction. Our system was able to extract most physician-asserted drug side effects. It can be used in either an automated mode for side effect extraction or semi-automated mode to identify side effect sentences that can significantly simplify abstraction by a human expert.

  4. A unified frame of predicting side effects of drugs by using linear neighborhood similarity. (United States)

    Zhang, Wen; Yue, Xiang; Liu, Feng; Chen, Yanlin; Tu, Shikui; Zhang, Xining


    Drug side effects are one of main concerns in the drug discovery, which gains wide attentions. Investigating drug side effects is of great importance, and the computational prediction can help to guide wet experiments. As far as we known, a great number of computational methods have been proposed for the side effect predictions. The assumption that similar drugs may induce same side effects is usually employed for modeling, and how to calculate the drug-drug similarity is critical in the side effect predictions. In this paper, we present a novel measure of drug-drug similarity named "linear neighborhood similarity", which is calculated in a drug feature space by exploring linear neighborhood relationship. Then, we transfer the similarity from the feature space into the side effect space, and predict drug side effects by propagating known side effect information through a similarity-based graph. Under a unified frame based on the linear neighborhood similarity, we propose method "LNSM" and its extension "LNSM-SMI" to predict side effects of new drugs, and propose the method "LNSM-MSE" to predict unobserved side effect of approved drugs. We evaluate the performances of LNSM and LNSM-SMI in predicting side effects of new drugs, and evaluate the performances of LNSM-MSE in predicting missing side effects of approved drugs. The results demonstrate that the linear neighborhood similarity can improve the performances of side effect prediction, and the linear neighborhood similarity-based methods can outperform existing side effect prediction methods. More importantly, the proposed methods can predict side effects of new drugs as well as unobserved side effects of approved drugs under a unified frame.

  5. Immediate side effects of stereotactic radiotherapy and radiosurgery

    International Nuclear Information System (INIS)

    Werner-Wasik, Maria; Rudoler, Shari; Preston, Peter E.; Hauck, Walter W.; Downes, Beverly M.; Leeper, Dennis; Andrews, David; Corn, Benjamin W.; Curran, Walter J.


    Purpose: Despite increased utilization of fractionated stereotactic radiation therapy (SRT) or stereotactic radiosurgery (SRS), the incidence and nature of immediate side effects (ISE) associated with these treatment techniques are not well defined. We report immediate side effects from a series of 78 patients. Materials and Methods: Intracranial lesions in 78 adult patients were treated with SRT or SRS, using a dedicated linear accelerator. Those lesions included 13 gliomas, 2 ependymomas, 19 metastatic tumors, 15 meningiomas, 12 acoustic neuromas, 4 pituitary adenomas, 1 optic neuroma, 1 chondrosarcoma, and 11 arteriovenous malformations (AVM). SRT was used in 51 and SRS in 27 patients. Mean target volume was 9.0 cc. Eleven patients received prior external-beam radiation therapy within 2 months before SRT/SRS. Any side effects occurring during and up to 2 weeks after the course of radiation were defined as ISE and were graded as mild, moderate, or severe. The incidence of ISE and the significance of their association with several treatment and pretreatment variables were analyzed. Results: Overall, 28 (35%) of 78 patients experienced one or more ISE. Most of the ISE (87%) were mild, and consisted of nausea (in 5), dizziness/vertigo (in 5), seizures (in 6), and new persistent headaches (in 17). Two episodes of worsening neurological deficit and 2 of orbital pain were graded as moderate. Two patients experienced severe ISE, requiring hospitalization (1 seizure and 1 worsening neurological deficit). ISE in 6 cases prompted computerized tomography of the brain, which revealed increased perilesional edema in 3 cases. The incidence of ISE by diagnosis was as follows: 46% (6 of 13) for gliomas, 50% (6 of 12) for acoustic neuromas, 36% (4 of 11) for AVM, 33% (5 of 15) for meningiomas, and 21% (4 of 19) for metastases. A higher incidence of dizziness/vertigo (4 of 12 = 33%) was seen among acoustic neuroma patients than among other patients (p < 0.01). There was no


    Directory of Open Access Journals (Sweden)

    Enas ELsayed Mohamed Abutaleb


    Full Text Available Background: Control of balance is a complex motor skill that involves integration of sensory inputs and the planning and execution of flexible movement patterns. Carrying side packs is famous in our society especially shoulder side packs. Most students carry shoulder side packs and they don't care about the way to carry them to be more balanced. The purpose of the study is to investigate the effect of carrying shoulder side pack on dynamic postural stability and to determine the best way of carrying a shoulder side pack either on the dominant side or non-dominant side that doesn’t affect dynamic postural stability in young healthy female. Methods: Sixty female volunteers aged from 18 to 25 years old participated in the study. Biodex balance system was used to measure the dynamic postural stability in three different occasions (without carrying a shoulder side pack, with carrying a shoulder side pack on the dominant side, and on the non-dominant side with a rest period in between. Results: Repeated measure analysis of variance (ANOVA followed by Bonferroni post hoc test were used to compare dynamic posture balance without carrying and during carrying a shoulder side pack on dominant and non-dominant sides. Analysis revealed that overall, anteroposterior and mediolateral stability indexes reduced significantly (P<0.0001 when carrying shoulder side pack on dominant side in comparison with when carrying shoulder side pack on non-dominant side and without carrying bag. Conclusion: It was concluded that carrying a shoulder side pack on the non-dominant side didn't disturb the postural stability when compared to carrying on the dominant side so, we recommend the students to carry shoulder side packs on the non-dominant side.

  7. Statin Therapy: Review of Safety and Potential Side Effects. (United States)

    Ramkumar, Satish; Raghunath, Ajay; Raghunath, Sudhakshini


    Hydroxymethyl glutaryl coenzyme A reductase inhibitors, commonly called statins, are some of the most commonly prescribed medications worldwide. Evidence suggests that statin therapy has significant mortality and morbidity benefit for both primary and secondary prevention from cardiovascular disease. Nonetheless, concern has been expressed regarding the adverse effects of long term statin use. The purpose of this article was to review the current medical literature regarding the safety of statins. Major trials and review articles on the safety of statins were identified in a search of the MEDLINE database from 1980 to 2016, which was limited to English articles. Myalgia is the most common side effect of statin use, with documented rates from 1-10%. Rhabdomyolysis is the most serious adverse effect from statin use, though it occurs quite rarely (less than 0.1%). The most common risk factors for statin-related myopathy include hypothyroidism, polypharmacy and alcohol abuse. Derangement in liver function tests is common, affecting up to 1% of patients; however, the clinical significance of this is unknown. Some statin drugs are potentially diabetogenic and the risk appears to increase in those patients on higher doses. Pitavastatin has not been associated with increased risk of diabetes. Statins have not been proven to increase the risk of malignancy, dementia, mood disorders or acute interstitial nephritis. However, statins do have multiple drug interactions, primarily those which interact with the cytochrome p450 enzyme group. Overall, statin drugs appear to be safe for use in the vast majority of patients. However, patients with multiple medical co-morbidities are at increased risk of adverse effects from long-term statin use.

  8. On the retinal toxicity of intraocular glucocorticoids. (United States)

    Torriglia, Alicia; Valamanesh, Fatemeh; Behar-Cohen, Francine


    Corticosteroids are hormones involved in many physiological responses such as stress, immune modulation, protein catabolism and water homeostasis. The subfamily of glucocorticoids is used systemically in the treatment of inflammatory diseases or allergic reactions. In the eye, glucocorticoides are used to treat macular edema, inflammation and neovascularization. The most commonly used glucocorticoid is triamcinolone acetonide (TA). The pharmaceutical formulation of TA is not adapted for intravitreal administration but has been selected by ophthalmologists because its very low intraocular solubility provides sustained effect. Visual benefits of intraocular TA do not clearly correlate with morpho-anatomical improvements, suggesting potential toxicity. We therefore studied, non-common, but deleterious effects of glucocorticoids on the retina. We found that the intravitreal administration of TA is beneficial in the treatment of neovascularization because it triggers cell death of endothelial cells of neovessels by a caspase-independent mechanism. However, this treatment is toxic for the retina because it induces a non-apoptotic, caspase-independent cell death related to paraptosis, mostly in the retinal pigmented epithelium cells and the Müller cells. Copyright © 2010 Elsevier Inc. All rights reserved.

  9. Are BDNF and glucocorticoid activities calibrated? (United States)

    Jeanneteau, Freddy; Chao, Moses V.


    One hypothesis to account for the onset and severity of neurological disorders is the loss of trophic support. Indeed, changes in the levels and activities of brain-derived neurotrophic factor (BDNF) occur in numerous neurodegenerative and neuropsychiatric diseases. A deficit promotes vulnerability whereas a gain of function facilitates recovery by enhancing survival, synapse formation and synaptic plasticity. Implementation of ‘BDNF therapies’, however, faces numerous methodological and pharmacokinetic issues. Identifying BDNF mimetics that activate the BDNF receptor or downstream targets of BDNF signaling represent an alternative approach. One mechanism that shows great promise is to study the interplay of BDNF and glucocorticoid hormones, a major class of natural steroid secreted during stress reactions and in synchrony with circadian rhythms. While small amounts of glucocorticoids support normal brain function, excess stimulation by these steroid hormones precipitate stress-related affective disorders. To date, however, because of the paucity of knowledge of underlying cellular mechanisms, deleterious effects of glucocorticoids are not prevented following extreme stress. In the present review, we will discuss the complementary roles share by BDNF and glucocorticoids in synaptic plasticity, and delineate possible signaling mechanisms mediating these effects. PMID:23022538

  10. Steam inhalation therapy: severe scalds as an adverse side effect (United States)

    Baartmans, Martin; Kerkhof, Evelien; Vloemans, Jos; Dokter, Jan; Nijman, Susanne; Tibboel, Dick; Nieuwenhuis, Marianne


    Background Steam inhalation therapy is often recommended in the treatment of a common cold. However, it has no proven benefit and may in fact have serious adverse side effects in terms of burn injuries. Aim To quantify the human and economic costs of steam inhalation therapy in terms of burn injury. Design and setting A prospective database study of all patients admitted to the burn centres (Beverwijk, Groningen, Rotterdam) and the hospital emergency departments in the Netherlands. Method Number and extent of burn injuries as a result of steam inhalation therapy were analysed, as well as an approximation made of the direct costs for their medical treatment. Results Annually, on average three people are admitted to in one of the Dutch burn centres for burns resulting from steam inhalation therapy. Most victims were children, and they needed skin grafting more often than adults. The total direct medical costs for burn centre and emergency department treatment were €115 500 (£93 000), emotional costs are not reflected. Conclusion As steam inhalation therapy has no proven benefit and the number and extent of complications of this therapy in terms of burn injury are significant, especially in children, steam inhalation therapy should be considered a dangerous procedure and not recommended anymore in professional guidelines and patient brochures. PMID:22781995

  11. Central diabetes insipidus: a previously unreported side effect of temozolomide. (United States)

    Faje, Alexander T; Nachtigall, Lisa; Wexler, Deborah; Miller, Karen K; Klibanski, Anne; Makimura, Hideo


    Temozolomide (TMZ) is an alkylating agent primarily used to treat tumors of the central nervous system. We describe 2 patients with apparent TMZ-induced central diabetes insipidus. Using our institution's Research Patient Database Registry, we identified 3 additional potential cases of TMZ-induced diabetes insipidus among a group of 1545 patients treated with TMZ. A 53-year-old male with an oligoastrocytoma and a 38-year-old male with an oligodendroglioma each developed symptoms of polydipsia and polyuria approximately 2 months after the initiation of TMZ. Laboratory analyses demonstrated hypernatremia and urinary concentrating defects, consistent with the presence of diabetes insipidus, and the patients were successfully treated with desmopressin acetate. Desmopressin acetate was withdrawn after the discontinuation of TMZ, and diabetes insipidus did not recur. Magnetic resonance imaging of the pituitary and hypothalamus was unremarkable apart from the absence of a posterior pituitary bright spot in both of the cases. Anterior pituitary function tests were normal in both cases. Using the Research Patient Database Registry database, we identified the 2 index cases and 3 additional potential cases of diabetes insipidus for an estimated prevalence of 0.3% (5 cases of diabetes insipidus per 1545 patients prescribed TMZ). Central diabetes insipidus is a rare but reversible side effect of treatment with TMZ.

  12. Early and Late Onset Side Effects of Photodynamic Therapy

    Directory of Open Access Journals (Sweden)

    Francesco Borgia


    Full Text Available Photodynamic Therapy (PDT is a non-invasive treatment successfully used for neoplastic, inflammatory and infectious skin diseases. One of its strengths is represented by the high safety profile, even in elderly and/or immuno-depressed subjects. PDT, however, may induce early and late onset side effects. Erythema, pain, burns, edema, itching, desquamation, and pustular formation, often in association with each other, are frequently observed in course of exposure to the light source and in the hours/days immediately after the therapy. In particular, pain is a clinically relevant short-term complication that also reduces long-term patient satisfaction. Rare complications are urticaria, contact dermatitis at the site of application of the photosensitizer, and erosive pustular dermatosis. Debated is the relationship between PDT and carcinogenesis: the eruptive appearance of squamous cell carcinoma (SCC in previously treated areas has been correlated to a condition of local and/or systemic immunosuppression or to the selection of PDT-resistant SCC. Here we review the literature, with particular emphasis to the pathogenic hypotheses underlying these observations.

  13. Treatment of neuroblastoma with metaiodobenzylguanidine: results and side effects

    International Nuclear Information System (INIS)

    Treuner, J.; Klingebiel, T.; Bruchelt, G.; Feine, U.; Niethammer, D.


    Between April 1984 and December 1985 we treated ten children suffering from neuroblastoma in a total of 25 metaiodobenzylguanidine (MIBG) courses. Five had had a relapse of neuroblastoma stage III or IV, three had never achieved a remission in spite of intensive chemotherapy, and two were treated with an unstable remission. The children were each administered from 1 to 5 courses with a dosage per course of between 1295 and 9065 MBq. The sum of the single doses during the whole course of therapy ranged between 3145 and 21,904 MBq per child. Five of five children suffering from bone pain and fever became free of complaints during the first three treatment days. Six of eight children with manifest tumor at onset of therapy responded well to the treatment: response extended from transitory decrease in elevated catecholamine levels in serum and urine to complete disappearance of large abdominal tumor masses. We also observed a decrease in bone marrow involvement and a stabilization of osteolytic lesions. Seven of these eight children died in spite of a good response from 55 to 350 days after the first MIBG treatment course. The only side effect we witnessed was a reversible bone marrow depression. In three children we combined the MIBG therapy with bone marrow transplantation

  14. Link between diet and chemotherapy related gastrointestinal side effects

    Directory of Open Access Journals (Sweden)

    Marcin Mardas


    Full Text Available Aim of the study : To evaluate an association between food products consumption, dietary intake and the incidence of selected gastrointestinal symptoms (nausea, vomiting, diarrhea and constipation in cancer patients undergoing chemotherapy. Material and methods : Fifty six women receiving chemotherapy for ovarian cancer were eligible for the study. Anthropometrical measurements were assessed. The dietary intake was evaluated by 24-hours food records. The association between the consumption of selected food products and gastrointestinal symptoms incidences was assessed by modified semi-quantitative food frequency questionnaire including 77-different food items that was developed and applied in cancer patients undergoing chemotherapy. Results : BMI values indicated 9%, 45%, 30% and 16% of patients as underweight, normal weight, overweight and obese respectively. Only 23% and 32% of patients never experienced nausea and constipation when 43% and 45% never experienced vomiting and diarrhea. Nausea was promoted by oils, constipation by chocolate and chocolate products and diarrhea by dairy products, stone fruit and apple. Significant inverse correlations were found between vomiting and the intake of energy, fat, protein, carbohydrates, B groups vitamins, vitamin D, phosphorus and zinc. The difference in energy intake between marginal values of vomiting incidence exceeded 400 kcal. Conclusions : Dietary intake as well as specific food products influence on gastrointestinal side effect of chemotherapy in cancer patients. The dietary approach based on either exclusion or limited intake of selected food products and improvement of diet could reduce and prevent chemotherapy induced gastrointestinal symptoms therefore should be taken under consideration in clinical practice.

  15. Effects of prasterone on bone mineral density in women with active systemic lupus erythematosus receiving chronic glucocorticoid therapy. (United States)

    Sánchez-Guerrero, Jorge; Fragoso-Loyo, Hilda E; Neuwelt, C Michael; Wallace, Daniel J; Ginzler, Ellen M; Sherrer, Yvonne R S; McIlwain, Harris H; Freeman, Pamela G; Aranow, Cynthia; Petri, Michelle A; Deodhar, Atul A; Blanton, Ellen; Manzi, Susan; Kavanaugh, Arthur; Lisse, Jeffrey R; Ramsey-Goldman, Rosalind; McKay, James D; Kivitz, Alan J; Mease, Philip J; Winkler, Anne E; Kahl, Leslie E; Lee, Albert H; Furie, Richard A; Strand, C Vibeke; Lou, Lillian; Ahmed, Mumtaz; Quarles, Betty; Schwartz, Kenneth E


    To assess prevention of bone mineral density (BMD) loss and durability of the response during treatment with prasterone in women with systemic lupus erythematosus (SLE) receiving chronic glucocorticoids. 155 patients with SLE received 200 mg/day prasterone or placebo for 6 months in a double-blind phase. Subsequently, 114 patients were re-randomized to receive 200 or 100 mg/day prasterone for 12 months in an open-label phase. Primary efficacy endpoints were changes in BMD at the lumbar spine (L-spine) from baseline to Month 6 and maintenance of BMD from Month 6 to 18 for patients who received prasterone during the double-blind phase. In the double-blind phase, there was a trend for a small gain in BMD at the L-spine for patients who received 200 mg/day prasterone for 6 months versus a loss in the placebo group (mean +/- SD, 0.003 +/- 0.035 vs -0.005 +/- 0.053 g/cm(2), respectively; p = 0.293 between groups). In the open-label phase, there was dose-dependent increase in BMD at the L-spine at Month 18 between patients who received 200 versus 100 mg/day prasterone (p = 0.021). For patients who received 200 mg/day prasterone for 18 months, the L-spine BMD gain was 1.083 +/- 0.512% (p = 0.042). There was no overall change in BMD at the total hip over 18 months with 200 mg/day prasterone treatment. The safety profile reflected the weak androgenic properties of prasterone. This study suggests prasterone 200 mg/day may offer mild protection against bone loss in women with SLE receiving glucocorticoids. ( Identifiers NCT00053560 and NCT00082511).

  16. Glucocorticoid Regulation of the Vitamin D Receptor (United States)

    Hidalgo, Alejandro A.; Trump, Donald L.; Johnson, Candace S.


    Many studies indicate calcitriol has potent anti-tumor activity in different types of cancers. However, high levels of vitamin D can produce hypercalcemia in some patients. Glucocorticoids are used to ameliorate hypercalcemia and to enhance calcitriol anti-tumor activity. Calcitriol in combination with the glucocorticoid dexamethasone (Dex) increased vitamin D receptor (VDR) protein levels and ligand binding in squamous cell carcinoma VII (SCC). In this study we found that both calcitriol and Dex induce VDR- and glucocorticoid receptor (GR)-mediated transcription respectively, indicating both hormone receptors are active in SCC. Pre-treatment with Dex increases VDR-mediated transcription at the human CYP24A1 promoter. Whereas, pre-treatment with other steroid hormones, including dihydrotestosterone and R1881, has no effect on VDR-mediated transcription. Real-time PCR indicates treatment with Dex increases Vdr transcripts in a time-dependent manner, suggesting Dex may directly regulate expression of Vdr. Numerous putative glucocorticoid response elements (GREs) were found in the Vdr gene. Chromatin immunoprecipitation (ChIP) assay demonstrated GR binding at several putative GREs located within the mouse Vdr gene. However, none of the putative GREs studied increase GR-mediated transcription in luciferase reporter assays. In an attempt to identify the response element responsible for Vdr transcript regulation, future studies will continue to analyze newly identified GREs more distal from the Vdr gene promoter. PMID:20398752

  17. Side Effect Perceptions and Their Impact on Treatment Decisions in Women. (United States)

    Waters, Erika A; Pachur, Thorsten; Colditz, Graham A


    Side effects prompt some patients to forego otherwise-beneficial therapies. This study explored which characteristics make side effects particularly aversive. We used a psychometric approach, originating from research on risk perception, to identify the factors (or components) underlying side effect perceptions. Women ( N = 149) aged 40 to 74 years were recruited from a patient registry to complete an online experiment. Participants were presented with hypothetical scenarios in which an effective and necessary medication conferred a small risk of a single side effect (e.g., nausea, dizziness). They rated a broad range of side effects on several characteristics (e.g., embarrassing, treatable). In addition, we collected 4 measures of aversiveness for each side effect: choosing to take the medication, willingness to pay to avoid the side effect (WTP), negative affective attitude associated with the side effect, and how each side effect ranks among others in terms of undesirability. A principal components analysis (PCA) was used to identify the components underlying side effect perceptions. Then, for each aversiveness measure separately, regression analyses were used to determine which components predicted differences in aversiveness among the side effects. The PCA revealed 4 components underlying side effect perceptions: affective challenge (e.g., frightening), social challenge (e.g., disfiguring), physical challenge (e.g., painful), and familiarity (e.g., common). Side effects perceived as affectively and physically challenging elicited the highest levels of aversiveness across all 4 measures. Understanding what side effect characteristics are most aversive may inform interventions to improve medical decisions and facilitate the translation of novel biomedical therapies into clinical practice.

  18. Kidney tissue targeted metabolic profiling of glucocorticoid-induced osteoporosis and the proposed therapeutic effects of Rhizoma Drynariae studied using UHPLC/MS/MS. (United States)

    Huang, Yue; Liu, Xinyu; Zhao, Longshan; Li, Famei; Xiong, Zhili


    Traditional Chinese medicine and modern science have indicated that there is a close relationship between bone and kidney. In light of this, this project was designed to study the metabolic profiling by UHPLC/MS/MS of glucocorticoid-induced osteoporosis in kidney tissue and the possible therapeutic effects of Rhizoma Drynariae (RD), a classic traditional Chinese medicine, in improving the kidney function and strengthening bone. Twenty-one Wistar rats were divided into three groups: control group (rats before prednisolone inducing), a model group (prednisolone-induced group) and a treatment group (prednisolone-induced rats that were then administered RD ethanol extracts). By using pattern recognition analysis, a significant change in the metabolic profile of kidney tissue samples was observed in the model group and restoration of the profile was observed after the administration of RD ethanol extracts. Some significantly changed biomarkers related to osteoporosis such as sphingolipids (C16 dihydrosphingosine, C18 dihydrosphingosine, C18 phytosphingosine, C20 phytosphingosine), lysophosphatidycholines (C16:0 LPC, C18:0 LPC) and phenylalanine were identified. As a complement to the metabolic profiling of RD in plasma, these biomarkers suggest that kidney damage, cell cytotoxicity and apoptosis exist in osteoporosis rats, which is helpful in further understanding the underlying process of glucocorticoid-induced osetoporosis and the suggested therapeutic effects of RD. The method shows that tissue target metabonomics might provide a powerful tool to further understand the process of disease and the mechanism of therapeutic effect of Chinese medicines. Copyright © 2014 John Wiley & Sons, Ltd.

  19. Glucocorticoids, chronic stress, and obesity

    NARCIS (Netherlands)

    Dallman, Mary F.; Pecoraro, Norman C.; la Fleur, Susanne E.; Warne, James P.; Ginsberg, Abigail B.; Akana, Susan F.; Laugero, Kevin C.; Houshyar, Hani; Strack, Alison M.; Bhatnagar, Seema; Bell, Mary E.


    Glucocorticoids either inhibit or sensitize stress-induced activity in the hypothalamo-pituitary-adrenal (HPA) axis, depending on time after their administration, the concentration of the steroids, and whether there is a concurrent stressor input. When there are high glucocorticoids together with a

  20. Immediate side effects of stereotactic radiotherapy and radiosurgery

    International Nuclear Information System (INIS)

    Werner-Wasik, Maria; Rudoler, Shari; Preston, Peter E.; Downes, Beverly M.; Andrews, David; Corn, Benjamin W.; Rosenstock, Jeffrey; Curran, Walter J.


    Purpose/Objective: Despite increased utilization of fractionated stereotactic radiation therapy (SRT) or stereotactic radiosurgery (SRS), the incidence and nature of immediate side effects (ISE) associated with these treatment techniques is not well defined. Materials and Methods: Intracranial lesions in 78 adult patients were treated with SRT or SRS, using a dedicated linear accelerator. They comprised 13 gliomas, 2 ependymomas, 19 metastatic tumors, 15 meningiomas, 12 acoustic neuromas, 4 pituitary adenomas, 1 optic neuroma, 1 chondrosarcoma and 11 arteriovenous malformations (AVM). SRT was used in 51 and SRS in 27 patients. Mean target volume was 9.0 cc. Eleven patients received prior external beam radiation therapy within 2 months before SRT/SRS. Any side effects occurring during and up to two weeks after radiation course were defined as ISE and were graded as mild, moderate or severe. The incidence of ISE and the significance of their association with several pretreatment variables were analyzed. Results: Overall, (28(78)) (35%) patients experienced one or more ISE. Most of ISE (87%) were mild and consisted of nausea (5), dizziness/vertigo (5), seizures (7) and new persistent headaches (17). Two episodes of worsening neurological deficit and 2 of orbital pain were graded as moderate. Two patients experienced severe ISE, requiring hospitalization (1 seizure and 1 worsening neurological deficit). ISE in 5 cases prompted computerized tomography of the brain which revealed increased perilesional edema in 3 cases. The incidence of ISE by diagnosis was as follows: 46% ((6(13))) for gliomas, 50% ((6(12))) for acoustic neuromas, 36% ((4(11))) for AVM, 33% ((5(15))) for meningiomas and 21% ((4(19))) for metastases. Increasing dose to the margin and increasing maximum dose were associated with a higher incidence of ISE (p=0.02 and 0.005, respectively). Prior recent conventional external beam radiation therapy, target volume, number of isocenters, collimator size, dose

  1. Effects of utility demand-side management programs on uncertainty

    International Nuclear Information System (INIS)

    Hirst, E.


    Electric utilities face a variety of uncertainties that complicate their long-term resource planning. These uncertainties include future economic and load growths, fuel prices, environmental and economic regulations, performance of existing power plants, cost and availability of purchased power, and the costs and performance of new demand and supply resources. As utilities increasingly turn to demand-side management (DSM) programs to provide resources, it becomes more important to analyze the interactions between these programs and the uncertainties facing utilities. This paper uses a dynamic planning model to quantify the uncertainty effects of supply-only vs DSM + supply resource portfolios. The analysis considers four sets of uncertainties: economic growth, fuel prices, the costs to build new power plants, and the costs to operate DSM programs. The two types of portfolios are tested against these four sets of uncertainties for the period 1990 to 2010. Sensitivity, scenario, and worst-case analysis methods are used. The sensitivity analyses show that the DSM + supply resource portfolio is less sensitive to unanticipated changes in economic growth, fuel prices, and power-plant construction costs than is the supply-only portfolio. The supply-only resource mix is better only with respect to uncertainties about the costs of DSM programs. The base-case analysis shows that including DSM programs in the utility's resource portfolio reduces the net present value of revenue requirements (NPV-RR) by 490 million dollars. The scenario-analysis results show an additional 30 million dollars (6%) in benefits associated with reduction in these uncertainties. In the worst-case analysis, the DSM + supply portfolio again reduces the cost penalty associated with guessing wrong for both cases, when the utility plans for high needs and learns it has low needs and vice versa. 20 refs

  2. Side effects of intraoral devices for OSAS treatment. (United States)

    Teixeira, Andressa Otranto de Britto; Andrade, Ana Luiza Ladeia; Almeida, Rhita Cristina da Cunha; Almeida, Marco Antonio de Oliveira


    Intraoral devices have increasingly assumed a key role in the treatment of obstructive sleep apnea syndrome, but there are limitations to their indication and side effects that result from their continuous use, as well as the use of the continuous positive airway pressure device. To evaluate the changes in dental positioning caused by the continuous use of mandibular advancement devices. A prospective longitudinal study with a sample of 15 patients, with evaluation of complete documentation after a mean time of 6.47 months, assessed changes in dental positioning due to the use of the Twin Block oral device for the treatment of patients with apnea. The following variables were evaluated: overjet, overbite, upper and lower intermolar distances, upper and lower intercanine distances, Little's irregularity index and the incisor mandibular plane angle. An intraclass correlation test was performed and a correlation index>0.08 was accepted. After verifying the normal sample distribution (Shapiro-Wilks), a parametric test was used (t test), with a significance level set at 5%. There was a decrease in the values of overjet, overbite and Little's irregularity index, whereas there was an increase in the lower intercanine distance and IMPA values. All these variables are influenced, at different levels, by the forward inclination of the lower incisors, an action that can be expected due to the force applied by the device on the dentition. The other variables did not show statistically significant differences. After a mean time of 6.47 months of use of the mandibular advancement device, there were statistically significant changes in the dental positioning, but they were not clinically relevant. However, it is relevant that this device is commonly in use over long periods of time, making the monitoring of these patients of the utmost importance for the duration of their therapy. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia C

  3. The side-effects to CPAP treatment inventory: the development and initial validation of a new tool for the measurement of side-effects to CPAP treatment. (United States)

    Broström, Anders; Arestedt, Kristofer Franzén; Nilsen, Per; Strömberg, Anna; Ulander, Martin; Svanborg, Eva


    Continuous positive airway pressure (CPAP) is the treatment of choice for obstructive sleep apnoea syndrome (OSAS), but side-effects are common. No validated self-rating scale measuring side-effects to CPAP treatment exists today. The aim was to develop the side-effects to CPAP treatment inventory (SECI), and investigate the validity and reliability of the instrument among patients with OSAS. SECI was developed on the basis of: (1) in-depth interviews with 23 patients; (2) examination of the scientific literature and (3) consensus agreement of a multi-professional expert panel. This yielded 15 different types of side-effects related to CPAP treatment. Each side-effect has three sub-questions (scales): perceived frequency (a) and magnitude (b) of the side-effect, as well as its perceived impact on CPAP use (c). A cross-sectional descriptive design was used. A total of 329 patients with OSAS with an average use of CPAP treatment for 39 months (2 weeks to 182 months) were recruited. Data were collected with SECI, and obtained from medical records (clinical variables and data related to CPAP treatment). Construct validity was confirmed with factor analysis (principal component analysis with orthogonal rotation). A logical two-factor solution, the device subscale and symptom subscale, emerged across all three scales. The symptom subscale describing physical and psychological side-effects and the device subscale described mask and device-related side-effects. Internal consistency reliability of the three scales was good (Cronbach's α = 0.74-0.86) and acceptable for the subscales (Cronbach's α = 0.62-0.86). The satisfactory measurement properties of this new instrument are promising and indicate that SECI can be used to measure side-effects to CPAP treatment. © 2010 European Sleep Research Society.

  4. Live cell imaging unveils multiple domain requirements for in vivo dimerization of the glucocorticoid receptor.

    Directory of Open Access Journals (Sweden)

    Diego M Presman


    Full Text Available Glucocorticoids are essential for life, but are also implicated in disease pathogenesis and may produce unwanted effects when given in high doses. Glucocorticoid receptor (GR transcriptional activity and clinical outcome have been linked to its oligomerization state. Although a point mutation within the GR DNA-binding domain (GRdim mutant has been reported as crucial for receptor dimerization and DNA binding, this assumption has recently been challenged. Here we have analyzed the GR oligomerization state in vivo using the number and brightness assay. Our results suggest a complete, reversible, and DNA-independent ligand-induced model for GR dimerization. We demonstrate that the GRdim forms dimers in vivo whereas adding another mutation in the ligand-binding domain (I634A severely compromises homodimer formation. Contrary to dogma, no correlation between the GR monomeric/dimeric state and transcriptional activity was observed. Finally, the state of dimerization affected DNA binding only to a subset of GR binding sites. These results have major implications on future searches for therapeutic glucocorticoids with reduced side effects.

  5. Dibutyltin disrupts glucocorticoid receptor function and impairs glucocorticoid-induced suppression of cytokine production.

    Directory of Open Access Journals (Sweden)

    Christel Gumy

    Full Text Available BACKGROUND: Organotins are highly toxic and widely distributed environmental chemicals. Dibutyltin (DBT is used as stabilizer in the production of polyvinyl chloride plastics, and it is also the major metabolite formed from tributyltin (TBT in vivo. DBT is immunotoxic, however, the responsible targets remain to be defined. Due to the importance of glucocorticoids in immune-modulation, we investigated whether DBT could interfere with glucocorticoid receptor (GR function. METHODOLOGY: We used HEK-293 cells transiently transfected with human GR as well as rat H4IIE hepatoma cells and native human macrophages and human THP-1 macrophages expressing endogenous receptor to study organotin effects on GR function. Docking of organotins was used to investigate the binding mechanism. PRINCIPAL FINDINGS: We found that nanomolar concentrations of DBT, but not other organotins tested, inhibit ligand binding to GR and its transcriptional activity. Docking analysis indicated that DBT inhibits GR activation allosterically by inserting into a site close to the steroid-binding pocket, which disrupts a key interaction between the A-ring of the glucocorticoid and the GR. DBT inhibited glucocorticoid-induced expression of phosphoenolpyruvate carboxykinase (PEPCK and tyrosine-aminotransferase (TAT and abolished the glucocorticoid-mediated transrepression of TNF-alpha-induced NF-kappaB activity. Moreover, DBT abrogated the glucocorticoid-mediated suppression of interleukin-6 (IL-6 and TNF-alpha production in lipopolysaccharide (LPS-stimulated native human macrophages and human THP-1 macrophages. CONCLUSIONS: DBT inhibits ligand binding to GR and subsequent activation of the receptor. By blocking GR activation, DBT may disturb metabolic functions and modulation of the immune system, providing an explanation for some of the toxic effects of this organotin.

  6. Effects of acute restraint-induced stress on glucocorticoid receptors and brain-derived neurotrophic factor after mild traumatic brain injury. (United States)

    Griesbach, G S; Vincelli, J; Tio, D L; Hovda, D A


    We have previously reported that experimental mild traumatic brain injury results in increased sensitivity to stressful events during the first post-injury weeks, as determined by analyzing the hypothalamic-pituitary-adrenal (HPA) axis regulation following restraint-induced stress. This is the same time period when rehabilitative exercise has proven to be ineffective after a mild fluid-percussion injury (FPI). Here we evaluated effects of stress on neuroplasticity. Adult male rats underwent either an FPI or sham injury. Additional rats were only exposed to anesthesia. Rats were exposed to 30 min of restraint stress, followed by tail vein blood collection at post-injury days (PID) 1, 7, and 14. The response to dexamethasone (DEX) was also evaluated. Hippocampal tissue was collected 120 min after stress onset. Brain-derived neurotrophic factor (BDNF) along with glucocorticoid (GR) and mineralocorticoid (MR) receptors was determined by Western blot analysis. Results indicated injury-dependent changes in glucocorticoid and mineralocorticoid receptors that were influenced by the presence of dexamethasone. Control and FPI rats responded differentially to DEX in that GR increases after receiving the lower dose of DEX were longer lasting in the FPI group. A suppression of MR was found at PID 1 in vehicle-treated FPI and Sham groups. Decreases in the precursor form of BDNF were observed in different FPI groups at PIDs 7 and 14. These findings suggest that the increased sensitivity to stressful events during the first post-injury weeks, after a mild FPI, has an impact on hippocampal neuroplasticity. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Effects of management strategies on glucocorticoids and behavior in Indian rhinoceros (Rhinoceros unicornis): translocation and operant conditioning. (United States)

    Capiro, Jonnie M; Stoops, Monica A; Freeman, Elizabeth W; Clawson, Dave; Schook, Mandi W


    The ex situ Indian rhino population experienced a decrease in genetic diversity indicating that the breeding program could possibly benefit from novel reproductive management strategies to ensure population sustainability. We sought to determine how management tools used for reproductive management, specifically translocation and operant conditioning, impact physiological and behavioral measures of welfare in Indian rhinos. First, an adrenocorticotropic hormone challenge performed in an adult male resulted in a 38-fold increase in urinary and a 3.5-fold increase in fecal glucocorticoid metabolites (FGM). Mean and peak FGM differed among three females, but all demonstrated elevated (P operant conditioning to stand during transrectal ultrasound exams were monitored and rhinos differed in their mean and peak FGM concentrations. However, FGM were not different before versus during training or on pasture versus in the barn. One female exhibited more stereotypic behavior during training in the barn than on pasture (P operant conditioning only resulted in minimal changes in behaviors and FGM. © 2014 Wiley Periodicals Inc.

  8. The emerging importance of ultradian glucocorticoid rhythms within metabolic pathology. (United States)

    Flynn, Benjamin P; Conway-Campbell, Becky L; Lightman, Stafford L


    Glucocorticoid (GC) hormones play significant roles within homeostasis and the chrono-dynamics of their regulatory role has become increasingly recognised within dysregulated GC pathology, particularly with metabolic phenotypes. Within this article, we will discuss the relevance of the ultradian homeostatic rhythm, how its dysregulation effects glucocorticoid receptor and RNA polymeraseII recruitment and may play a significant role within aberrant metabolic action. Copyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

  9. Side effects of oral antibiotics in small children with cystic fibrosis

    DEFF Research Database (Denmark)

    Jakobsen, Karin Riisager; Bregnballe, Vibeke


    or/and stomach pain during antibiotic treatment. 48% reported their child to be eating little during antibiotic treatment and of these 87% were reporting diarrhoea or/and stomach pain. Half of the children with diarrhoea or/and stomach pain got treatment for the side effects. Conclusion: Most...... of the small children with CF suffered from side effect of antibiotics, but only half of them got treatment for the side effects....

  10. Yoga-Based Rehabilitation Program in Reducing Physical and Emotional Side Effects in Patients With Cancer (United States)


    Alopecia; Anxiety; Breast Carcinoma; Cognitive Side Effects of Cancer Therapy; Colorectal Carcinoma; Depression; Fatigue; Lung Carcinoma; Nausea and Vomiting; Pain; Psychological Impact of Cancer; Sleep Disorder; Weight Change

  11. Patient-provider communication and hormonal therapy side effects in breast cancer survivors. (United States)

    Lin, Jenny J; Chao, Jennifer; Bickell, Nina A; Wisnivesky, Juan P


    Side effects from hormonal therapy (HT) for breast cancer treatment occur frequently and are associated with worse quality of life and HT non-adherence. Whether improved patient-physician communication is associated with patients' reporting of side effects is unknown. We undertook this study to assess factors associated with women's reports of HT side effects. Between December 2012 and April 2013, we conducted a cross-sectional survey of breast cancer patients undergoing HT in an urban medical center. Descriptive statistics, univariate analyses, and multivariate analyses were used to evaluate associations. Of the 100 participants, 67% reported having HT side effects. However, when prompted, an additional 9% reported experiencing specific HT-related symptoms. Despite very high communication scores, one-third of participants reported they had not discussed side effects with providers. Multivariate analysis showed that after controlling for age, education, race, and medication beliefs, women who had difficulty asking providers for more information were more likely to report side effects (odds ratio 8.27, 95% confidence interval 1.01-69.88). Although HT side effects often occur and are bothersome, patient-provider discussions about side effects remain suboptimal. Providers should actively ask patients about medication side effects so that they can be addressed to improve quality of life and potentially, medication adherence.

  12. "There is a chain of connections": using syndemics theory to understand HIV treatment side effects. (United States)

    Gagnon, Marilou


    Side effects are central to the experience of living longer with HIV but rarely have they been studied alone. Unlike other aspects of that experience, like quality of life, treatment adherence, chronicity, episodic disability, aging, health, and viral load suppression, side effects have not benefited from the same level of empirical and theoretical engagement from qualitative researchers. In this paper, we draw on syndemics theory and 50 qualitative interviews to better understand the experience of HIV treatment side effects. Two main categories were identified in the data: side effects as a product and side effects as a risk factor. The first category suggests that side effects are not just the product of taking antiretroviral drugs. They are also the product of particular conditions and tend to cluster with other health problems. The second category puts forward the idea that side effects can act as a syndemic risk factor by exposing PLWH to a greater risk of developing health problems and creating conditions in which psychosocial issues are more likely to emerge. The paper concludes by calling for more research on the complex nature of side effects and for the development of comprehensive approaches for the assessment and management of side effects.

  13. Side-gate modulation effects on high-quality BN-Graphene-BN nanoribbon capacitors

    International Nuclear Information System (INIS)

    Wang, Yang; Chen, Xiaolong; Ye, Weiguang; Wu, Zefei; Han, Yu; Han, Tianyi; He, Yuheng; Cai, Yuan; Wang, Ning


    High-quality BN-Graphene-BN nanoribbon capacitors with double side-gates of graphene have been experimentally realized. The double side-gates can effectively modulate the electronic properties of graphene nanoribbon capacitors. By applying anti-symmetric side-gate voltages, we observed significant upward shifting and flattening of the V-shaped capacitance curve near the charge neutrality point. Symmetric side-gate voltages, however, only resulted in tilted upward shifting along the opposite direction of applied gate voltages. These modulation effects followed the behavior of graphene nanoribbons predicted theoretically for metallic side-gate modulation. The negative quantum capacitance phenomenon predicted by numerical simulations for graphene nanoribbons modulated by graphene side-gates was not observed, possibly due to the weakened interactions between the graphene nanoribbon and side-gate electrodes caused by the Ga + beam etching process

  14. Impact of brand or generic labeling on medication effectiveness and side effects. (United States)

    Faasse, Kate; Martin, Leslie R; Grey, Andrew; Gamble, Greg; Petrie, Keith J


    Branding medication with a known pharmaceutical company name or product name bestows on the drug an added assurance of authenticity and effectiveness compared to a generic preparation. This study examined the impact of brand name and generic labeling on medication effectiveness and side effects. 87 undergraduate students with frequent headaches took part in the study. Using a within-subjects counterbalanced design, each participant took tablets labeled either as brand name "Nurofen" or "Generic Ibuprofen" to treat each of 4 headaches. In reality, half of the tablets were placebos, and half were active ibuprofen (400 mg). Participants recorded their headache pain on a verbal descriptor and visual analogue scale prior to taking the tablets, and again 1 hour afterward. Medication side effects were also reported. Pain reduction following the use of brand name labeled tablets was similar in active ibuprofen or a placebo. However, if the tablets had a generic label, placebo tablets were significantly less effective compared to active ibuprofen. Fewer side effects were attributed to placebo tablets with brand name labeling compared to the same placebo tablets with a generic label. Branding of a tablet appears to have conferred a treatment benefit in the absence of an active ingredient, while generic labeled tablets were substantially less effective if they contained no active ingredient. Branding is also associated with reduced attribution of side effects to placebo tablets. Future interventions to improve perceptions of generics may have utility in improving treatment outcomes from generic drugs. (c) 2016 APA, all rights reserved).

  15. Norms Inform Mental State Ascriptions: A Rational Explanation for the Side-Effect Effect (United States)

    Uttich, Kevin; Lombrozo, Tania


    Theory of mind, the capacity to understand and ascribe mental states, has traditionally been conceptualized as analogous to a scientific theory. However, recent work in philosophy and psychology has documented a "side-effect effect" suggesting that moral evaluations influence mental state ascriptions, and in particular whether a behavior is…

  16. Side effects affected my daily activities a lot”: a qualitative exploration of the impact of contraceptive side effects in Bangladesh

    Directory of Open Access Journals (Sweden)

    Jain A


    Full Text Available Aparna Jain,1 Laura Reichenbach,1 Iqbal Ehsan,2 Ubaidur Rob2 1Evidence Project, Population Council, Washington, DC, USA; 2Evidence Project, Population Council, Dhaka, Bangladesh Purpose: In a country like Bangladesh that has made great progress in contraceptive use with one of the lowest levels of fertility and highest levels of contraceptive use, understanding what factors influence women’s decisions to discontinue a contraceptive method and not switch to a new method is critical in designing interventions and programs that will help enable Bangladesh to reach its FP2020 goals. Research on side effects has focused on physical manifestations like headaches, moodiness, abdominal pain, and menstrual irregularities. While physical effects alone may stop women from continuing a contraceptive method, less is known about how side effects influence women’s daily activities and lives. The purpose of this study is to understand the ways that side effects affect Bangladeshi women’s participation in different social settings.Methods: Thirty-five in-depth interviews with married women who recently discontinued or switched to a different contraceptive method were conducted in Sylhet and Khulna Divisions. Interviews explored reasons for discontinuation including experience of side effects and impact of side effects on women’s lives.Results: Key themes emerged including that side effects are not only experienced physically but are barriers to women’s participation in many aspects of their lives. The spheres of life that most commonly appeared to be influenced by side effects include religion, household, and sexual intimacy irrespective of method used or residence.Conclusion: Family planning providers need to be aware of these additional consequences associated with contraceptive side effects to provide tailored counseling that recognizes these issues and helps women to mitigate them. For Bangladesh to achieve its FP2020 goals, understanding the

  17. The effect of consignment to broodmare sales on physiological stress measured by faecal glucocorticoid metabolites in pregnant Thoroughbred mares. (United States)

    Schulman, Martin; Becker, Annet; Ganswindt, Stefanie; Guthrie, Alan; Stout, Tom; Ganswindt, Andre


    Validation of a method for the minimally-invasive measurement of physiological stress will help understanding of risk factors that may contribute to stress-associated events including recrudescence of Equid herpesvirus (EHV), which is anecdotally associated with sales consignment of pregnant Thoroughbred mares. In this study we compared two similar groups of late-gestation Thoroughbred broodmares on the same farm: a consigned Sales group (N = 8) and a non-consigned Control group (N = 6). The Sales mares were separated from their paddock companions and grouped prior to their preparation for, transport to, and return from the sales venue. Both groups were monitored by sampling at regular intervals from 5 days prior to until 14 days after the sales date (D0) to measure physiological stress in terms of changes in faecal glucocorticoid metabolite (FGM) concentrations, and for event-related viral recrudescence via daily body temperature measurements and periodic nasal swabs for PCR analysis for EHV-1 and -4 DNA. In both groups, FGM levels increased post-sales before returning to pre-sales levels. Specifically, FGM concentrations in the Sales mares were significantly higher on D + 3 and D + 10 than on D-4 and D-3 (F = 12.03, P Sales) mare showed PCR evidence of EHV-1 shedding. Using FGM to measure physiological stress was supported by the increases observed in all mares after Sales consignment, including those not consigned to the sale. Monitoring FGM levels therefore represents an appropriate, minimally-invasive method for future studies to assess the contribution of physiological stress to EHV recrudescence in horses transported to sales or equestrian events.

  18. Reirradiation on recurrent cervical cancer case: Treatment response and side effects (United States)

    Siregar, M. F.; Supriana, N.; Nuranna, L.; Prihartono, J.


    Management of recurrent cervical cancer by reirradiation after radiation treatment remains controversial. In Indonesia, there is currently no data about reirradiation tumor response and side effects. This study aims to assess the tumor response to and side effects of reirradiation, the effect of time interval between first radiation treatment and cancer recurrence on the tumor response and side effects, and the effect of tumor size on tumor response. A cohort retrospective study with no comparison was done with the Radiotherapy Department at Cipto Mangunkusumo General Hospital, Jakarta. Participants were recurrent cervical cancer patients undergoing reirradiation. Data was collected from patients’ medical records and follow-up phone calls. Twenty-two patients participated in this study. Nine patients (40.9%) had complete responses, 10 patients (45.5%) had partial responses, 1 patient (4.5%) had a stable response, and 2 patients (9.1%) had tumor progressions. In general, 15 patients (68.2%) had no to light side effects (grade 0-2 RTOG) and 7 patients (31.8%) had severe side effects (grade 3-4 RTOG). Four patients (18.1%) had severe gastrointestinal acute side effects, 6 patients (27.3%) had severe gastrointestinal late side effects, 2 patients (9.1%) had severe urogenital side effects, and there were no patients had severe urogenital late side effects. There was no significant difference in tumor response between patients with time interval between first radiation treatment and recurrence of 4 cm. Reirradiation can be considered as a modality in recurrent cervical cancer management since good tumor response was achieved and the majority of patients had no to light side effects (grade 0-2 RTOG). This study found no correlation between tumor response, side effects, and time gap between first radiation treatment and recurrence of 4 cm.

  19. Impact of glucocorticoid on neurogenesis

    Directory of Open Access Journals (Sweden)

    Haruki Odaka


    Full Text Available Neurogenesis is currently an area of great interest in neuroscience. It is closely linked to brain diseases, including mental disorders and neurodevelopmental disease. Both embryonic and adult neurogeneses are influenced by glucocorticoids secreted from the adrenal glands in response to a variety of stressors. Moreover, proliferation/differentiation of the neural stem/progenitor cells (NSPCs is affected by glucocorticoids through intracellular signaling pathways such as phosphoinositide 3-kinase (PI3K/Akt, hedgehog, and Wnt. Our review presents recent evidence of the impact of glucocorticoids on NSPC behaviors and the underlying molecular mechanisms; this provides important information for understanding the pathological role of glucocorticoids on neurogenesis-associated brain diseases.

  20. A maternal high-fat, high-sucrose diet has sex-specific effects on fetal glucocorticoids with little consequence for offspring metabolism and voluntary locomotor activity in mice.

    Directory of Open Access Journals (Sweden)

    Eunice H Chin

    Full Text Available Maternal overnutrition and obesity during pregnancy can have long-term effects on offspring physiology and behaviour. These developmental programming effects may be mediated by fetal exposure to glucocorticoids, which is regulated in part by placental 11β-hydroxysteroid dehydrogenase (11β-HSD type 1 and 2. We tested whether a maternal high-fat, high-sucrose diet would alter expression of placental 11β-HSD1 and 2, thereby increasing fetal exposure to maternal glucocorticoids, with downstream effects on offspring physiology and behaviour. C57BL/6J mice were fed a high-fat, high-sucrose (HFHS diet or a nutrient-matched low-fat, no-sucrose control diet prior to and during pregnancy and lactation. At day 17 of gestation, HFHS dams had ~20% lower circulating corticosterone levels than controls. Furthermore, there was a significant interaction between maternal diet and fetal sex for circulating corticosterone levels in the fetuses, whereby HFHS males tended to have higher corticosterone than control males, with no effect in female fetuses. However, placental 11β-HSD1 or 11β-HSD2 expression did not differ between diets or show an interaction between diet and sex. To assess potential long-term consequences of this sex-specific effect on fetal corticosterone, we studied locomotor activity and metabolic traits in adult offspring. Despite a sex-specific effect of maternal diet on fetal glucocorticoids, there was little evidence of sex-specific effects on offspring physiology or behaviour, although HFHS offspring of both sexes had higher circulating corticosterone at 9 weeks of age. Our results suggest the existence of as yet unknown mechanisms that mitigate the effects of altered glucocorticoid exposure early in development, making offspring resilient to the potentially negative effects of a HFHS maternal diet.


    Directory of Open Access Journals (Sweden)

    Roman Aleksandrovich Bekker


    Full Text Available Purpose. To study and summarize the existing evidence base for the use of melatonin as a mean to counteract or diminish the side effects of various psychotropic drugs and electroconvulsive therapy, and to provide the reader with relevant conclusions. Methodology. The authors have searched for the scientific literature regarding the use of melatonin as a mean to counteract or diminish the side effects of various psychotropic drugs and electroconvulsive therapy, using the PubMed and Google Scholar as a search tool. Then the authors thoroughly reviewed the data they found. The resulting review is presented in this article. Results. The data we have obtained from this review of the literature indicate that melatonin can be effectively used both in monotherapy and in combination with other therapeutic means in order to reduce several different side effects of psychotropic drugs and electroconvulsive therapy. Melatonin also deserves further study in this regard. The evidence base for its use in this manner is very variable in quality for different side effects. For now, the greatest evidence base exists regarding the potential effectiveness of melatonin in the prevention and treatment of drug-induced insomnia, memory and cognitive impairment, akathisia, tardive dyskinesias, and metabolic syndrome. Practical implications. The results we have obtained can be widely applied in psychiatry, neurology and addiction medicine, as well as in all those areas of general medicine, which make use of psychotropic drugs.

  2. Effect of Rotational Speed on the Stability of Two Rotating Side-by-side Circular Cylinders at Low Reynolds Number (United States)

    Dou, Huashu; Zhang, Shuo; Yang, Hui; Setoguchi, Toshiaki; Kinoue, Yoichi


    Flow around two rotating side-by-side circular cylinders of equal diameter D is numerically studied at the Reynolds number 40≤ Re ≤200 and various rotation rate θ i . The incoming flow is assumed to be two-dimensional laminar flow. The governing equations are the incompressible Navier-Stokes equations and solved by the finite volume method (FVM). The ratio of the center-to-center spacing to the cylinder diameter is T/D=2. The objective of the present work is to investigate the effect of rotational speed and Reynolds number on the stability of the flow. The simulation results are compared with the experimental data and a good agreement is achieved. The stability of the flow is analyzed by using the energy gradient theory, which produces the energy gradient function K to identify the region where the flow is the most prone to be destabilized and the degree of the destabilization. Numerical results reveal that K is the most significant at the separated shear layers of the cylinder pair. With Re increases, the length of the wake is shorter and the vortex shedding generally exhibits a symmetrical distribution for θ i < θ crit . It is also shown that the unsteady vortex shedding can be suppressed by rotating the cylinders in the counter-rotating mode.

  3. Pretreatment with divided doses of steroids strongly decreases side effects of OKT3

    NARCIS (Netherlands)

    Bemelman, F. J.; Buysmann, S.; Surachno, J.; Wilmink, J. M.; Schellekens, P. T.; ten Berge, I. J.


    The aim of this study was to attenuate side effects of OKT3 by variation of the time interval between administration of corticosteroids and OKT3 in renal allograft recipients. In view of a maximal lymphocytopenia at six hours following MPNS, we postulated a greater preventive action on side effects

  4. Comparison of the Efficacy and Side Effects of Chlorhexidine Mouthrinses with (Hexidine and without (Epimax Alcohol

    Directory of Open Access Journals (Sweden)

    Ahmad Mogharehabed


    Conclusion: Although Epimax mouthwash did not show any side effects, it was less suitable and caused more dental stain. Ethanol-free Hexidine mouthwash seems to be more proper for gingivitis, but its side effects are required to be taken into consideration.

  5. Nursing-led management of side effects of radiation: evidence-based recommendations for practice

    Directory of Open Access Journals (Sweden)

    Poirier P


    Full Text Available Patricia PoirierUniversity of Maine School of Nursing, Orono, ME, USAAbstract: It has been estimated that 50%–60% of patients diagnosed with cancer will receive radiation therapy at some point in their treatment. Although radiation therapy can play a significant role in the cure or control of cancer, and the palliation of symptoms, it also has side effects. Side effects of radiation therapy can interfere with patient quality of life and daily functioning. Severe side effects can lead to delays in treatment, potentially affecting the outcome of treatment. All patients receiving radiation therapy are at risk of fatigue and skin reactions in the area of the body being treated. Other side effects of radiation therapy are specific to the part of the body being treated. Radiation therapy to the head and neck area may cause oral mucositis, dryness, and nutritional deficiencies. Radiation therapy to the chest or lung area may lead to difficulty in swallowing and eating. Radiation therapy to the pelvis frequently causes diarrhea. There are many nursing interventions available to manage the side effects of treatment based on best available evidence and expert opinion. Nurses in all settings are essential in helping patients manage the side effects of treatment and maintain their quality of life. The purpose of this review is to provide nurses with evidence-based recommendations and suggestions for managing common acute side effects of radiation therapy.Keywords: evidence-based practice, radiation therapy, side effects, nursing management

  6. Pharmacogenomic and clinical data link non-pharmacokinetic metabolic dysregulation to drug side effect pathogenesis

    DEFF Research Database (Denmark)

    Zielinski, Daniel C.; Filipp, F. V.; Bordbar, A.


    Drug side effects cause a significant clinical and economic burden. However, mechanisms of drug action underlying side effect pathogenesis remain largely unknown. Here, we integrate pharmacogenomic and clinical data with a human metabolic network and find that non-pharmacokinetic metabolic pathways...

  7. Underreporting of side effects of standard first-line ART in the routine ...

    African Journals Online (AJOL)

    Malawi Medical Journal; 23(4): 116-118 December 2011. Side effects of standard first line in ART 116. Underreporting of side effects of standard first-line. ART in the routine setting in Blantyre, Malawi. Abstract. Introduction. In the Malawi ART programme, 92% of 250,000 patients are using the standard first-line regime of ...

  8. A hierarchical anatomical classification schema for prediction of phenotypic side effects. (United States)

    Wadhwa, Somin; Gupta, Aishwarya; Dokania, Shubham; Kanji, Rakesh; Bagler, Ganesh


    Prediction of adverse drug reactions is an important problem in drug discovery endeavors which can be addressed with data-driven strategies. SIDER is one of the most reliable and frequently used datasets for identification of key features as well as building machine learning models for side effects prediction. The inherently unbalanced nature of this data presents with a difficult multi-label multi-class problem towards prediction of drug side effects. We highlight the intrinsic issue with SIDER data and methodological flaws in relying on performance measures such as AUC while attempting to predict side effects.We argue for the use of metrics that are robust to class imbalance for evaluation of classifiers. Importantly, we present a 'hierarchical anatomical classification schema' which aggregates side effects into organs, sub-systems, and systems. With the help of a weighted performance measure, using 5-fold cross-validation we show that this strategy facilitates biologically meaningful side effects prediction at different levels of anatomical hierarchy. By implementing various machine learning classifiers we show that Random Forest model yields best classification accuracy at each level of coarse-graining. The manually curated, hierarchical schema for side effects can also serve as the basis of future studies towards prediction of adverse reactions and identification of key features linked to specific organ systems. Our study provides a strategy for hierarchical classification of side effects rooted in the anatomy and can pave the way for calibrated expert systems for multi-level prediction of side effects.

  9. Side Effects of Adjuvant Radiotherapy in Patients With Testicular Seminoma Stage I

    International Nuclear Information System (INIS)

    Gamulin, M.; Grgic, M.


    In the present study the side effects of adjuvant radiotherapy of testicular seminoma stage I patients were followed up in the period between 13 to 84 months (median 28 months). The most frequent side effects in these patients during radiotherapy were gastrointestinal problems (nausea/vomiting), psychologic and cognitive problems and minor sexual problems. The reported side effects were treated by antimmimetics and anxiolytics. After radiotherapy, the side effects persisted in 6 % of patients but therapy was needed only in few. Healthy children were born to 76 % of patients in the age group 18 - 39 years after radiotherapy. The present study shows that adjuvant irradiation of paraaortal lymph nodes with total a dose of 24 Gy in 16 daily fractions in testicular seminoma patients causes acceptable side effects with acceptable quality of life and fertility, however in conditions of individual approach and family consulting. (author)

  10. Effects of small-sided games on physical conditioning and performance in young soccer players. (United States)

    Katis, Athanasios; Kellis, Eleftherios


    The purpose of this study was to examine, first, the movement actions performed during two different small-sided games and, second, their effects on a series of field endurance and technical tests. Thirty-four young soccer players (age: 13 ± 0.9 yrs; body mass: 62.3 ± 15.1 kg; height: 1.65 ± 0.06 m) participated in the study. Small-sided games included three-a-side (3 versus 3 players) and six-a-side (6 versus 6 players) games consisting of 10 bouts of 4 min duration with 3 min active recovery between bouts. Soccer player performance was evaluated using five field tests: a) 30m sprint, b) throw-in for distance, c) Illinois Agility Test, d) dribbling the ball and e) horizontal jump before, in the middle and after the implementation of both game situations. Heart rate was monitored during the entire testing session. Each game was also filmed to measure soccer movements within the game. The ANOVA analysis indicated that the three-a- side games displayed significantly higher heart rate values compared with the six-a-side games (p players performed more long passes and headed the ball more often during the six-a-side (p performance (p performance were observed (p physical conditioning and technical improvement than six-a-side games and their use for training young soccer players is recommended. Key pointsThree-a-side games display higher HR compared with six-a-side games.In the three-a-side games players performed more short passes, kicks, dribbles, tackles and scored more goals compared with the six-a-side games.Impairment in endurance and field test performance was observed mainly after three-a-side games.The use of the three-a-side games to develop physical fitness and technique in young soccer players is recommended.

  11. The study of CD side to side error in line/space pattern caused by post-exposure bake effect (United States)

    Huang, Jin; Guo, Eric; Ge, Haiming; Lu, Max; Wu, Yijun; Tian, Mingjing; Yan, Shichuan; Wang, Ran


    In semiconductor manufacturing, as the design rule has decreased, the ITRS roadmap requires crucial tighter critical dimension (CD) control. CD uniformity is one of the necessary parameters to assure good performance and reliable functionality of any integrated circuit (IC) [1] [2], and towards the advanced technology nodes, it is a challenge to control CD uniformity well. The study of corresponding CD Uniformity by tuning Post-Exposure bake (PEB) and develop process has some significant progress[3], but CD side to side error happening to some line/space pattern are still found in practical application, and the error has approached to over the uniformity tolerance. After details analysis, even though use several developer types, the CD side to side error has not been found significant relationship to the developing. In addition, it is impossible to correct the CD side to side error by electron beam correction as such error does not appear in all Line/Space pattern masks. In this paper the root cause of CD side to side error is analyzed and the PEB module process are optimized as a main factor for improvement of CD side to side error.

  12. Optimal glucocorticoid therapy. (United States)

    Debono, Miguel; Ross, Richard J


    The rhythmic regulation of human physiology and behaviour is controlled by a central endogenous clock located in the suprachiasmatic nucleus. Most tissues have peripheral clocks that oscillate in time with this central clock. How the central time keeper controls peripheral clocks is not established, however there is evidence to suggest that the cortisol rhythm is one important secondary messenger. Loss of the endogenous cortisol rhythm is associated with sleep disturbance, depression, and metabolic abnormalities. In adrenal insufficiency, current glucocorticoid replacement regimens cannot replace the normal circadian rhythm of cortisol, and patients have an increased mortality and impaired quality of life. We propose that reproducing circadian cortisol levels may improve quality of life in patients with adrenal insufficiency and we have been investigating the impact of circadian hydrocortisone replacement. Using Chronocort, a modified release preparation of hydrocortisone, we have demonstrated that it is possible to simulate the overnight rise in cortisol release and, in preliminary studies in patients with congenital adrenal hyperplasia, control morning androgen levels. Future studies are now required to determine whether Chronocort can improve quality of life in patients with adrenal insufficiency. Copyright © 2011 S. Karger AG, Basel.

  13. In vivo and in vitro IL-18 production during uveitis associated with Behçet disease: effect of glucocorticoid therapy. (United States)

    Belguendouz, H; Messaoudene, D; Lahmar-Belguendouz, K; Djeraba, Z; Otmani, F; Terahi, M; Tiar, M; Hartani, D; Lahlou-Boukoffa, O S; Touil-Boukoffa, C


    Uveitis represents one of the major diagnostic criteria in Behçet's disease. It is most prevalent in the countries of the Mediterranean area, including Algeria, and along the Silk Road. Clinical features include oral and genital ulcers, ocular and skin lesions, as well as central nervous system, joint, vascular, gastrointestinal, or pulmonary manifestations. Many studies have reported that Th1 immune responses are involved in the physiopathology. We have previously studied the production of IL-12 and IFN-γ, cytokine markers in the Th1 pathway involved in Behçet's disease. In our study, we investigate in vivo and in vitro IL-18 production in Algerian patients with Behçet's disease with ocular manifestations in various stages of the disease. We examined the effect of glucocorticoids on IL-18 production during the active stage of the disease. Our results suggest that IL-18 could be a good biomarker for monitoring disease activity and its regression, demonstrating the effectiveness of treatment on the underlying immunopathologic process. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  14. Parental Expectation of Side Effects Following Vaccination Is Self-fulfilling: A Prospective Cohort Study. (United States)

    Smith, Louise E; Weinman, John; Amlôt, Richard; Yiend, Jenny; Rubin, G James


    One of the major factors contributing to parental refusal of vaccinations is the perception that vaccines cause side effects. Although symptoms are commonly reported following vaccinations, their causes are not always straightforward. Although some may be directly attributable to the vaccine itself, others may reflect pre-existing or coincidental symptoms that are misattributed to the vaccine. To investigate psychological factors associated with parental report of side effects following vaccination with the child influenza vaccine, and parental intention to re-vaccinate one's child the following year. A prospective cohort study was run in primary care practices in London in the 2016-2017 influenza season ( number NCT02909855). Two hundred seventy parents from 14 practices completed a questionnaire before their child's vaccination. Follow-up questionnaires were completed 3 days after vaccination and one month after vaccination. Parental report of side effects and vaccination intention for the subsequent year were measured. Parental report of side effects was strongly associated with pre-vaccination expectation of side effects. Suggestions received from the media, National Health Service (NHS) vaccination leaflet, and health care workers, as well as uncertainty-related beliefs, perceived sensitivity of the child to medicines, pessimism, and anxiety were also associated with reporting side effects. Side effect report was associated with lower vaccination intention for the following influenza season. Side effect perception following vaccination is influenced by psychological factors, in particular expectations. Perceiving side effects reduces future vaccination intention. Future public health communications should aim to decrease unrealistic expectations of side effects to increase vaccine uptake.

  15. Biochemical endpoints of glucocorticoid hormone action

    Energy Technology Data Exchange (ETDEWEB)

    Young, D.A.; Nicholson, M.L.; Guyette, W.A.; Giddings, S.J.; Mendelsohn, S.L.; Nordeen, S.K.; Lyons, R.T.


    Both the rapidly evolving metabolic effects of glucocorticoids and the more slowly developing lethal actions appear to be initiated via the synthesis of new mRNAs and proteins. The chronic suppression of cell growth may be the consequence of suppression of overall rates of protein synthesis (and probably RNA and DNA synthesis as well) that in turn may represent the cellular response to the small changes in ratios of adenine nucleotides that result from the suppression of oxidative ATP production. The inhibition of glucose transport may also play a role here to prevent a compensatory increase in glycolytic ATP production. Some other hormone actions, the decrease in the ability of cells to concentrate AIB and the increase in nuclear fragility are unrelated to, and evolve separately from, the hormonal inhibitions on energy production. Cell killing is not the result of suppression of protein synthesis, nor of hormone-induced increases in calcium uptake. While the mechanisms are unknown, the increase in nuclear fragility appears to be the earliest measure of their operation. In tumor cells resistance to lethal actions of glucocorticoids may emerge via the selection of cells with hardier membranes, that are better able to withstand the intracellular destructive events set in motion by high levels of glucocorticoids.

  16. Pharmacogenomic study of side-effects for antidepressant treatment options in STAR*D. (United States)

    Clark, S L; Adkins, D E; Aberg, K; Hettema, J M; McClay, J L; Souza, R P; van den Oord, E J C G


    Understanding individual differences in susceptibility to antidepressant therapy side-effects is essential to optimize the treatment of depression. We performed genome-wide association studies (GWAS) to search for genetic variation affecting the susceptibility to side-effects. The analysis sample consisted of 1439 depression patients, successfully genotyped for 421K single nucleotide polymorphisms (SNPs), from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Outcomes included four indicators of side-effects: general side-effect burden, sexual side-effects, dizziness and vision/hearing-related side-effects. Our criterion for genome-wide significance was a prespecified threshold ensuring that, on average, only 10% of the significant findings are false discoveries. Thirty-four SNPs satisfied this criterion. The top finding indicated that 10 SNPs in SACM1L mediated the effects of bupropion on sexual side-effects (p = 4.98 × 10(-7), q = 0.023). Suggestive findings were also found for SNPs in MAGI2, DTWD1, WDFY4 and CHL1. Although our findings require replication and functional validation, this study demonstrates the potential of GWAS to discover genes and pathways that could mediate adverse effects of antidepressant medication.

  17. Genome-wide pharmacogenomic study of citalopram-induced side effects in STAR*D. (United States)

    Adkins, D E; Clark, S L; Åberg, K; Hettema, J M; Bukszár, J; McClay, J L; Souza, R P; van den Oord, E J C G


    Affecting about 1 in 12 Americans annually, depression is a leading cause of the global disease burden. While a range of effective antidepressants are now available, failure and relapse rates remain substantial, with intolerable side effect burden the most commonly cited reason for discontinuation. Thus, understanding individual differences in susceptibility to antidepressant therapy side effects will be essential to optimize depression treatment. Here we perform genome-wide association studies (GWAS) to identify genetic variation influencing susceptibility to citalopram-induced side effects. The analysis sample consisted of 1762 depression patients, successfully genotyped for 421K single-nucleotide polymorphisms (SNPs), from the Sequenced Treatment Alternatives to Relieve Depression (STAR(*)D) study. Outcomes included five indicators of citalopram side effects: general side effect burden, overall tolerability, sexual side effects, dizziness and vision/hearing side effects. Two SNPs met our genome-wide significance criterion (qeffects of citalopram on vision/hearing side effects (P=3.27 × 10(-8), q=0.026). The second genome-wide significant finding, representing a haplotype spanning ∼30 kb and eight genotyped SNPs in a gene desert on chromosome 13, was associated with general side effect burden (P=3.22 × 10(-7), q=0.096). Suggestive findings were also found for SNPs at LAMA1, AOX2P, EGFLAM, FHIT and RTP2. Although our findings require replication and functional validation, this study demonstrates the potential of GWAS to discover genes and pathways that potentially mediate adverse effects of antidepressant medications.

  18. Dynamics of energy-related CO2 emissions in China during 1980-2002: the relative importance of energy supply-side and demand-side effects

    International Nuclear Information System (INIS)

    Libo Wu; Kaneko, Shinji; Matsuoka, Shunji


    Based on a newly developed model that integrates energy production, transformation and consumption processes, this paper compares the relative importance of some traditionally recognized factors operating on the energy demand side with a body of newly defined factors on the supply side, in terms of their contribution to trends in China's CO 2 emissions related to the total primary energy supply (C-TPES). Before 1996, changes in China's C-TPES were mainly driven by changes on the energy demand side. Factors operating on the energy supply side played trivial roles. During the period 1996-2000, however, increasing demand-side effects declined dramatically and at the same time decreasing effects from supply side expanded significantly. Such changes resulted directly in a decline in the C-TPES. The decreasing effects from international trade as well as statistical imbalances between supply and demand reinforced the declining trend. The shrinkage of demand side effects mainly arose from the slowdown of economic growth and speed of decrease in energy intensity. The expansion of supply-side effects was principally attributed to the speed of decrease in gross unit consumption in transformation sectors, especially in electricity sector. Therefore, the acceleration of efficiency improvements in end-use and transformation sectors accounted for the decline in the C-TPES over the period 1996-2000. (author)

  19. OGT-related mitochondrial motility is associated with sex differences and exercise effects in depression induced by prenatal exposure to glucocorticoids. (United States)

    Liu, Weina; Wang, Hongmei; Xue, Xiangli; Xia, Jie; Liu, Jiatong; Qi, Zhengtang; Ji, Liu


    Prenatal exposure to glucocorticoids (GCs) has been found to trigger abnormal behaviors and deleterious neurological effects on offspring both in animals and in humans. The sex differences in depression have been replicated in numerous studies across cultures, persisting throughout the reproductive years. As an X-linked gene in rodents and in humans, O-GlcNAc transferase (OGT) may provide a novel perspective for the sex differences in depression. In the last third of pregnancy (gestational day 14-21), rats were subcutaneously administered either 0.13mg/kg dexamethasone-21-phosphate disodium salt (0.1mg/kg DEX) or vehicle (0.9% saline) once a day for 7 days. Adolescent (4 weeks) offspring were then trained in a swimming program or not. Here we found that adult offspring rats exposed to DEX prenatally exhibited sex-specific depression-like behaviors, males being more vulnerable than females. Swimming exercise ameliorated the above-mentioned depressive syndromes, which may be a compensatory effect for male disadvantage suffering from prenatal stress. Furthermore, the effects of prenatal DEX exposure and swimming exercise on depression were associated with OGT-related mitochondrial motility, including PINK1/Parkin pathway and AKT/GSK3β pathway. Representative kymographs of mitochondrial motility were not detected and no causal effects were obtained by OGT gene overexpression or gene knockout in this study. Our results provide a new perspective for better understanding sex differences and exercise effects in depression and may offer new mechanism-based therapeutic targets for depression. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Medication side effects among people with epilepsy taking phenobarbital in Zambia. (United States)

    Elafros, Melissa A; Bui, Esther; Birbeck, Gretchen L


    Phenobarbital remains one of the most widely used antiepileptic drugs worldwide, yet there are limited data regarding side effects associated with its use in routine clinical care settings in low-income countries. Available data suggests that phenobarbital is as effective as other first-line drugs for treating tonic-clonic seizures, but side effect reports differ widely between high and low-income settings. A better understanding of phenobarbital side effect profile and severity in low-income settings is warranted given its role in efforts to decrease the epilepsy treatment gap. We used the Liverpool adverse events profile (LEAP) to assess side effects in consecutive patients with epilepsy on phenobarbital seeking care in rural Zambia. Data regarding age, gender, medication dose, and medication adherence were also collected. T-tests and Spearman's correlation coefficient were used to assess predictors of LEAP score and medication adherence. Thirty-five patients receiving a mean dose of 2.1mg/kg/day (SD: 2.78 mg/kg/day) of phenobarbital were assessed. All participants reported at least one side effect in the previous four weeks with a median of 6 symptoms (IQR: 4-8) and a mean side effects score of 28/76 (SD: 5.38). Over half reported sleepiness and dizziness. Memory problems and depression were also common (both 46%). Total LAEP score was not associated with age (p=0.88), gender (p=0.17), or phenobarbital dose (p=0.13). Medication adherence was not associated with side effects total score (p=0.56). Rural Zambian adults taking phenobarbital at doses recommended by the World Health Organization report a significant number of side effects. The most common side effects reported were similar to those reported in high-income countries. The significant burden of phenobarbital-associated side effects in this African cohort is in contrast to data from non-randomized clinical trials in China that reported phenobarbital to be well-tolerated with few side effects. Additional

  1. Prognosis after acute lymphoblastic leukaemia. [Side effects of radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Howarth, C B


    Following chemotherapy of lymphoblastic leukemia in children with folic acid antagonists, remission is achieved in 94 percent of patients. After chemotherapy has been stopped the risk of relapse is greatest during the first year, but relapses do occur. Sequelae of radiotherapy include bone growth impairment, brain cell damage, radioinduced neoplasms, and immunosuppression. Adverse effects of chemotherapy include hepatic fibrosis, impaired gonadal development, and oncogenic effects. (HLW)

  2. Factors associated with the perception of side-effects relating to the use of contraceptive methods

    Directory of Open Access Journals (Sweden)

    Gerda Erasmus


    Full Text Available Limited research has been done in South Africa regarding the incidence of side-effects and perceptions of these among users of contraceptives. Numerous knowledge, attitude and practice (KAP surveys have been conducted by the Human Sciences Research Council (Erasmus 1981a; Erasmus 1981b; Erasmus 1982 ; Groenewald 1978 ; Lótter, Van Tonder 1976; Mostert, Malherbe 1974; Mostert 1974; Strydom 1981; Van der Merwe 1982 and in some of these studies questions concerning side-effects were included to determine reasons for discontinuation of specific contraceptive methods. The literature concerning research on side-effects related to contraceptive use usually pertains either to clinical studies

  3. Symptoms and side effects in chronic non-cancer pain: patient report vs. systematic assessment

    DEFF Research Database (Denmark)

    Jonsson, Torsten; Christrup, Lona Louring; Højsted, J


    relieving distressing symptoms and managing the side effects of analgesics are essential in order to improve quality of life and functional capacity in chronic non-cancer pain patients. A quick, reliable and valid tool for assessing symptoms and side effects is needed in order to optimize treatment....... We aimed to investigate the symptoms reported by chronic non-cancer pain patients after open-ended questioning vs. a systematic assessment using a list of symptoms, and to assess whether the patients could distinguish between the symptoms and the side effects induced by analgesics....

  4. Symptoms and side effects in chronic non-cancer pain:patient report vs. systematic assessment

    DEFF Research Database (Denmark)

    Jonsson, Torsten; Christrup, Lona Louring; Højsted, Jette


    relieving distressing symptoms and managing the side effects of analgesics are essential in order to improve quality of life and functional capacity in chronic non-cancer pain patients. A quick, reliable and valid tool for assessing symptoms and side effects is needed in order to optimize treatment....... We aimed to investigate the symptoms reported by chronic non-cancer pain patients after open-ended questioning vs. a systematic assessment using a list of symptoms, and to assess whether the patients could distinguish between the symptoms and the side effects induced by analgesics....

  5. Lymphadenitis as a Rare Side Effect of H1N1 Vaccine in a Child

    Directory of Open Access Journals (Sweden)

    Zuhal Gundogdu


    Full Text Available We present a 5-year-old boy who had the complaint of swelling and pain on the right vaccine shot and right axillary areas. The right axillary area was diagnosed as reactive lymphadenitis, which we believe is a rare local side effect of the swine flu vaccine. The key message to take away from this case is that the patient had lymphadenitis as a local side effect of the swine flu vaccine. Lymphadenitis should be reported as a possible local side effect of the swine flu vaccine.

  6. Lymphadenitis as a Rare Side Effect of H1N1 Vaccine in a Child (United States)

    Gundogdu, Zuhal; Seyhogullari, Mualla


    We present a 5-year-old boy who had the complaint of swelling and pain on the right vaccine shot and right axillary areas. The right axillary area was diagnosed as reactive lymphadenitis, which we believe is a rare local side effect of the swine flu vaccine. The key message to take away from this case is that the patient had lymphadenitis as a local side effect of the swine flu vaccine. Lymphadenitis should be reported as a possible local side effect of the swine flu vaccine. PMID:21209734

  7. Side Effects of Nitrification Inhibitors on Non Target Microbial Processes in Soils


    Johannes Carl Gottlieb Ottow; Gero Benckiser; Ferisman Tindaon


    Agricultural chemicals have been used extensively in modern agriculture and toxicological studies suggest a great potential for inducing undesirable effects on non target organisms. A model experiment was conducted in order to determine side effects of three nitrification inhibitors (NIs, 3,4dimethylpyrazolephosphate = DMPP, 4-Chlormethylpyrazole phosphate = ClMPP and dicyandiamide = DCD) on non target microbial processes in soils. Side effects and dose response curve of three NIs were quanti...

  8. Backreaction effects on the matter side of Einstein's field equations

    CERN Document Server

    Floerchinger, Stefan; Wiedemann, Urs Achim


    Recently, we have derived a novel and compact expression for how perturbations in the matter fields of the cosmological fluid can lead to deviations from the standard Friedmann equations. Remarkably, the dissipative damping of velocity perturbations by bulk and shear viscosity in the dark sector can modify the expansion history of the universe on arbitrarily large scales. In universes in which this effect is sufficiently sizeable, it could account for the acceleration of the cosmological expansion. But even if dark matter should be less viscous and if the effect would be correspondingly smaller, it may have observable consequences in the era of precision cosmology. Here, we review the origin of this backreaction effect and possibilities to constrain it further.

  9. Correlation effects in side-coupled quantum dots

    International Nuclear Information System (INIS)

    Zitko, R; Bonca, J


    Using Wilson's numerical renormalization group (NRG) technique, we compute zero-bias conductance and various correlation functions of a double quantum dot (DQD) system. We present different regimes within a phase diagram of the DQD system. By introducing a negative Hubbard U on one of the quantum dots, we simulate the effect of electron-phonon coupling and explore the properties of the coexisting spin and charge Kondo state. In a triple quantum dot (TQD) system, a multi-stage Kondo effect appears where localized moments on quantum dots are screened successively at exponentially distinct Kondo temperatures

  10. Side effects of antiviral therapy in hepatitis C virus infection-sarcoidosis - case report. (United States)

    Teodor, D; Teodor, Andra; Grigore, Lucia; Jugănariu, Gabriela; Dorobăţ, Carmen Mihaela; Miftode, Egidia; Azoicăi, Doina


    Standard therapy in chronic hepatitis C virus infection is still a combination of peginterferon alfa2a/2b and ribavirin for 48 weeks. As of side effects, there are organic side effects, such as hematologic disorders, and functional side effects, reflected in the quality of life of hepatitis C patients. Up to 30% of the patients develop specific side effects such as headache, fever, fatigue. Sarcoidosis, known as a granulomatous disease of uncertain cause, is an uncommon finding in this category of patients. This cause-effect relation is accounted for by the convergent action of peginterferon and ribavirin of stimulating type 1 T helper cells and reducing type 2 helper T cells activation. We present the case of male patient known with chronic hepatitis C who developed pulmonary sarcoidosis following antiviral therapy. The first manifestation of the disease was unexplained fever accompanied by pulmonary tract disease. The diagnosis was established by immunophenotyping in bronchial aspirate

  11. Cell-specific expression of the glucocorticoid receptor within granular convoluted tubules of the rat submaxillary gland

    International Nuclear Information System (INIS)

    Antakly, T.; Zhang, C.X.; Sarrieau, A.; Raquidan, D.


    The submaxillary gland, a heterogeneous tissue composed essentially of two functionally distinct cell types (tubular epithelial and acinar), offers an interesting system in which to study the mechanisms of steroid-dependent growth and differentiation. One cell type, the granular convoluted tubular (GCT) cell, secretes a large number of physiologically important polypeptides, including epidermal and nerve growth factors. Two steroids, androgens and glucocorticoids, greatly influence the growth, differentiation, and secretory activity of GCT cells. Because glucocorticoids can partially mimic or potentiate androgen effects, it has been thought that glucocorticoids act via androgen receptors. Since the presence of glucocorticoid receptors is a prerequisite for glucocorticoid action, we have investigated the presence and cellular distribution of glucocorticoid receptors within the rat submaxillary gland. Binding experiments using [3H]dexamethasone revealed the presence of high affinity binding sites in rat submaxillary tissue homogenates. Most of these sites were specifically competed by dexamethasone, corticosterone, and a pure glucocorticoid agonist RU 28362. Neither testosterone nor dihydrotestosterone competed for glucocorticoid binding. The cellular distribution of glucocorticoid receptors within the submaxillary gland was investigated by immunocytochemistry, using two highly specific glucocorticoid receptor antibodies. The receptor was localized in the GCT cells, but not in the acinar cells of rat and mouse submaxillary tissue sections. In GCT cells, the glucocorticoid receptor colocalized with several secretory polypeptides, including epidermal growth factor, nerve growth factor, alpha 2u-globulin, and atrial natriuretic factor

  12. Performance outcomes and unwanted side effects associated with energy drinks. (United States)

    Mora-Rodriguez, Ricardo; Pallarés, Jesús G


    Energy drinks are increasingly popular among athletes and others. Advertising for these products typically features images conjuring great muscle power and endurance; however, the scientific literature provides sparse evidence for an ergogenic role of energy drinks. Although the composition of energy drinks varies, most contain caffeine; carbohydrates, amino acids, herbs, and vitamins are other typical ingredients. This report analyzes the effects of energy drink ingredients on prolonged submaximal (endurance) exercise as well as on short-term strength and power (neuromuscular performance). It also analyzes the effects of energy drink ingredients on the fluid and electrolyte deficit during prolonged exercise. In several studies, energy drinks have been found to improve endurance performance, although the effects could be attributable to the caffeine and/or carbohydrate content. In contrast, fewer studies find an ergogenic effect of energy drinks on muscle strength and power. The existing data suggest that the caffeine dose given in studies of energy drinks is insufficient to enhance neuromuscular performance. Finally, it is unclear if energy drinks are the optimal vehicle to deliver caffeine when high doses are needed to improve neuromuscular performance. © 2014 International Life Sciences Institute.

  13. Side effects of pain and analgesia in animal experimentation. (United States)

    Jirkof, Paulin


    This review highlights selected effects of untreated pain and of widely used analgesics such as opioids, non-steroid anti-inflammatory drugs and antipyretics, to illustrate the relevance of carefully planned, appropriate and controlled analgesia for greater reproducibility in animal experiments involving laboratory rodents.

  14. Fructose, Glucocorticoids and Adipose Tissue: Implications for the Metabolic Syndrome. (United States)

    Legeza, Balázs; Marcolongo, Paola; Gamberucci, Alessandra; Varga, Viola; Bánhegyi, Gábor; Benedetti, Angiolo; Odermatt, Alex


    The modern Western society lifestyle is characterized by a hyperenergetic, high sugar containing food intake. Sugar intake increased dramatically during the last few decades, due to the excessive consumption of high-sugar drinks and high-fructose corn syrup. Current evidence suggests that high fructose intake when combined with overeating and adiposity promotes adverse metabolic health effects including dyslipidemia, insulin resistance, type II diabetes, and inflammation. Similarly, elevated glucocorticoid levels, especially the enhanced generation of active glucocorticoids in the adipose tissue due to increased 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) activity, have been associated with metabolic diseases. Moreover, recent evidence suggests that fructose stimulates the 11β-HSD1-mediated glucocorticoid activation by enhancing the availability of its cofactor NADPH. In adipocytes, fructose was found to stimulate 11β-HSD1 expression and activity, thereby promoting the adipogenic effects of glucocorticoids. This article aims to highlight the interconnections between overwhelmed fructose metabolism, intracellular glucocorticoid activation in adipose tissue, and their metabolic effects on the progression of the metabolic syndrome.

  15. The effect of chronic phenytoin administration on single prolonged stress induced extinction retention deficits and glucocorticoid upregulation in the rat medial prefrontal cortex. (United States)

    George, Sophie A; Rodriguez-Santiago, Mariana; Riley, John; Rodriguez, Elizabeth; Liberzon, Israel


    Post-traumatic stress disorder (PTSD) is a chronic, debilitating disorder. Only two pharmacological agents are approved for PTSD treatment, and they often do not address the full range of symptoms nor are they equally effective in all cases. Animal models of PTSD are critical for understanding the neurobiology involved and for identification of novel therapeutic targets. Using the rodent PTSD model, single prolonged stress (SPS), we have implicated aberrant excitatory neural transmission and glucocorticoid receptor (GR) upregulation in the medial prefrontal cortex (mPFC) and hippocampus (HPC) in fear memory abnormalities associated with PTSD. The objective of this study is to examine the potential protective effect of antiepileptic phenytoin (PHE) administration on SPS-induced extinction retention deficits and GR expression. Forty-eight SPS-treated male Sprague Dawley rats or controls were administered PHE (40, 20 mg/kg, vehicle) for 7 days following SPS stressors; then, fear conditioning, extinction, and extinction retention were tested. Fear conditioning and extinction were unaffected by SPS or PHE, but SPS impaired extinction retention, and both doses of PHE rescued this impairment. Similarly, SPS increased GR expression in the mPFC and dorsal HPC, and PHE prevented SPS-induced GR upregulation in the mPFC. These data demonstrate that PHE administration can prevent the development of extinction retention deficits and upregulation of GR. PHE exerts inhibitory effects on voltage-gated sodium channels and decreases excitatory neural transmission via glutamate antagonism. If glutamate hyperactivity in the days following SPS contributes to SPS-induced deficits, then these data may suggest that the glutamatergic system constitutes a target for secondary prevention.

  16. Melatonin protects chondrocytes from impairment induced by glucocorticoids via NAD+-dependent SIRT1. (United States)

    Yang, Wei; Kang, Xiaomin; Qin, Na; Li, Feng; Jin, Xinxin; Ma, Zhengmin; Qian, Zhuang; Wu, Shufang


    Intra-articular injection of glucocorticoids is used to relieve pain and inflammation in osteoarthritis patients, which is occasionally accompanied with the serious side effects of glucocorticoids in collagen-producing tissue. Melatonin is the major hormone released from the pineal gland and its beneficial effects on cartilage has been suggested. In the present study, we investigated the protective role of melatonin on matrix degeneration in chondrocytes induced by dexamethasone (Dex). The chondrocytes isolated from mice knee joint were treated with Dex, melatonin, EX527 and siRNA targeted for SIRT6, respectively. Dex treatment induced the loss of the extracellular matrix, NAD + /NADH ratio and NADPH concentration in chondrocytes. Melatonin alone have no effect on the quantity of proteoglycans and collagen type IIa1, however, the pretreatment of melatonin reversed the negative effects induced by Dex. Meanwhile, the significant decrease in NAD + /NADH ratio and NADPH concentration in Dex group were up-regulated by pretreatment of melatonin. Furthermore, it was revealed that inhibition of SIRT1 blocked the protective effects of melatonin. The enhancement of NAD + -dependent SIRT1 activity contributes to the chondroprotecfive effects of melatonin, which has a great benefit to prevent dexamethasone-induced chondrocytes impairment. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Being green on sulphur: Targets, measures and side-effects

    DEFF Research Database (Denmark)

    Kontovas, Christos A.; Panagakos, George; Psaraftis, Harilaos N.


    to sea to reduce congestion, and might ultimately (under certain circumstances) increase the overall level of CO2 emissions along the entire supply chain. The purpose of this chapter is to investigate the potential effect of sulphur regulations on the share of cargo transported by the waterborne mode vis......Green House Gas (GHG) emissions are not the only emissions of concern to the international transport community. SOx emissions are non-GHG emissions that are caused by the presence of sulphur in the fuel. As the maximum percentage of sulphur in automotive and aviation fuels is strictly regulated...

  18. The frequency of occurrence and severity of side-effects of immersion virtual reality. (United States)

    Regan, E C; Price, K R


    Virtual reality (VR) has become increasingly well-known over the last few years. However, little is known about the side-effects of prolonged immersion in VR. This study set out to investigate the frequency of occurrence and severity of side-effects of using an immersion VR system. Out of 146 subjects, 61% reported symptoms of malaise at some point during a 20-min immersion and 10-min post-immersion period. These ranged from symptoms such as dizziness, stomach awareness, headaches, eyestrain and lightheadedness to severe nausea. These symptoms caused 5% of the subjects to withdraw from the experiment before completing their 20-min immersion period. Further research needs to be conducted that attempts to identify those factors that play a causative role in the side-effects of the VR system, and that looks for methods of reducing these side-effects.

  19. Side effects and risks of radioiodine treatment of benign thyroid diseases

    International Nuclear Information System (INIS)

    Becker, W.; Hohenberger, W.; Wolf, F.; Erlangen-Nuernberg Univ., Erlangen


    Radioiodine treatment is considered to be the treatment of choice in benign thyroid diseases because of its very low side effects. Real and hypothetic risks and side effects have to be differentiated. Both may occur early and late after the treatment. Radioiodinethyroiditis in small volumes at high doses is very rare. Exacerbation of a thyroid storm (0.34%) as well as local compressions accompanied with reactive edema of the thyroid are early real side effects of radioiodine treatment. Late real side effects are failure of treatment (7-30% of thyrotoxicosis) and induction of hypothyroidism (4-20% of functional autonomy and increasing frequency in Graves' diseases with time). Late hypothetic risks are somatic (1-9/10000 bis 1-9/100000) or genetic (1-9/100000). An early risk might be the misdiagnosis of an additional thyroid carcinoma. (orig.) [de

  20. Fatigue and gene expression in human leukocytes: Increased NF-κB and decreased glucocorticoid signaling in breast cancer survivors with persistent fatigue (United States)

    Bower, Julienne E.; Ganz, Patricia A.; Irwin, Michael R.; Arevalo, Jesusa M.G.; Cole, Steve W.


    Fatigue is highly prevalent in the general population and is one of the most common side effects of cancer treatment. There is growing evidence that pro-inflammatory cytokines play a role in cancer-related fatigue, although the molecular mechanisms for chronic inflammation and fatigue have not been determined. The current study utilized genome-wide expression microarrays to identify differences in gene expression and associated alterations in transcriptional activity in leukocytes from breast cancer survivors with persistent fatigue (n = 11) and non-fatigued controls (n = 10). We focused on transcription of inflammation-related genes, particularly those responsive to the pro-inflammatory NF-κB transcription control pathway. Further, given the role of glucocorticoids as key regulators of inflammatory processes, we examined transcription of glucocorticoid-responsive genes indicative of potential glucocorticoid receptor (GR) desensitization. Plasma levels of cortisol were also assessed. Consistent with hypotheses, results showed increased expression of transcripts with response elements for NF-κB, and reduced expression of transcripts with response elements for glucocorticoids (p < .05) in fatigued breast cancer survivors. No differences in plasma levels of cortisol were observed. These data indicate that increased activity of pro-inflammatory transcription factors may contribute to persistent cancer-related fatigue and provide insight into potential mechanisms for tonic increases in NF-κB activity, specifically decreased expression of GR anti-inflammatory transcription factors. PMID:20854893

  1. Reduced peripheral expression of the glucocorticoid receptor α isoform in individuals with posttraumatic stress disorder: a cumulative effect of trauma burden. (United States)

    Gola, Hannah; Engler, Andrea; Morath, Julia; Adenauer, Hannah; Elbert, Thomas; Kolassa, Iris-Tatjana; Engler, Harald


    Posttraumatic stress disorder (PTSD) is a serious psychiatric condition that was found to be associated with altered functioning of the hypothalamic-pituitary-adrenal (HPA) axis and changes in glucocorticoid (GC) responsiveness. The physiological actions of GCs are primarily mediated through GC receptors (GR) of which isoforms with different biological activities exist. This study aimed to investigate whether trauma-experience and/or PTSD are associated with altered expression of GR splice variants. GRα and GRβ mRNA expression levels were determined by real-time quantitative PCR in whole blood samples of individuals with chronic and severe forms of PTSD (n = 42) as well as in ethnically matched reference subjects (non-PTSD, n = 35). Individuals suffering from PTSD exhibited significantly lower expression of the predominant and functionally active GRα isoform compared to non-PTSD subjects. This effect remained significant when accounting for gender, smoking, psychotropic medication or comorbid depression. Moreover, the GRα expression level was significantly negatively correlated with the number of traumatic event types experienced, both in the whole sample and within the PTSD patient group. Expression of the less abundant and non-ligand binding GRβ isoform was comparable between patient and reference groups. Reduced expression of the functionally active GRα isoform in peripheral blood cells of individuals with PTSD seems to be a cumulative effect of trauma burden rather than a specific feature of PTSD since non-PTSD subjects with high trauma load showed an intermediate phenotype between PTSD patients and individuals with no or few traumatic experiences.

  2. Reduced peripheral expression of the glucocorticoid receptor α isoform in individuals with posttraumatic stress disorder: a cumulative effect of trauma burden.

    Directory of Open Access Journals (Sweden)

    Hannah Gola

    Full Text Available BACKGROUND: Posttraumatic stress disorder (PTSD is a serious psychiatric condition that was found to be associated with altered functioning of the hypothalamic-pituitary-adrenal (HPA axis and changes in glucocorticoid (GC responsiveness. The physiological actions of GCs are primarily mediated through GC receptors (GR of which isoforms with different biological activities exist. This study aimed to investigate whether trauma-experience and/or PTSD are associated with altered expression of GR splice variants. METHODS: GRα and GRβ mRNA expression levels were determined by real-time quantitative PCR in whole blood samples of individuals with chronic and severe forms of PTSD (n = 42 as well as in ethnically matched reference subjects (non-PTSD, n = 35. RESULTS: Individuals suffering from PTSD exhibited significantly lower expression of the predominant and functionally active GRα isoform compared to non-PTSD subjects. This effect remained significant when accounting for gender, smoking, psychotropic medication or comorbid depression. Moreover, the GRα expression level was significantly negatively correlated with the number of traumatic event types experienced, both in the whole sample and within the PTSD patient group. Expression of the less abundant and non-ligand binding GRβ isoform was comparable between patient and reference groups. CONCLUSIONS: Reduced expression of the functionally active GRα isoform in peripheral blood cells of individuals with PTSD seems to be a cumulative effect of trauma burden rather than a specific feature of PTSD since non-PTSD subjects with high trauma load showed an intermediate phenotype between PTSD patients and individuals with no or few traumatic experiences.

  3. Study of ageing side effects in the DELPHI HPC calorimeter

    CERN Document Server

    Bonivento, W


    The readout proportional chambers of the HPC electromagnetic calorimeter in the DELPHI experiment are affected by large ageing. In order to study the long-term behaviour fo the calorimeter, one HPC module was extracted from DELPHI in 1992 and was brought to a test area where it was artificially aged during a period of two years; an ageing level exceeding the one expected for the HPC at the end of the LEP era was reached. During this period the performance of the module was periodically tested by means of dedicated beam tests whose results are discussed in this paper. These show that ageing has no significant effects on the response linearity and on the energy resolution for electromagnetic showers, once the analog response loss is compensated for by increasing the chamber gain through the anode voltage.

  4. The Effect of Material and Side Walls on Hull Deflection during a Blast Event (United States)


    ARL-CR-0822 ● DEC 2017 US Army Research Laboratory The Effect of Material and Side Walls on Hull Deflection during a Blast Event...Army Research Laboratory The Effect of Material and Side Walls on Hull Deflection during a Blast Event prepared by Danielle Abell SURVICE...Walls on Hull Deflection during a Blast Event 5a. CONTRACT NUMBER W911QX-16-D-0014 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S





    Introduction: Acne vulgaris is an inflammatory disease of pilosebaceous folicles. Tretinoin is used as one of the topical treatments for acne vulgaris. It has different cutaneous side effects such as erythema, scaling, irritation and photosensitivity. The aim of this study was to evaluate the efficacy of oral Vitamine E in preventing the cutaneous side effects of topical tretinoin in acne patients...

  6. Hypertension as risk factor for radiation induced side-effects in breast cancer

    International Nuclear Information System (INIS)

    Boehler, F.K.; Rhomberg, W.; Doringer, W.


    130 breast cancer patients were retrospectively evaluated for side-effects to estimate the influence of arterial hypertension. All were treated with mastecomy and irradiation (telecobalt). 79 patients had normal blood pressure, 51 showed arterial hypertension. Hypertension proved to be the strongest endogeneous factor for the development of side-effects. In contrast to the patients with normal blood pressure those with hypertension showed significant more arm lymphedema (p [de

  7. Self-Limited Kleptomania Symptoms as a Side Effect of Duloxetine


    Miller, Christopher W. T.; Gallagher, Keith E.


    Introduction. Impulse control disorders (ICDs) have been described as a side effect of dopamine agonists, frequently used in neurodegenerative conditions affecting the nigrostriatal pathway. Serotonin-norepinephrine reuptake inhibitors (e.g., duloxetine) have dose-dependent differential affinity for monoaminergic transporters, inhibiting the dopamine transporter at higher doses, thus increasing availability of synaptic dopamine, with the potential for similar impulse control side effects. Cas...

  8. Integrative relational machine-learning for understanding drug side-effect profiles. (United States)

    Bresso, Emmanuel; Grisoni, Renaud; Marchetti, Gino; Karaboga, Arnaud Sinan; Souchet, Michel; Devignes, Marie-Dominique; Smaïl-Tabbone, Malika


    Drug side effects represent a common reason for stopping drug development during clinical trials. Improving our ability to understand drug side effects is necessary to reduce attrition rates during drug development as well as the risk of discovering novel side effects in available drugs. Today, most investigations deal with isolated side effects and overlook possible redundancy and their frequent co-occurrence. In this work, drug annotations are collected from SIDER and DrugBank databases. Terms describing individual side effects reported in SIDER are clustered with a semantic similarity measure into term clusters (TCs). Maximal frequent itemsets are extracted from the resulting drug x TC binary table, leading to the identification of what we call side-effect profiles (SEPs). A SEP is defined as the longest combination of TCs which are shared by a significant number of drugs. Frequent SEPs are explored on the basis of integrated drug and target descriptors using two machine learning methods: decision-trees and inductive-logic programming. Although both methods yield explicit models, inductive-logic programming method performs relational learning and is able to exploit not only drug properties but also background knowledge. Learning efficiency is evaluated by cross-validation and direct testing with new molecules. Comparison of the two machine-learning methods shows that the inductive-logic-programming method displays a greater sensitivity than decision trees and successfully exploit background knowledge such as functional annotations and pathways of drug targets, thereby producing rich and expressive rules. All models and theories are available on a dedicated web site. Side effect profiles covering significant number of drugs have been extracted from a drug ×side-effect association table. Integration of background knowledge concerning both chemical and biological spaces has been combined with a relational learning method for discovering rules which explicitly

  9. An Elementary affine λ-calculus with multithreading and side effects (extended version)


    Madet, Antoine; Amadio, Roberto M.


    Linear logic provides a framework to control the complexity of higher-order functional programs. We present an extension of this framework to programs with multithreading and side effects focusing on the case of elementary time. Our main contributions are as follows. First, we provide a new combinatorial proof of termination in elementary time for the functional case. Second, we develop an extension of the approach to a call-by-value $lambda$-calculus with multithreading and side effects. Thi...

  10. Antiepileptic drug behavioral side effects and baseline hyperactivity in children and adolescents with new onset epilepsy. (United States)

    Guilfoyle, Shanna M; Follansbee-Junger, Katherine; Smith, Aimee W; Combs, Angela; Ollier, Shannon; Hater, Brooke; Modi, Avani C


    To examine baseline psychological functioning and antiepileptic drug (AED) behavioral side effects in new onset epilepsy and determine, by age, whether baseline psychological functioning predicts AED behavioral side effects 1 month following AED initiation. A retrospective chart review was conducted between July 2011 and December 2014 that included youths with new onset epilepsy. As part of routine interdisciplinary care, caregivers completed the Behavior Assessment System for Children, 2nd Edition: Parent Rating Scale to report on baseline psychological functioning at the diagnostic visit and the Pediatric Epilepsy Side Effects Questionnaire to identify AED behavioral side effects at the 1-month follow-up clinic visit following AED initiation. Children (age = 2-11 years) and adolescents (age = 12-18 years) were examined separately. A total of 380 youths with new onset epilepsy (M age  = 8.9 ± 4.3 years; 83.4% Caucasian; 34.8% focal epilepsy, 41.1% generalized epilepsy, 23.7% unclassified epilepsy) were included. Seventy percent of youths had at-risk or clinically elevated baseline psychological symptoms. Children had significantly greater AED behavioral side effects (M = 25.08 ± 26.36) compared to adolescents (M = 12.36 ± 17.73), regardless of AED. Valproic acid demonstrated significantly greater behavioral side effects compared to all other AEDs, with the exception of levetiracetam. Higher hyperactivity/impulsivity at baseline significantly predicted higher AED behavioral side effects 1 month after AED initiation in both age groups. Younger children seem to be more prone to experience behavioral side effects, and these are likely to be higher if youths with epilepsy have baseline hyperactivity/impulsivity. Baseline psychological screening, specifically hyperactivity, can be used as a precision medicine tool for AED selection. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  11. Spontaneous mental associations with the words "side effect": Implications for informed and shared decision making. (United States)

    Izadi, Sonya; Pachur, Thorsten; Wheeler, Courtney; McGuire, Jaclyn; Waters, Erika A


    To gain insight into patients' medical decisions by exploring the content of laypeople's spontaneous mental associations with the term "side effect." An online cross-sectional survey asked 144 women aged 40-74, "What are the first three things you think of when you hear the words 'side effect?"' Data were analyzed using content analysis, chi-square, and Fisher's exact tests. 17 codes emerged and were grouped into 4 themes and a Miscellaneous category: Health Problems (70.8% of participants), Decision-Relevant Evaluations (52.8%), Negative Affect (30.6%), Practical Considerations (18.1%) and Miscellaneous (9.7%). The 4 most frequently identified codes were: Risk (36.1%), Health Problems-Specific Symptoms (35.4%), Health Problems-General Terms (32.6%), and Negative Affect-Strong (19.4%). Code and theme frequencies were generally similar across demographic groups (ps>0.05). The term "side effect" spontaneously elicited comments related to identifying health problems and expressing negative emotions. This might explain why the mere possibility of side effects triggers negative affect for people making medical decisions. Some respondents also mentioned decision-relevant evaluations and practical considerations in response to side effects. Addressing commonly-held associations and acknowledging negative affects provoked by side effects are first steps healthcare providers can take towards improving informed and shared patient decision making. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Image-guided conformation arc therapy for prostate cancer: Early side effects

    International Nuclear Information System (INIS)

    Soete, Guy; Verellen, Dirk; Michielsen, Dirk; Rappe, Bernard; Keuppen, Frans; Storme, Guy


    Purpose: To evaluate early side effects in prostate cancer patients treated with image-guided conformation arc therapy (IGCAT) using a minimultileaf collimator and daily X-ray-assisted patient positioning. Methods and Materials: Between May 2000 and November 2004, 238 cT1-T3N0M0 tumors were treated with doses of 70 or 78 Gy. Seventy patients also received neoadjuvant or concurrent hormonal treatment. Median follow-up is 18 months (range, 4-55 months). Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer toxicity scoring system was used to evaluate early side effects. Results: Grade 1, 2, and >2 acute side effects occurred in 19, 6, and 0% (gastrointestinal) and 37, 16, and 0% (genitourinary) of the patients. No relation between radiation dose and early side effects was observed. Conclusion: Patients treated with image-guided conformation arc therapy experience a low rate of Grade 2 (i.e., requiring medication) early side effects. The definitive evaluation of late side effects and biochemical control requires further follow-up

  13. Cardiac Side-effects From Breast Cancer Radiotherapy. (United States)

    Taylor, C W; Kirby, A M


    Breast cancer radiotherapy reduces the risk of cancer recurrence and death. However, it usually involves some radiation exposure of the heart and analyses of randomised trials have shown that it can increase the risk of heart disease. Estimates of the absolute risks of radiation-related heart disease are needed to help oncologists plan each individual woman's treatment. The risk for an individual woman varies according to her estimated cardiac radiation dose and her background risk of ischaemic heart disease in the absence of radiotherapy. When it is known, this risk can then be compared with the absolute benefit of the radiotherapy. At present, many UK cancer centres are already giving radiotherapy with mean heart doses of less than 3 Gy and for most women the benefits of the radiotherapy will probably far outweigh the risks. Technical approaches to minimising heart dose in breast cancer radiotherapy include optimisation of beam angles, use of multileaf collimator shielding, intensity-modulated radiotherapy, treatment in a prone position, treatment in deep inspiration (including the use of breath-hold and gating techniques), proton therapy and partial breast irradiation. The multileaf collimator is suitable for many women with upper pole left breast cancers, but for women with central or lower pole cancers, breath-holding techniques are now recommended in national UK guidelines. Ongoing work aims to identify ways of irradiating pan-regional lymph nodes that are effective, involve minimal exposure of organs at risk and are feasible to plan, deliver and verify. These will probably include wide tangent-based field-in-field intensity-modulated radiotherapy or arc radiotherapy techniques in combination with deep inspiratory breath-hold, and proton beam irradiation for women who have a high predicted heart dose from intensity-modulated radiotherapy. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  14. Glucocorticoids Enhance Taste Aversion Memory via Actions in the Insular Cortex and Basolateral Amygdala (United States)

    Miranda, Maria Isabel; Quirarte, Gina L.; Rodriguez-Garcia, Gabriela; McGaugh, James L.; Roozendaal, Benno


    It is well established that glucocorticoid hormones strengthen the consolidation of hippocampus-dependent spatial and contextual memory. The present experiments investigated glucocorticoid effects on the long-term formation of conditioned taste aversion (CTA), an associative learning task that does not depend critically on hippocampal function.…

  15. Investigation of radioprotective properties of synthetic antagonist of glucocorticoids RU 38 486

    International Nuclear Information System (INIS)

    Sejliev, A.A.; Zvonareva, N.B.; Zhivotovskij, B.D.; Khanson, K.P.; Akademiya Meditsinskikh Nauk SSSR, Leningrad


    Radioprotective properties of synthetic antiglucocorticoid RU 38 486 were investigated. It was demonstrated that this antigonist of glucocorticoids possesses radioprotective effect in vitro and in vivo systems. Radioprotective properties at molecular level exhibited in inhibition of postirradiation endonuclease activation and in prevention of internucleosome chromatin degradation. Involvement of cytosol glucocorticoid receptors in initiation of radiation-induced programmed cell death is discussed

  16. Live cell imaging unveils multiple domain requirements for in vivo dimerization of the glucocorticoid receptor

    DEFF Research Database (Denmark)

    Presman, Diego M; Ogara, M Florencia; Stortz, Martín


    Glucocorticoids are essential for life, but are also implicated in disease pathogenesis and may produce unwanted effects when given in high doses. Glucocorticoid receptor (GR) transcriptional activity and clinical outcome have been linked to its oligomerization state. Although a point mutation wi...

  17. Glucocorticoid metabolites in newborns: A marker for traffic noise related stress?

    DEFF Research Database (Denmark)

    Lech Cantuaria, Manuella; Usermann, Jakob; Proietti, Elena


    Traffic noise has been associated with an increased risk for several non-auditory health effects, which may be explained by a noise-induced release of stress hormones (e.g. glucocorticoids). Although several studies in children and adults have indicated an increased secretion of glucocorticoids...

  18. Glucocorticoids in early rheumatoid arthritis

    NARCIS (Netherlands)

    Everdingen, Amalia A. van


    For 50 years, glucocorticoids (GC) are used for symptomatic treatment of rheumatoid arthritis (RA). In the last decade, results from clinical studies of treatment with GC as additional therapy to long-acting antirheumatic drugs in patients with early RA suggested also disease-modifying properties of

  19. Maternal separation in early life modifies anxious behavior and Fos and glucocorticoid receptor expression in limbic neurons after chronic stress in rats: effects of tianeptine. (United States)

    Trujillo, Verónica; Durando, Patricia E; Suárez, Marta M


    Early-life adversity can lead to long-term consequence persisting into adulthood. Here, we assess the implications of an adverse early environment on vulnerability to stress during adulthood. We hypothesized that the interplay between early and late stress would result in a differential phenotype regarding the number of neurons immunoreactive for glucocorticoid receptor (GR-ir) and neuronal activity as assessed by Fos immunoreactivity (Fos-ir) in brain areas related to stress responses and anxiety-like behavior. We also expected that the antidepressant tianeptine could correct some of the alterations induced in our model. Male Wistar rats were subjected to daily maternal separation (MS) for 4.5 h during the first 3 weeks of life. As adults, the rats were exposed to chronic stress for 24 d and they were treated daily with tianeptine (10 mg/kg intraperitoneal) or vehicle (isotonic saline). Fos-ir was increased by MS in all structures analyzed. Chronic stress reduced Fos-ir in the hippocampus, but increased it in the paraventricular nucleus. Furthermore, chronic stress increased GR-ir in hippocampus (CA1) and amygdala in control non-MS rats. By contrast, when MS and chronic stress were combined, GR-ir was decreased in these structures. Additionally, whereas tianeptine did not affect Fos-ir, it regulated GR-ir in a region-dependent manner, in hippocampus and amygdala opposing in some cases the stress or MS effects. Furthermore, tianeptine reversed the MS- or stress-induced anxious behavior. The interplay between MS and chronic stress observed indicates that MS rats have a modified phenotype, which is expressed when they are challenged by stress in later life.

  20. Effect of Discontinuation or Initiation of Methotrexate or Glucocorticoids on Tofacitinib Efficacy in Patients with Rheumatoid Arthritis: A Post Hoc Analysis. (United States)

    Fleischmann, Roy; Wollenhaupt, Jürgen; Cohen, Stanley; Wang, Lisy; Fan, Haiyun; Bandi, Vara; Andrews, John; Takiya, Liza; Bananis, Eustratios; Weinblatt, Michael E


    Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We evaluated the effect of concomitant methotrexate (MTX) or glucocorticoid (GC) use on tofacitinib clinical efficacy. Data were pooled from two open-label, long-term extension studies of tofacitinib 5 or 10 mg twice daily in patients with RA. Response according to Clinical Disease Activity Index (CDAI) was assessed separately in patients who discontinued (no MTX/GC use within 30 days prior to year-3 visit; assessment at month 3/year 3) or initiated (on/before year 3; assessment at initiation and year 3) MTX/GC. By year 3, among patients receiving background MTX at baseline, 186/1608 (11.6%) discontinued MTX, and 319/1434 (22.2%) patients receiving GC at baseline discontinued GC. Overall, 70.4/69.1% of patients who discontinued/continued MTX and 72.7/65.9% who discontinued/continued GC achieved CDAI remission or low disease activity (LDA) at year 3. Month 3 remission/LDA rates were maintained at year 3 in the majority of patients, irrespective of MTX/GC discontinuation/continuation. By year 3, 6.2% of patients receiving tofacitinib without MTX at baseline had initiated concomitant MTX, and 25.1% receiving tofacitinib without GC initiated GC; 69.0% and 45.4% initiating MTX or GC, respectively, had a CDAI-defined incomplete response prior to initiation. RA signs/symptoms improved following MTX initiation; only modest improvement was observed with GC initiation. Patients achieving remission/LDA with tofacitinib may discontinue MTX or GC and maintain treatment response. Patients with an incomplete response may benefit from adding concomitant MTX. Pfizer Inc. Study A3921024 [NCT00413699] and Study A3921041 [NCT00661661].

  1. The role of glucocorticoids in emotional memory reconsolidation. (United States)

    Meir Drexler, Shira; Wolf, Oliver T


    Glucocorticoids are secreted following exposure to stressful events. Their modulating role on memory reconsolidation, a post-retrieval process of re-stabilization, has been investigated only recently, at times with conflicting results. The goal of this review is twofold. First, to establish the modulating role of glucocorticoids on memory reconsolidation. Second, to point the potential factors and confounds that might explain the seemingly paradoxical findings. Here we review recent pharmacological studies, conducted in rodents and humans, which suggest a critical role of glucocorticoids in this post-retrieval process. In particular, the activation of glucocorticoid receptors in the amygdala and hippocampus is suggested to be involved in emotional memories reconsolidation, pointing to a similarity between post-retrieval reconsolidation and initial memory consolidation. In addition, based on the general reconsolidation literature, we suggest several factors that might play a role in determining the direction and strength of the reconsolidation effect following glucocorticoids treatment: memory-related factors, manipulation-related factors, and individual differences. We conclude that only when taking these additional factors into account can the paradox be resolved. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Effect of side chain position on solar cell performance in cyclopentadithiophene-based copolymers

    International Nuclear Information System (INIS)

    Lee, Sang Kyu; Seo, Jung Hwa; Cho, Nam Sung; Cho, Shinuk


    The photovoltaic properties of a series of low band-gap conjugated copolymers, in which alkyl side chains were substituted at various positions, were investigated using donor–acceptor (D–A) conjugated copolymers consisting of a cyclopentadithiophene derivative and dithienyl-benzothiadiazole. The base polymer, which has no alkyl side chains, yielded promising power conversion efficiency of 3.8%. Polymers with alkyl side chains, however, exhibited significantly decreased performance. In addition, the effects of processing additive became negligible. The results indicate that substituted side chains, which were introduced to improve solubility, critically affected the optical and electronic properties of D–A conjugated copolymers. Furthermore, the position of the side chain was also very important for controlling the morphological properties of the D–A conjugated copolymers. - Highlights: ► Effect of side chain position on solar cell performance was investigated. ► Polymer without alkyl chains yielded promising power conversion efficiency of 3.8%. ► Position of side chains critically affected the optical and electronic properties.

  3. Salivary cortisol day curves in assessing glucocorticoid replacement therapy in Addison's disease. (United States)

    Smans, Lisanne; Lentjes, Eef; Hermus, Ad; Zelissen, Pierre


    Patients with Addison's disease require lifelong treatment with glucocorticoids. At present, no glucocorticoid replacement therapy (GRT) can exactly mimic normal physiology. As a consequence, under- and especially overtreatment can occur. Suboptimal GRT may lead to various side effects. The aim of this study was to investigate the use of salivary cortisol day curves (SCDC) in the individual adjustment of GRT in order to approach normal cortisol levels as closely as possible, reduce over- and underreplacement and study the short-term effects on quality of life (QoL). Twenty patients with Addison's disease were included in this prospective study. A SCDC was obtained and compared to normal controls; general and disease specific QoL-questionnaires were completed. Based on SCDC assessment of over- and undertreatment (calculated as duration (h) × magnitude (nmol/L) at different time points, glucocorticoid dose and regime were adjusted. After 4 weeks SCDC and QoL assessment were repeated and the effect of adjusting GRT was analysed. At baseline, underreplacement was present in 3 and overreplacement in 18 patients; total calculated overreplacement was 32.8 h.nmol/L. Overreplacement decreased significantly to 13.3 h. nmol/L (p =0.005) after adjustment of GRT. Overreplacement was found particularly in the afternoon and evening. After reducing overreplacement in the evening, complaints about sleep disturbances significantly decreased. Individual adjustment of GRT based on SCDC to approach normal cortisol concentrations during the day can reduce overreplacement, especially in the evening. This can lead to a reduction of sleep disturbances and fatigue in patients with Addison's disease. A SCDC is a simple and patient-friendly tool for adjusting GRT and can be useful in the follow-up of patients with Addison's disease.

  4. Maternal PTSD associates with greater glucocorticoid sensitivity in offspring of Holocaust survivors. (United States)

    Lehrner, Amy; Bierer, Linda M; Passarelli, Vincent; Pratchett, Laura C; Flory, Janine D; Bader, Heather N; Harris, Iris R; Bedi, Aarti; Daskalakis, Nikolaos P; Makotkine, Iouri; Yehuda, Rachel


    Intergenerational effects of trauma have been observed clinically in a wide range of populations, and parental PTSD has been associated with an increased risk for psychopathology in offspring. In studies of Holocaust survivor offspring, parental PTSD, and particularly maternal PTSD, has been associated with increased risk for PTSD, low basal urinary cortisol excretion and enhanced cortisol suppression in response to dexamethasone. Such findings implicate maternally derived glucocorticoid programming in the intergenerational transmission of trauma-related consequences, potentially resulting from in utero influences or early life experiences. This study investigated the relative influence of Holocaust exposure and PTSD in mothers and fathers on glucocorticoid sensitivity in offspring. Eighty Holocaust offspring and 15 offspring of non-exposed Jewish parents completed evaluations and provided blood and urine samples. Glucocorticoid sensitivity was evaluated using the lysozyme suppression test (LST), an in vitro measure of glucocorticoid receptor sensitivity in a peripheral tissue, the dexamethasone suppression test (DST), and 24-h urinary cortisol excretion. Maternal PTSD was associated with greater glucocorticoid sensitivity in offspring across all three measures of glucocorticoid function. An interaction of maternal and paternal PTSD on the DST and 24-h urinary cortisol showed an effect of decreased glucocorticoid sensitivity in offspring with paternal, but not maternal, PTSD. Although indirect, these findings are consistent with the hypothesis that epigenetic programming may be involved in the intergenerational transmission of trauma-related effects on glucocorticoid regulation. Published by Elsevier Ltd.

  5. The Effects of popcorn time on Netflix in a two–sided market


    Ghini, Matteo Blomberg


    My thesis discusses the effects on legal streaming agents of entry of free, but illegal, substitutes, in a two–sided video streaming market. Legal streaming agents rely on support from two very different, but inevitably linked, groups: studios and consumers, while their free counterparts rely on support only from consumers. As a result, the pricing decisions for legal streaming agents are far more complex than those of firms operating in regular single–sided markets and of firms ...

  6. Quantitative prediction of drug side effects based on drug-related features. (United States)

    Niu, Yanqing; Zhang, Wen


    Unexpected side effects of drugs are great concern in the drug development, and the identification of side effects is an important task. Recently, machine learning methods are proposed to predict the presence or absence of interested side effects for drugs, but it is difficult to make the accurate prediction for all of them. In this paper, we transform side effect profiles of drugs as their quantitative scores, by summing up their side effects with weights. The quantitative scores may measure the dangers of drugs, and thus help to compare the risk of different drugs. Here, we attempt to predict quantitative scores of drugs, namely the quantitative prediction. Specifically, we explore a variety of drug-related features and evaluate their discriminative powers for the quantitative prediction. Then, we consider several feature combination strategies (direct combination, average scoring ensemble combination) to integrate three informative features: chemical substructures, targets, and treatment indications. Finally, the average scoring ensemble model which produces the better performances is used as the final quantitative prediction model. Since weights for side effects are empirical values, we randomly generate different weights in the simulation experiments. The experimental results show that the quantitative method is robust to different weights, and produces satisfying results. Although other state-of-the-art methods cannot make the quantitative prediction directly, the prediction results can be transformed as the quantitative scores. By indirect comparison, the proposed method produces much better results than benchmark methods in the quantitative prediction. In conclusion, the proposed method is promising for the quantitative prediction of side effects, which may work cooperatively with existing state-of-the-art methods to reveal dangers of drugs.

  7. Effect of levomepromazine on EEG and on clinical side effects after lumbar myelography with metrizamide

    International Nuclear Information System (INIS)

    Standnes, B.; Oftedal, S.-I.; Weber, H.


    In patients with lumbago-sciatica levomepromazine is a potent supplement to analgetics in pain treatment. The hypothesis that neuroleptics increase the risk of epileptic seizures after metrizamide myelography was not comfirmed in a series of 77 patients, 26 with and 51 without levomepromazine medication, before and after lumbar metrizamide myelography. No differences existed between the groups with regard to the appearance of EEG abnormalities such as slow waves or spikes. Mild side effects were more frequent in the levomepromazine group, except nausea and vomiting. Lumbar metrizamide epidurography in 30 patients did not cause any abnormal EEG. (Auth.)

  8. Effect of levomepromazine on EEG and on clinical side effects after lumbar myelography with metrizamide

    Energy Technology Data Exchange (ETDEWEB)

    Standnes, B.; Oftedal, S.I.; Weber, H. (Ullevaal Sykehus, Oslo (Norway))


    In patients with lumbago-sciatica levomepromazine is a potent supplement to analgesics in pain treatment. The hypothesis that neuroleptics increase the risk of epileptic seizures after metrizamide myelography was not comfirmed in a series of 77 patients, 26 with and 51 without levomepromazine medication, before and after lumbar metrizamide myelography. No differences existed between the groups with regard to the appearance of EEG abnormalities such as slow waves or spikes. Mild side effects were more frequent in the levomepromazine group, except nausea and vomiting. Lumbar metrizamide epidurography in 30 patients did not cause any abnormal EEG.

  9. Prevalent glucocorticoid and androgen activity in US water sources. (United States)

    Stavreva, Diana A; George, Anuja A; Klausmeyer, Paul; Varticovski, Lyuba; Sack, Daniel; Voss, Ty C; Schiltz, R Louis; Blazer, Vicki S; Iwanowicz, Luke R; Hager, Gordon L


    Contamination of the environment with endocrine disrupting chemicals (EDCs) is a major health concern. The presence of estrogenic compounds in water and their deleterious effect are well documented. However, detection and monitoring of other classes of EDCs is limited. Here we utilize a high-throughput live cell assay based on sub-cellular relocalization of GFP-tagged glucocorticoid and androgen receptors (GFP-GR and GFP-AR), in combination with gene transcription analysis, to screen for glucocorticoid and androgen activity in water samples. We report previously unrecognized glucocorticoid activity in 27%, and androgen activity in 35% of tested water sources from 14 states in the US. Steroids of both classes impact body development, metabolism, and interfere with reproductive, endocrine, and immune systems. This prevalent contamination could negatively affect wildlife and human populations.

  10. Side-effects of cowpea treatment with botanical insecticides on two parasitoids of Callosobruchus maculatus

    NARCIS (Netherlands)

    Boeke, S.J.; Sinzogan, A.A.C.; Almeida, de R.P.; Boer, de P.W.M.; Jeong, G.S.; Kossou, D.K.; Loon, van J.J.A.


    Studies on the protective effect of botanical products against pest insects have infrequently been extended to side-effects on natural enemies. Indirect effects of botanicals on the storability of seeds could occur through their possible negative impact on biological control agents. Four plant

  11. Risperidone-Induced Renal Damage and Metabolic Side Effects: The Protective Effect of Resveratrol

    Directory of Open Access Journals (Sweden)

    Sedat Bilgiç


    Full Text Available Objective. The aim of the study was to investigate the possible protective qualities of resveratrol (RSV against the side effects of risperidone (RIS in an experimental model in rat kidneys with histologic and biochemical assessments. Materials and Methods. Experimental procedures were performed on 35 female Sprague Dawley rats. Rats were randomly divided into five groups: control, untreated rats (n=7 were in group 1; group 2 was given 2 mg/kg/day RIS (n=7; group 3 was treated with 2 mg/kg/day RIS and 20 mg/kg/day RSV (n=7; group 4 was treated with 2 mg/kg/day RIS and 40 mg/kg/day RSV (n=7; and group 5 was treated with 2 mg/kg/day RIS and 80 mg/kg/day RSV (n=7. All treatments were administered for two weeks by gavage. On treatment day 15, kidney tissues were removed for analysis. Results. The results showed that RSV treatment reduced weight gain induced by RIS. In addition, RSV increased the total antioxidant status (TAS and decreased serum creatinine (Cr, blood urea nitrogen (BUN, oxidative stress index (OSI, and total oxidant status (TOS levels significantly (p<0.05. Conclusion. This study revealed that treatment with RSV might protect kidney tissues against the side effects of RIS. RSV could be an effective course of therapy to enhance therapeutic efficacy.

  12. Muscle-related side-effects of statins: from mechanisms to evidence-based solutions. (United States)

    Taylor, Beth A; Thompson, Paul D


    This article highlights the recent findings regarding statin-associated muscle side effects, including mechanisms and treatment as well as the need for more comprehensive clinical trials in statin myalgia. Statin myalgia is difficult to diagnose and treat, as major clinical trials have not routinely assessed muscle side-effects, there are few clinically relevant biomarkers and assessment tools for the symptoms, many apparent statin-related muscle symptoms may be nonspecific and related to other drugs or health conditions, and prevalence estimates vary widely. Data thus suggest that only 30-50% of patients with self-reported statin myalgia actually experience muscle pain on statins during blinded, placebo-controlled trials. In addition, evidence to date involving mechanisms underlying statin myalgia and its range of symptoms and presentations supports the hypothesis that there are multiple, interactive and potentially additive mechanisms underlying statin-associated muscle side-effects. There are likely multiple and interactive mechanisms underlying statin myalgia, and recent studies have produced equivocal data regarding prevalence of statin-associated muscle side-effects, contributing factors and effectiveness of common interventions. Therefore, more clinical trials on statin myalgia are critical to the field, as are systematic resources for quantifying, predicting and reporting statin-associated muscle side-effects.

  13. Experimental research on end-to-side anastomosis of peripheral nerves and effect of FK506 on end-to-side anastomosis. (United States)

    Yang, L M; Wu, Y X; Zhang, X P; Li, X H


    To study the effects of end-to-side anastomosis of initially-denatured nerves at different times. 60 male Wistar albino rats were used to fabricate animal models for the experiment on end-to-side anastomosis of peripheral nerves and 50 female Wistar albino rats were used to fabricate animal models for the experiment on the effect of FK506 on end-to-side anastomosis. Bilateral common peroneal nerve, tibialis anterior muscle electrophysiological and histological examinations, tibialis anterior muscle wet muscle weight determination, and motor end plate examination were performed 3 months after operation. All recovery rates of action potential, single muscle contraction force and tetanic contraction force of the FK506 experimental group are significantly higher than those of the control group and the sectional area of muscle fiber is also higher than that of the control group of normal saline. The best time for end-to-side anastomosis of nerves should be controlled within 2 weeks and the effect of end-to-side anastomosis of nerves will gradually become unsatisfactory. FK506 plays a role in promoting functional rehabilitation following nerve end-to-side anastomosis (Tab. 7, Fig. 4, Ref. 31).

  14. Glucocorticoid receptor beta increases migration of human bladder cancer cells. (United States)

    McBeth, Lucien; Nwaneri, Assumpta C; Grabnar, Maria; Demeter, Jonathan; Nestor-Kalinoski, Andrea; Hinds, Terry D


    Bladder cancer is observed worldwide having been associated with a host of environmental and lifestyle risk factors. Recent investigations on anti-inflammatory glucocorticoid signaling point to a pathway that may impact bladder cancer. Here we show an inverse effect on the glucocorticoid receptor (GR) isoform signaling that may lead to bladder cancer. We found similar GRα expression levels in the transitional uroepithelial cancer cell lines T24 and UMUC-3. However, the T24 cells showed a significant (p bladder cancer cells. Therefore, GRβ may have a significant role in bladder cancer, and possibly serve as a therapeutic target for the disease.

  15. Side effects of rational dose iodine-131 therapy for metastatic well-differentiated thyroid carcinoma

    International Nuclear Information System (INIS)

    Van Nostrand, D.; Neutze, J.; Atkins, F.


    Benua, Leeper, and others (BEL) have advocated the estimation of radiation exposure to the blood to select a more rational maximum safe dose of radioiodine (dosimetry) to treat metastatic functioning well-differentiated thyroid carcinoma. After adopting the BEL dosimetry approach, we reviewed the immediate (during hospitalization) and intermediate (from discharge up to 3 mo) side effects after our initial 15 therapies in ten patients. The doses ranged from 51 mCi (1887 MBq) to 450 mCi (16.65 GBq). Immediate side effects were observed in 12/15 (80%), are described in detail, and were as follows: gastrointestinal 10/15, salivary 9/15, nonsalivary neck pain, swelling, etc. 2/15, pulmonary 0/15. Intermediate side effects were observed in 10/15 (67%), are described in detail, and were as follows: gastrointestinal 0/15, salivary 3/15, nonsalivary neck pain, swelling, etc. 3/15, nasal complaints 2/15, transient bone marrow suppression 9/10, pulmonary 0/15. No patient required blood transfusions or had complications secondary to reduced blood counts. All patient complaints resolved; however, several patients may have reduced baseline blood counts one year after therapy. No other long-term side effect has been noted but the mean follow-up has been only 15 mo. In our opinion, we have not observed any side effect to date which would contraindicate the continued use and evaluation of the BEL dosimetry approach

  16. Side effects of rational dose iodine-131 therapy for metastatic well-differentiated thyroid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Van Nostrand, D.; Neutze, J.; Atkins, F.


    Benua, Leeper, and others (BEL) have advocated the estimation of radiation exposure to the blood to select a more rational maximum safe dose of radioiodine (dosimetry) to treat metastatic functioning well-differentiated thyroid carcinoma. After adopting the BEL dosimetry approach, we reviewed the immediate (during hospitalization) and intermediate (from discharge up to 3 mo) side effects after our initial 15 therapies in ten patients. The doses ranged from 51 mCi (1887 MBq) to 450 mCi (16.65 GBq). Immediate side effects were observed in 12/15 (80%), are described in detail, and were as follows: gastrointestinal 10/15, salivary 9/15, nonsalivary neck pain, swelling, etc. 2/15, pulmonary 0/15. Intermediate side effects were observed in 10/15 (67%), are described in detail, and were as follows: gastrointestinal 0/15, salivary 3/15, nonsalivary neck pain, swelling, etc. 3/15, nasal complaints 2/15, transient bone marrow suppression 9/10, pulmonary 0/15. No patient required blood transfusions or had complications secondary to reduced blood counts. All patient complaints resolved; however, several patients may have reduced baseline blood counts one year after therapy. No other long-term side effect has been noted but the mean follow-up has been only 15 mo. In our opinion, we have not observed any side effect to date which would contraindicate the continued use and evaluation of the BEL dosimetry approach.

  17. Managing the oral side-effects of medications used to treat multiple sclerosis. (United States)

    Cockburn, N; Pateman, K; Taing, M W; Pradhan, A; Ford, P J


    Many medications used to manage multiple sclerosis (MS) affect oral health. This review aimed to identify the oral side-effects of the current drugs recommended in Australia to treat MS and make dental practitioners aware of the range of symptoms. The Australian Therapeutic Guidelines and the Australian Medicines Handbook were searched for medications used to treat MS. For each medication, the generic name, class, route of administration, dosage and drug company reported side-effects were extracted from the online Monthly Index of Medical Specialties (MIMs) database. Meyler's Side-effect of Drugs Encyclopaedia was used to identify any additional oral adverse reactions to medications used to treat MS. Fourteen drugs were identified for the treatment of MS progression and 13 drugs for the treatment of MS symptoms. For these medications, 18 oral side-effects were documented: xerostomia was the most common, followed by dysgeusia, dysphagia, mouth ulceration and sinusitis. Anticholinergic drugs caused xerostomia while immunosuppressants resulted in more infection-related side-effects. Dental practitioners should be aware of the range of symptoms likely to be reported by this population. Clinicians are encouraged to continue providing dental care for their patients who develop MS and refer complex cases to specialists. © 2017 Australian Dental Association.

  18. Cataplexy as a side effect of modafinil in a patient without narcolepsy☆ (United States)

    Lopes, Eduardo; Pereira, Danielle; da Silva Behrens, Nilce Sanny Costa; de Almeida Fonseca, Hassana; Calvancanti, Paola Oliveira; de Araújo Lima, Taís Figueiredo; Pradella-Hallinan, Marcia; Castro, Juliana; Tufik, Sergio; Coelho, Fernando Morgadinho Santos


    Narcolepsy is a disease in which there is diurnal excessive sleepiness with sleep attacks and a prevalence in the general population of 1/4000 individuals. Classically, it is characterized by cataplexy, sleep paralysis, hypnagogic hallucinations and fragmented sleep. The use of modafinil in the treatment of narcolepsy is the first option of treatment for diurnal excessive sleepiness. Although considered a safe drug for use in patients with narcolepsy, being utilized for more than 20 years, modafinil possesses a series of side effects, some of them still not fully researched or described. Side effects such as headache, nausea, anxiety, insomnia, lumbago, diarrhea, dyspepsia, rhinitis and vertigo are the most frequent. However, the clinical follow-up of patients under treatment with modafinil must be intensive and the side effects ought to be noted and evaluated. The under-response to treatment or the unexpected side effects must always be directed to differential diagnostics. The objective of this article is to describe an unexpected side effect of the use of modafinil in a patient with incorrect diagnosis of narcolepsy. PMID:26483900

  19. The role of tryptophan 2,3-dioxygenase in the hormonal control of tryptophan metabolism in isolated rat liver cells. Effects of glucocorticoids and experimental diabetes.


    Salter, M; Pogson, C I


    The metabolism of L-tryptophan by isolated liver cells prepared from control, adrenalectomized, glucocorticoid-treated, acute-diabetic, chronic-diabetic and insulin-treated chronic-diabetic rats was studied. Liver cells from adrenalectomized rats metabolized tryptophan at rates comparable with the minimum diurnal rates of controls, but different from rates determined for cells from control rats 4h later. Administration of dexamethasone phosphate increased the activity of tryptophan 2,3-dioxyg...

  20. Intentions to use Hypnosis to Control the Side Effects of Cancer and its Treatment (United States)

    Sohl, Stephanie J.; Stossel, Lauren; Schnur, Julie B.; Tatrow, Kristin; Gherman, Amfiana; Montgomery, Guy H.


    Evidence suggests that hypnosis is an effective intervention for reducing distress, pain and other side effects associated with cancer and its treatment. However, hypnosis has failed to be adopted into standard clinical practice. This study (n=115) investigated overall intentions to use hypnosis to control side effects of cancer and its treatment, as well as demographic predictors of such intentions among healthy volunteers. Results suggest that the vast majority of patients (89%) would be willing to use hypnosis to control side effects associated with cancer treatment. Mean intention levels did not differ by gender, ethnicity, education or age. These results indicate that in the general public, there is a willingness to consider the use of hypnosis, and that willingness is not determined by demographic factors. This broad acceptance of hypnosis argues for more widespread dissemination. PMID:21049742

  1. Side-effects in ascending cervical myelography using iopamidol and metrizamide - a double blind study

    International Nuclear Information System (INIS)

    Bockenheimer, S.; Eichenlaub, H.


    A double blind study was performed to examine the side-effects of Metrizamide (group 1) and of Jopamidol (group 2) in ascending cervical myelography. Both groups were compared to a control group (group 3) comprising patients who had undergone lumbar puncture only. EEG was taken of the patients in groups 1 and 2 before as well as 6 and 24 h after intervention. Side-effects were collected by means of a questionnaire. Response time, concentration, memory and mood were examined psychometrically. Training effects or defensive attitudes in the multiple test examinations were checked against another control group of patients (group 4) which had no myelographic nor lumbar-puncture-induced impairment. Statistical findings corroborated our clinical impression that side-effects occurred after Metrizamide administration at a more than simply random rate. (orig.) [de

  2. Potentiation of glucocorticoid release does not modify the long-term effects of a single exposure to immobilization stress. (United States)

    Dal-Zotto, Silvina; Martí, Octavi; Delgado, Raúl; Armario, Antonio


    Previous work has shown that a single exposure of rats to a severe stressor (immobilization, IMO) results, days to weeks later, in a reduced response (desensitization) of the hypothalamic-pituitary-adrenal (HPA) axis to a second exposure to the same stressor. In the present work, we studied the influence of both length of exposure to IMO and circulating levels of corticosterone on the first day on the degree of desensitization of two sets of physiological variables: HPA hormones and food intake. Rats were given SC saline or ACTH administration and then exposed to IMO for 0, 1 or 20 min. Seven days later, all rats were exposed to 20 min IMO. HPA response was followed on both experimental days by repeated blood sampling and food intake was measured on a 24-h basis. Both ACTH administration and IMO activates the HPA axis and IMO reduced food intake for several days. A single previous experience with IMO enhanced the post-IMO return of HPA hormones to basal levels on day 8 and reduced the degree of anorexia. The protective effect of previous IMO on food intake was independent of, whereas that on HPA activation was positively related to, the length of exposure on day 1. Concomitant ACTH administration on day 1 did not modify the observed effects. Long-term protective effects of a single exposure to IMO are observed even with a brief exposure, but they are not potentiated by increasing corticosterone levels during the first exposure.


    Directory of Open Access Journals (Sweden)

    Athanasios Katis


    Full Text Available The purpose of this study was to examine, first, the movement actions performed during two different small-sided games and, second, their effects on a series of field endurance and technical tests. Thirty-four young soccer players (age: 13 ± 0.9 yrs; body mass: 62.3 ± 15.1 kg; height: 1.65 ± 0.06 m participated in the study. Small-sided games included three-a-side (3 versus 3 players and six-a-side (6 versus 6 players games consisting of 10 bouts of 4 min duration with 3 min active recovery between bouts. Soccer player performance was evaluated using five field tests: a 30m sprint, b throw-in for distance, c Illinois Agility Test, d dribbling the ball and e horizontal jump before, in the middle and after the implementation of both game situations. Heart rate was monitored during the entire testing session. Each game was also filmed to measure soccer movements within the game. The ANOVA analysis indicated that the three-a- side games displayed significantly higher heart rate values compared with the six-a-side games (p < 0.05. The number of short passes, kicks, tackles, dribbles and scoring goals were significantly higher during the three-a-side compared with the six-a-side game condition (p < 0. 05 while players performed more long passes and headed the ball more often during the six-a-side (p < 0.05. After the three-a-side games, there was a significant decline in sprint and agility performance (p < 0.05, while after both game conditions significant alterations in the throw-in and the horizontal jump performance were observed (p < 0.05. The results of the present study indicated that three-a-side games provide higher stimulus for physical conditioning and technical improvement than six-a-side games and their use for training young soccer players is recommended

  4. The effect of depression and side effects of antiepileptic drugs on injuries in patients with epilepsy. (United States)

    Gur-Ozmen, S; Mula, M; Agrawal, N; Cock, H R; Lozsadi, D; von Oertzen, T J


    People with epilepsy are at increased risk of accidents and injuries but, despite several studies on this subject, data regarding preventable causes are still contradictory. The aim of this study was to investigate the relationship between injuries, side effects of antiepileptic drugs (AEDs) and depression. Data from a consecutive sample of adult patients with epilepsy attending the outpatient clinics at St George's University Hospital in London were included. All patients were asked if they had had any injury since the last clinic appointment and completed the Liverpool Adverse Event Profile (LAEP) and Neurological Disorders Depression Inventory for Epilepsy. Among 407 patients (243 females, mean age 43.1 years), 71 (17.4%) reported injuries since the last appointment. A two-step cluster analysis revealed two clusters with the major cluster (53.5% of the injured group) showing a total score for LAEP ≥45, a positive Neurological Disorders Depression Inventory for Epilepsy screening and presence of AED polytherapy. A total score for LAEP ≥45 was the most important predictor. Antiepileptic drug treatment should be reviewed in patients reporting injuries in order to evaluate the potential contribution and burden of AED side effects. © 2017 EAN.

  5. Total brain, cortical and white matter volumes in children previously treated with glucocorticoids

    DEFF Research Database (Denmark)

    Holm, Sara K; Madsen, Kathrine S; Vestergaard, Martin


    BACKGROUND: Perinatal exposure to glucocorticoids and elevated endogenous glucocorticoid-levels during childhood can have detrimental effects on the developing brain. Here, we examined the impact of glucocorticoid-treatment during childhood on brain volumes. METHODS: Thirty children and adolescents...... with rheumatic or nephrotic disease previously treated with glucocorticoids and 30 controls matched on age, sex, and parent education underwent magnetic resonance imaging (MRI) of the brain. Total cortical grey and white matter, brain, and intracranial volume, and total cortical thickness and surface area were...... were mainly driven by the children with rheumatic disease. Total cortical thickness and cortical surface area did not significantly differ between groups. We found no significant associations between glucocorticoid-treatment variables and volumetric measures. CONCLUSION: Observed smaller total brain...

  6. Instructions for producing a mouse model of glucocorticoid-induced osteoporosis

    DEFF Research Database (Denmark)

    Thiele, S.; Baschant, U.; Rauch, A.


    Glucocorticoids are effective drugs used for the treatment of inflammatory diseases such as rheumatoid arthritis or asthma. Furthermore, they regulate various physiological processes, including bone remodeling. However, long-term high- and even low-dose glucocorticoid use is associated...... with a compromised bone quality and an increased fracture risk. At the cellular level, glucocorticoids suppress bone formation and stimulate bone resorption, which leads to loss of bone mass. To investigate the underlying mechanisms and new therapeutic strategies, the in vivo model for glucocorticoid-induced bone...... loss is widely used. This protocol outlines the common procedure that is currently used for the induction of bone loss in mice using glucocorticoids. It further provides useful hints and highlights possible pitfalls to take into account before starting an experiment....

  7. Effect of weight, height and BMI on injury outcome in side impact crashes without airbag deployment. (United States)

    Pal, Chinmoy; Tomosaburo, Okabe; Vimalathithan, K; Jeyabharath, M; Muthukumar, M; Satheesh, N; Narahari, S


    A comprehensive analysis is performed to evaluate the effect of weight, height and body mass index (BMI) of occupants on side impact injuries at different body regions. The accident dataset for this study is based on the National Automotive Sampling System-Crashworthiness Data System (NASS-CDS) for accident year 2000-08. The mean BMI values for driver and front passenger are estimated from all types of crashes using NASS database, which clearly indicates that mean BMI has been increasing over the years in the USA. To study the effect of BMI in side impact injuries, BMI was split into three groups namely (1) thin (BMI30). For more clear identification of the effect of BMI in side impact injuries, a minimum gap of three BMI is set in between each adjacent BMI groups. Car model years from MY1995-1999 to MY2000-2008 are chosen in order to identify the degree of influence of older and newer generation of cars in side impact injuries. Impact locations particularly side-front (F), side-center (P) and side-distributed (Y) are chosen for this analysis. Direction of force (DOF) considered for both near side and far side occupants are 8 o'clock, 9 o'clock, 10 o'clock and 2 o'clock, 3 o'clock and 4 o'clock respectively. Age <60 years is also one of the constraints imposed on data selection to minimize the effect of bone strength on the occurrence of occupant injuries. AIS2+ and AIS3+ injury risk in all body regions have been plotted for the selected three BMI groups of occupant, delta-V 0-60kmph, two sets (old and new) of car model years. The analysis is carried with three approaches: (a) injury risk percentage based on simple graphical method with respect to a single variable, (b) injury distribution method where the injuries are marked on the respective anatomical locations and (c) logistic regression, a statistical method, considers all the related variables together. Lower extremity injury risk appears to be high for thin BMI group. It is found that BMI does not have much

  8. Molecular Integration of Incretin and Glucocorticoid Action Reverses Immunometabolic Dysfunction and Obesity. (United States)

    Quarta, Carmelo; Clemmensen, Christoffer; Zhu, Zhimeng; Yang, Bin; Joseph, Sini S; Lutter, Dominik; Yi, Chun-Xia; Graf, Elisabeth; García-Cáceres, Cristina; Legutko, Beata; Fischer, Katrin; Brommage, Robert; Zizzari, Philippe; Franklin, Bernardo S; Krueger, Martin; Koch, Marco; Vettorazzi, Sabine; Li, Pengyun; Hofmann, Susanna M; Bakhti, Mostafa; Bastidas-Ponce, Aimée; Lickert, Heiko; Strom, Tim M; Gailus-Durner, Valerie; Bechmann, Ingo; Perez-Tilve, Diego; Tuckermann, Jan; Hrabě de Angelis, Martin; Sandoval, Darleen; Cota, Daniela; Latz, Eicke; Seeley, Randy J; Müller, Timo D; DiMarchi, Richard D; Finan, Brian; Tschöp, Matthias H


    Chronic inflammation has been proposed to contribute to the pathogenesis of diet-induced obesity. However, scarce therapeutic options are available to treat obesity and the associated immunometabolic complications. Glucocorticoids are routinely employed for the management of inflammatory diseases, but their pleiotropic nature leads to detrimental metabolic side effects. We developed a glucagon-like peptide-1 (GLP-1)-dexamethasone co-agonist in which GLP-1 selectively delivers dexamethasone to GLP-1 receptor-expressing cells. GLP-1-dexamethasone lowers body weight up to 25% in obese mice by targeting the hypothalamic control of feeding and by increasing energy expenditure. This strategy reverses hypothalamic and systemic inflammation while improving glucose tolerance and insulin sensitivity. The selective preference for GLP-1 receptor bypasses deleterious effects of dexamethasone on glucose handling, bone integrity, and hypothalamus-pituitary-adrenal axis activity. Thus, GLP-1-directed glucocorticoid pharmacology represents a safe and efficacious therapy option for diet-induced immunometabolic derangements and the resulting obesity. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. The cost effectiveness of teriparatide as a first-line treatment for glucocorticoid-induced and postmenopausal osteoporosis patients in Sweden

    Directory of Open Access Journals (Sweden)

    Murphy Daniel R


    Full Text Available Abstract Background This paper presents the model and results to evaluate the use of teriparatide as a first-line treatment of severe postmenopausal osteoporosis (PMO and Glucocorticoid-induced osteoporosis (GIOP. The study’s objective was to determine if teriparatide is cost effective against oral bisphosphonates for two large and high risk cohorts. Methods A computer simulation model was created to model treatment, osteoporosis related fractures, and the remaining life of PMO and GIOP patients. Natural mortality and additional mortality from osteoporosis related fractures were included in the model. Costs for treatment with both teriparatide and oral bisphosphonates were included. Drug efficacy was modeled as a reduction to the relative fracture risk for subsequent osteoporosis related fractures. Patient health utilities associated with age, gender, and osteoporosis related fractures were included in the model. Patient costs and utilities were summarized and incremental cost-effectiveness ratios (ICERs for teriparatide versus oral bisphosphonates and teriparatide versus no treatment were estimated. For each of the PMO and GIOP populations, two cohorts differentiated by fracture history were simulated. The first contained patients with both a historical vertebral fracture and an incident vertebral fracture. The second contained patients with only an incident vertebral fracture. The PMO cohorts simulated had an initial Bone Mineral Density (BMD T-Score of −3.0. The GIOP cohorts simulated had an initial BMD T-Score of −2.5. Results The ICERs for teriparatide versus bisphosphonate use for the one and two fracture PMO cohorts were €36,995 per QALY and €19,371 per QALY. The ICERs for teriparatide versus bisphosphonate use for the one and two fracture GIOP cohorts were €20,826 per QALY and €15,155 per QALY, respectively. Conclusions The selection of teriparatide versus oral bisphosphonates as a first-line treatment for the high risk PMO

  10. Sexual side effects of serotonergic antidepressants: mediated by inhibition of serotonin on central dopamine release? (United States)

    Bijlsma, Elisabeth Y; Chan, Johnny S W; Olivier, Berend; Veening, Jan G; Millan, Mark J; Waldinger, Marcel D; Oosting, Ronald S


    Antidepressant-induced sexual dysfunction adversely affects the quality of life of antidepressant users and reduces compliance with treatment. Animal models provide an instructive approach for examining potential sexual side effects of novel drugs. This review discusses the stability and reproducibility of our standardized test procedure that assesses the acute, subchronic and chronic effects of psychoactive compounds in a 30 minute mating test. In addition, we present an overview of the effects of several different (putative) antidepressants on male rat sexual behavior, as tested in our standardized test procedure. By comparing the effects of these mechanistically distinct antidepressants (paroxetine, venlafaxine, bupropion, buspirone, DOV 216,303 and S32006), this review discusses the putative mechanism underlying sexual side effects of antidepressants and their normalization. This review shows that sexual behavior is mainly inhibited by antidepressants that increase serotonin neurotransmission via blockade of serotonin transporters, while those that mainly increase the levels of dopamine and noradrenaline are devoid of sexual side effects. Those sexual disturbances cannot be normalized by simultaneously increasing noradrenaline neurotransmission, but are normalized by increasing both noradrenaline and dopamine neurotransmission. Therefore, it is hypothesized that the sexual side effects of selective serotonin reuptake inhibitors may be mediated by their inhibitory effects on dopamine signaling in sex brain circuits. Clinical development of novel antidepressants should therefore focus on compounds that simultaneously increase both serotonin and dopamine signaling. © 2013 Elsevier Inc. All rights reserved.

  11. Assessing Side Effects of Pharmacotherapy Treatment of Bipolar Disorder: A 20-Year Review of the Literature (United States)

    Matson, Johnny L.; Gonzalez, Melissa L.; Smith, Kimberly R.; Terlonge, Cindy; Thorson, Ryan T.; Dixon, Dennis R.


    A substantial literature on the effective treatment of bipolar disorder has begun to appear, particularly in the last 20 years.The majority of treatments studied have employed medications, particularly mood stabilizers, a typical antipsychotics and antidepressants. Most treatments produce side effects and medications are no exception. A review of…

  12. Age-related differences in renal side-effects of radiation and chemotherapy in the rat

    NARCIS (Netherlands)

    M.H.T.M. Jongejan (Mieke)


    textabstractThe improved life-expectancy of cancer patient has brought to light late sequelae of oncology therapy. This is especially true for pediatric patients. Renal damage is one of the adverse side-effects of anti-tumor therapy that may occur. Studies conceming damaging effects of

  13. Side effects of anabolic androgenic steroids: pathological findings and structure-activity relationships. (United States)

    Büttner, Andreas; Thieme, Detlef


    Side effects of anabolic steroids with relevance in forensic medicine are mainly due to life-threatening health risks with potential fatal outcome and cases of uncertain limitations of criminal liability after steroid administration. Both problems are typically associated with long-term abuse and excessive overdose of anabolic steroids. Side effects may be due to direct genomic or nongenomic activities (myotrophic, hepatotoxic), can result from down-regulation of endogenous biosynthesis (antiandrogenic) or be indirect consequence of steroid biotransformation (estrogenic).Logically, there are no systematic clinical studies available and the number of causally determined fatalities is fairly limited. The following compilation reviews typical abundant observations in cases where nonnatural deaths (mostly liver failure and sudden cardiac death) were concurrent with steroid abuse. Moreover, frequent associations between structural characteristics and typical side effects are summarized.

  14. Cardiovascular Side Effects of Atomoxetine and Its Interactions with Inhibitors of the Cytochrome P450 System

    Directory of Open Access Journals (Sweden)

    Pashtoon Murtaza Kasi


    Full Text Available Attention deficit hyperactivity disorder (ADHD is one of the most common neurobehavioral disorders of childhood and adolescence. Classically, stimulants have been used in the treatment of this condition. Atomoxetine (Strattera; Eli Lilly and Company is a selective norepinephrine reuptake inhibitor (SNRI, one of the first medications in the nonstimulant class of medications that has been approved by the FDA for the treatment of ADHD. Atomoxetine is a phenoxypropylamine derivative and is structurally related to the antidepressant fluoxetine. The common side effects reported with the use of atomoxetine include mainly GI disturbances. Cardiovascular side effects are less commonly reported. The increase in the noradrenergic tone may explain some of the side effects noted with the use of this medication. Here, we present a case of a patient who presented with syncope, orthostatic hypotension, and tachycardia and discuss the various clinical implications based on the pharmacokinetics and pharmacodynamics of the drug.

  15. Do the benefits outweigh the side effects of colorectal cancer surveillance? A systematic review. (United States)

    Augestad, Knut Magne; Rose, Johnie; Crawshaw, Benjamin; Cooper, Gregory; Delaney, Conor


    Most patients treated with curative intent for colorectal cancer (CRC) are included in a follow-up program involving periodic evaluations. The survival benefits of a follow-up program are well delineated, and previous meta-analyses have suggested an overall survival improvement of 5%-10% by intensive follow-up. However, in a recent randomized trial, there was no survival benefit when a minimal vs an intensive follow-up program was compared. Less is known about the potential side effects of follow-up. Well-known side effects of preventive programs are those of somatic complications caused by testing, negative psychological consequences of follow-up itself, and the downstream impact of false positive or false negative tests. Accordingly, the potential survival benefits of CRC follow-up must be weighed against these potential negatives. The present review compares the benefits and side effects of CRC follow-up, and we propose future areas for research.

  16. [Randomised study on histaminelike side-effects of 5 common plasmasubstitutes in orthopedic surgery (author's transl)]. (United States)

    Schöning, B; Koch, H


    Preceding anaesthesia 750 randomised patients, sub-divided into 5 different age groups, were given 500 ml of a standard plasma-substitute at a flow rate of 25-30 ml/min. There was direct correlation (p=0.1%) of the frequency of side-effects to the substance used; none, however, to the age or general surgical risk. Side-effects were observed in 21.3% with derivates of gelatin as compared to 3.7% with Macrodex and Plasmasteril combined. The rate of more serious anaphylactoid reactions was 6% with Haemaccel, 1.3% with Gelifundol-S, 0.67% with Macrodex and less than 0.67% with Neo-Plasmagel. The study reveals that serious side-effects may be expected in orthopaedictic patients after application of plasma substitutes. As a prophylactic procedure for those patients we recommend, therefore, the application of these substances only after careful consideration of the indications for their use.

  17. Metabolic and Endocrine Side Effects of Atypical Antipsychotic Drugs in Children and Adolescents

    Directory of Open Access Journals (Sweden)

    Aysegul Tahiroglu


    Full Text Available omorbid psychiatric disorders, frequent hospitalization, multiple outpatient treatment, prior history of hypertension, obesity and lipid dysregulation are associated with higher risk of metabolic syndrome in children. Side effects of antipsychotic drugs and their management have recently become a major subject of research due to enhanced antipsychotic drug usage in child and adolescents. Prevention strategies are usually preferred to secondary or tertiary strategies in the management of metabolic syndrome associated with antipsychotic drugs. Clinicians should present multidisciplinary approach to endocrine and metabolic side effects due to antipsychotic use in pediatric patient groups and avoid multiple drug use in such patients. In this paper, we briefly reviewed metabolic side effects of second generation antipsychotic drugs in child and adolescent population, possible mechanisms of susceptibility to metabolic syndrome and pharmacological and non pharmacological treatment approach to prevention of weight gain.

  18. Quantitative expression of osteopontin in nasal mucosa of patients with allergic rhinitis: effects of pollen exposure and nasal glucocorticoid treatment

    Directory of Open Access Journals (Sweden)

    O'Neil Serena E


    Full Text Available Abstract Background Osteopontin (OPN is a multifunctional cytokine that has been primarily investigated in Th1 diseases. Recently, it has also been implicated in Th2-mediated allergic diseases, such as asthma. The expression of OPN in allergic rhinitis (AR is currently unknown, as is the effect of intranasal glucocorticosteroids (GCs on that expression. Methods Subjects with AR were randomised to receive treatment with fluticasone propionate (FP (n = 12 or a placebo (n = 16 over the grass pollen season and nasal biopsies were taken prior to, and during the season. OPN expression in the nasal mucosa was examined with immunohistochemistry. Healthy non-AR controls (n = 5 were used as a comparator. Results OPN expression was detected in epithelial cells, subepithelial infiltrating/inflammatory cells and cells lining the vessels and glands of all subjects. Comparison of the pre- and peak-pollen season biopsy sections in placebo treated patients revealed no increase in OPN expression during the grass pollen season (5.7% vs 6.4%. Treatment with a local glucocorticosteroid did not alter the expression of OPN during pollen exposure (6.2% vs 6.7%. Conclusion OPN has been increasingly associated with the pathogenesis of various Th2-mediated diseases. However, our finding that the OPN expression in the nasal mucosa of AR patients is not significantly affected by allergen exposure and is comparable to that of the healthy controls, suggests that intracellular OPN is not directly involved in the pathogenesis of allergic rhinitis.

  19. Tumor-promoting phorbol ester amplifies the inductions of tyrosine aminotransferase and ornithine decarboxylase by glucocorticoid

    International Nuclear Information System (INIS)

    Kido, H.; Fukusen, N.; Katunuma, N.


    In adrenalectomized rats, the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) markedly enhanced the inductions of tyrosine aminotransferase (TAT) and ornithine decarboxylase by glucocorticoids, even with sufficient concentration of glucocorticoids to have a maximal effect, whereas it had no effect on TAT activity and increased ornithine decarboxylase activity only slightly in the absence of glucocorticoids. Phorbol derivatives and components of TPA such as 4β-phorbol, phorbol 12-tetradecanoate, phorbol 13-acetate, and 4-O-methylphorbol 12-tetradecanoate 13-acetate, which have no tumor-promoting activity or ability to activate protein kinase C, did not have any effect on TAT induction by glucocorticoid. TPA enhanced the induction of TAT by various glucocorticoids but had no effect on induction of TAT by glucagon or insulin and did not enhance the induction of glucose-6-phosphate dehydrogenase by 17β-estradiol. These results suggest that TPA specifically enhances the induction of TAT and ornithine decarboxylase by glucocorticoids. Similar effects of TPA on TAT induction by glucocorticoid were observed in primary cultures of adult rat hepatocytes. Another activator of protein kinase C, rac-1,2-dioctanoylglycerol, was also found to have similar effects on the cells

  20. Clozapine-Induced Cardiovascular Side Effects and Autonomic Dysfunction: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Jessica W. Y. Yuen


    Full Text Available Background: Clozapine is the antipsychotic of choice for treatment-resistant schizophrenia and has minimal risk for extrapyramidal symptoms. Therapeutic benefits, however, are accompanied by a myriad of cardiometabolic side-effects. The specific reasons for clozapine's high propensity to cause adverse cardiometabolic events remain unknown, but it is believed that autonomic dysfunction may play a role in many of these.Objective: This systematic review summarizes the literature on autonomic dysfunction and related cardiovascular side effects associated with clozapine treatment.Method: A search of the EMBASE, MEDLINE, and EBM Cochrane databases was conducted using the search terms antipsychotic agents, antipsychotic drug*, antipsychotic*, schizophrenia, schizophren*, psychos*, psychotic*, mental ill*, mental disorder*, neuroleptic*, cardiovascular*, cardiovascular diseases, clozapine*, clozaril*, autonomic*, sympathetic*, catecholamine*, norepinephrine, noradrenaline, epinephrine, adrenaline.Results: The search yielded 37 studies that were reviewed, of which only 16 studies have used interventions to manage cardiovascular side effects. Side effects reported in the studies include myocarditis, orthostatic hypotension and tachycardia. These were attributed to sympathetic hyperactivity, decreased vagal contribution, blockade of cholinergic and adrenergic receptors, reduced heart rate variability and elevated catecholamines with clozapine use. Autonomic neuropathy was identified by monitoring blood pressure and heart rate changes in response to stimuli and by spectral analysis of heart rate variability. Metoprolol, lorazepam, atenolol, propranolol, amlodipine, vasopressin and norepinephrine infusion were used to treat tachycardia and fluctuations in blood pressure, yet results were limited to case reports.Conclusion: The results indicate there is a lack of clinical studies investigating autonomic dysfunction and a limited use of interventions to manage

  1. Glucocorticoid receptor signaling in health and disease (United States)

    Kadmiel, Mahita; Cidlowski, John A.


    Glucocorticoids are steroid hormones regulated in a circadian and stres-associated manner to maintain various metabolic and homeostatic functions that are necessary for life. Synthetic glucocorticoids are widely prescribed drugs for many conditions including asthma, chronic obstructive pulmonary disease (COPD), and inflammatory disorders of the eye. Research in the last few years has begun to unravel the profound complexity of glucocorticoid signaling and has contributed remarkably to improved therapeutic strategies. Glucocorticoids signal through the glucocorticoid receptor, a member of the superfamily of nuclear receptors, in both genomic and non-genomic ways in almost every tissue in the human body. In this review, we will provide an update on glucocorticoid receptor signaling and highlight the role of GR signaling in physiological and pathophysiological conditions in the major organ systems in the human body. PMID:23953592

  2. Effect of Glucocorticoids on the Clinical and Radiographic Efficacy of Tofacitinib in Patients with Rheumatoid Arthritis: A Posthoc Analysis of Data from 6 Phase III Studies. (United States)

    Charles-Schoeman, Christina; van der Heijde, Désirée; Burmester, Gerd R; Nash, Peter; Zerbini, Cristiano A F; Connell, Carol A; Fan, Haiyun; Kwok, Kenneth; Bananis, Eustratios; Fleischmann, Roy


    Tofacitinib has been investigated for the treatment of rheumatoid arthritis (RA) in phase III studies in which concomitant glucocorticoids (GC) were allowed. We analyzed the effect of GC use on efficacy outcomes in patients with RA receiving tofacitinib and/or methotrexate (MTX) or conventional synthetic disease-modifying antirheumatic drugs (csDMARD) in these studies. Our posthoc analysis included data from 6 phase III studies (NCT01039688; NCT00814307; NCT00847613; NCT00853385; NCT00856544; NCT00960440). MTX-naive patients or patients with inadequate response to csDMARD or biological DMARD received tofacitinib 5 or 10 mg twice daily alone or with csDMARD, with or without concomitant GC. Patients receiving GC (≤ 10 mg/day prednisone or equivalent) before enrollment maintained a stable dose throughout. Endpoints included the American College of Rheumatology (ACR) 20/50/70 response rates, rates of Clinical Disease Activity Index (CDAI)-defined low disease activity (LDA; CDAI ≤ 10) and remission (CDAI ≤ 2.8), and changes from baseline in CDAI, 28-joint count Disease Activity Score (DAS28-4)-erythrocyte sedimentation rate (ESR), Health Assessment Questionnaire-Disability Index (HAQ-DI), pain visual analog scale (VAS), and modified total Sharp score. Of 3200 tofacitinib-treated patients, 1258 (39.3%) received tofacitinib monotherapy and 1942 (60.7%) received tofacitinib plus csDMARD; 1767 (55.2%) received concomitant GC. ACR20/50/70 response rates, rates of CDAI LDA and remission, and improvements in CDAI, DAS28-4-ESR, HAQ-DI, and pain VAS with tofacitinib were generally similar with or without GC in monotherapy and combination therapy studies. GC use did not appear to affect radiographic progression in tofacitinib-treated MTX-naive patients. MTX plus GC appeared to inhibit radiographic progression to a numerically greater degree than MTX alone. Concomitant use of GC with tofacitinib did not appear to affect clinical or radiographic efficacy. MTX plus GC showed a

  3. Anti-Stigma HIV-Related Social Advertising: No Evidence for Side Effects on Condom Use. (United States)

    Arendt, Florian; Hauck, Patricia; Mayr, Johanna; Negwer, Flavia


    Recent campaigns try to reduce social stigma associated with persons living with HIV. For example, a German campaign raised awareness that infection is unlikely in low-risk day-to-day interactions. Research has yet to show that there are no harmful side effects. This is essential because such messages promote a less threatening picture of HIV and thus may unintentionally increase complacency. We tested the possible side effects on the willingness to have sex without condoms. An experiment was conducted in which participants were exposed to anti-stigma messages or not. Anti-stigma messages did not elicit an increase in the willingness to have sex without condoms.

  4. Autism and Obesity: Co-Occurring Conditions or Drug Side Effects (United States)


    AWARD NUMBER: W81XWH-14-1-0374 TITLE: Autism and Obesity: Co-Occurring Conditions or Drug Side Effects? PRINCIPAL INVESTIGATOR: Zohreh...SUBTITLE Autism and Obesity: Co-Occurring Conditions or Drug Side Effects? 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0374 5c. PROGRAM ELEMENT...project is to better understand the relationship between autism and obesity. It is not clear if obesity is co-occurring with autism or is related to

  5. Calcium vitamin D3 supplementation in clinical practice: side effect and satisfaction


    Sanaei, Maryam; Banasiri, Mohammad; Shafiee, Gita; Rostami, Mahsa; Alizad, Saba; Ebrahimi, Mehdi; Larijani, Bagher; Heshmat, Ramin


    Background The objective of this study was to assess side effects and satisfaction about OsteoCalVitFort (500?mg calcium and 400 I.U. of vitamin D3) usage. Methods A total 186 people were participated with range age from 18 to 65?years old. Each participant received 1 pack that contains 60 OsteoCalVitFort tablet and used two tablet OsteoCalVitFort daily (1 tablet after breakfast and 1 after dinner). By a phone call, side effects and satisfaction about OsteoCalVitFort were assessed. Results Th...

  6. CINRG: Systems Biology of Glucocorticoids in Muscle Disease (United States)


    Contract W81XWH-09-1-0726 SYSTEMS BIOLOGY OF GLUCOCORTICOIDS IN MUSCLE DISEASE Introduction Duchenne muscular dystrophy (DMD) is the most... muscle and enable the development of better targeted and more effective therapies for Duchenne muscular dystrophy dynamically. This MDA grant...common and incurable muscular dystrophy of childhood. Muscle regeneration fails with advancing age, leading to considerable fibrosis. Corticosteroid

  7. Short-term side effects and patient-reported outcomes of bleomycin sclerotherapy in vascular malformations. (United States)

    Mack, Joana M; Richter, Gresham T; Becton, David; Salem, Omar; Hill, Sarah E M; Crary, Shelley E


    Vascular malformations (VM) are congenital lesions that can be debilitating and cause significant aesthetic and functional limitations. The chemotherapeutic agent bleomycin has been utilized as a sclerosant, directly injected percutaneously into the VM. Unfortunately, little is known about the benefits and short-term side effects of bleomycin with intralesional injections. An IRB approved, retrospective chart review was performed on patients with VM who had been treated with intralesional bleomycin. Data included type of VM, number of treatments, total bleomycin dose per m², and adverse effects. A questionnaire was administered to available patients to assess subjective outcomes and side effects. Forty-six patients were treated with 141 procedures of bleomycin sclerotherapy for VM. Patient ages ranged from 1 to 20 years (median age 10 years). The median cumulative bleomycin dose was 16.3 units/m²/person (range of 1.7-97.0 units/m²/person). Sixty-three percent of patients were reached for a questionnaire to assess short-term side effects. Ninety percent of patients surveyed were satisfied to very satisfied with the results from the procedure. About 24% of patients experienced transient nausea, vomiting and/or local hyperpigmentation. Bleomycin sclerotherapy can be an effective treatment of VM with repeat exposure with minor risk of short-term side effects, however, long-term risks are of great concern. Further studies are required to assess systemic absorption and long-term risks. © 2018 Wiley Periodicals, Inc.

  8. Computational Analysis of an effect of aerodynamic pressure on the side view mirror geometry (United States)

    Murukesavan, P.; Mu'tasim, M. A. N.; Sahat, I. M.


    This paper describes the evaluation of aerodynamic flow effects on side mirror geometry for a passenger car using ANSYS Fluent CFD simulation software. Results from analysis of pressure coefficient on side view mirror designs is evaluated to analyse the unsteady forces that cause fluctuations to mirror surface and image blurring. The fluctuation also causes drag forces that increase the overall drag coefficient, with an assumption resulting in higher fuel consumption and emission. Three features of side view mirror design were investigated with two input velocity parameters of 17 m/s and 33 m/s. Results indicate that the half-sphere design shows the most effective design with less pressure coefficient fluctuation and drag coefficient.

  9. Secondary-side feed-and-bleed effectiveness in pressurized water reactors

    International Nuclear Information System (INIS)

    Annunziato, A.


    An analysis is presented of physical phenomena occurring during secondary-side feed-and-bleed, which is being considered as an accident management procedure for pressurized water reactors. Problem areas related to the reliability of this procedure are identified and discussed. Secondary-side feed-and-bleed, as examined in the LOBI (which is the Light Water Reactor Off-Normal Behavior Investigation) integral system test facility, was not successful because of a delay in the secondary-side heat removal caused by the release of stored heat from the steam generator downcomer wall. Countercurrent flow limiting in the hot leg was another major phenomenon that can influence the effectiveness of this procedure. The discussion of the experimental results is complemented by relevant calculations by RELAP5/MOD3. In general, it was found that the effectiveness of the feed-and-bleed procedure is maximized if the number of steam generators used to implement it is reduced

  10. Do the emotional side-effects of hormonal contraceptives come from pharmacologic or psychological mechanisms? (United States)

    Robinson, Stephen A; Dowell, Matt; Pedulla, Dominic; McCauley, Larry


    Hormonal preparations have become one of the most popular methods used for controlling fertility. The literature over the last 40 years continues to reveal how their numerous side effects negatively impact many users and even society at large. Three large cohort trials were the first to demonstrate, on a grand scale, certain emotional and behavioral associations with contraceptive use. Current contraceptive use was associated with an increase rate in depression, divorce, tranquilizer use, sexual dysfunction, and suicide and other violent and accidental deaths. Despite the advent of more "user friendly" contraceptives, the discontinuation rate secondary to side effects has changed little through the years. While in rare cases hormonal preparations can be deadly to the user, there is substantial evidence that their negative effect issues more from their emotional and behavioral properties. This paper reviews the results of over seven studies which further characterize these prominent associations, particularly with hormonal contraception, in an attempt to demonstrate their association with the intrinsic pharmacologic properties of hormonal preparations. Hormonal contraceptive users, in contrast with non users, were found to have higher rates of depression, anxiety, fatigue, neurotic symptoms, sexual disturbances, compulsion, anger, and negative menstrual effects. The question of whether the association of these maladies is directly due to the effect of taking exogenous hormones versus the psychological impact of the contraceptive behavior itself had yet to be studied. Seven small randomized-controlled trials were found in a review of the literature which studied this hypothesis in a direct way. They do not support the origination of these side effects being from the pharmacological properties of hormones. No association was found between hormone levels and emotional functioning in females. Psychiatric evaluations among IUD and oral contraceptive pill (OCP) users

  11. Synovial DKK1 expression is regulated by local glucocorticoid metabolism in inflammatory arthritis. (United States)

    Hardy, Rowan; Juarez, Maria; Naylor, Amy; Tu, Jinwen; Rabbitt, Elizabeth H; Filer, Andrew; Stewart, Paul M; Buckley, Christopher D; Raza, Karim; Cooper, Mark S


    Inflammatory arthritis is associated with increased bone resorption and suppressed bone formation. The Wnt antagonist dickkopf-1 (DKK1) is secreted by synovial fibroblasts in response to inflammation and this protein has been proposed to be a master regulator of bone remodelling in inflammatory arthritis. Local glucocorticoid production is also significantly increased during joint inflammation. Therefore, we investigated how locally derived glucocorticoids and inflammatory cytokines regulate DKK1 synthesis in synovial fibroblasts during inflammatory arthritis. We examined expression and regulation of DKK1 in primary cultures of human synovial fibroblasts isolated from patients with inflammatory arthritis. The effect of TNFα, IL-1β and glucocorticoids on DKK1 mRNA and protein expression was examined by real-time PCR and ELISA. The ability of inflammatory cytokine-induced expression of the glucocorticoid-activating enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) to sensitise fibroblasts to endogenous glucocorticoids was explored. Global expression of Wnt signalling and target genes in response to TNFα and glucocorticoids was assessed using a custom array. DKK1 expression in human synovial fibroblasts was directly regulated by glucocorticoids but not proinflammatory cytokines. Glucocorticoids, but not TNFα, regulated expression of multiple Wnt agonists and antagonists in favour of inhibition of Wnt signalling. However, TNFα and IL-1β indirectly stimulated DKK1 production through increased expression of 11β-HSD1. These results demonstrate that in rheumatoid arthritis synovial fibroblasts, DKK1 expression is directly regulated by glucocorticoids rather than TNFα. Consequently, the links between synovial inflammation, altered Wnt signalling and bone remodelling are not direct but are dependent on local activation of endogenous glucocorticoids.

  12. Iatrogenic adrenal insufficiency as a side-effect of combined treatment of itraconazole and budesonide

    DEFF Research Database (Denmark)

    Skov, M; Main, K M; Sillesen, Ida Blok


    . Suppression of the adrenal glucocorticoid synthesis was observed in 11 of 25 cystic fibrosis patients treated with both itraconazole and budesonide. The pathogenesis is most likely an itraconazole caused increase in systemic budesonide concentration through a reduced/inhibited metabolism leading to inhibition...

  13. Balancing opioid-induced gastrointestinal side effects with pain management: Insights from the online community. (United States)

    Whitman, Cynthia B; Reid, Mark W; Arnold, Corey; Patel, Haridarshan; Ursos, Lyann; Sa'adon, Roee; Pourmorady, Jonathan; Spiegel, Brennan M R


    Opioids cause gastrointestinal (GI) symptoms such as nausea, vomiting, pain, and (in 40 percent) constipation that diminish patients' quality of life. Outside traditional surveys, little is known about the opioid-induced constipation (OIC) patient experience and its impact on pain management. The purpose of this study was to use data from social media platforms to qualitatively examine patient beliefs about OIC and other prominent GI side effects, their impact on effective pain management and doctor-patient interaction. The authors collected Tweets from March 25 to July 31, 2014, and e-forum posts from health-related social networking sites regardless of timestamp. The authors identified specific keywords related to opioids and GI side effects to locate relevant content in the dataset, which was then manually coded using ATLAS.ti software. The authors examined 2,519,868 Tweets and more than 1.8 billion e-forum posts, of which, 88,586 Tweets and 9,767 posts satisfied the search criteria. Three thousand three individuals experienced opioidinduced GI side effects, mostly related to phenanthrenes (n = 1,589), and 1,274 (42.4 percent) individuals described constipation. Over-the-counter medications and nonevidence-based natural approaches were most commonly used to alleviate constipation. Many individuals questioned, rotated, reduced, or stopped their opioid treatments as a result of their GI side effects. Investigation of social media reveals a struggle to balance pain management with opioid-induced GI side effects, especially constipation. Individuals are often unprepared to treat OIC, to modify opioid regiments without medical advice, and to resort to using natural remedies and treatments lacking scientific evidence of effectiveness. These results identify opportunities to improve physician-patient communication and explore effective treatment alternatives.

  14. Managing the side effects of multiple sclerosis therapy: pharmacotherapy options for patients. (United States)

    Rommer, Paulus S; Zettl, Uwe K


    Multiple sclerosis (MS) is an immune-mediated and neurodegenerative disease with an unpredictable outcome. Immune-modulatory treatment aims at decreasing long-term disability. With the increasing number of treatment options, it is essential to fully digest the possible side effects of the available therapeutics and to monitor patients is essential. Areas covered: All approved disease-modifying drugs (DMD) for MS are discussed in this review. Mode of action, adverse effects, reported risks for infections and malignancies, and pregnancy related issues are discussed in the review. The authors also provide suggestions for monitoring therapy. For all approved DMDs the pivotal studies have been included for possible side effects, as well as reports by health authorities. For this manuscript, PubMed was checked for reports on side effects for various drugs. Expert opinion: Treatment options in MS are manifold, each carrying different risks. The safety-risk profile for approved agents is favorable. Knowing and monitoring these possible side effects is essential to minimize risks associated with treatment. Presently, the long-term experience for some of these therapies is missing and this must be addressed.

  15. Exploring the Process of Conveying Information about Side Effects: A Qualitative Study among Pharmacists

    Directory of Open Access Journals (Sweden)

    Therése Kairuz


    Full Text Available This study explored how a sample of Australian pharmacists would convey information about the side effects of a medicine, if they were to counsel a patient. A qualitative method was selected and written responses to a case-based scenario were analysed using inductive thematic analysis. The grounded theory approach elicited a fluid and dynamic model for side effect counselling. The study identified strategies for counselling, such as encouraging adherence through emphasising the benefits of the medication, referral to the prescriber, and providing empathy and reassurance to ease anxiety and address concerns. Pharmacists acknowledged the potential for risk, although only a minority used numerical descriptors. The final themes or outcomes were that pharmacists aim to allay fears, minimise harm and promote medication use when counselling about side effects. Professional empathy, the acknowledgment of patient concerns, and the importance of providing tailored information to promote medication adherence, emerged as features of the quality use of medicines. This study contributes to existing literature by identifying the role of allaying patients’ fears when conveying side effect information. It also describes a process to convey tailored information. Implications for practice include the importance of effective use of communication strategies to encourage adherence, as the appropriate use of medication can lead to positive health outcomes.

  16. Cutaneous, gastrointestinal, hepatic, endocrine, and renal side-effects of anti-PD-1 therapy. (United States)

    Hofmann, Lars; Forschner, Andrea; Loquai, Carmen; Goldinger, Simone M; Zimmer, Lisa; Ugurel, Selma; Schmidgen, Maria I; Gutzmer, Ralf; Utikal, Jochen S; Göppner, Daniela; Hassel, Jessica C; Meier, Friedegund; Tietze, Julia K; Thomas, Ioannis; Weishaupt, Carsten; Leverkus, Martin; Wahl, Renate; Dietrich, Ursula; Garbe, Claus; Kirchberger, Michael C; Eigentler, Thomas; Berking, Carola; Gesierich, Anja; Krackhardt, Angela M; Schadendorf, Dirk; Schuler, Gerold; Dummer, Reinhard; Heinzerling, Lucie M


    Anti-programmed cell death receptor-1 (PD-1) antibodies represent an effective treatment option for metastatic melanoma as well as for other cancer entities. They act via blockade of the PD-1 receptor, an inhibitor of the T-cell effector mechanisms that limit immune responses against tumours. As reported for ipilimumab, the anti-PD-1 antibodies pembrolizumab and nivolumab can induce immune-related adverse events (irAEs). These side-effects affect skin, gastrointestinal tract, liver, endocrine system and other organ systems. Since life-threatening and fatal irAEs have been reported, adequate diagnosis and management are essential. In total, 496 patients with metastatic melanoma from 15 skin cancer centers were treated with pembrolizumab or nivolumab; 242 side-effects were described in 138 patients. In 116 of the 138 patients, side-effects affected the skin, gastrointestinal tract, liver, endocrine, and renal system. Rare side-effects included diabetes mellitus, lichen planus, and pancreas insufficiency due to pancreatitis. Anti-PD1 antibodies can induce a plethora of irAEs. The knowledge of them will allow prompt diagnosis and improve the management resulting in decreased morbidity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Symptoms and side effects in chronic non-cancer pain: patient report vs. systematic assessment. (United States)

    Jonsson, T; Christrup, L L; Højsted, J; Villesen, H H; Albjerg, T H; Ravn-Nielsen, L V; Sjøgren, P


    relieving distressing symptoms and managing the side effects of analgesics are essential in order to improve quality of life and functional capacity in chronic non-cancer pain patients. A quick, reliable and valid tool for assessing symptoms and side effects is needed in order to optimize treatment. We aimed to investigate the symptoms reported by chronic non-cancer pain patients after open-ended questioning vs. a systematic assessment using a list of symptoms, and to assess whether the patients could distinguish between the symptoms and the side effects induced by analgesics. patients treated with either opioids and/or adjuvant analgesics were asked to report their symptoms spontaneously, followed by a 41-item investigator-developed symptom checklist. A control group also filled in the checklist. a total of 62 patients and 64 controls participated in the study. The numbers of symptoms reported by the patients (9.9 ± 5.9) were significantly higher than those reported by the controls (3.2 ± 3.9) (Pside effects due to analgesics was: (1) Dry mouth (42%); (2) Sweating (34%); (3) Weight gain (29%); (4) Memory deficits (24%); (5) Fatigue (19%); and (6) Concentration deficits (19%). the number of symptoms reported using systematic assessment was eightfold higher than those reported voluntarily. Fatigue, cognitive dysfunction, dry mouth, sweating and weight gain were the most frequently reported. The patients reported the side effects of their analgesics to contribute substantially to the reported symptoms. 2010 The Acta Anaesthesiologica Scandinavica Foundation.

  18. Clinically insubstantial cognitive side effects of bitemporal electroconvulsive therapy at 0.5 msec pulse width. (United States)

    Warnell, Ronald L; Swartz, Conrad M; Thomson, Alice


    We measured cognitive side effects from bitemporal electroconvulsive therapy (ECT) using stimuli of 0.5 msec pulse width 900 milliamperes (mA). Mini-Mental State Exam (MMSE) and 21-item Hamilton Rating Scale for Depression (HRSD-21) were rated within 36 hours before and 36 hours after a series of 6 bitemporal ECT sessions on 15 patients age ≥45. MMSE remained high after ECT (pre-ECT mean 29, standard deviation [SD] 1.60, post-ECT mean 28.53, SD 1.36) with no significant change. The mean HRSD-21 fell from 27.5 to 16.3. Post-ECT MMSE was significantly and markedly higher than in previous studies of bitemporal ECT; all had used ECT stimuli of pulse width at least 1 msec. With stimuli of 0.5 msec pulse width and 900 mA, 6 bitemporal ECTs did not decrease MMSE score. This result leaves no opportunity for further decrease in basic cognitive side effects, and complements published reports of stronger physiological effects with stimuli of 0.5 msec pulse width and 900 mA. ECT stimuli of 0.5 msec pulse width and 900 mA are more desirable than wider pulse widths. Six bitemporal ECT sessions using these stimuli generally will not have more cognitive side effects than treatments with other placements, allowing maintenance of full efficacy with clinically insubstantial side effects.

  19. Molecular mechanisms of glucocorticoid receptor signaling Mecanismos moleculares de señalización del receptor de glucocorticoides

    Directory of Open Access Journals (Sweden)

    Marta Labeur


    Full Text Available This review highlights the most recent findings on the molecular mechanisms of the glucocorticoid receptor (GR. Most effects of glucocorticoids are mediated by the intracellular GR which is present in almost every tissue and controls transcriptional activation via direct and indirect mechanisms. Nevertheless the glucocorticoid responses are tissue -and gene- specific. GR associates selectively with corticosteroid ligands produced in the adrenal gland in response to changes of humoral homeostasis. Ligand interaction with GR promotes either GR binding to genomic glucocorticoid response elements, in turn modulating gene transcription, or interaction of GR monomers with other transcription factors activated by other signalling pathways leading to transrepression. The GR regulates a broad spectrum of physiological functions, including cell differentiation, metabolism and inflammatory responses. Thus, disruption or dysregulation of GR function will result in severe impairments in the maintenance of homeostasis and the control of adaptation to stress.Esta revisión destaca los más recientes hallazgos sobre los mecanismos moleculares del receptor de glucocorticoides (GR. La mayoría de los efectos de los glucocorticoides son mediados por los GR intracelulares presentes en casi todos los tejidos y controlan la activación transcripcional por mecanismos directos e indirectos. Las respuestas a los glucocorticoides son específicas para cada gen y tejido. Los GR se asocian en forma selectiva con ligandos producidos en la glándula adrenal, corticosteroides, en respuesta a cambios neuroendocrinos. La interacción del ligando con el GR promueve: a la unión del GR a elementos genómicos de respuesta a glucocorticoides, modulando la transcripción; b la interacción de monómeros del GR con otros factores de transcripción activados por otras vías, llevando a la transrepresión. El GR regula un amplio espectro de funciones fisiológicas, incluyendo la

  20. Antipsychotic Medication in Children and Adolescents : A Descriptive Review of the Effects on Prolactin Level and Associated Side Effects

    NARCIS (Netherlands)

    Roke, Yvette; van Harten, Peter N.; Boot, Annemieke M.; Buitelaar, Jan K.

    Objective: This review reports the incidence of hyperprolactinemia, its relationship with genotype, and prolactin-related side effects in children and adolescents treated with antipsychotics. Method: Data on prolactin levels were available for haloperidol, pimozide, risperidone, olanzapine,

  1. Antipsychotic medication in children and adolescents: a descriptive review of the effects on prolactin level and associated side effects.

    NARCIS (Netherlands)

    Roke, Y.; Harten, P.N. van; Boot, A.M.; Buitelaar, J.K.


    OBJECTIVE: This review reports the incidence of hyperprolactinemia, its relationship with genotype, and prolactin-related side effects in children and adolescents treated with antipsychotics. METHOD: Data on prolactin levels were available for haloperidol, pimozide, risperidone, olanzapine,


    Directory of Open Access Journals (Sweden)



    Full Text Available Introduction: Acne vulgaris is an inflammatory disease of pilosebaceous folicles. Tretinoin is used as one of the topical treatments for acne vulgaris. It has different cutaneous side effects such as erythema, scaling, irritation and photosensitivity. The aim of this study was to evaluate the efficacy of oral Vitamine E in preventing the cutaneous side effects of topical tretinoin in acne patients.
    Methods: A clinical trial was performed in AI-Zahra Hospital in Isfahan for six months in 2000. 80 patients with mild to moderate facial acne were randomized into 2 groups. Group 1 (controls received topical solution of tretinoin 0.05 percent nightly and group 2 (cases received daily oral 100mg of Vit. E in addition. All patients were followed at 1, 4 and 6 weeks after initiation of treatment. Children under 12 years old, pregnant or lactating women were excluded.
    Results: At the end of one week, no cutaneous side effects were observed in 25 percent (10 of group 1 and 15 percent (6 of group 2 (P > 0.05. At the end of 4 weeks, 25 percent (10 of group 1 and 60 percent (24 of group 2 were without any cutaneous complications, while at the end of 6 weeks, 35 percent (14 of group 1 in comparison to 75 percent (30 of group 2 were free of any cutaneous side effects (P < 0.05. The most common side effect in both groups was exfoliation.
    Discussion: Daily oral 100 mg of Vit. E has been effective in preventing cutaneous complications of topical tretinoin in acne management, but there is a delay of one week in its onset of action. Meanwhile, Vitamine E is a safe modality with no undesirable effects in acne patients.

  3. Treatment side effects and follow-up of malignant melanoma; Therapienebenwirkungen und Nachsorge bei malignem Melanom

    Energy Technology Data Exchange (ETDEWEB)

    Stahl, T. [Klinikum der Stadt Ludwigshafen gGmbH, Zentralinstitut fuer diagnostische und interventionelle Radiologie, Ludwigshafen (Germany); Loquai, C. [Universitaetsmedizin der Johannes-Gutenberg Universitaet Mainz, Hautklinik und Poliklinik, Mainz (Germany)


    Side effects in the therapy of malignant melanoma are primarily of importance for radiologists in advanced tumor stages. The available treatment options and their respective side effect profiles have undergone a profound change in recent years after the introduction of modern oncological therapies (e.g. immunotherapy and targeted therapy) with an increasing focus on individual tumor biology and differ significantly from those of classical chemotherapy. The immunotherapeutic agents, in particular ipilimumab, take on a special position because of their specific immune-mediated mechanisms of action and the associated side effects, so-called immune-related adverse events (irAE). The majority of the treatment effects are manifested on the skin (> 50 %) and are generally not detectable by diagnostic radiology. Only a comparatively small proportion of treatment side effects is detectable with diagnostic imaging (15-20 %) but as in the example of therapy-induced colitis with ipilimumab, may be rapidly fatal. In addition to colitis (10-20 %) further therapy side effects apparent in diagnostic imaging are hypophysitis (1.8-17 %), thyroiditis (0.8 %), myositis (1.7 %), fasciitis and sarcoid-like lymph node alterations (6.8 %). To detect radiologically detectable side effects early on and to delineate them especially from tumor progression and (opportunistic) infections, detailed knowledge of the therapeutic methods for melanoma, the mechanisms of action and in particular the sometimes very specific side effects is imperative for radiologists. (orig.) [German] Nebenwirkungen der Therapie des malignen Melanoms sind fuer den Radiologen primaer in fortgeschrittenen Tumorstadien von Bedeutung. Die zur Verfuegung stehenden Therapieoptionen und ihre jeweiligen Nebenwirkungsprofile haben sich in den letzten Jahren nach Einfuehrung moderner onkologischer Therapieoptionen, die sich zunehmend an der individuellen Tumorbiologie orientieren (zielgerichtete Therapie, Immuntherapie), einem

  4. Glucocorticoid treatment and impaired mood, memory and metabolism in people with diabetes: the Edinburgh Type 2 Diabetes Study (United States)

    Reynolds, Rebecca M; Labad, Javier; Sears, Alison V; Williamson, Rachel M; Strachan, Mark W J; Deary, Ian J; Lowe, Gordon D O; Price, Jackie F; Walker, Brian R


    Objective Both type 2 diabetes and glucocorticoid therapy are highly prevalent. Although people with type 2 diabetes may be more susceptible to adverse effects of glucocorticoids, and it is recommended that glucocorticoid therapy is avoided for fear of worsening glycaemic control, the extent to which this advice is followed and the consequences when glucocorticoids are prescribed are poorly documented. The aim was to assess the characteristics of people with type 2 diabetes prescribed glucocorticoids in a real-world setting and to quantify resulting adverse effects. Design Cross-sectional cohort study. Methods Cardiometabolic variables, body fat distribution, cognitive function and mood were studied in the 1066 participants of the Edinburgh Type 2 Diabetes Study, of whom 162 (15%) were taking systemic, topical or inhaled glucocorticoids. Results Glucocorticoid therapy was more common in women and in smokers but was not avoided in patients with diabetic complications or cardiovascular risk factors. People taking glucocorticoids were more centrally obese with slightly higher HbA1c and total serum cholesterol but were no more likely to have hepatic steatosis or hypertension. Glucocorticoid treatment was associated with substantially lower mood and greater anxiety. Women taking glucocorticoid therapy were twice as likely to report depressive symptoms compared with those not taking treatment. Glucocorticoid therapy was also associated with poorer cognitive function among those with subclinical atherosclerosis, as indicated by low ankle–brachial pressure index. Conclusions Glucocorticoids are prescribed commonly for people with type 2 diabetes despite being associated with adverse indices of glycaemic control, cardiovascular risk factors, mood and cognitive function. PMID:22408122

  5. Herbal medicines for the treatment of cancer chemotherapy-induced side effects


    Ohnishi, Shunsuke; Takeda, Hiroshi


    Accumulating evidence suggests that Japanese herbal medicines, called Kampo, have beneficial effects on cancer chemotherapy-induced side effects. Rikkunshito ameliorates cisplatin-induced anorexia through an antagonistic effect on the 5-HT receptors and by increasing the serum ghrelin levels. Hangeshashinto improves irinotecan-induced diarrhea and chemotherapy-induced mucositis by inhibiting the activity of β-glucuronidase as well as the synthesis of prostaglandin E2. Goshajinkigan prevents o...

  6. Health Related Quality of Life in Patients with Side-Effects after Antimuscarinic Treatment for Overactive Bladder. (United States)

    Kim, Aram; Lee, Kyu-Sung; Jung, Rangrhee; Na, Selee; Kim, Joon-Chul; Kim, Hyeong Gon; Choo, Myung-Soo


    Drug therapy is the mainstay of treatment for overactive bladder (OAB), but antimuscarinic agents possess side-effects. These side-effects decrease the patients' quality of life. We therefore assessed the impact of side-effects on health-related quality of life (HR-QoL) through an analysis of EQ-5D questionnaire. This study was designed to investigate the patients' satisfaction by quality weight of health status as affected by the side-effects of OAB medications. Patients who had OAB symptoms lasting longer than 3 months and have experienced side-effects after any antimuscarinic treatments filled in the EQ-5D questionnaire. The enrolled patients had two EQ-5D questionnaires for two different health statuses, i.e., presence or absence of side-effects. Quality weight was calculated using the ED-5D health status score with Korean tariff. One hundred patients were enrolled and completed the HR-QoL questionnaire. The most prevalent side-effect was dry mouth (61%) and 28% patients had dry mouth and constipation concurrently. Most of the patients with side-effects tried to endure and overcome these side-effects (79%), but 10% desired a change in medication, and 6% stopped medication altogether. The quality weight of EQ-5D without side-effects was 0.863, while the quality weight with side-effects was 0.666 (P effects and 57 in those with side-effects, supporting the results of quality weight assessment. Overactive bladder patients may enjoy a better quality of life if side-effects associated with antimuscarinic therapy are fewer. © 2016 John Wiley & Sons Australia, Ltd.

  7. Efficient hiding of confidential high-utility itemsets with minimal side effects (United States)

    Lin, Jerry Chun-Wei; Hong, Tzung-Pei; Fournier-Viger, Philippe; Liu, Qiankun; Wong, Jia-Wei; Zhan, Justin


    Privacy preserving data mining (PPDM) is an emerging research problem that has become critical in the last decades. PPDM consists of hiding sensitive information to ensure that it cannot be discovered by data mining algorithms. Several PPDM algorithms have been developed. Most of them are designed for hiding sensitive frequent itemsets or association rules. Hiding sensitive information in a database can have several side effects such as hiding other non-sensitive information and introducing redundant information. Finding the set of itemsets or transactions to be sanitised that minimises side effects is an NP-hard problem. In this paper, a genetic algorithm (GA) using transaction deletion is designed to hide sensitive high-utility itemsets for PPUM. A flexible fitness function with three adjustable weights is used to evaluate the goodness of each chromosome for hiding sensitive high-utility itemsets. To speed up the evolution process, the pre-large concept is adopted in the designed algorithm. It reduces the number of database scans required for verifying the goodness of an evaluated chromosome. Substantial experiments are conducted to compare the performance of the designed GA approach (with/without the pre-large concept), with a GA-based approach relying on transaction insertion and a non-evolutionary algorithm, in terms of execution time, side effects, database integrity and utility integrity. Results demonstrate that the proposed algorithm hides sensitive high-utility itemsets with fewer side effects than previous studies, while preserving high database and utility integrity.

  8. Patient satisfaction and side effects in primary care: An observational study comparing homeopathy and conventional medicine

    Directory of Open Access Journals (Sweden)

    Thurneysen André


    Full Text Available Abstract Background This study is part of a nationwide evaluation of complementary medicine in Switzerland (Programme Evaluation of Complementary Medicine PEK and was funded by the Swiss Federal Office of Public Health. The main objective of this study is to investigate patient satisfaction and perception of side effects in homeopathy compared with conventional care in a primary care setting. Methods We examined data from two cross-sectional studies conducted in 2002–2003. The first study was a physician questionnaire assessing structural characteristics of practices. The second study was conducted on four given days during a 12-month period in 2002/2003 using a physician and patient questionnaire at consultation and a patient questionnaire mailed to the patient one month later (including Europep questionnaire. The participating physicians were all trained and licensed in conventional medicine. An additional qualification was required for medical doctors providing homeopathy (membership in the Swiss association of homeopathic physicians SVHA. Results A total of 6778 adult patients received the questionnaire and 3126 responded (46.1%. Statistically significant differences were found with respect to health status (higher percentage of chronic and severe conditions in the homeopathic group, perception of side effects (higher percentage of reported side effects in the conventional group and patient satisfaction (higher percentage of satisfied patients in the homeopathic group. Conclusion Overall patient satisfaction was significantly higher in homeopathic than in conventional care. Homeopathic treatments were perceived as a low-risk therapy with two to three times fewer side effects than conventional care

  9. Movement disorders in patients with schizophrenia and in their siblings: symptoms, side effects and mechanical measurements

    NARCIS (Netherlands)

    Koning, J.P.F.


    This thesis focuses on several aspects of movement disorders in patients with schizophrenia and in their unaffected siblings. The main hypothesis is that movement disorders are not just side effects of antipsychotic medication but may also be symptoms of the illness itself and are related to the

  10. Side effects of radiotherapy in regime of dynamic dose multifractioning for local larynx cancer forms

    International Nuclear Information System (INIS)

    Slobina, E.L.


    A regime for dynamic multifractioning of radiotherapy dose used for treating larynx cancer was developed. The method favored reducing the side effects frequency as compared with the conventional fractioning in larynx mucosa from 70% to 46%, in neck skin being irradiated - from 60% to 48%

  11. Pharmacy customers' knowledge of side effects of purchased medicines in Mexico. (United States)

    Wirtz, Veronika J; Taxis, Katja; Dreser, Anahi


    To analyse pharmacy customers' knowledge and information sources about side effects of medicines they purchased and factors associated with this knowledge. Cross-sectional survey and semi-structured interviews with customers of 52 randomly selected community pharmacies in Morelos state, Mexico. Customers were included if they were older than 18 years, bought at least one drug either with or without medical prescription, and agreed to take part in the survey. Data were analysed using a multinomial logistic regression model. A total of 1445 customers buying 1946 drugs were surveyed (age 42.9 +/- 15.7 years, 56.9% female); 627 (59%) of 1055 customers who purchased prescription-only medicines (POM) did so without a prescription. Of all customers interviewed, 172 (11.9%) affirmed that the bought medicine(s) could cause harm. Only half of those (87 or 6%) were able to identify correctly at least one side effect of the purchased medicines. The majority received the information about side effects from a physician. Customers in semirural areas knew less about side effects (odds ratio: 0.26; 95% CI: 0.11-0.61; P = 0.00); whereas customers buying medicines for chronic pain, hypertension or diabetes knew more (odds ratio 2.63; 95% CI: 1.44-4.80; P = 0.00). The overall majority of customers did not know that medicines they bought could be harmful. This is particularly alarming because they frequently used POM without consulting a physician.

  12. Multinational study exploring patients' perceptions of side-effects induced by chemo-radiotherapy

    DEFF Research Database (Denmark)

    Ruhlmann, Christina H; Iversen, Trine Zeeberg; Okera, Meena


    PURPOSE: We aimed to prospectively assess the incidence, severity and patients' perceptions of side-effects induced by radiotherapy and concomitant weekly cisplatin. PATIENTS AND METHODS: This multinational survey included patients with a diagnosis of gynaecological or head and neck cancer schedu...

  13. Impact of side-effects of atypical antipsychotics on non-compliance, relapse and cost. (United States)

    Mortimer, A; Williams, P; Meddis, D


    Atypical antipsychotics generally have milder side-effects than conventional antipsychotics, but also differ among themselves in this respect. This study aimed to compare the impact of different side-effect profiles of individual atypical antipsychotics on non-compliance, relapse and cost in schizophrenia. A state-transition model was built using literature data supplemented by expert opinion. The model found that quetiapine and ziprasidone were similar in estimated non-compliance and relapse rates. Olanzapine and risperidone had higher estimated non-compliance and relapse rates, and incremental, 1-year, per-patient direct costs, using US-based cost data, of approximately $530 (95% confidence interval [CI] approximately $275, $800), and approximately $485 (95% CI approximately $235, $800), respectively, compared with quetiapine. Incremental costs attributable to different side-effect profiles were highly significant. This study shows that differing side-effect profiles of the newer antipsychotic agents are likely to lead to different compliance rates, and consequent variation in relapse rates. The cost implications of these heterogenous clinical outcomes are substantial.

  14. Managing Radiation Therapy Side Effects: What to Do about Changes When You Urinate (United States)

    ... Therapy Side Effects: Changes when you urinate Ask about drinks or foods that you may need to avoid. Some things can make these problems worse. Your doctor or nurse may suggest that you limit or don’t have: I Drinks with alcohol (such as beer, wine, and liquor) I Drinks with caffeine (such as ...

  15. Side effect experiences of South Korean women in their twenties and thirties after facial plastic surgery

    Directory of Open Access Journals (Sweden)

    Kim YA


    Full Text Available Young A Kim,1 Hyang-In Cho Chung2 1Department of Nursing, Jeju National University College of Nursing, Jeju-si, Republic of Korea; 2Department of Nursing, Chonnam National University College of Nursing, Gwangju, Republic of Korea Background: Rates of plastic surgery procedures have increased dramatically over the past several decades, especially for the women in South Korea.Purpose: The purpose of this study was to explore the subjective experience of South Korean women in their twenties and thirties with facial plastic surgery (FPS side effects.Participants and methods: Seven women who have suffered from FPS side effects participated in this study. Data were collected from July to September 2015 through individual in-depth interviews using open-ended questions and analyzed using Colaizzi’s method, which is a Husserlian phenomenological approach.Results: Six themes, and 25 subthemes, were found. Major themes were “choosing FPS to gain a new self”, “facing an unintended self”, “trying to accept a changed self”, “making efforts to overcome the situation”, “coming to know a new world”, and “pursuing a new lifestyle”.Conclusion: This study raises social awareness on the risk of plastic surgery side effects, which could prevent unnecessary plastic surgery. It also suggests the need for a deeper understanding of women’s biopsychosocial suffering from plastic surgery side effects. Keywords: cosmetic surgery, aesthetic plastic surgery, qualitative research, interview 

  16. Side Effects of Minocycline Treatment in Patients with Fragile X Syndrome and Exploration of Outcome Measures (United States)

    Utari, Agustini; Chonchaiya, Weerasak; Rivera, Susan M.; Schneider, Andrea; Hagerman, Randi J.; Faradz, Sultana M. H.; Ethell, Iryna M.; Nguyen, Danh V.


    Minocycline can rescue the dendritic spine and synaptic structural abnormalities in the fragile X knock-out mouse. This is a review and preliminary survey to document side effects and potential outcome measures for minocycline use in the treatment of individuals with fragile X syndrome. We surveyed 50 patients with fragile X syndrome who received…

  17. Family Planning in a Sub-district near Kumasi, Ghana: Side Effect ...

    African Journals Online (AJOL)


    African Journal of Reproductive Health September 2011; 15(3): 121 ... women recognized at least one family planning method, half of all recent or ... use of Primolut N tablets, addressing real and perceived side effects of family ... planning programs, research and policy. ... Utah to improve the quality of life in communities.

  18. Side effects after radiotherapy of age-related macular degeneration with the Nijmegen technique.

    NARCIS (Netherlands)

    Hoyng, C.B.; Tromp, A.I.; Meulendijks, C.F.M.; Leys, A.; Maazen, R.W.M. van der; Deutman, A.F.; Vingerling, J.R.


    BACKGROUND: In a randomized trial concerning radiotherapy for age-related macular degeneration, fluorescein angiograms were taken of controls and patients. In this study the frequency of side effects in eyes receiving radiotherapy with the Nijmegen technique is compared with the findings in the eyes

  19. Novel Profiling Model and Side Effects of Helical Scan Silicon Heads

    NARCIS (Netherlands)

    Hozoi, A.; Groenland, J.P.J.; Albertini, J.B.; Lodder, J.C.


    Partial erasure of track edges was directly measured from triple-track patterns using a novel model to interpret the output profiles. The model is based on representing the read head as the sum of a reference width, wavelength independent, and two side reading effective widths that are wavelength

  20. Pharmacy customers' knowledge of side effects of purchased medicines in Mexico

    NARCIS (Netherlands)

    Wirtz, Veronika J.; Taxis, Katja; Dreser, Anahi

    To analyse pharmacy customers' knowledge and information sources about side effects of medicines they purchased and factors associated with this knowledge. Cross-sectional survey and semi-structured interviews with customers of 52 randomly selected community pharmacies in Morelos state, Mexico.

  1. Incidence of neuropsychiatric side effects of efavirenz in HIV-positive ...

    African Journals Online (AJOL)


    Jun 30, 2016 ... HIV-positive treatment-naïve patients in public-sector ... current depression or other mental disorders would increase ... medication and the importance of adherence is discussed ..... neuropsychiatric side effects, substance abuse and emotional ... All authors contributed towards the conceptualisation and.

  2. Of ants and men the unexpected side effects of complexity in society

    CERN Document Server

    Green, David G


    Why do things go wrong? Why, despite all the planning and care in the world, do things go from bad to worse? This book argues that it is because we are like the ants. Just as ants create an anthill without being aware of it, unintended side effects of human activity create all manner of social trends and crises. The book traces the way these trends emerge and the role they play in some of the major issues of our time. One of the greatest challenges today is the complexity of our social and economic systems. Every action has side effects that people often ignore or fail to see. The book examines the ways in which limitations in our thinking and behaviour lead to unintended side effects. It looks at the role played by complex networks of interactions. Finally, it looks at the way side effects of new technologies, especially computers and communication, have created an Information Revolution, the full repercussions of which are yet to be seen. In our race to create new technologies and sustain indefinite economi...

  3. Are sexual side effects of prolactin-raising antipsychotics reducible to serum prolactin?

    NARCIS (Netherlands)

    Knegtering, Henderikus; van den Bosch, Rob; Castelein, Stynke; Bruggeman, Richard; Sytema, Sjoerd; van Os, Jim

    Objective: To assess the degree to which sexual side effects (SSE) are associated with prolactin-raising antipsychotics, and to what degree such SSE are reducible to serum prolactin levels. Method: A large sample (n = 264) of patients treated for 6 weeks with protactin-raising and prolactin-sparing

  4. Positive Side Effects of a Job-Related Training Program for Older Adults in South Korea (United States)

    Lee, Minhong; Choi, Jae-Sung


    The objective of the current study was to evaluate empirically positive side effects of a job-related training program on older adults' self-esteem, depression, and social networks. A total of 70 older adults participated in the study after completing the Older Paraprofessional Training Program developed and provided by the Continuing Education…

  5. Glucocorticoid management in rheumatoid arthritis: morning or night low dose?

    Directory of Open Access Journals (Sweden)

    Sabrina Paolino


    Full Text Available Morning symptoms of rheumatoid arthritis (RA are linked to circadian increase of night inflammation, supported by inadequate cortisol secretion in active disease. Therefore, exogenous glucocorticoid administration in RA is recommended by EULAR and ACR from the beginning of the diagnosis, since may partially act like a “replacement therapy”. In addition, the prevention/treatment of the night up-regulation of the immune/inflammatory reaction has been shown more effective when exogenous glucocorticoid administration is managed with a night-time-release formulation. Despite a considerably higher cost than conventional prednisone (immediate release, chronotherapy with night-time-release prednisone has been recognized a cost-effective option for RA patients not on glucocorticoids who are eligible for therapy with biologic disease-modifying antirheumatic drugs (DMARDs. Interestingly, since different cell populations involved in the inflammatory process are particularly activated during the night (i.e. monocytes, macrophages, other therapeutical approaches used in RA, such as conventional DMARDs and non-steroidal anti-inflammatory drugs (NSAIDs should follow the same concepts of glucocorticoid chronotherapy. Therefore, bedtime methotrexate chronotherapy was found to better manage RA symptoms, and several available NSAIDs (i.e. indomethacin, aceclofenac, ketoprofen, flurbiprofen, lornoxicam have been recently modified in their formulation, in order to obtain more focused night action.

  6. Histone deacetylase inhibitors reverse age-related increases in side effects of haloperidol in mice. (United States)

    Montalvo-Ortiz, Janitza L; Fisher, Daniel W; Rodríguez, Guadalupe; Fang, Deyu; Csernansky, John G; Dong, Hongxin


    Older patients can be especially susceptible to antipsychotic-induced side effects, and the pharmacodynamic mechanism underlying this phenomenon remains unclear. We hypothesized that age-related epigenetic alterations lead to decreased expression and functionality of the dopamine D2 receptor (D2R), contributing to this susceptibility. In this study, we treated young (2-3 months old) and aged (22-24 months old) C57BL/6 mice with the D2R antagonist haloperidol (HAL) once a day for 14 days to evaluate HAL-induced motor side effects. In addition, we pretreated separate groups of young and aged mice with histone deacetylase (HDAC) inhibitors valproic acid (VPA) or entinostat (MS-275) and then administered HAL. Our results show that the motor side effects of HAL are exaggerated in aged mice as compared to young mice and that HDAC inhibitors are able to reverse the severity of these deficits. HAL-induced motor deficits in aged mice are associated with an age- and drug-dependent decrease in striatal D2R protein levels and functionality. Further, histone acetylation was reduced while histone tri-methylation was increased at specific lysine residues of H3 and H4 within the Drd2 promoter in the striatum of aged mice. HDAC inhibitors, particularly VPA, restored striatal D2R protein levels and functionality and reversed age- and drug-related histone modifications at the Drd2 promoter. These results suggest that epigenetic changes at the striatal Drd2 promoter drive age-related increases in antipsychotic side effect susceptibility, and HDAC inhibitors may be an effective adjunct treatment strategy to reduce side effects in aged populations.

  7. National survey addressing the information needs of primary care physicians: Side effect management of patients on androgen deprivation therapy. (United States)

    Soeyonggo, Tony; Locke, Jennifer; Giudice, Maria Elizabeth Del; Alibhai, Shabbir; Fleshner, Neil Eric; Warde, Padraig


    Androgen deprivation therapy (ADT) is a common treatment for prostate cancer with numerous side effects. We assess primary care physicians' (PCPs) knowledge of ADT side effects and their interest in increasing their knowledge in this area. A list of active Canadian PCPs was obtained using the Canadian Medical Directory. A cross-sectional survey was distributed to 600 randomly selected physicians. We collected PCPs' demographic information, experience with ADT management, knowledge regarding ADT side effects and desired sources for obtaining knowledge on ADT management. In total, we received 103 completed questionnaires. Of these, 89% of PCPs had patients on ADT. One-third of respondents prescribed ADT and over half of them administered ADT annually. Thirty-eight percent felt their knowledge of ADT side effects was inadequate and 50% felt uncomfortable counselling patients on ADT. Many PCPs were less familiar with the incidence of functional side effects of ADT (i.e., hot flashes, fatigue and erectile dysfunction) compared to life-threatening side effects (i.e., cardiovascular events, metabolic syndrome, fractures). In terms of increasing their knowledge of ADT side effects, 82% of PCPs would use educational resources if they were available (52% and 32% preferred continued medical education [CME] events and educational pamphlets, respectively). PCPs play an important role in managing ADT side effects. There is poor awareness of the prevalence of ADT side effects, and many are uncomfortable in managing these side effects. These areas may be addressed through CME programs and educational pamphlets.

  8. NALP3 inflammasome upregulation and CASP1 cleavage of the glucocorticoid receptor cause glucocorticoid resistance in leukemia cells

    NARCIS (Netherlands)

    S.W. Paugh (Steven); E.J. Bonten (Erik J.); D. Savic (Daniel); L.B. Ramsey (Laura B.); W.E. Thierfelder (William E.); P. Gurung (Prajwal); R.K.S. Malireddi (R. K. Subbarao); M. Actis (Marcelo); A. Mayasundari (Anand); J. Min (Jaeki); D.R. Coss (David R.); L.T. Laudermilk (Lucas T.); J.C. Panetta (John); J.R. McCorkle (J. Robert); Y. Fan (Yiping); K.R. Crews (Kristine R.); G. Stocco (Gabriele); M.R. Wilkinson (Mark R.); A.M. Ferreira (Antonio M.); C. Cheng (Cheng); W. Yang (Wenjian); S.E. Karol (Seth E.); C.A. Fernandez (Christian A.); B. Diouf (Barthelemy); C. Smith (Colton); J.K. Hicks (J Kevin); A. Zanut (Alessandra); A. Giordanengo (Audrey); D.J. Crona; J.J. Bianchi (Joy J.); L. Holmfeldt (Linda); C.G. Mullighan (Charles); M.L. den Boer (Monique); R. Pieters (Rob); S. Jeha (Sima); T.L. Dunwell (Thomas L.); F. Latif (Farida); D. Bhojwani (Deepa); W.L. Carroll (William L.); C.-H. Pui (Ching-Hon); R.M. Myers (Richard M.); R.K. Guy (R Kiplin); T.-D. Kanneganti (Thirumala-Devi); M.V. Relling (Mary); W.E. Evans (William)


    textabstractGlucocorticoids are universally used in the treatment of acute lymphoblastic leukemia (ALL), and resistance to glucocorticoids in leukemia cells confers poor prognosis. To elucidate mechanisms of glucocorticoid resistance, we determined the prednisolone sensitivity of primary leukemia

  9. Functional effects of polymorphisms on glucocorticoid receptor modulation of human anxiogenic substance-P gene promoter activity in primary amygdala neurones


    Hay, Colin W.; Shanley, Lynne; Davidson, Scott; Cowie, Philip; Lear, Marissa; McGuffin, Peter; Riedel, Gernot; McEwan, Iain J.; MacKenzie, Alasdair


    Summary Expression or introduction of the neuropeptide substance-P (SP; encoded by the TAC1 gene in humans and Tac1 in rodents) in the amygdala induces anxiety related behaviour in rodents. In addition, pharmacological antagonism of the main receptor of SP in humans; NK1, is anxiolytic. In the current study, we show that the Tac1 locus is up-regulated in primary rat amygdala neurones in response to activation of the glucocorticoid receptor (GR); a classic component of the stress response. Usi...

  10. An Internet-based survey on characteristics of laser tattoo removal and associated side effects. (United States)

    Klein, Annette; Rittmann, Ines; Hiller, Karl-Anton; Landthaler, Michael; Bäumler, Wolfgang


    Tattoo removal by laser therapy is a frequently performed procedure in dermatological practices. Quality-switched ruby, alexandrite, or Nd:YAG lasers are the most suitable treatment devices. Although these techniques are regarded as safe, both temporary and permanent side effects might occur. Little has been published on the frequency of complications associated with laser tattoo removal. We performed an Internet survey in German-speaking countries on characteristics of laser tattoo removal and associated side effects. A total number of 157 questionnaires entered the final analysis. Motivations for laser tattoo removal were mainly considering the tattoo as youthful folly (29%), esthetic reasons (28%), and 6% indicated medical problems. One third of participants were unsatisfied with the result of laser tattoo removal, and a complete removal of the tattoo pigment was obtained in 38% only. Local transient side effects occurred in nearly all participants, but an important rate of slightly visible scars (24%) or even important scarring (8%) was reported. Every fourth participant described mild or intense tan when the laser treatment was performed, and the same number of people indicated UV exposure following laser therapy, which should normally be avoided in these circumstances. As reported in the literature, nearly half of the participants experienced hypopigmentation in the treated area. Our results show that from the patients' point of view there is an important rate of side effects occurring after laser tattoo removal. Appropriate pretreatment counseling with regard to realistic expectations, possible side effects, and the application of test spots is mandatory to ensure patient satisfaction. Laser treatment should be performed by appropriately trained personnel only.

  11. [Current prevention and treatment strategies for osteoporosis. Fracture-oriented, effective, low side effects and inexpensive]. (United States)

    Bartl, R; Bartl, C


    Osteoporosis is still an underdiagnosed and insufficiently therapied widespread disease in Germany. Of the estimated 7 million osteoporosis patients only 1.5 million receive a guideline conform diagnosis and even less receive appropriate treatment. Some 90 % of patients are provided with analgesics but only 10 % receive an effective therapy, although efficacious, well-tested and affordable medications are available. In addition, approximately one half of the patients terminate treatment after only 1 year although according to the results of recent studies the duration of therapy should be at least 3-5 years. In view of the increasing average life expectancy, a consistent management for prevention of fractures associated with osteoporosis is always most important for society, even if only for reasons of costs. Achievement of this target depends on four circumstances: clarification of the origin of osteoporosis and fractures (bone consciousness), prophylaxis of bone loss and fractures (primary prevention), consistent guideline conform diagnostics and therapy (secondary and tertiary prevention) and cooperation of all disciplines in medicine (bone is everybody's business). This article describes the current state of diagnostics (bone density measurement with dual X-ray absorptiometry, FRAX®), prophylaxis of fractures (screening program) and therapy (use of economic and effective medications with low side effects). Novel medications are already undergoing clinical testing and a "healing" of bone reduction with restoration of the normal bone structure is to be expected.

  12. R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects (United States)

    Yang, C; Shirayama, Y; Zhang, J-c; Ren, Q; Yao, W; Ma, M; Dong, C; Hashimoto, K


    Although the efficacy of racemate ketamine, a rapid onset and sustained antidepressant, for patients with treatment-resistant depression was a serendipitous finding, clinical use of ketamine is limited, due to psychotomimetic side effects and abuse liability. Behavioral and side-effect evaluation tests were applied to compare the two stereoisomers of ketamine. To elucidate their potential therapeutic mechanisms, we examined the effects of these stereoisomers on brain-derived neurotrophic factor (BDNF)–TrkB signaling, and synaptogenesis in selected brain regions. In the social defeat stress and learned helplessness models of depression, R-ketamine showed a greater potency and longer-lasting antidepressant effect than S-ketamine (esketamine). Furthermore, R-ketamine induced a more potent beneficial effect on decreased dendritic spine density, BDNF–TrkB signaling and synaptogenesis in the prefrontal cortex (PFC), CA3 and dentate gyrus (DG) of the hippocampus from depressed mice compared with S-ketamine. However, neither stereoisomer affected these alterations in the nucleus accumbens of depressed mice. In behavioral tests for side effects, S-ketamine, but not R-ketamine, precipitated behavioral abnormalities, such as hyperlocomotion, prepulse inhibition deficits and rewarding effects. In addition, a single dose of S-ketamine, but not R-ketamine, caused a loss of parvalbumin (PV)-positive cells in the prelimbic region of the medial PFC and DG. These findings suggest that, unlike S-ketamine, R-ketamine can elicit a sustained antidepressant effect, mediated by increased BDNF–TrkB signaling and synaptogenesis in the PFC, DG and CA3. R-ketamine appears to be a potent, long-lasting and safe antidepressant, relative to S-ketamine, as R-ketamine appears to be free of psychotomimetic side effects and abuse liability. PMID:26327690

  13. Clinical application and side effects of non-ionic, low-osmolar contrast media: Iopromide (Ultavist)

    International Nuclear Information System (INIS)

    Lee, Jong Tae; Suh, Jung Ho; Suh, Jin Suk; Lee, Yeon Hee


    Generally non-ionic, water-soluble contrast media has been known to be considerably better than the conventional ionic contrast agents, because of its physiochemical properties which are more hydrophilic, lower in osmolality than the ionic agents of equivalent iodine concentration. It means that the non-ionic agent has less side reaction and better general tolerance. Iopromide (Ultavist) is a newly developed non-ionic contrast media that is suitable for angiography. Some non-ionic contrast media such as Metrizamide and lopamidol were clinically introduced and proved tobe the most compromising agents for neuroradiographic study, but lopromide is not yet freely available in the vascular study. In order to evaluate the clinical fitness and its side effects of lopromide for angiography various type of angiography were done in 136 patients using lopromide and 51 received Diatrizoate meglumine (DTM). Similar volumes of the contrast media was administered at similar rate to both groups. The results were as the follows: 1. In celiac angiography of 31 patients with lopromide (Ultravist 370) and 18 with DTM 60, there were observed 9.7% mild pain and 25.8% mild heat sensation in lopromide. In DTM 60 mild pain was approximately 3 times more frequently observed than lopromide. Heat sensation is mild and similar in frequency of both groups. There was no clinically significant side effects related to the osmolality and its difference between two groups. 2. In peripheral angiography of 47 patients with lopromide 300 and 24 with DTM 60, there were observed 19.1% mild, 6.4 moderate in pain and 46.8% mild, 1% moderate heat sensation in lopromide. But in DTM there were 33.3% mild, 58.3% moderate and 8.3% severe pain, and also 70.8% mild and 16.7% moderate heat sensation in DTM were observed. lopromide is more advantageous and better contrast agents than the DTM for peripheral vascular study on the point of low side effect related to osmolality. 3. In renal angiography, there was no

  14. Effects of early weaning and social isolation on the expression of glucocorticoid and mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase 1 and 2 mRNAs in the frontal cortex and hippocampus of piglets. (United States)

    Poletto, R; Steibel, J P; Siegford, J M; Zanella, A J


    Pigs weaned at young ages show more abnormal and aggressive behaviors and cognitive deficits compared to later weaned pigs. We investigated the effects of age, weaning and/or social isolation on the expression of genes regulating glucocorticoid response [glucocorticoid receptor (GR), mineralocorticoid receptor (MR), 11beta-hydroxysteroid dehydrogenases 1 and 2 (11beta-HSD1 and 11beta-HSD2)] in the frontal cortex and hippocampus. Early- (EW; n = 6) and conventionally-weaned (CW; n = 6) piglets were weaned at 10 and 21 days after birth, respectively. Non-weaned (NW) piglets of both ages (NW; n = 6/group) remained with their dams. Immediately before euthanasia, half of CW, EW and NW animals were socially isolated for 15 min at 12 (EW, NW) and 23 (CW, NW) days of age. Differences in amounts of 11beta-HSD1, 11beta-HSD2, GR and MR mRNA were determined by quantitative real-time RT-PCR and data subjected to multivariate linear mixed model analysis. When compared with NW piglets at 12 days of age, the hippocampi of EW piglets showed decreased gene expression (P Social isolation decreased gene expression (P social isolation affected frontal cortex regardless of age. These results may be correlated with behavioral and cognitive changes reported in EW piglets.

  15. A systematic review of the psychiatric side-effects of efavirenz. (United States)

    Kenedi, Christopher A; Goforth, Harold W


    Concerns regarding the use of efavirenz in patients with a history of mental illness may predispose clinicians to not offer this agent to psychiatrically ill populations in spite of the convenience of once daily dosing, which can result in improved adherence in these at-risk populations. This systematic review examines the current data regarding the neuropsychiatric effects of efavirenz, and also attempts to provide guidance to clinicians using efavirenz to treat patients with mental illness. The review identified high rates of neuropsychiatric side effects including vivid dreams, insomnia and mood changes in approximately 50% of patients who initiate efavirenz. The effects begin quickly, commonly peak in the first 2 weeks, and are generally mild and transient in nature. Isolated case reports and uncontrolled data suggest higher rates of severe side effects; however, there is no clear evidence of a broadly increased risk of suicide or dangerous behavior for patients taking efavirenz as part of their antiretroviral regimen.

  16. Herbal medicines for the treatment of cancer chemotherapy-induced side effects. (United States)

    Ohnishi, Shunsuke; Takeda, Hiroshi


    Accumulating evidence suggests that Japanese herbal medicines, called Kampo, have beneficial effects on cancer chemotherapy-induced side effects. Rikkunshito ameliorates cisplatin-induced anorexia through an antagonistic effect on the 5-HT receptors and by increasing the serum ghrelin levels. Hangeshashinto improves irinotecan-induced diarrhea and chemotherapy-induced mucositis by inhibiting the activity of β-glucuronidase as well as the synthesis of prostaglandin E2. Goshajinkigan prevents oxaliplatin-induced neurotoxicity, possibly through suppressing functional alterations of the transient receptor potential channels. In this review, we will summarize the currently available literature regarding the clinical efficacy and potential mechanisms of Kampo medicines in the treatment of cancer chemotherapy-induced side effects.

  17. Potential functional and pathological side effects related to off-target pharmacological activity. (United States)

    Lynch, James J; Van Vleet, Terry R; Mittelstadt, Scott W; Blomme, Eric A G


    Most pharmaceutical companies test their discovery-stage proprietary molecules in a battery of in vitro pharmacology assays to try to determine off-target interactions. During all phases of drug discovery and development, various questions arise regarding potential side effects associated with such off-target pharmacological activity. Here we present a scientific literature curation effort undertaken to determine and summarize the most likely functional and pathological outcomes associated with interactions at 70 receptors, enzymes, ion channels and transporters with established links to adverse effects. To that end, the scientific literature was reviewed using an on-line database, and the most commonly reported effects were summarized in tabular format. The resultant table should serve as a practical guide for research scientists and clinical investigators for the prediction and interpretation of adverse side effects associated with molecules interacting with components of this screening battery. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Glucocorticoids and inhibition of bone formation induced by skeletal unloading

    International Nuclear Information System (INIS)

    Halloran, B.P.; Bikle, D.D.; Cone, C.M.; Morey-Holton, E.


    Skeletal unloading or loss of normal weight bearing in the growing animal inhibits bone formation and reduces bone calcium. To determine whether the inhibition of bone formation induced by skeletal unloading is a consequence of an increase in plasma glucocorticoids and/or an increase in bone sensitivity to glucocorticoids, the authors measured plasma corticosterone throughout the day in unloaded and normally loaded rats (hindlimb elevation model) and examined the effect of adrenalectomy on the response of bone to skeletal unloading. Plasma corticosterone levels were similar in normally loaded and unloaded rats at all times. Skeletal unloading in sham-adrenalectomized animals reduced tibial and vertebral calcium by 11.5 and 11.1%, respectively, and in adrenalectomized animals by 15.3 and 20.3%, respectively. Uptake of 45 Ca and [ 3 H]proline in the tibia was reduced by 8 and 14%, respectively, in the sham-adrenalectomized animals and by 13 and 19% in the adrenalectomized animals. Bone formation and apposition rates were reduced to the same level in sham- and adrenalectomized animals. These results suggest that the inhibition of bone formation induced by skeletal unloading is not a consequence of increased plasma glucocorticoids or an increase in bone sensitivity to the glucocorticoids but, rather, point to a local mediator in bone that senses mechanical load and transmits that information to the bone-forming cells directly

  19. Postreactivation glucocorticoids impair recall of established fear memory. (United States)

    Cai, Wen-Hui; Blundell, Jacqueline; Han, Jie; Greene, Robert W; Powell, Craig M


    Pavlovian fear conditioning provides one of the best rodent models of acquired anxiety disorders, including posttraumatic stress disorder. Injection of a variety of drugs after training in fear-conditioning paradigms can impair consolidation of fear memories. Indeed, early clinical trials suggest that immediate administration of such drugs after a traumatic event may decrease the risk of developing posttraumatic stress disorder in humans (Pitman et al., 2002; Vaiva et al., 2003). The use of such a treatment is limited by the difficulty of treating every patient at risk and by the difficulty in predicting which patients will experience chronic adverse consequences. Recent clinical trials suggest that administration of glucocorticoids may have a beneficial effect on established posttraumatic stress disorder (Aerni et al., 2004) and specific phobia (Soravia et al., 2006). Conversely, glucocorticoid administration after training is known to enhance memory consolidation (McGaugh and Roozendaal, 2002; Roozendaal, 2002). From a clinical perspective, enhancement of a fear memory or a reactivated fear memory would not be desirable. We report here that when glucocorticoids are administered immediately after reactivation of a contextual fear memory, subsequent recall is significantly diminished. Additional experiments support the interpretation that glucocorticoids not only decrease fear memory retrieval but, in addition, augment consolidation of fear memory extinction rather than decreasing reconsolidation. These findings provide a rodent model for a potential treatment of established acquired anxiety disorders in humans, as suggested by others (Aerni et al., 2004; Schelling et al., 2004), based on a mechanism of enhanced extinction.

  20. Effects of yoga on cancer-related fatigue and global side-effect burden in older cancer survivors. (United States)

    Sprod, Lisa K; Fernandez, Isabel D; Janelsins, Michelle C; Peppone, Luke J; Atkins, James N; Giguere, Jeffrey; Block, Robert; Mustian, Karen M


    Sixty percent of cancer survivors are 65years of age or older. Cancer and its treatments lead to cancer-related fatigue and many other side effects, in turn, creating substantial global side-effect burden (total burden from all side effects) which, ultimately, compromises functional independence and quality of life. Various modes of exercise, such as yoga, reduce cancer-related fatigue and global side-effect burden in younger cancer survivors, but no studies have specifically examined the effects of yoga on older cancer survivors. The purpose of this study was to assess the effects of a 4-week yoga intervention (Yoga for Cancer Survivors: YOCAS©®) on overall cancer-related fatigue, and due to its multidimensional nature, the subdomains of cancer-related fatigue (general, physical, emotional, and mental) and global side-effect burden in older cancer survivors. We conducted a secondary analysis on data from a multicenter phase III randomized controlled clinical trial with 2 arms (standard care and standard care plus a 4-week YOCAS©® intervention). The sample for this secondary analysis was 97 older cancer survivors (≥60years of age), between 2months and 2years post-treatment, who participated in the original trial. Participants in the YOCAS©® intervention arm reported significantly lower cancer-related fatigue, physical fatigue, mental fatigue, and global side-effect burden than participants in the standard care arm following the 4-week intervention period (peffective standardized yoga intervention for reducing cancer-related fatigue, physical fatigue, mental fatigue, and global side-effect burden among older cancer survivors. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Age-related differences in renal side-effects of radiation and chemotherapy in the rat


    Jongejan, Mieke


    textabstractThe improved life-expectancy of cancer patient has brought to light late sequelae of oncology therapy. This is especially true for pediatric patients. Renal damage is one of the adverse side-effects of anti-tumor therapy that may occur. Studies conceming damaging effects of radiotherapy or chemotherapy on the kidney have generally been performed in adults. There is scant experimental or clinical information on renal function after anti -tumor therapy in the young. Rapid growth occ...

  2. Coping with side effects from cancer treatment in daily life from the perspective of cancer patients: A qualitative empirical study

    DEFF Research Database (Denmark)

    Pedersen, Birgith; Koktved, Dorte Pallesen; Nielsen, Lene Lyngø

    Aim The aim of this paper is to deepen our understanding of how patients cope with side effects from cancer treatment in daily life. Background Patients receiving cancer treatment experience acute side effects and need individualized information and guidance in order to manage treatment......-related adverse events in everyday life. However development in cancer treatment and the societal demands for efficiency may limit the possibility for individualized support. Methods Nine patients were interviewed from March to July 2009 to explore the patients’ experience of coping with side effects in daily...... their identity but the side effects can control the daily life. Patients do not always possess the knowledge of how to handle the side effects and adaptation to the institutional efficiency can lead to lack of confidence and feelings of responsibility and guilt concerning coping with these side effects...

  3. Regulating Effect of Asymmetrical Impeller on the Flow Distributions of Double-sided Centrifugal Compressor (United States)

    Yang, Ce; Liu, Yixiong; Yang, Dengfeng; Wang, Benjiang


    To achieve the rebalance of flow distributions of double-sided impellers, a method of improving the radius of rear impeller is presented in this paper. It is found that the flow distributions of front and rear impeller can be adjusted effectively by increasing the radius of rear impeller, thus improves the balance of flow distributions of front and rear impeller. Meanwhile, the working conversion mode process of double-sided centrifugal compressor is also changed. Further analysis shows that the flowrates of blade channels in front impeller are mainly influenced by the circumferential distributions of static pressure in the volute. But the flowrates of rear impeller blade channels are influenced by the outlet flow field of bent duct besides the effects of static pressure distributions in the volute. In the airflow interaction area downstream, the flowrate of blade channel is obviously smaller. By increasing the radius of rear impeller, the work capacity of rear impeller is enhanced, the working mode conversion process from parallel working mode of double-sided impeller to the single impeller working mode is delayed, and the stable working range of double-sided compressor is broadened.

  4. Sleep Disturbance During Smoking Cessation: Withdrawal or Side Effect of Treatment? (United States)

    Ashare, Rebecca L; Lerman, Caryn; Tyndale, Rachel F; Hawk, Larry W; George, Tony P; Cinciripini, Paul; Schnoll, Robert A


    The nicotine-metabolite ratio (NMR) predicts treatment response and is related to treatment side effect severity. Sleep disturbance may be one important side effect, but understanding sleep disturbance effects on smoking cessation is complicated by the fact that nicotine withdrawal also produces sleep disturbance. To evaluate the effects of withdrawal and treatment side effects on sleep disturbance. This is a secondary analysis of data from a clinical trial (Lerman et al., 2015) of 1,136 smokers randomised to placebo ( n = 363), transdermal nicotine (TN; n = 381), or varenicline ( n = 392) and stratified based on NMR (559 slow metabolisers; 577 normal metabolisers). Sleep disturbance was assessed at baseline and at 1-week following the target quit date (TQD). We also examined whether sleep disturbance predicted 7-day point-prevalence abstinence at end-of-treatment (EOT). The varenicline and TN groups exhibited greater increases in sleep disturbance (vs. placebo; treatment × time interaction; p = 0.005), particularly among those who quit smoking at 1-week post-TQD. There was a main effect of NMR ( p = 0.04), but no interactions with treatment. TN and varenicline attenuated withdrawal symptoms unrelated to sleep (vs. placebo). Greater baseline sleep disturbance predicted relapse at EOT ( p = 0.004). Existing treatments may not mitigate withdrawal-related sleep disturbance and adjunctive treatments that target sleep disturbance may improve abstinence rates.

  5. Glucocorticoid receptors in anorexia nervosa and Cushing's disease. (United States)

    Invitti, C; Redaelli, G; Baldi, G; Cavagnini, F


    Patients with anorexia nervosa do not display cushingoid features in spite of elevated cortisol plasma levels. Whether a cortisol resistance or a reduced availability of the metabolic substrates necessary to develop the effect of glucocorticoids is responsible for this has not been established. Twenty-two patients with severe restrictive anorexia nervosa, 10 patients with active Cushing's disease, and 24 healthy volunteers without psychiatric disorders or mood alterations were investigated. Glucocorticoid receptor characteristics were examined on mononuclear leukocytes by measuring [3H]dexamethasone binding and the effect of dexamethasone on [3H]thymidine incorporation, which represents an index of DNA synthesis. The number of glucocorticoid receptors on mononuclear leukocytes (MNL) was comparable in patients with anorexia nervosa, patients with active Cushing's disease, and normal subjects (binding capacity 3.3 +/- 0.23 vs. 3.7 +/- 0.30 and 3.5 +/- 0.20 fmol/10(6) cells). Conversely, glucocorticoid receptor affinity was significantly decreased in anorexia nervosa as well as in Cushing's patients compared to control subjects (dissociation constant 4.0 +/- 0.31 and 4.1 +/- 0.34 vs. 2.9 +/- 0.29 nmol/L, p Cushing's patients compared to control subjects (p Cushing's disease. In patients with anorexia nervosa, the incorporation of [3H]thymidine into the MNL was inversely correlated with urinary free cortisol levels. These data indicate that the lack of cushingoid features in patients with anorexia nervosa is not ascribable to a reduced sensitivity to glucocorticoids but is more likely due to the paucity of metabolic substrates.

  6. A role for glucocorticoids in stress-impaired reproduction: beyond the hypothalamus and pituitary. (United States)

    Whirledge, Shannon; Cidlowski, John A


    In addition to the well-characterized role of the sex steroid receptors in regulating fertility and reproduction, reproductive events are also mediated by the hypothalamic-pituitary-adrenal axis in response to an individual's environment. Glucocorticoid secretion in response to stress contributes to the well-characterized suppression of the hypothalamic-pituitary-gonadal axis through central actions in the hypothalamus and pituitary. However, both animal and in vitro studies indicate that other components of the reproductive system are also regulated by glucocorticoids. Furthermore, in the absence of stress, it appears that homeostatic glucocorticoid signaling plays a significant role in reproduction and fertility in all tissues comprising the hypothalamic-pituitary-gonadal axis. Indeed, as central regulators of the immune response, glucocorticoids are uniquely poised to integrate an individual's infectious, inflammatory, stress, nutritional, and metabolic status through glucocorticoid receptor signaling in target tissues. Endocrine signaling between tissues regulating the immune and stress response and those determining reproductive status provides an evolutionary advantage, facilitating the trade-off between reproductive investment and offspring fitness. This review focuses on the actions of glucocorticoids in tissues important for fertility and reproduction, highlighting recent studies that show glucocorticoid signaling plays a significant role throughout the hypothalamic-pituitary-gonadal axis and characterizing these effects as permissive or inhibitory in terms of facilitating reproductive success.

  7. Decreased plasma cholesterol esterification and cholesteryl ester transfer in hypopituitary patients on glucocorticoid replacement therapy

    NARCIS (Netherlands)

    Beentjes, JAM; Van Tol, A; Sluiter, WJ; Dullaart, RPF

    Cardiovascular risk is increased in hypopituitary patients. No data are available with respect to the effect of glucocorticoid replacement therapy on high density lipoproteins (HDL) metabolism in such patients. Plasma lecithin:choresterol acyl transferase (LCAT), cholesteryl ester transfer protein

  8. Psychiatric side effects of ketamine in hospitalized medical patients administered subanesthetic doses for pain control. (United States)

    Rasmussen, Keith G


    To assess the psychiatric side effects of ketamine when administered in subanesthetic doses to hospitalized patients. It is hypothesized that such effects occur frequently. In this retrospective study, the medical records of 50 patients hospitalized on medical and surgical units at our facility who had continuous intravenous infusions of ketamine for pain or mild sedation were reviewed. Patient progress in the days following the start of ketamine infusion was reviewed and response to ketamine was noted. Twenty-two percent of the patients were noted to have some type of psychiatric reaction to ketamine, including agitation, confusion, and hallucinations. These reactions were relatively short lived, namely, occurring during or shortly after the infusions. No association was found between patient response to ketamine and gender, age, or infusion rate. Awareness of the psychiatric side effects of ketamine is an important consideration for clinicians administering this medication either for pain control or for depressive illness.

  9. Pharmacogenetics of clozapine treatment response and side-effects in schizophrenia: an update. (United States)

    Sriretnakumar, Venuja; Huang, Eric; Müller, Daniel J


    Clozapine (CLZ) is the most effective treatment for treatment-resistant schizophrenia (SCZ) patients, with potential added benefits of reduction in suicide risk and aggression. However, CLZ is also mainly underused due to its high risk for the potentially lethal side-effect of agranulocytosis as well as weight gain and related metabolic dysregulation. Pharmacogenetics promises to enable the prediction of patient treatment response and risk of adverse effects based on patients' genetics, paving the way toward individualized treatment. This article reviews pharmacogenetics studies of CLZ response and side-effects with a focus on articles from January 2012 to February 2015, as an update to the previous reviews. Pharmacokinetic genes explored primarily include CYP1A2, while pharmacodynamic genes consisted of traditional pharmacogenetic targets such as brain-derived neurotrophic factor as well novel mitochondrial genes, NDUFS-1 and translocator protein. Pharmacogenetics is a promising avenue for individualized medication of CLZ in SCZ, with several consistently replicated gene variants predicting CLZ response and side-effects. However, a large proportion of studies have yielded mixed results. Large-scale Genome-wide association studies (e.g., CRESTAR) and targeted gene studies with standardized designs (response measurements, treatment durations, plasma level monitoring) are required for further progress toward clinical translation. Additionally, in order to improve study quality, we recommend accounting for important confounders, including polypharmacy, baseline measurements, treatment duration, gender, and age at onset.

  10. Preadmission Use of Glucocorticoids and 30-Day Mortality After Stroke. (United States)

    Sundbøll, Jens; Horváth-Puhó, Erzsébet; Schmidt, Morten; Dekkers, Olaf M; Christiansen, Christian F; Pedersen, Lars; Bøtker, Hans Erik; Sørensen, Henrik T


    The prognostic impact of glucocorticoids on stroke mortality remains uncertain. We, therefore, examined whether preadmission use of glucocorticoids is associated with short-term mortality after ischemic stroke, intracerebral hemorrhage (ICH), or subarachnoid hemorrhage (SAH). We conducted a nationwide population-based cohort study using medical registries in Denmark. We identified all patients with a first-time inpatient diagnosis of stroke between 2004 and 2012. We categorized glucocorticoid use as current use (last prescription redemption ≤90 days before admission), former use, and nonuse. Current use was further classified as new or long-term use. We used Cox regression to compute 30-day mortality rate ratios with 95% confidence intervals (CIs), controlling for confounders. We identified 100 042 patients with a first-time stroke. Of these, 83 735 patients had ischemic stroke, 11 779 had ICH, and 4528 had SAH. Absolute mortality risk was higher for current users compared with nonusers for ischemic stroke (19.5% versus 10.2%), ICH (46.5% versus 34.4%), and SAH (35.0% versus 23.2%). For ischemic stroke, the adjusted 30-day mortality rate ratio was increased among current users compared with nonusers (1.58, 95% CI: 1.46-1.71), driven by the effect of glucocorticoids among new users (1.80, 95% CI: 1.62-1.99). Current users had a more modest increase in the adjusted 30-day mortality rate ratio for hemorrhagic stroke (1.26, 95% CI: 1.09-1.45 for ICH and 1.40, 95% CI: 1.01-1.93 for SAH) compared with nonusers. Former use was not substantially associated with mortality. Preadmission use of glucocorticoids was associated with increased 30-day mortality among patients with ischemic stroke, ICH, and SAH. © 2016 American Heart Association, Inc.

  11. Image-guided preoperative prediction of pyramidal tract side effect in deep brain stimulation (United States)

    Baumgarten, C.; Zhao, Y.; Sauleau, P.; Malrain, C.; Jannin, P.; Haegelen, C.


    Deep brain stimulation of the medial globus pallidus is a surgical procedure for treating patients suffering from Parkinson's disease. Its therapeutic effect may be limited by the presence of pyramidal tract side effect (PTSE). PTSE is a contraction time-locked to the stimulation when the current spreading reaches the motor fibers of the pyramidal tract within the internal capsule. The lack of side-effect predictive model leads the neurologist to secure an optimal electrode placement by iterating clinical testing on an awake patient during the surgical procedure. The objective of the study was to propose a preoperative predictive model of PTSE. A machine learning based method called PyMAN (for Pyramidal tract side effect Model based on Artificial Neural network) that accounted for the current of the stimulation, the 3D electrode coordinates and the angle of the trajectory, was designed to predict the occurrence of PTSE. Ten patients implanted in the medial globus pallidus have been tested by a clinician to create a labeled dataset of the stimulation parameters that trigger PTSE. The kappa index value between the data predicted by PyMAN and the labeled data was .78. Further evaluation studies are desirable to confirm whether PyMAN could be a reliable tool for assisting the surgeon to prevent PTSE during the preoperative planning.

  12. An investigation on the side-effect and complications of the thyroid artery embolization for hyperthyroidism

    International Nuclear Information System (INIS)

    Li Yi; Zeng Xianqiang; Yang Jijin; Tian Jianming


    Objective: To study the side-effect and complications of interventional therapy of hyperthyroidism and the prevention and treatment. Methods: Super selective catheterization followed by embolization with PVA microspheres and Gelfoam particles were performed within the abnormal thyroid superior and inferior arteries of in patients with hyperthyroidism. Results: All the patients felt discomfort in their neck, 53 patients felt painful in their neck and had difficulty in swallowing. Other 11 patients had difficulty in pronunciation or hoarse pronunciation, 17 patients had toothache, 18 patients have purpuric skin rash, one patient had brain infarct, and one patient has life-threatening thyrotoxicosis. No hypothyroidism and hypoparathyroidism are observed. Conclusion: There are some side-effect and complications in the thyroid artery embolization for hyperthyroidism. Careful manipulation during the procedure and close post-intervention care can prevent and manage some serious complications

  13. Daily-diary evaluated side-effects of conformal versus conventional prostatic cancer radiotherapy technique

    International Nuclear Information System (INIS)

    Widmark, A.; Fransson, P.; Franzen, L.; Littbrand, B.; Henriksson, R.


    Conventional 4-field box radiotherapy technique induces high morbidity for patients with localized prostatic cancer. Using a patient daily diary, the present study compared side-effects after conventional radiotherapy with conformal radiotherapy for prostate cancer. Fifty-eight patients treated with the conventional technique (with or without sucralfate) were compared with 72 patients treated with conformal technique. The patient groups were compared with an age-matched control population. Patients treated with conformal technique were also evaluated regarding acute and late urinary problems. Results showed that patients treated with conformal technique reported significantly fewer side-effects as compared with conventional technique. Patients treated with sucralfate also showed slightly decreased intestinal morbidity in comparison to non-sucralfate group. Acute and late morbidity evaluated by the patients was decreased after conformal radiotherapy as compared with the conventional technique. Sucralfate may be of value if conformal radiotherapy is used for dose escalation in prostatic cancer patients. (orig.)

  14. Age and Gender Related Renal Side Effects of Cisplatin in Animal Model (United States)

    Pezeshki, Zahra; Maleki, Maryam; Talebi, Ardeshir; Nematbakhsh, Mehdi


    Backgrounds: Cisplatin (CDDP) is a choice of anti-cancer drug for cancer chemotherapy with serious side effects such as nephrotoxicity. It seems that age is an important factor influencing the side effects of CDDP. This study was designed to determine the role of age and gender simultaneously in CDDP induced renal toxicity. Methods: 40 Wistar male and female rats were assigned as 6 groups in 3 different age categories (10, 16, and 20 weeks old). The single dose of CDDP (7.5 mg/kg, ip) was administrated, and a week later measurements were performed. Results: Body weight changes in male (not in female) animals aged 16 and 20 weeks were more than 10 weeks old animals (PGender difference in serum level of Cr, BUN and nitrite, and Cr-clearance were observed in animals aged10 weeks (Pgender depended, and may be different at various ages. Creative Commons Attribution License

  15. Radiotherapy for cancer patients aged 80 and older: a study of effectiveness and side effects

    International Nuclear Information System (INIS)

    Zachariah, Babu; Balducci, Lodovico; Venkattaramanabalaji, G.V.; Casey, Linda; Greenberg, Harvey M.; Del Regato, Juan A.


    Purpose: To profile cancer patients aged 80 and older undergoing radiotherapy and to study the tumor response and side effects of therapy. Methods and Materials: We retrospectively analyzed the records of patients aged 80 and older who received radiation therapy at James A. Haley Veterans Hospital and H. Lee Moffitt Cancer Center between 1988 and 1995. A total of 203 patients aged 80-94 received radiotherapy during this period. Treatment sites included head and neck [50], breast [16], chest [37], pelvis [53], and miscellaneous [39]. Age, treatment site, field size, total dose, response to treatment, treatment interruptions, incidence and severity of weight loss, myelosuppression, diarrhea, mucositis, dermatitis, and follow-up status are assessed using our departmental records and hospital tumor registry. Results: Of 191 patients evaluated, 179 (94%) completed the treatment without serious complications. A total of 195 sites were irradiated. Twelve patients (6%) required interruption of the treatment. Therapeutic responses were seen in 86 out of 112 patients (77%) treated with curative intent (with 67% complete response) and in 67 out of 83 patients (81%) treated with palliative intent. The causes of treatment interruptions included weight loss from diarrhea, dysphagia, and progressive disease. Treatment interruptions were more likely in patients treated with large treatment fields. In patients treated for upper aero-digestive tract cancer, Grade 3 and 4 mucositis was noted in 20 and 2% of patients, respectively. Grade 1 and 2 enteritis was noted in 43% of patients treated for pelvic malignancies. Grade 3 dermatitis was noted only in 2% of patients. Conclusion: Radiotherapy is highly effective and well tolerated by the oldest old. Age is not a contraindication to aggressive radiotherapy

  16. Probing the dark side of the Universe with weak gravitational lensing effects

    International Nuclear Information System (INIS)

    Fu Li-Ping; Fan Zu-Hui


    Arising from gravitational deflections of light rays by large-scale structures in the Universe, weak-lensing effects have been recognized as one of the most important probes in cosmological studies. In this paper, we review the main progress in weak-lensing analyses, and discuss the challenges in future investigations aiming to understand the dark side of the Universe with unprecedented precisions. (invited reviews)

  17. Minimizing quality deteriorations of refrigerated foodstuffs as a side effect of defrosting

    DEFF Research Database (Denmark)

    Cai, Junping; Stoustrup, Jakob


    This paper proposes an optimization scheme for traditional refrigeration systems with hysteresis controllers and scheduled defrosts. It aims at minimizing the side effect of defrost cycles on the storage quality of refrigerated foodstuffs in supermarkets. By utilizing the thermal mass of air...... and products inside a display cabinet, this optimization scheme forces the compressor to work harder and cool down more prior to the scheduled defrosts, thus guaranteeing the product temperature after defrost cycles still to be within a controlled safe level....

  18. Influence of psychiatric diagnosis on treatment uptake and interferon side effects in patients with hepatitis C. (United States)

    Wu, Jing Yuan J; Shadbolt, Bruce; Teoh, Narci; Blunn, Anne; To, Caroline; Rodriguez-Morales, Ilys; Chitturi, Shivakumar; Kaye, Graham; Rodrigo, Kalyana; Farrell, Geoff


    Pegylated-interferon-α/ribavirin (PEG-IFN/RBV) treatment can cure hepatitis C virus (HCV) infection but has frequent neuropsychiatric side-effects. Patients with pre-existing psychiatric illness may not be offered therapy. We established prevalence of self-reported psychiatric comorbidity among HCV-infected patients in a hospital-liver clinic, and determined the impact of such diagnoses on uptake and tolerance to PEG-IFN/RBV. All HCV cases referred for assessment in Australian Capital Territory/surrounding regions April 2004-March 2012 were entered into a clinical database. We conducted univariate and multivariate analyses of variables correlating with uptake of antiviral therapy and frequency of treatment-related side-effects. Of 773 referred patients, 235 (30%) described pre-existing psychiatric illness. Among these, 26% received antiviral therapy, compared with 30% of 538 without psychiatric comorbidity. History of depression (usually validated by liaison psychiatry) was associated with higher incidence of treatment-related neuropsychiatric side-effects (odds ratio 2.79 [1.35-5.70], P schizophrenia: three (11%) received antiviral therapy, compared with 30% admitting depression and 20% with bipolar affective disorder (all assessed by psychiatrist). In most schizophrenia cases, the reason for not offering antiviral treatment was psychological illness, yet none of five treated (these three plus two others in a psychiatric rehabilitation facility) experienced worsening psychiatric symptoms. A history of depression is common with hepatitis C but does not affect initiation of antiviral treatment, despite substantially increased risk of psychiatric side-effects. In contrast, pre-existing schizophrenia appears to influence treatment decisions, despite little evidence that PEG-IFN/RBV exacerbates the psychiatric condition, and well-supervised antiviral therapy can have good outcomes.

  19. Comparison of the efficiency, side effects and complications of the synthetic dural grafts: Beriplast and Tissudura


    HAMZAOĞLU, Vural; ÖZALP, Hakan; KARKUCAK, Ahmet; ÇOKLUK, Cengiz


    The purpose of this study was to compare human fibrinogen-thrombin-based liquid dural graft; Beriplast® (Behring, Malburg, Germany) and collagen-based dural graft; Tissudura® (Baxter, Heidelberg, Germany) in terms of efficiency, side effects and complications. Thirty Spraque Dawley rats were used in this experimental study. A burrhole was opened on the left parietal bone of each subject and experimental dural defect was created. While 10 subjects were in sham group without any dural defect re...

  20. Side effects and complications of intraosseous anesthesia and conventional oral anesthesia


    Peñarrocha-Oltra, David; Ata-Ali, Javier; Oltra-Moscardó, María J.; Peñarrocha-Diago, María; Peñarrocha, Miguel


    Objective: To analyze the side effects and complications following intraosseous anesthesia (IA), comparing them with those of the conventional oral anesthesia techniques. Material and method: A simple-blind, prospective clinical study was carried out. Each patient underwent two anesthetic techniques: conventional (local infiltration and locoregional anesthetic block) and intraosseous, for respective dental operations. In order to allow comparison of IA versus conventional anesthesia, the two ...

  1. Exercise for the Management of Side Effects and Quality of Life among Cancer Survivors


    Mustian, Karen M.; Sprod, Lisa K.; Palesh, Oxana G.; Peppone, Luke J.; Janelsins, Michelle C.; Mohile, Supriya G.; Carroll, Jennifer


    Physical activity may play an important role in the rehabilitation of cancer survivors during and following treatment. Current research suggests numerous beneficial outcomes are experienced in cancer survivors undergoing exercise interventions during or following cancer treatment. Exercise not only plays a role in managing side effects but also improves functional capacity and quality of life. The purpose of this article is to provide an overview of the oncology literature supporting the use ...

  2. Novel Anticonvulsant Analogs of Dextromethorphan: Improved Efficacy, Potency, Duration and Side-Effect Profile (United States)


    dextromethorphan (014, [+J-3-aethyl-l7-methylmorphinan) may be, in part, due to its ____________________metabolism to the PCP-like compound... Dextromethorphan : Improved Efficacy, Potency, Duration and Side-Effect Profile1 FRANK C. TORTELLA, LYDIA ROBLES, JEFFREY M. WITKIN and AMY HAUCK NEWMAN... dextromethorphan ; NMDA, N-methyl-D-aspartate; PCP, phencyclidine hydrochloride; DX, dextrorphan; AHN649, [(+)-3- amino-1 7-methylmorphinan]; AHN1 -036

  3. Acceptability and perceived side effects of insecticide indoor residual spraying under different resistance management strategies

    Directory of Open Access Journals (Sweden)

    Rodríguez Américo David


    Full Text Available OBJECTIVE: To assess household acceptability and perceived side effects of residual indoor pyrethroid (PYR, carbamate and organophosphate insecticides sprayed by annual rotation (ROT, spatial mosaic (MOS, and a single insecticide (DDT or PYR in communities of the coastal plain of Chiapas, Mexico. MATERIAL AND METHODS: A questionnaire to assess the acceptability and perceived side effects of indoor insecticides was administered to one member of 30% of the families in eight villages of Chiapas. The association of different insecticide treatments with their responses was evaluated (Chi-square. The intensity of side effects indicated under different treatments was compared in an ordered logistic model, using a severity index as the response variable. RESULTS: Insecticide spraying as a probable cause of symptoms was identified by 2.1% of interviewees. A significantly high percentage of persons with blurred vision, dizziness, sneezing, coughing, numbness, watery eyes, and itching lived in villages under MOS and ROT and a high severity index was significantly associated with ROT treatment. Reduction of mosquito bites and cockroaches were the perceived main benefits, and most villagers that perceived no benefits lived in DDT treated villages. Most of the interviewees welcomed spraying (83.7%, but the smell and having to remove furniture from houses were the main arguments against it. CONCLUSIONS: Acceptability correlated with insecticide spray coverage, although the most frequent suggestion for improvement was to increase the understanding of the objectives of spraying in the communities. The frequency of side effects was low, but higher in localities where a combination of insecticides was applied. This is a limitation for the use of this type of resistance management strategy in public health.

  4. The effect of a multidimensional exercise programme on symptoms and side-effects in cancer patients undergoing chemotherapy

    DEFF Research Database (Denmark)

    Andersen, Christina; Adamsen, Lis; Møller, Tom


    The aim of this study was to evaluate the effects of a 6-week intervention with structured physical activity, relaxation, body-awareness techniques and massage on the symptoms/side-effects of cancer patients undergoing chemotherapy. The study was prospective and exploratory, and 54 patients....../side-effects than patients with no evidence of disease (n=28) (P=0.027). The results indicate that a six weeks multidimensional exercise intervention undertaken by cancer patients with or without residual disease while undergoing chemotherapy can lead to a reduction in treatment-related symptoms....

  5. Hormonal contraception and physiology: a research-based theory of discontinuation due to side effects. (United States)

    Vitzthum, Virginia J; Ringheim, Karin


    Side effects influence the acceptability and continuation of hormonal contraceptives. Counseling the client about the management of side effects is a principal approach advocated for increasing continuation. Evidence of a biological basis for variation in women's tolerance of hormonal contraceptives argues, however, that greater attention should be given to altering the product rather than principally attempting to alter a woman's ability to deal with the product. Discontinuation rates for hormonal contraceptives, largely attributable to side effects and health concerns, are high in nearly all less-developed countries for which Demographic and Health Survey data are available. Oral contraceptives appear to be particularly problematic for Latin American women, most notably in Bolivia. Clinical trials suggest substantial variation in the physiological response to exogenous hormones, and new evidence confirms the hypothesis that the normal hormonal profiles of Bolivian women are significantly lower than those of women in the United States. These findings suggest a need for more population-specific physiological research linked to analyses of the possible association between endogenous hormone differences and contraceptive continuation. Appropriately adjusting the level of the steroid delivered may benefit women's health and improve the acceptability and continuation of hormonal contraceptives.

  6. Immune thrombocytopenic purpura: A rare side effect in a patient treated with Imiquimod for lentigo maligna

    Directory of Open Access Journals (Sweden)

    E.A. Whatling


    Full Text Available Topical Imiquimod is increasingly used in the treatment of lentigo maligna (LM for patients not suitable or willing for surgery. It acts as an immune response modifier and is recommended for use with caution in patients with autoimmune disorders. A review of the literature did not reveal any reported cases of Idiopathic Thrombocytopenic Purpura (ITP with the use of Imiquimod so far. We report a case of a 55-year-old woman with a history of Addison's and Graves' disease who had been diagnosed with lentigo maligna on the right nasal ala. Within two days of commencing of topical Imiquimod treatment, she was admitted to the hospital with extensive cutaneous and mucosal bruising and treated as acute Idiopathic Throbocytopenic Purpura. Deranged platelets were reversed promptly with treatment and Imiquimod discontinued. We demonstrate that Idiopathic Throbocytopenic Purpura is a potential life-threatening side effect of Imiquimod treatment and patients who have autoimmune disorders are at increased risk of developing this side effect. We recommend that Imiquimod is contraindicated in patients with autoimmune disease. Here we describe the clinical presentation and review the relevant literature on Imiquimod treatment for lentigo maligna and its potential side effects.

  7. A Rare Side Effect due to TNF-Alpha Blocking Agent: Acute Pleuropericarditis with Adalimumab

    Directory of Open Access Journals (Sweden)

    Hakan Ozkan


    Full Text Available Tumor necrosis factor-alpha antagonism is an important treatment strategy in patients with rheumatoid arthritis, psoriatic arthritis, vasculitis, and ankylosing spondylitis. Adalimumab is one of the well-known tumor necrosis factor-alpha blocking agents. There are several side effects reported in patients with adalimumab therapy. Cardiac side effects of adalimumab are rare. Only a few cardiac side effects were reported. A 61-year-old man treated with adalimumab for the last 6 months due to psoriatic arthritis presented with typically acute pleuropericarditis. Chest X-ray and echocardiography demonstrated marked pericardial effusion. Patient was successfully evaluated for the etiology of acute pleuro-pericarditis. Every etiology was excluded except the usage of adalimumab. Adalimumab was discontinued, and patient was treated with 1200 mg of ibuprofen daily. Control chest X-ray and echocardiography after three weeks demonstrated complete resolution of both pleural and pericardial effusions. This case clearly demonstrated the acute onset of pericarditis with adalimumab usage. Acute pericarditis and pericardial effusion should be kept in mind in patients with adalimumab treatment.

  8. Calcium vitamin D3 supplementation in clinical practice: side effect and satisfaction. (United States)

    Sanaei, Maryam; Banasiri, Mohammad; Shafiee, Gita; Rostami, Mahsa; Alizad, Saba; Ebrahimi, Mehdi; Larijani, Bagher; Heshmat, Ramin


    The objective of this study was to assess side effects and satisfaction about OsteoCalVitFort (500 mg calcium and 400 I.U. of vitamin D3) usage. A total 186 people were participated with range age from 18 to 65 years old. Each participant received 1 pack that contains 60 OsteoCalVitFort tablet and used two tablet OsteoCalVitFort daily (1 tablet after breakfast and 1 after dinner). By a phone call, side effects and satisfaction about OsteoCalVitFort were assessed. The rate of constipating (8.0 %) and bloating (12.5 %) were decreased significantly after OsteoCalVitFort supplement intake (1.2 %, and 0.6 %, respectively). Similar results were observed in metallic taste in mouth, tiredness, weakness, loss of appetite, bone/muscle pain and mental/mood change after Calcium Vitamin D3 supplementation intake. Totally, 94 % of patients were satisfied about OsteoCalVitFort usage. The results of the research indicate despite the high quality of OsteoCalVitFort supplement, there are no side effects which have been seen in other supplements.

  9. Bronchoalveolar lavage in patients with interstitial lung diseases: side effects and factors affecting fluid recovery. (United States)

    Dhillon, D P; Haslam, P L; Townsend, P J; Primett, Z; Collins, J V; Turner-Warwick, M


    One hundred and seventy patients with interstitial lung diseases undergoing bronchoalveolar lavage (BAL), were contrasted with 51 patients undergoing fibreoptic bronchoscopy alone to define the factors which predispose to post-lavage side-effects. Transient post-bronchoscopy fall in the peak expired flow (PEF) greater than or equal to 20% occurred in both groups (24% and 23% respectively), and thus was probably related to the bronchoscopy procedure. Post-lavage pyrexia (greater than or equal to 1 degree C) occurred only in the patients undergoing BAL (26%), p less than 0.001. Only 4% with pyrexia required antibiotics, and only 2% with falls in PEF needed bronchodilator therapy. The only significant clinical association was more frequent pyrexia in patients on treatment with prednisolone, particularly in women (p less than 0.01). Pyrexia was also associated with higher lavage fluid introduction volumes (greater than 240 ml). Side effects did not relate to the percentages of lavage fluid recovered, although smokers had lower recoveries and, recoveries tended to be higher in sarcoidosis than cryptogenic fibrosing alveolitis. Serial lavages in 25 patients caused no significant increase in side effects.

  10. Nonlinear side effects of fs pulses inside corneal tissue during photodisruption (United States)

    Heisterkamp, A.; Ripken, T.; Mamom, T.; Drommer, W.; Welling, H.; Ertmer, W.; Lubatschowski, H.

    In order to evaluate the potential for refractive surgery, fs laser pulses of 150-fs pulse duration were used to process corneal tissue of dead and living animal eyes. By focusing the laser radiation down to spot sizes of several microns, very precise cuts could be achieved inside the treated cornea, accompanied with minimum collateral damage to the tissue by thermal or mechanical effects. During histo-pathological analysis by light and transmission electron microscopy considerable side effects of fs photodisruption were found. Due to the high intensities at the focal region several nonlinear effects occurred. Self-focusing, photodissociation, UV-light production were observed, leading to streak formation inside the cornea.

  11. Decreasing the Burden of Side Effects Through Positive Message Framing: an Experimental Proof-of-Concept Study. (United States)

    Wilhelm, Marcel; Rief, Winfried; Doering, Bettina K


    Informing patients about treatment side effects increases the occurrence and intensity of side effects. Since the obligatory informed consent procedure in drug treatments requires transparency and nocebo research suggests that the informed consent of a drug leads to an increased occurrence of the mentioned side effects, the aim of this proof of concept study was to determine the effect of two different framings of informed consent on the occurrence, intensity, and perceived threat of side effects. Healthy male participants (n = 80) were randomized to one of two framing groups. The positive framing group was informed that the common side effect dizziness was a sign that the drug had started to work, while the neutral framing group was told that dizziness is an unpleasant but well-known side effect. Side effects were measured after the administration of metoprolol, an antihypertensive agent. Post hoc moderator analyses investigated the effect of pre-existing negative beliefs about the general harm of medication on the framing manipulation. Metoprolol-specific drug-attributed side effects were rated significantly less threatening in the positive framing group. The between-group effect size (Cohen's d) was small (d = 0.38, p = 0.049). Exploratory post hoc moderator analyses suggest that participants who believed that medication is a source of harmful effects benefited from positive framing, compared to neutral framing of drug-attributed side effects. Positive framing was partially effective in decreasing specific side effect measures, particularly among participants with a tendency to believe that medicine is harmful. Informed consent procedures should therefore be personalized, focusing on patients with negative treatment beliefs.

  12. Review Article: Fabricated Microparticles: An Innovative Method to Minimize the Side Effects of NSAIDs in Arthritis. (United States)

    Abadi, Shaivad Shabee Hulhasan; Moin, Afrasim; Veerabhadrappa, Gangadharappa Hosahalli


    Microparticles are polymeric bodies ranging 1-1000 µm that constitute a variety of forms such as microcapsules, microspheres, microcages, microshells, microrods, biosensors microparticles, radiolabeled microparticles, and so forth. This review focuses on general microparticles, mainly microcapsules and microspheres. Nonsteriodal anti-inflammatory drugs (NSAIDs) are one of the mostcommonly prescribed medications in the world. Most of the NSAIDs available have severe side effects. With increased awareness of NSAID-induced gastrointestinal (GI) side effects, safety has become a priority in treatment of arthritis and other inflammatory diseases with NSAIDs. A trend in NSAID development has been to improve therapeutic efficacy while reducing the severity of GI side effects by altering dosage through modified release to optimize drug delivery. One such approach is the use of fabricated microparticles such as microcapsules and microspheres as carriers of drugs. Microparticles provide delivery of macromolecules and micromolecules via different routes and effectively control the release profile of such drugs. Microcapsules and microspheres are compatible with most natural and synthetic polymers and can be used for several routes of administration, including parenteral, oral, nasal, intra-ocular, topical, and the like. Because of greater stability and multiple manufacturing techniques, microspheres and microcapsules are preferred as drug carriers over other colloidal drug delivery systems. Microparticles provide effective protection of the encapsulated agent against degradation by enzymatic activities, controlled and confined delivery of drugs from a few hours to months, and ingenious administration compared to alternative forms of controlled-release parenteral dosages, such as macro-sized implants. This comprehensive overview of fabricated microparticles describes microencapsulation technologies to produce microparticles for targeted therapy of arthritis and other

  13. Effects of surgical side and site on mood and behavior outcome in children with pharmacoresistant epilepsy

    Directory of Open Access Journals (Sweden)

    Elizabeth N Andresen


    Full Text Available Children with epilepsy have a high rate of mood and behavior problems yet few studies consider the emotional and behavioral impact of surgery. No study to date has been sufficiently powered to investigate effects of both side (left/right and site (temporal/frontal of surgery. One hundred patients (aged 6-16 and their families completed measures of depression, anxiety and behavioral function as part of neuropsychological evaluations before and after surgery for pharmacoresistant epilepsy. Among children who had left-sided surgeries (frontal=16; temporal=38, there were significant interactions between time (pre to postoperative neuropsychological assessment and resection site (frontal/temporal on Anhedonia, Social Anxiety, and Withdrawn/Depressed scales. Patients with frontal lobe epilepsy (FLE endorsed greater presurgical anhedonia and social anxiety than patients with temporal lobe epilepsy (TLE, with scores normalizing following surgery. While scores on the Withdrawn/Depressed scale were similar between groups before surgery, the FLE group showed greater symptom improvement after surgery. In children who underwent right-sided surgeries (FLE=20; TLE=26 main effects of time (patients in both groups improved and resection site (caregivers of FLE patients endorsed greater symptoms than those with TLE were observed primarily on behavior scales. Individual data revealed that a greater proportion of children with left FLE demonstrated clinically significant improvements in Anhedonia, Social Anxiety, and Aggressive Behavior than children with TLE. This is the first study to demonstrate differential effects of both side and site of surgery in children with epilepsy at group and individual levels. Results suggest that children with FLE have greater emotional and behavioral dysfunction before surgery, but show marked improvement after surgery. Overall, most children had good emotional and behavioral outcomes, with most scores remaining stable or improving.

  14. Supply- and demand-side effects of power sector planning with demand-side management options and SO2 emission constraints

    International Nuclear Information System (INIS)

    Shrestha, R.M.; Marpaung, C.O.P.


    This paper examines the implications of SO 2 emission mitigation constraints in the power sector planning in Indonesia--a developing country--during 2003-2017 from a long term integrated resource planning perspective. A decomposition model is developed to assess the contributions of supply- and demand-side effects to the total changes in CO 2 , SO 2 and NO x emissions from the power sector due to constraints on SO 2 emissions. The results of the study show that both the supply- and demand-side effects would act towards the reduction of CO 2 , SO 2 and NO x emissions. However, the supply-side effect would play the dominant role in emission mitigations from the power sector in Indonesia. The average incremental SO 2 abatement cost would increase from US$ 970 to US$ 1271 per ton of SO 2 , while electricity price would increase by 2-18% if the annual SO 2 emission reduction target is increased from 10% to 25%

  15. Vitamin A decreases pre-receptor amplification of glucocorticoids in obesity: study on the effect of vitamin A on 11beta-hydroxysteroid dehydrogenase type 1 activity in liver and visceral fat of WNIN/Ob obese rats

    Directory of Open Access Journals (Sweden)

    Ayyalasomayajula Vajreswari


    Full Text Available Abstract Background 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1 catalyzes the conversion of inactive glucocorticoids to active glucocorticoids and its inhibition ameliorates obesity and metabolic syndrome. So far, no studies have reported the effect of dietary vitamin A on 11β-HSD1 activity in visceral fat and liver under normal and obese conditions. Here, we studied the effect of chronic feeding of vitamin A-enriched diet (129 mg/kg diet on 11β-HSD1 activity in liver and visceral fat of WNIN/Ob lean and obese rats. Methods Male, 5-month-old, lean and obese rats of WNIN/Ob strain (n = 16 for each phenotype were divided into two subgroups consisting of 8 rats of each phenotype. Control groups received stock diet containing 2.6 mg vitamin A/kg diet, where as experimental groups received diet containing 129 mg vitamin A/Kg diet for 20 weeks. Food and water were provided ad libitum. At the end of the experiment, tissues were collected and 11β-HSD1 activity was assayed in liver and visceral fat. Results Vitamin A supplementation significantly decreased body weight, visceral fat mass and 11β-HSD1 activity in visceral fat of WNIN/Ob obese rats. Hepatic 11β-HSD1 activity and gene expression were significantly reduced by vitamin A supplementation in both the phenotypes. CCAAT/enhancer binding protein α (C/EBPα, the main transcription factor essential for the expression of 11β-HSD1, decreased in liver of vitamin A fed-obese rats, but not in lean rats. Liver × receptor α (LXRα, a nuclear transcription factor which is known to downregulate 11β-HSD1 gene expression was significantly increased by vitamin A supplementation in both the phenotypes. Conclusions This study suggests that chronic consumption of vitamin A-enriched diet decreases 11β-HSD1 activity in liver and visceral fat of WNIN/Ob obese rats. Decreased 11β-HSD1 activity by vitamin A may result in decreased levels of active glucocorticoids in adipose tissue and possibly

  16. The effect of cigarette smoking on cancer treatment-related side effects. (United States)

    Peppone, Luke J; Mustian, Karen M; Morrow, Gary R; Dozier, Ann M; Ossip, Deborah J; Janelsins, Michelle C; Sprod, Lisa K; McIntosh, Scott


    Cigarette smoking has long been implicated in cancer development and survival. However, few studies have investigated the impact of smoking on symptom burden in cancer survivors during treatment and at survivorship stage. This study examines the influence of cigarette smoking on side effects among 947 cancer patients during and 6 months following treatment. Patients diagnosed with cancer and scheduled to receive chemotherapy and/or radiation therapy reported on current smoking status (yes, no) and total symptom burden [the sum of 12 common symptoms (fatigue, hair loss, memory, nausea, depression, sleep, pain, concentration, hot flashes, weight loss, skin problems, and dyspnea) scored on an 11-point scale ranging from 0 = "not present" to 10 = "as bad as you can imagine"] during treatment and at 6-month follow-up. The adjusted mean total symptom burden by smoking status was determined by analysis of covariance controlling for age, gender, race, education, occupation, treatment, cancer site, and Karnofsky performance score. During treatment, smokers (S) had a significantly higher total symptom burden than nonsmokers (NS) (S = 46.3 vs. NS = 41.2; p < 0.05). At 6-month follow-up, smokers continued to report a higher total symptom burden than nonsmokers (S = 27.7 vs. NS = 21.9; p < 0.05). Participants who quit smoking before treatment levels had a total symptom burden similar to nonsmokers. Smoking was associated with an increased symptom burden during and following treatments for cancer. Targeted cessation efforts for smokers to decrease symptom burden may limit the likelihood of treatment interruptions and increase quality of life following treatment.

  17. Side effects of permanent I125 prostate seed implants in 667 patients treated in Leeds

    International Nuclear Information System (INIS)

    Bottomley, David; Ash, Dan; Al-Qaisieh, Bashar; Carey, Brendan; Joseph, Joji; St Clair, Shaun; Gould, Kathy


    Purpose: To report the side effects and complications after I-125 seeds prostate implant after 8.5 years experience. Methods and materials: Six hundred and sixty seven (667) patients were treated between March 1995 and December 2001. The median follow up is 31 months with a maximum of 98.2 months. Morbidity data were collected from a review of patient case-notes. Patients also provided prospective data on urinary symptoms using the International Prostate Symptom Score (IPSS) scoring chart before treatment and at regular follow up. Patients were also sent a questionnaire detailing symptoms and side effects following their brachytherapy. This enabled them to record urinary, bowel and sexual function side effects independently. Logistic regression analysis was carried out to identify the risk of catheterisation in relation to the pre-implant prostate volume and potential implant factors such as the number of seeds and needles and implant dose. Result: The urinary symptom score rises in the first few months after implantation and returns to within one or two points of the pre-treatment score within one year. Nine patients reported incontinence prior to treatment and 15, 12 and 10 patients reported incontinence 6, 12 and 24 months after treatment, respectively. Catheterisation was reported in 97 (14.5%) patients. At six months 84.9% of patients reported no change in bowel function and 78.9% at 12 months. 6.4% of patients complained of some increased bowel frequency at 6 months and 5.7% at 12 months. 402 (77.2%) patients reported being fully potent before treatment and that this fell to 32.4% after treatment. Logistic regression showed that the most significant factors which correlate with the probability of catheterisation are the pre-treatment prostate volume and the number of seeds and needles implanted. Conclusion: The side effects and complications after prostate brachytherapy as reported here and elsewhere confirm that the treatment is not only convenient but also

  18. [Glucocorticoid therapy: what is the information sought by patients? Traffic analysis of the website]. (United States)

    Poisson, J; Six, M; Morin, C; Fardet, L


    About 1% of the general population are receiving systemic glucocorticoids. The information about this treatment sought by patients is unknown. The website aims to provide therapeutic information about glucocorticoids and glucocorticoid therapy. It was posted on January 16, 2012. The information available on the website is documented and based on the recent medical literature. The website is made of 43 pages divided into five main sections (generalities about glucocorticoids, adverse events, measures associated with glucocorticoid therapy, discontinuation of glucocorticoids and, situations requiring attention). The website traffic between February 1st, 2012 and January 4, 2013 was analyzed using Google Analytics. During the study period, the website was visited by 67,496 people (average number of visitors per day: 33 in February 2012, 326 in December 2012). The number of page views was 230,496 or an average of 3.5 pages per visitor. Of these 230,496 page views, 145,431 (63.1%) were related to adverse events and 37,722 (16.4%) were related to generalities about glucocorticoids (e.g., what is cortisone? For which disease? How does it work?). Information particularly sought by visitors was related to the diet to follow during glucocorticoid therapy (page accessed 11,946 times), data about what cortisone is (page accessed 11,829 times) and the effects of glucocorticoids on weight (page accessed 10,442 times). Knowledge of glucocorticoid-treated patients' expectations may help physicians to optimize information they give, thereby helping to reduce patients' concerns about glucocorticoids and to improve adherence to the treatment. Copyright © 2013 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  19. SDF-1 improves wound healing ability of glucocorticoid-treated adipose tissue-derived mesenchymal stem cells. (United States)

    Kato, Toshiki; Khanh, Vuong Cat; Sato, Kazutoshi; Takeuchi, Kosuke; Carolina, Erica; Yamashita, Toshiharu; Sugaya, Hisashi; Yoshioka, Tomokazu; Mishima, Hajime; Ohneda, Osamu


    Glucocorticoids cause the delayed wound healing by suppressing inflammation that is required for wound healing process. Adipose tissue-derived mesenchymal stem cells (AT-MSCs) play an important role for wound healing by their cytokine productions including stromal derived factor 1 (SDF-1). However, it has not been clear how glucocorticoids affect the wound healing ability of AT-MSCs. In this study, we found that glucocorticoid downregulated SDF-1 expression in AT-MSCs. In addition, glucocorticoid-treated AT-MSCs induced less migration of inflammatory cells and impaired wound healing capacity compared with glucocorticoid-untreated AT-MSCs. Of note, prostaglandin E2 (PGE2) synthesis-related gene expression was downregulated by glucocorticoid and PGE2 treatment rescued not only SDF-1 expression in the presence of glucocorticoid but also their wound healing capacity in vivo. Furthermore, we found SDF-1-overexpressed AT-MSCs restored wound healing capacity even after treatment of glucocorticoid. Consistent with the results obtained from glucocorticoid-treated AT-MSCs, we found that AT-MSCs isolated from steroidal osteonecrosis donors (sAT-MSCs) who received chronic glucocorticoid therapy showed less SDF-1 expression and impaired wound healing capacity compared with traumatic osteonecrosis donor-derived AT-MSCs (nAT-MSCs). Moreover, the SDF-1 level was also reduced in plasma derived from steroidal osteonecrosis donors compared with traumatic osteonecrosis donors. These results provide the evidence that concomitant application of AT-MSCs with glucocorticoid shows impaired biological modulatory effects that induce impaired wound healing. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Effects of Mach Numbers on Side Force, Yawing Moment and Surface Pressure (United States)

    Sohail, Muhammad Amjad; Muhammad, Zaka; Husain, Mukkarum; Younis, Muhammad Yamin


    In this research, CFD simulations are performed for air vehicle configuration to compute the side force effect and yawing moment coefficients variations at high angle of attack and Mach numbers. As the angle of attack is increased then lift and drag are increased for cylinder body configurations. But when roll angle is given to body then side force component is also appeared on the body which causes lateral forces on the body and yawing moment is also produced. Now due to advancement of CFD methods we are able to calculate these forces and moment even at supersonic and hypersonic speed. In this study modern CFD techniques are used to simulate the hypersonic flow to calculate the side force effects and yawing moment coefficient. Static pressure variations along the circumferential and along the length of the body are also calculated. The pressure coefficient and center of pressure may be accurately predicted and calculated. When roll angle and yaw angle is given to body then these forces becomes very high and cause the instability of the missile body with fin configurations. So it is very demanding and serious problem to accurately predict and simulate these forces for the stability of supersonic vehicles.