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Sample records for chronic glucocorticoid treatment

  1. Brief treatment with the glucocorticoid receptor antagonist mifepristone normalizes the reduction in neurogenesis after chronic stress.

    NARCIS (Netherlands)

    Oomen, C.A.; Mayer, J.L.; de Kloet, E.R.; Joëls, M.; Lucassen, P.J.

    2007-01-01

    In rodents, stress suppresses adult neurogenesis. This is thought to involve activation of glucocorticoid receptors in the brain. In the present study, we therefore questioned whether glucocorticoid receptor blockade by mifepristone can normalize the effects of chronic stress on adult neurogenesis.

  2. Chronic treatment with glucocorticoids alters rat hippocampal and prefrontal cortical morphology in parallel with endogenous agmatine and arginine decarboxylase levels.

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    Zhu, Meng-Yang; Wang, Wei-Ping; Huang, Jingjing; Regunathan, Soundar

    2007-12-01

    In the present study, we examined the possible effect of chronic treatment with glucocorticoids on the morphology of the rat brain and levels of endogenous agmatine and arginine decarboxylase (ADC) protein, the enzyme essential for agmatine synthesis. Seven-day treatment with dexamethasone, at a dose (10 and 50 mug/kg/day) associated to stress effects contributed by glucocorticoids, did not result in obvious morphologic changes in the medial prefrontal cortex and hippocampus, as measured by immunocytochemical staining with beta-tubulin III. However, 21-day treatment (50 mug/kg/day) produced noticeable structural changes such as the diminution and disarrangement of dendrites and neurons in these areas. Simultaneous treatment with agmatine (50 mg/kg/day) prevented these morphological changes. Further measurement with HPLC showed that endogenous agmatine levels in the prefrontal cortex and hippocampus were significantly increased after 7-day treatments with dexamethasone in a dose-dependent manner. On the contrary, 21-day treatment with glucocorticoids robustly reduced agmatine levels in these regions. The treatment-caused biphasic alterations of endogenous agmatine levels were also seen in the striatum and hypothalamus. Interestingly, treatment with glucocorticoids resulted in a similar change of ADC protein levels in most brain areas to endogenous agmatine levels: an increase after 7-day treatment versus a reduction after 21-day treatment. These results demonstrated that agmatine has neuroprotective effects against structural alterations caused by glucocorticoids in vivo. The parallel alterations in the endogenous agmatine levels and ADC expression in the brain after treatment with glucocorticoids indicate the possible regulatory effect of these stress hormones on the synthesis and metabolism of agmatine in vivo.

  3. Glucocorticoids, chronic stress, and obesity.

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    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

    2006-01-01

    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 chronic stressor, the steroids act in brain in a feed-forward fashion to recruit a stress-response network that biases ongoing autonomic, neuroendocrine, and behavioral outflow as well as responses to novel stressors. We review evidence for the role of glucocorticoids in activating the central stress-response network, and for mediation of this network by corticotropin-releasing factor (CRF). We briefly review the effects of CRF and its receptor antagonists on motor outflows in rodents, and examine the effects of glucocorticoids and CRF on monoaminergic neurons in brain. Corticosteroids stimulate behaviors that are mediated by dopaminergic mesolimbic "reward" pathways, and increase palatable feeding in rats. Moreover, in the absence of corticosteroids, the typical deficits in adrenalectomized rats are normalized by providing sucrose solutions to drink, suggesting that there is, in addition to the feed-forward action of glucocorticoids on brain, also a feedback action that is based on metabolic well being. Finally, we briefly discuss the problems with this network that normally serves to aid in responses to chronic stress, in our current overindulged, and underexercised society.

  4. Acute and chronic glucocorticoid treatments regulate astrocyte-enriched mRNAs in multiple brain regions in vivo

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    Bradley S. Carter

    2013-08-01

    Full Text Available Previous studies have primarily interpreted gene expression regulation by glucocorticoids in the brain in terms of impact on neurons; however, less is known about the corresponding impact of glucocorticoids on glia and specifically astrocytes in vivo. Recent microarray experiments have identified glucocorticoid-sensitive mRNAs in primary astrocyte cell culture, including a number of mRNAs that have reported astrocyte-enriched expression patterns relative to other brain cell types. Here, we have tested whether elevations of glucocorticoids regulate a subset of these mRNAs in vivo following acute and chronic corticosterone exposure in adult mice. Acute corticosterone exposure was achieved by a single injection of 10 mg/kg corticosterone, and tissue samples were harvested two hours post-injection. Chronic corticosterone exposure was achieved by administering 10 mg/mL corticosterone via drinking water for two weeks. Gene expression was then assessed in two brain regions associated with glucocorticoid action (prefrontal cortex and hippocampus by qPCR and by in situ hybridization. The majority of measured mRNAs regulated by glucocorticoids in astrocytes in vitro were similarly regulated by acute and/or chronic glucocorticoid exposure in vivo. In addition, the expression levels for mRNAs regulated in at least one corticosterone exposure condition (acute/chronic demonstrated moderate positive correlation between the two conditions by brain region. In situ hybridization analyses suggest that select mRNAs are regulated by chronic corticosterone exposure specifically in astroctyes based on (1 similar general expression patterns between corticosterone-treated and vehicle-treated animals and (2 similar expression patterns to the pan-astrocyte marker Aldh1l1. Our findings demonstrate that glucocorticoids regulate astrocyte-enriched mRNAs in vivo and suggest that glucocorticoids regulate gene expression in the brain in a cell type-dependent fashion.

  5. Glucocorticoid therapy-induced memory deficits: acute versus chronic effects.

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    Coluccia, Daniel; Wolf, Oliver T; Kollias, Spyros; Roozendaal, Benno; Forster, Adrian; de Quervain, Dominique J-F

    2008-03-26

    Conditions with chronically elevated glucocorticoid levels are usually associated with declarative memory deficits. Considerable evidence suggests that long-term glucocorticoid exposure may cause cognitive impairment via cumulative and long-lasting influences on hippocampal function and morphology. However, because elevated glucocorticoid levels at the time of retention testing are also known to have direct impairing effects on memory retrieval, it is possible that such acute hormonal influences on retrieval processes contribute to the memory deficits found with chronic glucocorticoid exposure. To investigate this issue, we examined memory functions and hippocampal volume in 24 patients with rheumatoid arthritis who were treated either chronically (5.3 +/- 1.0 years, mean +/- SE) with low to moderate doses of prednisone (7.5 +/- 0.8 mg, mean +/- SE) or without glucocorticoids. In both groups, delayed recall of words learned 24 h earlier was assessed under conditions of either elevated or basal glucocorticoid levels in a double-blind, placebo-controlled crossover design. Although the findings in this patient population did not provide evidence for harmful effects of a history of chronic prednisone treatment on memory performance or hippocampal volume per se, acute prednisone administration 1 h before retention testing to either the steroid or nonsteroid group impaired word recall. Thus, these findings indicate that memory deficits observed under chronically elevated glucocorticoid levels result, at least in part, from acute and reversible glucocorticoid effects on memory retrieval.

  6. Identification of a selective glucocorticoid receptor ligand for the treatment of chronic inflammation in type 2 diabetes mellitus.

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    Tan, Haifeng; Wang, Wei; Yin, Xiangang; Li, Yao; Yin, Rui

    2014-10-01

    The present study aimed to identify a new selective glucocorticoid receptor (GR) ligand for the treatment of chronic inflammation in type 2 diabetes mellitus. The IN Cell Analyzer 1000 platform was employed to screen for compounds that may promote GR nuclear translocation. A mammalian two-hybrid system and transactivation assay-were used to analyze the selected GR ligands and evaluate their activities for GR transcription and the recruitment of co-activators. A novel selective GR ligand, compound Q40, was identified that was able to promote GR nuclear translocation in a short period of time. It increased the ability of GR to recruit co-activators in a concentration-dependent manner, but had no positive effect on GR transcriptional activity. In conclusion, an increase in the expression levels of gluconeogeneic genes, induced by the transcriptional activation of GR, is the predisposing factor most commonly associated with the side-effects of glucocorticoids. The results suggest that compound Q40 is a ligand of the GR and exerts an agonistic action on the recruitment of co-activators without sugar dysmetabolism-related side-effects. Thus, compound Q40 has the potential to be used as an anti-inflammatory adjuvant therapy with minimal side-effects in patients with type 2 diabetes mellitus.

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

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    Harmen J Krugers

    2010-07-01

    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.

  8. Novel pathways for glucocorticoid effects on neutrophils in chronic inflammation.

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    Goulding, N J; Euzger, H S; Butt, S K; Perretti, M

    1998-10-01

    Neutrophils have been implicated in mediating much of the tissue damage associated with chronic inflammatory diseases such as rheumatoid arthritis, where they are involved in destruction of both cartilage and bone. Glucocorticoids are powerful anti-inflammatory agents, often used in the treatment of this autoimmune disease. They exert significant inhibitory effects on neutrophil activation and functions, such as chemotaxis, adhesion, transmigration, apoptosis, oxidative burst, and phagocytosis. The mechanisms by which glucocorticoids exert these effects on neutrophils are unclear. Evidence from studies of inflammation in human subjects and animal models suggests that annexin-I an endogenous, glucocorticoid-induced protein also known as lipocortin-1, has a pivotal role in modulating neutrophil activation, transmigratory, and phagocytic functions. Furthermore, we present evidence for altered neutrophil functions in rheumatoid arthritis that correspond to a significantly reduced capacity of these cells to bind annexin-I. A proposed novel pathway for glucocorticoid actions on neutrophils involving annexin-I could explain the development of chronic neutrophil activation in diseases such as rheumatoid arthritis.

  9. Chronic stress-induced hippocampal vulnerability: the glucocorticoid vulnerability hypothesis.

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    Conrad, Cheryl D

    2008-01-01

    The hippocampus, a limbic structure important in learning and memory, is particularly sensitive to chronic stress and to glucocorticoids. While glucocorticoids are essential for an effective stress response, their oversecretion was originally hypothesized to contribute to age-related hippocampal degeneration. However, conflicting findings were reported on whether prolonged exposure to elevated glucocorticoids endangered the hippocampus and whether the primate hippocampus even responded to glucocorticoids as the rodent hippocampus did. This review discusses the seemingly inconsistent findings about the effects of elevated and prolonged glucocorticoids on hippocampal health and proposes that a chronic stress history, which includes repeated elevation of glucocorticoids, may make the hippocampus vulnerable to potential injury. Studies are described to show that chronic stress or prolonged exposure to glucocorticoids can compromise the hippocampus by producing dendritic retraction, a reversible form of plasticity that includes dendritic restructuring without irreversible cell death. Conditions that produce dendritic retraction are hypothesized to make the hippocampus vulnerable to neurotoxic or metabolic challenges. Of particular interest is the finding that the hippocampus can recover from dendritic retraction without any noticeable cell loss. When conditions surrounding dendritic retraction are present, the potential for harm is increased because dendritic retraction may persist for weeks, months or even years, thereby broadening the window of time during which the hippocampus is vulnerable to harm, called the 'glucocorticoid vulnerability hypothesis'. The relevance of these findings is discussed with regard to conditions exhibiting parallels in hippocampal plasticity, including Cushing's disease, major depressive disorder (MDD), and post-traumatic stress disorder (PTSD).

  10. Selective glucocorticoid receptor-activating adjuvant therapy in cancer treatments

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    Sundahl, Nora; Clarisse, Dorien; Bracke, Marc; Offner, Fritz; Berghe, Wim Vanden; Beck, Ilse M.

    2016-01-01

    Although adverse effects and glucocorticoid resistance cripple their chronic use, glucocorticoids form the mainstay therapy for acute and chronic inflammatory disorders, and play an important role in treatment protocols of both lymphoid malignancies and as adjuvant to stimulate therapy tolerability in various solid tumors. Glucocorticoid binding to their designate glucocorticoid receptor (GR), sets off a plethora of cell-specific events including therapeutically desirable effects, such as cell death, as well as undesirable effects, including chemotherapy resistance, systemic side effects and glucocorticoid resistance. In this context, selective GR agonists and modulators (SEGRAMs) with a more restricted GR activity profile have been developed, holding promise for further clinical development in anti-inflammatory and potentially in cancer therapies. Thus far, the research into the prospective benefits of selective GR modulators in cancer therapy limped behind. Our review discusses how selective GR agonists and modulators could improve the therapy regimens for lymphoid malignancies, prostate or breast cancer. We summarize our current knowledge and look forward to where the field should move to in the future. Altogether, our review clarifies novel therapeutic perspectives in cancer modulation via selective GR targeting.

  11. Chronic Glucocorticoid-Rich Milieu and Liver Dysfunction

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    Hernán Gonzalo Villagarcía

    2016-01-01

    Full Text Available We investigated the impact of chronic hypercorticosteronemia (due to neonatal monosodium L-glutamate, MSG, and treatment on liver oxidative stress (OS, inflammation, and carbohydrate/lipid metabolism in adult male rats. We evaluated the peripheral concentrations of several metabolic and OS markers and insulin resistance indexes. In liver we assessed (a OS (GSH and protein carbonyl groups and inflammatory (IL-1b, TNFa, and PAI-1 biomarkers and (b carbohydrate and lipid metabolisms. MSG rats displayed degenerated optic nerves, hypophagia, low body and liver weights, and enlarged adipose tissue mass; higher peripheral levels of glucose, triglycerides, insulin, uric acid, leptin, corticosterone, transaminases and TBARS, and peripheral and liver insulin resistance; elevated liver OS, inflammation markers, and glucokinase (mRNA/activity and fructokinase (mRNA. Additionally, MSG liver phosphofructokinase-2, glucose-6-phosphatase (mRNA and activity and glucose-6-phosphate dehydrogenase, Chrebp, Srebp1c, fatty acid synthase, and glycerol-3-phosphate (mRNAs were increased. In conclusion adult MSG rats developed an insulin-resistant state and increased OS and serious hepatic dysfunction characterized by inflammation and metabolic signs suggesting increased lipogenesis. These features, shared by both metabolic and Cushing’s syndrome human phenotypes, support that a chronic glucocorticoid-rich endogenous environment mainly impacts on hepatic glucose cycle, displacing local metabolism to lipogenesis. Whether correcting the glucocorticoid-rich environment ameliorates such dysfunctions requires further investigation.

  12. Long-term effects of perinatal glucocorticoid treatment on the heart

    NARCIS (Netherlands)

    Vries, W.B. de

    2006-01-01

    Long-term effects of perinatal glucocorticoid treatment on the heart Chronic lung disease in the extremely preterm baby is still a major complication in neonatal intensive care medicine. Perinatal (ante- and neonatal) glucocorticoids are widely used to prevent severe infant respiratory syndrome and

  13. GLUCOCORTICOID-INDUCED OSTEOPOROSIS: PATHOGENESIS, PREVENTION, TREATMENT

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    Irina Aleksandrovna Baranova

    2010-06-01

    Full Text Available Osteoporosis (OP is a serious problem to patients who have long taken glucocorticoids. In the past two decade, much knowledge has been accumulated about the epidemiology of the disease and drugs with proven efficacy for its prevention and treatment have emerged. However, a large number of studies suggest that there is a serious shortage in care to patients with glucocorticoid-induced OP, which calls for effective measures to bring the real level of its prevention and treatment in compliance with the current clinical guidelines

  14. GLUCOCORTICOID-INDUCED OSTEOPOROSIS: PATHOGENESIS, PREVENTION, TREATMENT

    Directory of Open Access Journals (Sweden)

    Irina Aleksandrovna Baranova

    2010-01-01

    Full Text Available Osteoporosis (OP is a serious problem to patients who have long taken glucocorticoids. In the past two decade, much knowledge has been accumulated about the epidemiology of the disease and drugs with proven efficacy for its prevention and treatment have emerged. However, a large number of studies suggest that there is a serious shortage in care to patients with glucocorticoid-induced OP, which calls for effective measures to bring the real level of its prevention and treatment in compliance with the current clinical guidelines

  15. Islet-cell dysfunction induced by glucocorticoid treatment

    DEFF Research Database (Denmark)

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

    2013-01-01

    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....

  16. Influence of drug treatment on glucocorticoid receptor levels in patients with coronary heart disease

    Institute of Scientific and Technical Information of China (English)

    JI Hong; GUO Wei-zao; YAN Zhi-hong; LI Di; LU Cui-lian

    2010-01-01

    Background Glucocorticoid signaling exerts major roles in inflammation, metabolism and depression, which are three crucial factors accompanying or underlying coronary heart disease. Although accumulating evidence indicates the influence of glucocorticoids on the pathology and treatment of coronary heart disease, there is still a dearth of pharmaceutical mechanisms for this relationship. This study aimed to investigate the influence of drug treatment on glucocorticoid receptor levels in coronary heart disease.Methods Eighty hospitalized patients (average age (59.0 7.5) years, 46 male and 34 female) with coronary heart disease were categorized into four groups with 20 members in each according to one of the four drugs they were treated with. The four drugs were: nitrated derivative isosorbide dinitrate, the beta-adrenergic receptor blocker metoprolol, the calcium antagonist nifedipine, and the HMG-CoA reductase inhibitor lovastatin. Glucocorticoid receptor protein levels of peripheral blood lymphocytes were tested using immunoblotting analysis before and after one month of treatment. Results Immunoblotting analysis showed increased glucocorticoid receptor levels after treatment with metoprolol and nifedipine. There were no statistically significant changes of glucocorticoid receptor levels after treatment with isosorbide dinitrate or lovastatin, although there were trends of up-regulation of glucocorticoid receptor expression after both treatments.Conclusions Both the beta-blocker and the calcium blocker can increase glucocorticoid receptor levels after chronic administration. This effect suggests a mechanism for their anti-inflammatory and other therapeutic roles for coronary heart disease and comorbid disorders.

  17. Chronic Stress and Glucocorticoids: From Neuronal Plasticity to Neurodegeneration

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    Sheela Vyas

    2016-01-01

    Full Text Available Stress and stress hormones, glucocorticoids (GCs, exert widespread actions in central nervous system, ranging from the regulation of gene transcription, cellular signaling, modulation of synaptic structure, and transmission and glial function to behavior. Their actions are mediated by glucocorticoid and mineralocorticoid receptors which are nuclear receptors/transcription factors. While GCs primarily act to maintain homeostasis by inducing physiological and behavioral adaptation, prolonged exposure to stress and elevated GC levels may result in neuro- and psychopathology. There is now ample evidence for cause-effect relationships between prolonged stress, elevated GC levels, and cognitive and mood disorders while the evidence for a link between chronic stress/GC and neurodegenerative disorders such as Alzheimer’s (AD and Parkinson’s (PD diseases is growing. This brief review considers some of the cellular mechanisms through which stress and GC may contribute to the pathogenesis of AD and PD.

  18. Glucocorticoids and prostate cancer treatment:friend or foe?

    Institute of Scientific and Technical Information of China (English)

    Bruce Montgomery; Heather H Cheng; James Drechsler; Elahe A Mostaghel

    2014-01-01

    Glucocorticoids have been used in the treatment of prostate cancer to slow disease progression, improve pain control and offset side effects of chemo-and hormonal therapy. However, they may also have the potential to drive prostate cancer growth via mutated androgen receptors or glucocorticoid receptors (GRs). In this review we examine historical and contemporary use of glucocorticoids in the treatment of prostate cancer, review potential mechanisms by which they may inhibit or drive prostate cancer growth, and describe potential means of deifning their contribution to the biology of prostate cancer.

  19. Glucocorticoids in the treatment of rheumatoid arthritis.

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    Bijlsma, Johannes W J; Jacobs, Johannes W G; Buttgereit, Frank

    2015-01-01

    Glucocorticoids (GC) are now being used for over 65 years in the treatment of rheumatoid arthritis (RA). There is by now good evidence for their disease modifying effect, especially in early RA. When used in a dosage of 7.5-10 mg most adverse effects can be quite well handled, though monitoring and awareness for infections are important. The CAMERA II study is discussed, in which patients with early RA were treated with a tight control scheme of climbing dosages of methotrexate plus either 10 mg prednisone daily or placebo. After the two years of the trial, 70% of the patients treated with tight control strategy without GC had no erosions versus 82% of the patients treated with additional prednisone. Remission was reached more often and earlier on in the strategy with prednisone compared to the strategy with placebo. It may be suggested that GC have a greater beneficial effect on joint structure than can be explained by their anti-inflammatory effects only.

  20. Changing glucocorticoid action: 11β-hydroxysteroid dehydrogenase type 1 in acute and chronic inflammation.

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    Chapman, Karen E; Coutinho, Agnes E; Zhang, Zhenguang; Kipari, Tiina; Savill, John S; Seckl, Jonathan R

    2013-09-01

    Since the discovery of cortisone in the 1940s and its early success in treatment of rheumatoid arthritis, glucocorticoids have remained the mainstay of anti-inflammatory therapies. However, cortisone itself is intrinsically inert. To be effective, it requires conversion to cortisol, the active glucocorticoid, by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Despite the identification of 11β-HSD in liver in 1953 (which we now know to be 11β-HSD1), its physiological role has been little explored until recently. Over the past decade, however, it has become apparent that 11β-HSD1 plays an important role in shaping endogenous glucocorticoid action. Acute inflammation is more severe with 11β-HSD1-deficiency or inhibition, yet in some inflammatory settings such as obesity or diabetes, 11β-HSD1-deficiency/inhibition is beneficial, reducing inflammation. Current evidence suggests both beneficial and detrimental effects may result from 11β-HSD1 inhibition in chronic inflammatory disease. Here we review recent evidence pertaining to the role of 11β-HSD1 in inflammation. This article is part of a Special Issue entitled 'CSR 2013'.

  1. Gender differences in response of hippocampus to chronic glucocorticoid stress: role of glutamate receptors.

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    Liu, Howard H; Payne, H Ross; Wang, Bin; Brady, Scott T

    2006-04-01

    Glucocorticoids (GC) play critical roles in the pathophysiological reactions to environmental stress. In brain, morphological changes were examined in hippocampal CA3 neurons with 2 weeks of chronic elevation of GC in male and female mice. Molecular correlates and underlying mechanisms paralleling these morphologic changes in hippocampus were investigated. Although the hippocampal neurons in the CA3 area in male mice atrophy with chronically elevated GC, female mice show minimal morphological changes with comparable GC regimens. These sexual morphological differences correlate with differences in the postsynaptic dense protein (PSD95) as well as the spectrum of glutamate receptors induced by GC treatment in male and female mice, including NMDA, AMPA, and KA receptors. These findings suggest that synaptic receptor composition is adapted to the unique physiological requirements of males and females and illuminate underlying mechanisms of GC/stress responses in the brain.

  2. The different roles of glucocorticoids in the hippocampus and hypothalamus in chronic stress-induced HPA axis hyperactivity.

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    Zhu, Li-Juan; Liu, Meng-Ying; Li, Huan; Liu, Xiao; Chen, Chen; Han, Zhou; Wu, Hai-Yin; Jing, Xing; Zhou, Hai-Hui; Suh, Hoonkyo; Zhu, Dong-Ya; Zhou, Qi-Gang

    2014-01-01

    Hypothalamus-pituitary-adrenal (HPA) hyperactivity is observed in many patients suffering from depression and the mechanism underling the dysfunction of HPA axis is not well understood. Chronic stress has a causal relationship with the hyperactivity of HPA axis. Stress induces the over-synthesis of glucocorticoids, which will arrive at all the body containing the brain. It is still complicated whether glucocorticoids account for chronic stress-induced HPA axis hyperactivity and in which part of the brain the glucocorticoids account for chronic stress-induced HPA axis hyperactivity. Here, we demonstrated that glucocorticoids were indispensable and sufficient for chronic stress-induced hyperactivity of HPA axis. Although acute glucocorticoids elevation in the hippocampus and hypothalamus exerted a negative regulation of HPA axis, we found that chronic glucocorticoids elevation in the hippocampus but not in the hypothalamus accounted for chronic stress-induced hyperactivity of HPA axis. Chronic glucocorticoids exposure in the hypothalamus still exerted a negative regulation of HPA axis activity. More importantly, we found mineralocorticoid receptor (MR) - neuronal nitric oxide synthesis enzyme (nNOS) - nitric oxide (NO) pathway mediated the different roles of glucocorticoids in the hippocampus and hypothalamus in regulating HPA axis activity. This study suggests that the glucocorticoids in the hippocampus play an important role in the development of HPA axis hyperactivity and the glucocorticoids in the hypothalamus can't induce hyperactivity of HPA axis, revealing new insights into understanding the mechanism of depression.

  3. The different roles of glucocorticoids in the hippocampus and hypothalamus in chronic stress-induced HPA axis hyperactivity.

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    Li-Juan Zhu

    Full Text Available Hypothalamus-pituitary-adrenal (HPA hyperactivity is observed in many patients suffering from depression and the mechanism underling the dysfunction of HPA axis is not well understood. Chronic stress has a causal relationship with the hyperactivity of HPA axis. Stress induces the over-synthesis of glucocorticoids, which will arrive at all the body containing the brain. It is still complicated whether glucocorticoids account for chronic stress-induced HPA axis hyperactivity and in which part of the brain the glucocorticoids account for chronic stress-induced HPA axis hyperactivity. Here, we demonstrated that glucocorticoids were indispensable and sufficient for chronic stress-induced hyperactivity of HPA axis. Although acute glucocorticoids elevation in the hippocampus and hypothalamus exerted a negative regulation of HPA axis, we found that chronic glucocorticoids elevation in the hippocampus but not in the hypothalamus accounted for chronic stress-induced hyperactivity of HPA axis. Chronic glucocorticoids exposure in the hypothalamus still exerted a negative regulation of HPA axis activity. More importantly, we found mineralocorticoid receptor (MR - neuronal nitric oxide synthesis enzyme (nNOS - nitric oxide (NO pathway mediated the different roles of glucocorticoids in the hippocampus and hypothalamus in regulating HPA axis activity. This study suggests that the glucocorticoids in the hippocampus play an important role in the development of HPA axis hyperactivity and the glucocorticoids in the hypothalamus can't induce hyperactivity of HPA axis, revealing new insights into understanding the mechanism of depression.

  4. Chronic high-dose glucocorticoid therapy triggers the development of chronic organ damage and worsens disease outcome in systemic lupus erythematosus.

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    Tarr, Tünde; Papp, Gábor; Nagy, Nikolett; Cserép, Edina; Zeher, Margit

    2017-02-01

    Long-term survival of patients with systemic lupus erythematosus (SLE) improved worldwide; thus, prevention of cumulative organ damage became a major goal in disease management. The aim of our study was to investigate the chronic organ damages and their influence on disease outcome in SLE. We evaluated clinical conditions, laboratory findings and medications of 357 consecutive SLE patients and assessed their impact on Systemic Lupus Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index (SDI) and disease outcome. We detected one or more SDI scores in 77.87% of patients. Patients with disease duration of more than 10 years and subjects diagnosed at age above 40 had significantly higher SDI values. The most frequent damages were valvulopathies, cognitive dysfunction, angina pectoris and venous thrombosis. Higher cumulative glucocorticoid dose increased SDI, while chloroquin treatment was favourable for patients. Male gender, elevated SDI scores and higher cumulative doses of glucocorticoids increased mortality risk. Our data confirmed that disease duration, age at diagnosis and chronic high-dose glucocorticoid therapy have significant effects on the development of chronic organ damage. Higher SDI score is characterized with worse survival ratios. The most common chronic organ damages affected the cardiovascular or neuropsychiatric system. As long-term survival in SLE improves, it becomes increasingly important to identify the determinants of chronic organ damage. Most of the chronic organ damage occurs in the cardiovascular and the neuropsychiatric systems; thus, regular follow-up, screening and adequate therapy are essential for the best clinical outcome.

  5. Serotonergic Mechanisms Influence the Response to Glucocorticoid Treatment in TMJ Arthritis

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    Lars Fredriksson

    2005-01-01

    Full Text Available The aims of this study were to investigate the influence of serotonin (5-HT on the effects of intra-articular injections of glucocorticoid on pain of the temporomandibular joint (TMJ in patients with inflammatory disorders of the TMJ. The pretreatment synovial fluid 5-HT was negatively, and plasma 5-HT positively, correlated to change in TMJ pain after treatment. The pretreatment plasma 5-HT was positively correlated to change in pressure-pain threshold after treatment. In conclusion, this study shows that local and systemic serotonergic mechanisms partly determine the effect of intra-articular glucocorticoid treatment on TMJ pain in patients with chronic TMJ arthritis of systemic nature, while change in pressure-pain threshold over the TMJ is influenced by systemic serotonergic mechanisms.

  6. Chronic ethanol exposure increases the non-dominant glucocorticoid, corticosterone, in the near-term pregnant guinea pig.

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    Hewitt, Amy J; Dobson, Christine C; Brien, James F; Wynne-Edwards, Katherine E; Reynolds, James N

    2014-08-01

    Maternal-fetal signaling is critical for optimal fetal development and postnatal outcomes. Chronic ethanol exposure alters programming of the fetal hypothalamic-pituitary-adrenal (HPA) axis, resulting in a myriad of neurochemical and behavioral alterations in postnatal life. Based on a recent study which showed that human intra-partum fetal stress increased fetal secretion of corticosterone, the non-dominant glucocorticoid, this investigation tested the hypothesis that an established model of HPA axis programming, chronic maternal ethanol administration to the pregnant guinea pig, would result in preferential elevation of corticosterone, which is also the non-dominant glucocorticoid. Starting on gestational day (GD) 2, guinea pigs received oral administration of ethanol (4 g/kg maternal body weight/day) or isocaloric-sucrose/pair-feeding. Each treatment was administered daily and continued until GD 45, 55, or 65 (approximately 3 days pre-term), when pregnant animals were euthanized and fetuses delivered by Caesarean section. Maternal and fetal plasma samples were collected. After sample preparation (protein precipitation and C-18 solid phase extraction), plasma cortisol and corticosterone concentrations were determined simultaneously by liquid chromatography coupled to tandem mass spectrometry. As predicted, chronic ethanol exposure increased both fetal and maternal plasma corticosterone concentration in late gestation. In contrast, plasma cortisol did not differ across maternal treatments in maternal or fetal samples. The plasma concentration of both maternal glucocorticoids increased with gestational age. Thus, corticosterone, the non-dominant glucocorticoid, but not cortisol, was elevated by chronic ethanol exposure, which may have effects on HPA function in later life.

  7. Chronic Glucocorticoid Hypersecretion in Cushing's Syndrome Exacerbates Cognitive Aging

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    Michaud, Kathy; Forget, Helene; Cohen, Henri

    2009-01-01

    Cumulative exposure to glucocorticoid hormones (GC) over the lifespan has been associated with cognitive impairment and may contribute to physical and cognitive degeneration in aging. The objective of the present study was to examine whether the pattern of cognitive deficits in patients with Cushing's syndrome (CS), a disorder characterized by…

  8. Effects of chronic mild stress on behavioral and neurobiological parameters - Role of glucocorticoid.

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

    2016-02-01

    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.

  9. [Prevention and treatment of glucocorticoid-induced osteoporosis in International and Italian scenarios].

    Science.gov (United States)

    Di Munno, O; Delle Sedie, A

    2011-01-01

    Osteoporosis (OP) and increased risk of fracture (Fx) associated with chronic glucocorticoid treatment pushed panels of experts and scientific societies to produce recommendations for both prevention and treatment of glucocorticoid-induced OP (GIO). Recently the American College of Rheumatology developed and/or endorsed their updated guidelines and recommendations for the prevention and treatment of GIO. In these recommendations the use of FRAX tool, for the 10-year probability of a major osteoporotic Fx, was integrated with other clinical risk factors to define low-, medium-, and high-risk patients. Updated approaches are delineated for post-menopausal women and men >50 years, pre-menopausal women not of childbearing potential, men 50 years, receiving >5 mg/day prednisone equivalent for >3 months; more recently teriparatide has also been included, only for those patients presenting ≥1 prevalent fragility Fx and receiving >5 mg/day prednisone equivalent for >12 months. Also zoledronic acid has been approved by Italian Agency of the Drug (AIFA, 30/08/10) for "... post-menopausal women and men chronically treated with GC ad high risk of Fx", but the drug is dispensed exclusively at the hospital.

  10. Prevention and treatment of glucocorticoid-induced osteoporosis in International and Italian scenarios

    Directory of Open Access Journals (Sweden)

    A. Delle Sedie

    2011-09-01

    Full Text Available Osteoporosis (OP and increased risk of fracture (Fx associated with chronic glucocorticoid treatment pushed panels of experts and scientific societies to produce recommendations for both prevention and treatment of glucocorticoid-induced OP (GIO. Recently the American College of Rheumatology developed and/or endorsed their updated guidelines and recommendations for the prevention and treatment of GIO. In these recommendations the use of FRAX tool, for the 10-year probability of a major osteoporotic Fx, was integrated with other clinical risk factors to define low-, medium-, and high-risk patients. Updated approaches are delineated for post-menopausal women and men >50 years, pre-menopausal women not of childbearing potential, men 50 years, receiving >5 mg/day prednisone equivalent for >3 months; more recently teriparatide has also been included, only for those patients presenting ≥1 prevalent fragility Fx and receiving >5 mg/day prednisone equivalent for >12 months. Also zoledronic acid has been approved by Italian Agency of the Drug (AIFA, 30/08/10 for “… post-menopausal women and men chronically treated with GC ad high risk of Fx”, but the drug is dispensed exclusively at the hospital.

  11. Perinatal glucocorticoid treatment and perspectives for antioxidat therapy

    NARCIS (Netherlands)

    Tijsseling, D.

    2014-01-01

    Pre- and postnatal glucocorticoids are a life-saving therapy for prematurely born infants. However, glucocorticoids also trigger unwanted side effects. In part I we investigated the effects of antenatal glucocorticoids on hippocampal development. First in a mice model using a clinically relevant dos

  12. Antenatal glucocorticoid treatment affects hippocampal development in mice.

    Directory of Open Access Journals (Sweden)

    Cornelle W Noorlander

    Full Text Available Synthetic glucocorticoids are administered to pregnant women at risk for preterm delivery, to enhance fetal lung maturation. The benefit of this treatment is well established, however caution is necessary because of possible unwanted side effects on development of different organ systems, including the brain. Actions of glucocorticoids are mediated by corticosteroid receptors, which are highly expressed in the hippocampus, a brain structure involved in cognitive functions. Therefore, we analyzed the effects of a single antenatal dexamethasone treatment on the development of the mouse hippocampus. A clinically relevant dose of dexamethasone (0.4 mg/kg was administered to pregnant mice at embryonic day 15.5 and the hippocampus was analyzed from embryonic day 16 until adulthood. We investigated the effects of dexamethasone treatment on anatomical changes, apoptosis and proliferation in the hippocampus, hippocampal volume and on total body weight. Our results show that dexamethasone treatment reduced body weight and hippocampal volume transiently during development, but these effects were no longer detected at adulthood. Dexamethasone treatment increased the number of apoptotic cells in the hippocampus until birth, but postnatally no effects of dexamethasone treatment on apoptosis were found. During the phase with increased apoptosis, dexamethasone treatment reduced the number of proliferating cells in the subgranular zone of the dentate gyrus. The number of proliferative cells was increased at postnatal day 5 and 10, but was decreased again at the adult stage. This latter long-term and negative effect of antenatal dexamethasone treatment on the number of proliferative cells in the hippocampus may have important implications for hippocampal network function.

  13. Antenatal glucocorticoid treatment affects hippocampal development in mice.

    Science.gov (United States)

    Noorlander, Cornelle W; Tijsseling, Deodata; Hessel, Ellen V S; de Vries, Willem B; Derks, Jan B; Visser, Gerard H A; de Graan, Pierre N E

    2014-01-01

    Synthetic glucocorticoids are administered to pregnant women at risk for preterm delivery, to enhance fetal lung maturation. The benefit of this treatment is well established, however caution is necessary because of possible unwanted side effects on development of different organ systems, including the brain. Actions of glucocorticoids are mediated by corticosteroid receptors, which are highly expressed in the hippocampus, a brain structure involved in cognitive functions. Therefore, we analyzed the effects of a single antenatal dexamethasone treatment on the development of the mouse hippocampus. A clinically relevant dose of dexamethasone (0.4 mg/kg) was administered to pregnant mice at embryonic day 15.5 and the hippocampus was analyzed from embryonic day 16 until adulthood. We investigated the effects of dexamethasone treatment on anatomical changes, apoptosis and proliferation in the hippocampus, hippocampal volume and on total body weight. Our results show that dexamethasone treatment reduced body weight and hippocampal volume transiently during development, but these effects were no longer detected at adulthood. Dexamethasone treatment increased the number of apoptotic cells in the hippocampus until birth, but postnatally no effects of dexamethasone treatment on apoptosis were found. During the phase with increased apoptosis, dexamethasone treatment reduced the number of proliferating cells in the subgranular zone of the dentate gyrus. The number of proliferative cells was increased at postnatal day 5 and 10, but was decreased again at the adult stage. This latter long-term and negative effect of antenatal dexamethasone treatment on the number of proliferative cells in the hippocampus may have important implications for hippocampal network function.

  14. Glucocorticoids: structure, signaling and molecular mechanisms in the treatment of diabetic retinopathy and diabetic macular edema.

    Science.gov (United States)

    Zhang, X; Wang, N; Schachat, A P; Bao, S; Gillies, M C

    2014-03-01

    Diabetic retinopathy (DR) is one of the leading causes of blindness in the working population worldwide. Vascular leakage, angiogenesis and neuronal degeneration are key features of DR. Current effective interventions for DR include treatment of systemic risk factors such as elevated blood glucose, blood pressure and dyslipidemia. Ocular treatments include vascular endothelial growth factor A (VEGF-A) inhibitors, laser photocoagulation and surgery. While anti-VEGF therapy has become as first-line treatment for diabetic macular edema (DME) that causes reduced vision, intravitreal glucocorticoids also have been shown to be efficacious in this situation. It has been reported that all the major pathological processes of DR are susceptible to glucocorticoid treatment. The effects of glucocorticoids on vascular leakage and angiogenesis may be mediated through their well established anti-inflammatory role. Alternatively, glucocorticoids may affect other mechanisms known to be activated in DR. Potential mechanisms for the anti-inflammatory effects of glucocorticoids include blockage of cytokine production and inhibition of leukocyte adhesion induced by VEGF-A. Glucocorticoids decrease the expression of VEGF-A directly, and increase the production, or decrease phosphorylation, of tight junction-associated proteins. Glucocorticoids have also been shown to be neuroprotective, in contrast to VEGF-A inhibitors which animal studies suggest may be neurotoxic. This review outlines the biological properties of synthetic glucocorticoids, with particular emphasis on the potential beneficial effect of combining glucocorticoids with anti-VEGF treatment for DME and DR.

  15. Time trends for alendronate prescription practices in women with chronic obstructive pulmonary disease and women exposed to systemic glucocorticoids

    DEFF Research Database (Denmark)

    Brask-Lindemann, D; Eiken, P; Eskildsen, P;

    2013-01-01

    UNLABELLED: Chronic obstructive pulmonary disease (COPD) and systemic glucocorticoid exposure are well-known risk factors of osteoporosis. We evaluated alendronate prescription practices related to COPD and exposure to systemic corticosteroids from 1996 to 2008 and showed an increasing targeting ...

  16. Selective Activator of the Glucocorticoid Receptor Compound A Dissociates Therapeutic and Atrophogenic Effects of Glucocorticoid Receptor Signaling in Skin

    OpenAIRE

    Klopot, Anna; Baida, Gleb; Bhalla, Pankaj; Haegeman, Guy; Budunova, Irina

    2015-01-01

    Background: Glucocorticoids are effective anti-inflammatory drugs widely used in dermatology and for the treatment of blood cancer patients. Unfortunately, chronic treatment with glucocorticoids results in serious metabolic and atrophogenic adverse effects including skin atrophy. Glucocorticoids act via the glucocorticoid receptor (GR), a transcription factor that causes either gene transactivation (TA) or transrepression (TR). Compound A (CpdA), a novel non-steroidal GR ligand, does not prom...

  17. New possibilities for the treatment of glucocorticoid-induced osteoporosis

    Directory of Open Access Journals (Sweden)

    I.A. Baranova

    2014-01-01

    Full Text Available Glucocorticoid-induced osteoporosis (GIO is the most common cause of secondary osteoporosis (OP and a main cause of drug-induced OP. Fractures of the skeleton are registered in 30–50% of patients who have taken oral glucocorticoids (GCs for a long time, during which the frac- tures develop with the use of any daily GC dose and with higher bone mineral density (BMD than in postmenopausal OP. In patients who have taken oral GCs long or in high daily doses, decrease of BMD and low bone tissue quality leading to fractures are largely associated with the reduction of bone formation. This gives proof to the administration of antiosteoporotic agents that enhance the formation of bone during its remodeling. Teriparatide, a recombinant human parathyroid hormone, enhances osteoblast function, decreases the apoptosis of osteoblasts and osteocytes, increases the differentiation of osteoblast precursors, and can prevent the negative effect of exogenous GCs on bone. According to clinical trials results, teriparatide treatment increases BMD and reduces the risk of vertebral fractures in patients who have taken oral GCs long. In accordance of the clinical recommendations for the diagnosis, prevention, and treatment of GIO, which have been developed by the Russian Osteoporosis Association jointly with the Association of Rheumatologists of Russia and the Russian Respiratory Society, teriparatide is the drug of first choice for the treatment of GIO in men and women at high risk for fractures (with the history of fragility fractures or having high FRAX 10-year absolute fracture risk. Teriparatide may be prescribed in case of previous antiosteoporotic treatment failure (new fractures occurring during treatment and/or continuing to decrease BMD, as well as when other drugs to treat OP are intolerable or when there are contraindications to their use. 

  18. Chronic glucocorticoids exposure enhances neurodegeneration in the frontal cortex and hippocampus via NLRP-1 inflammasome activation in male mice.

    Science.gov (United States)

    Hu, Wen; Zhang, Yaodong; Wu, Wenning; Yin, Yanyan; Huang, Dake; Wang, Yuchan; Li, Weiping; Li, Weizu

    2016-02-01

    Neuroinflammation plays an important role in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD) and depression. Chronic glucocorticoids (GCs) exposure has deleterious effects on the structure and function of neurons and is associated with development and progression of AD. However, little is known about the proinflammatory effects of chronic GCs exposure on neurodegeneration in brain. Therefore, the aim of this study was to evaluate the effects of chronic dexamethasone (DEX) treatment (5mg/kg, s.c. for 7, 14, 21 and 28 days) on behavior, neurodegeneration and neuroinflammatory parameters of nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 1 (NLRP-1) inflammasome in male mice. The results showed that DEX treatment for 21 and 28 days significantly reduced the spontaneous motor activity and exploratory behavior of the mice. In addition, these mice showed significant neurodegeneration and a decrease of microtubule-associated protein 2 (MAP2) in the frontal cortex and hippocampus CA3. DEX treatment for 7, 14, 21 and 28 days significantly decreased the mRNA and protein expression of glucocorticoid receptor (GR). Moreover, DEX treatment for 21 and 28 days significantly increased the proteins expression of NLRP-1, Caspase-1, Caspase-5, apoptosis associated speck-like protein (ASC), nuclear factor-κB (NF-κB), p-NF-κB, interleukin-1β (IL-1β), IL-18 and IL-6 in the frontal cortex and hippocampus brain tissue. DEX treatment for 28 days also significantly increased the mRNA expression levels of NLRP-1, Caspase-1, ASC and IL-1β. These results suggest that chronic GCs exposure may increase brain inflammation via NLRP-1 inflammasome activation and induce neurodegeneration.

  19. Chronic stress accelerates ligature-induced periodontitis by suppressing glucocorticoid receptor-α signaling.

    Science.gov (United States)

    Lu, Huaixiu; Xu, Minguang; Wang, Feng; Liu, Shisen; Gu, Jing; Lin, Songshan; Zhao, Lisheng

    2016-03-25

    Periodontitis is a common chronic inflammatory disease. Recent studies have shown that chronic stress (CS) might modulate periodontal disease, but there are few models of CS-induced periodontitis, and the underlying mechanisms are unclear. The present study established a rat model of periodontitis associated with CS induced by nylon thread ligatures. The severity of periodontitis was evaluated in this model by radiographic and pathological examination. The inflammatory reaction indicated by the elevated serum levels of interleukin (IL)-1β, IL-6 and IL-8 was assessed by enzyme-linked immunosorbent assay. Toll-like receptor-4 (TLR4) and glucocorticoid receptor-α (GR-α) expressions were detected by reverse transcriptase-PCR and western blotting. Open-field tests and serum corticosterone were used to evaluate CS. The results showed that CS induced behavioral changes and increased corticosterone levels of the animals with periodontitis. CS stimulation markedly increased alveolar bone loss, periodontal pocket depth and the number of plaques. It also enhanced the inflammatory reaction. These results suggest that CS accelerated the ligature-induced pathological changes associated with periodontitis. Further analysis of the mechanisms involved showed that GR-α expression was significantly downregulated in periodontal tissues of the animals undergoing CS. Blocking GR-α signaling in lipopolysaccharide and corticosteroid-treated human periodontal ligament fibroblast cells in vitro significantly upregulated the expression of p-Akt (protein kinase B) and TLR4, promoted nuclear factor-κB activity and increased levels of IL-1β, IL-6 and IL-8. This research suggests that CS might accelerate the pathological progression of periodontitis by a GR-α signaling-mediated inflammatory response and that this may be a potential therapeutic target for the treatment of periodontal disease, particularly in patients with CS.

  20. Tumor necrosis factor suppresses NR5A2 activity and intestinal glucocorticoid synthesis to sustain chronic colitis.

    Science.gov (United States)

    Huang, Sheng-Chieh; Lee, Cheng-tse; Chung, Bon-chu

    2014-02-25

    Intestinal crypt epithelial cells synthesize glucocorticoids, steroid hormones that protect against inflammatory bowel disease. To investigate how intestinal glucocorticoids are regulated during chronic inflammation, we induced chronic colitis in mice by exposing them to the chemical dextran sulfate sodium (DSS). We found that intestinal glucocorticoid secretion and expression of the genes Cyp11a1 and Cyp11b1 (which encode enzymes that synthesize glucocorticoids) were initially stimulated, but declined during the chronic phase, whereas tumor necrosis factor (TNF) and inflammatory cytokines secreted by T helper type 1 (TH1) and TH17 cells continuously increased in abundance in the inflamed colon. This suggested that inadequate intestinal glucocorticoid synthesis is a feature of chronic intestinal inflammation. We screened for cytokines that regulated intestinal glucocorticoid synthesis and found that TNF suppressed corticosterone secretion and Cyp11a1 and Cyp11b1 expression in an intestinal crypt epithelial cell line. TNF suppressed steroidogenesis by activating the transcription factors c-Jun and nuclear factor κB (NF-κB), which both interacted with the transcription factor NR5A2 and repressed Cyp11a1 reporter activity. This repression was relieved by expression of a dominant-negative form of c-Jun amino-terminal kinase 1 (JNK1), inhibitor of NF-κB, or by a JNK inhibitor. Furthermore, the dominant-negative TNF inhibitor XPro1595 inhibited c-Jun and NF-κB activation in mice, restored intestinal Cyp11a1 and Cyp11b1 expression, reduced colonic cell death, and rescued chronic colitis caused by DSS. Thus, during chronic colitis, TNF suppresses intestinal steroidogenic gene expression by inhibiting the activity of NR5A2, thus decreasing glucocorticoid synthesis and sustaining chronic inflammation.

  1. The acceleration of amygdala kindling epileptogenesis by chronic low-dose corticosterone involves both mineralocorticoid and glucocorticoid receptors.

    Science.gov (United States)

    Kumar, Gaurav; Couper, Abbie; O'Brien, Terence J; Salzberg, Michael R; Jones, Nigel C; Rees, Sandra M; Morris, Margaret J

    2007-08-01

    We have previously demonstrated that low-dose corticosterone (CS) administration, used as a model of the effect of chronic stress, accelerates epileptogenesis in the electrical amygdala kindling rat model of temporal lobe epilepsy (TLE). This current study examined the relative contributions to this effect of mineralocorticoid (MR) and glucocorticoid (GR) subtypes of glucocorticoid receptors. Female non-epileptic wistar rats 10-13 weeks of age were implanted with a bipolar electrode into the left amygdala. Five treatment groups were subjected to rapid amygdala kindling: water-control (n=9), CS treated (6 mg/100 ml added to drinking water; n=9), CS+spironolactone (MR antagonist, 50 mg/kg sc; n=9), CS+mifepristone (GR antagonist, 25 mg/kg sc; n=9), and CS+both antagonists (n=7). Rats were injected with vehicle or the relevant antagonist twice daily for the entire kindling period. Experimental groups differed significantly in the number of stimulations required to reach the 'fully kindled state' (Racine, 1972) ANOVA, F(4,38)=2.73, p=0.04). Amygdala kindling was accelerated in the CS-treated group compared with water controls (mean stimulations for full kindling: 45.2 vs. 86.5, pkindling rates in these groups not significantly different from water-treated subjects (p=0.26 and 0.29, respectively). The kindling rates in the MR and GR antagonist treatment groups did not significantly differ from each other (p=0.93), nor from the combined treatment group (mean stimulations: 62.8, p=0.59 and 0.54, respectively). This study demonstrates that activation of both high-affinity (MR) and low-affinity (GR) glucocorticoid receptors are involved in mediating CS-induced acceleration of amygdala kindling epileptogenesis.

  2. Mode of Glucocorticoid Actions in Airway Disease

    Directory of Open Access Journals (Sweden)

    Kazuhiro Ito

    2006-01-01

    Full Text Available Synthetic glucocorticoids are the most potent anti-inflammatory agents used to treat chronic inflammatory disease, such as asthma. However, a small number (<5% of asthmatic patients and almost all patients with chronic obstructive pulmonary disease (COPD do not respond well, or at all, to glucocorticoid therapy. If the molecular mechanism of glucocorticoid insensitivity is uncovered, it may in turn provide insight into the key mechanism of glucocorticoid action and allow a rational way to implement treatment regimens that restore glucocorticoid sensitivity. Glucocorticoids exert their effects by binding to a cytoplasmic glucocorticoid receptor (GR, which is subjected to post-translational modifications. Receptor phosphorylation, acetylation, nitrosylation, ubiquitinylation, and other modifications influence hormone binding, nuclear translocation, and protein half-life. Analysis of GR interactions to other molecules, such as coactivators or corepressors, may explain the genetic specificity of GR action. Priming with inflammatory cytokine or oxidative/nitrative stress is a mechanism for the glucocorticoid resistance observed in chronic inflammatory airway disease via reduction of corepressors or GR modification. Therapies targeting these aspects of the GR activation pathway may reverse glucocorticoid resistance in patients with glucocorticoid-insensitive airway disease and some patients with other inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease.

  3. Chronic Myeloproliferative Neoplasms Treatment

    Science.gov (United States)

    ... way to treat some chronic myeloproliferative neoplasms. Platelet apheresis Platelet apheresis is a treatment that uses a special machine ... using interferon alfa or pegylated interferon alpha . Platelet apheresis . A clinical trial of a new treatment. Check ...

  4. METHOTREXATE IN THE TREATMENT OF GLUCOCORTICOID-DEPENDENT ASTHMA

    Institute of Scientific and Technical Information of China (English)

    王国杨; 朱利文; 姚婉贞; 赵呜武

    2001-01-01

    To study how low-dose of methotrexate affects steroid use, asthma symptom scores and pulmonary function in glucocorticoid-dependent asthmatic patients.Methods 13 patients with severe, steroid-dependent asthma were enrolled in the prospective study, who received weekly oral methotrexate 20 mg for 12 months. Of these 13 patients, 12 finished 12 monthcourseResults The mean prednisone dose reduced from 20.63mg/d to 7.71mg/d (P<0.001) in the 12 patients treated with long-term methotrexate: Eight patients discontinued the regular use of prednisone, 10 patients reduced predaisone dosage by more than 50%. Measurement of forced vital capacity(FVC) and forced expiratory volume in one second (FEV1) showed that there was no deterioration due to methotrexate treatment and steroid reduction. Mean daily symptom scores for cough, wheezing, shortness of breath, and chest tightness remained unchanged.Conclusion Our study provides evidence supporting the long-term efficacy and safety of methotrexate in patients with severe bronchial asthma.

  5. Treatment of Chronic Cough.

    Science.gov (United States)

    Soni, Resha S; Ebersole, Barbara; Jamal, Nausheen

    2017-01-01

    Objective Chronic cough remains a challenging condition, especially in cases where it persists despite comprehensive medical management. For these particular patients, there appears to be an emerging role for behavior modification therapy. We report a series of patients with refractory chronic cough to assess if there is any benefit of adding behavioral therapy to their treatment regimen. Study Design A case series with planned chart review of patients treated for chronic cough. Setting The review was performed with an outpatient electronic health record system at a tertiary care center. Subjects and Methods The charts of all patients treated for chronic cough by a single laryngologist over a 30-month period were analyzed. Patients' response to treatment and rate of cough improvement were assessed for those with refractory chronic cough who underwent behavior modification therapy. Results Thirty-eight patients with chronic cough were initially treated empirically for the most common causes of cough, of which 32% experienced improvement. Nineteen patients who did not significantly improve with medical management underwent behavior modification therapy with a speech-language pathologist. Of these patients, 84% experienced resolution or marked improvement of their symptoms. Conclusion Behavioral therapy may be underutilized in practice and could lead to improvement of otherwise recalcitrant cough.

  6. [Treatment of patients with severe glucocorticoid-refractory ulcerative colitis: cyclosporine or infliximab?

    NARCIS (Netherlands)

    Lowenberg, M.; Boer, N.K. de; Dewint, P.; Hoentjen, F.

    2013-01-01

    - Cyclosporine and infliximab are so-called 'rescue-therapies' as last resort for the treatment of patients with severe glucocorticoid-refractory ulcerative colitis.- A recent study found that cyclosporine and infliximab are similar in terms of efficacy in the treatment of patients with severe ulcer

  7. 抗生素联合糖皮质激素治疗老年慢性阻塞性肺气肿疗效分析%Curative effect analysis of antibiotics combined with glucocorticoids in the treatment of elderly patients with chronic obstructive pulmonary emphysema

    Institute of Scientific and Technical Information of China (English)

    吴珏

    2015-01-01

    Objective:To investigate the function and clinical effect of antibiotics combined with glucocorticoid in the treatment of elderly chronic obstructive pulmonary.Methods: 84 elderly patients with chronic obstructive pulmonary emphysema were selected from 2011 to 2013.They were randomly divided into the experimental group and the control group with 42 cases in each.The control group were treated with antibiotics,antispasmodic,phlegm,asthma,persistent low flow oxygen to support treatment,routine bed rest symptomatic.The experimental group on the basis of the control group combined with glucocorticoid treatment.We compared the curative effect and adverse reaction of the two groups.Results:The total effectiveness of the experimental group was 88.09% .The total effectiveness of the comparison group was 69.04% ,with significant difference(P<0.05).The incidence of adverse reaction:in the control group,2 cases of chest pain,2 cases of nausea;in the experience group,1 cases of vomiting,diarrhea in 1 cases,the differences between the two groups with statistically significant(P<0.05).Conclusion:The effect of antibiotics combined with corticosteroid in the treatment of elderly patients with chronic obstructive pulmonary emphysema is significant, convenient,less adverse reactions,so it is worth to be popularized in clinic.%目的:探讨抗生素联合糖皮质激素治疗老年慢性阻塞性肺气肿的作用及临床效果。方法:2011-2013年收治慢性阻塞性肺气肿老年患者84例,随机分为试验组与对照组,各42例。对照组给予抗生素、平喘、解痉、化痰、持续性低流量给氧、常规卧床休息等对症支持性治疗。试验组在对照组的基础之上联合糖皮质激素进行治疗,比较两组患者的治疗效果和不良反应等情况。结果:试验组总有效率88.09%,对照组总有效率69.04%,差异具有统计学意义(P<0.05)。不良反应发生情况:对照组胸痛2例,恶心2

  8. Chronic Psychosocial Stress and Negative Feedback Inhibition: Enhanced Hippocampal Glucocorticoid Signaling despite Lower Cytoplasmic GR Expression.

    Science.gov (United States)

    Füchsl, Andrea M; Reber, Stefan O

    2016-01-01

    Chronic subordinate colony housing (CSC), a pre-clinically validated mouse model for chronic psychosocial stress, results in increased basal and acute stress-induced plasma adrenocorticotropic hormone (ACTH) levels. We assessed CSC effects on hippocampal glucocorticoid (GC) receptor (GR), mineralocorticoid receptor (MR), and FK506 binding protein (FKBP51) expression, acute heterotypic stressor-induced GR translocation, as well as GC effects on gene expression and cell viability in isolated hippocampal cells. CSC mice showed decreased GR mRNA and cytoplasmic protein levels compared with single-housed control (SHC) mice. Basal and acute stress-induced nuclear GR protein expression were comparable between CSC and SHC mice, as were MR and FKBP51 mRNA and/or cytoplasmic protein levels. In vitro the effect of corticosterone (CORT) on hippocampal cell viability and gene transcription was more pronounced in CSC versus SHC mice. In summary, CSC mice show an, if at all, increased hippocampal GC signaling capacity despite lower cytoplasmic GR protein expression, making negative feedback deficits in the hippocampus unlikely to contribute to the increased ACTH drive following CSC.

  9. Glucocorticoid-induced reduction of traumatic memories: implications for the treatment of PTSD.

    Science.gov (United States)

    de Quervain, Dominique J-F

    2008-01-01

    Post-traumatic stress disorder (PTSD) is an anxiety disorder that can occur after a traumatic event such as military combat, terrorist attacks, or accidents. The disorder is characterized by traumatic memories that manifest as reexperiencing symptoms including daytime recollections, traumatic nightmares, or flashbacks in which components of the event are relived. These symptoms result from excessive retrieval of traumatic memories that often retain their vividness and power to evoke distress for decades or even a lifetime. We have reported previously that elevated glucocorticoid levels inhibit memory retrieval in animals and healthy human subjects. We therefore hypothesized that the administration of cortisol might also inhibit the retrieval of traumatic memories in patients with PTSD. In a recent pilot study we found the first evidence to support this hypothesis. During a 3-month observation period, low-dose cortisol (10 mg per day) was administered orally for 1 month to three patients with chronic PTSD using a double-blind, placebo-controlled, crossover design. In each patient investigated, there was a significant treatment effect with cortisol-related reductions in one of the daily-rated symptoms of traumatic memories without causing adverse side effects. Furthermore, we have reported 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. Future studies with more patients and longer treatment periods are required to evaluate the efficacy of cortisol treatment for PTSD.

  10. Glucocorticoids for the treatment of post-traumatic stress disorder and phobias: a novel therapeutic approach.

    Science.gov (United States)

    de Quervain, Dominique J-F; Margraf, Jürgen

    2008-04-07

    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

  11. Superiority of alfacalcidol over plain vitamin D in the treatment of glucocorticoid-induced osteoporosis.

    Science.gov (United States)

    Ringe, J D; Dorst, A; Faber, H; Schacht, E; Rahlfs, V W

    2004-03-01

    Supplementation therapy with plain vitamin D plus calcium is in general regarded as effective prevention or first-step treatment of glucocorticoid-induced osteoporosis (GIOP). The aim of our study was to compare the therapeutic efficacy of the D-hormone analog alfacalcidol with plain vitamin D in patients with established GIOP with or without vertebral fractures. Patients on long-term glucocorticoid (GC) therapy were included as matched pairs to receive randomly either 1 microg alfacalcidol plus 500 mg calcium per day (group A, n=103) or 1000 IU vitamin D3 plus 500 mg calcium (group B, n=101). The two groups were well matched in terms of mean age, sex ratio, mean height and weight, daily dosage, and duration of GC therapy, and the percentages of the three underlying diseases included chronic obstructive pulmonary disease, rheumatoid arthritis, and polymyalgia rheumatica. The baseline mean bone mineral density (BMD) values at the lumbar spine for the two groups were -3.26 (alfacalcidol) and -3.25 (vitamin D(3)) and, at the femoral neck, -2.81 and -2.84, respectively (T scores). Rates of prevalent vertebral and nonvertebral fractures did not differ between groups. During the 3-year study, we observed a median percentage increase of BMD at the lumbar spine of 2.4% in group A and a loss of 0.8% in group B ( Pvitamin D group (risk reduction 0.61, 95% CI 0.24-0.81, P=0.005). The 3-year rates of patients with at least one new nonvertebral fracture were 15% in the alfacalcidol group and 25% in the vitamin D group (risk reduction 0.41, 95% CI 0.06-0.68, P=0.081). The 3-year rates of patients with at least one new fracture of any kind were 19.4% among those treated with alfacalcidol and 40.65% with vitamin D (risk reduction 0.52, 95% CI 0.25-0.71, P=0.001). In accordance with the observed fracture rates, the alfacalcidol group showed a substantially larger decrease in back pain than the plain vitamin D group ( Pvitamin D group had moderate hypercalcemia. We conclude that

  12. Glucocorticoids regulation of FosB/ΔFosB expression induced by chronic opiate exposure in the brain stress system.

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    Daniel García-Pérez

    Full Text Available Chronic use of drugs of abuse profoundly alters stress-responsive system. Repeated exposure to morphine leads to accumulation of the transcription factor ΔFosB, particularly in brain areas associated with reward and stress. The persistent effects of ΔFosB on target genes may play an important role in the plasticity induced by drugs of abuse. Recent evidence suggests that stress-related hormones (e.g., glucocorticoids, GC may induce adaptations in the brain stress system that is likely to involve alteration in gene expression and transcription factors. This study examined the role of GC in regulation of FosB/ΔFosB in both hypothalamic and extrahypothalamic brain stress systems during morphine dependence. For that, expression of FosB/ΔFosB was measured in control (sham-operated and adrenalectomized (ADX rats that were made opiate dependent after ten days of morphine treatment. In sham-operated rats, FosB/ΔFosB was induced after chronic morphine administration in all the brain stress areas investigated: nucleus accumbens(shell (NAc, bed nucleus of the stria terminalis (BNST, central amygdala (CeA, hypothalamic paraventricular nucleus (PVN and nucleus of the solitary tract noradrenergic cell group (NTS-A(2. Adrenalectomy attenuated the increased production of FosB/ΔFosB observed after chronic morphine exposure in NAc, CeA, and NTS. Furthermore, ADX decreased expression of FosB/ΔFosB within CRH-positive neurons of the BNST, PVN and CeA. Similar results were obtained in NTS-A(2 TH-positive neurons and NAc pro-dynorphin-positive neurons. These data suggest that neuroadaptation (estimated as accumulation of FosB/ΔFosB to opiates in brain areas associated with stress is modulated by GC, supporting the evidence of a link between brain stress hormones and addiction.

  13. Effect of low-dose glucocorticoid on corticosteroid insufficient patients with acute exacerbation of chronic obstructive pulmonary disease

    Institute of Scientific and Technical Information of China (English)

    袁光雄

    2014-01-01

    Objective To investigate the effect of low-dose glucocorticoid on prognosis of critical illness-related corticosteroid insufficient(CIRCI)patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Methods A total of 385 eligible patients met the criteria of AECOPD were admitted from January 2010 to December 2012.The AECOPD patients co-morbid with CIRCI screened by an adrenal corticotrophic hormone test within 12 hours after admission were randomly divided

  14. Role of metabolically active hormones in the insulin resistance associated with short-term glucocorticoid treatment

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    Lip Gregory YH

    2006-09-01

    Full Text Available Abstract Background The mechanisms by which glucocorticoid therapy promotes obesity and insulin resistance are incompletely characterized. Modulations of the metabolically active hormones, tumour necrosis factor alpha (TNF alpha, ghrelin, leptin and adiponectin are all implicated in the development of these cardiovascular risk factors. Little is known about the effects of short-term glucocorticoid treatment on levels of these hormones. Research methods and procedures Using a blinded, placebo-controlled approach, we randomised 25 healthy men (mean (SD age: 24.2 (5.4 years to 5 days of treatment with either placebo or oral dexamethasone 3 mg twice daily. Fasting plasma TNFα, ghrelin, leptin and adiponectin were measured before and after treatment. Results Mean changes in all hormones were no different between treatment arms, despite dexamethasone-related increases in body weight, blood pressure, HDL cholesterol and insulin. Changes in calculated indices of insulin sensitivity (HOMA-S, insulin sensitivity index were strongly related to dexamethasone treatment (p Discussion Our data do not support a role for TNF alpha, ghrelin, leptin or adiponectin in the insulin resistance associated with short-term glucocorticoid treatment.

  15. Chronic exposure to exogenous glucocorticoids primes microglia to pro-inflammatory stimuli and induces NLRP3 mRNA in the hippocampus.

    Science.gov (United States)

    Frank, Matthew G; Hershman, Sarah A; Weber, Michael D; Watkins, Linda R; Maier, Steven F

    2014-02-01

    Chronic stress as well as chronic treatment with glucocorticoids (GCs) primes the neuroinflammatory response to a subsequent pro-inflammatory challenge. However, it remains unclear whether chronic GCs sensitize the response of key CNS immune substrates (i.e. microglia) to pro-inflammatory stimuli. In the present set of studies, male Sprague-Dawley rats underwent sham surgery or were adrenalectomized and then treated with varying concentrations of corticosterone (CORT; 0, 25, 50, and 75 μg/ml) administered in their drinking water. After 10 days of CORT exposure, whole hippocampus was collected and expression of glial activation markers measured or hippocampal microglia were isolated and challenged with LPS to probe for CORT-induced sensitization of pro-inflammatory responses. Chronic CORT exposure increased the gene expression of NLRP3, Iba-1, MHCII, and NF-κBIα in a concentration dependent manner. Chronic CORT (75 μg/ml) exposure potentiated the microglial proinflammatory response (TNFα, IL-1β, IL-6 and NLRP3) to LPS compared to the microglial response of sham surgery animals treated with vehicle. The present set of results demonstrate that chronic exposure to GCs primes microglia to pro-inflammatory stimuli and add to a growing body of evidence suggesting that a permissive function of GCs is that of an endogenous danger signal or alarmin.

  16. Treatment Strategies for Chronic Cases

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    Susan M Lord

    2003-01-01

    Full Text Available The treatment of chronic somatic pain, including pain referred to the head, neck, shoulder girdle and upper limb from somatic structures, is addressed. Levels of evidence for the various treatments that have been prescribed for chronic whiplash associated disorders are considered. The challenge to find a treatment strategy for chronic pain after whiplash that completely relieves the condition and prevents its sequelae is reviewed.

  17. Treatment Of Pemphigus Vulgaris With Brief, High-Dose Intravenous Glucocorticoids

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    Farshchian Mahmood

    2004-01-01

    Full Text Available Background: Glucocorticoid therapy remains the mainstay of treatment in pemphigus vulgaris although controversy exists about the optimal regiman. This study was conducted to compare the efficacy of routine oral prednisolone with high dose intravenous glucocorticoids in treatment of pemphigus vulgaris. Methods: A total of 55 patients with pemphigus vulgaris was enrolled in the study. The diagnosis of pemphigus vulgaris was confirmed histologically. The patients were divided into two groups: Group A (26 Patients was treated with high-dose intravenous glucocorticoids and group B or control group (29 patients was treated with routine oral prednisolone. Both groups were followed for at least 20 months after initiation of treatment. Results: The results showed complete clinical cure (without relapse in 20 months follow up in 81% of cases in group A and in 69% of cases in group B (p<0.05. The mean + SD prednisolone daily dose during the 20 months follow up after initiation of treatment was 12+0.38 for A and 15.3 + 1.33 for control group (p<0.05.

  18. Effect of lipopolysaccharide on glucocorticoid receptor function in control nasal mucosa fibroblasts and in fibroblasts from patients with chronic rhinosinusitis with nasal polyps and asthma.

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    Laura Fernández-Bertolín

    Full Text Available Chronic rhinosinusitis with nasal polyps (CRSwNP is a chronic inflammatory disease of the upper airways frequently associated with asthma. Bacterial infection is a feature of CRSwNP that can aggravate the disease and the response to glucocorticoid treatment.We examined whether the bacterial product lipopolysaccharide (LPS reduces glucocorticoid receptor (GR function in control nasal mucosa (NM fibroblasts and in nasal polyp (NP fibroblasts from patients with CRSwNP and asthma.NP (n = 12 and NM fibroblasts (n = 10 were in vitro pre-incubated with LPS (24 hours prior to the addition of dexamethasone. Cytokine/chemokine secretion was measured by ELISA and Cytometric Bead Array. GRα, GRβ, mitogen-activated protein-kinase phosphatase-1 (MKP-1 and glucocorticoid-induced leucine zipper (GILZ expression was measured by RT-PCR and immunoblotting, GRα nuclear translocation by immunocytochemistry, and GRβ localization by immunoblotting. The role of MKP-1 and GILZ on dexamethasone-mediated cytokine inhibition was analyzed by small interfering RNA silencing.Pre-incubation of nasal fibroblasts with LPS enhanced the secretion of IL-6, CXCL8, RANTES, and GM-CSF induced by FBS. FBS-induced CXCL8 secretion was higher in NP than in NM fibroblasts. LPS effects on IL-6 and CXCL8 were mediated via activation of p38α/β MAPK and IKK/NF-κB pathways. Additionally, LPS pre-incubation: 1 reduced dexamethasone's capacity to inhibit FBS-induced IL-6, CXCL8 and RANTES, 2 reduced dexamethasone-induced GRα nuclear translocation (only in NM fibroblasts, 3 did not alter GRα/GRβ expression, 4 decreased GILZ expression, and 5 did not affect dexamethasone's capacity to induce MKP-1 and GILZ expression. MKP-1 knockdown reduced dexamethasone's capacity to suppress FBS-induced CXCL8 release.The bacterial product LPS negatively affects GR function in control NM and NP fibroblasts by interfering with the capacity of the activated receptor to inhibit the production of pro

  19. Glucocorticoid treatment of MCMV infected newborn mice attenuates CNS inflammation and limits deficits in cerebellar development.

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    Kate Kosmac

    2013-03-01

    Full Text Available Infection of the developing fetus with human cytomegalovirus (HCMV is a major cause of central nervous system disease in infants and children; however, mechanism(s of disease associated with this intrauterine infection remain poorly understood. Utilizing a mouse model of HCMV infection of the developing CNS, we have shown that peripheral inoculation of newborn mice with murine CMV (MCMV results in CNS infection and developmental abnormalities that recapitulate key features of the human infection. In this model, animals exhibit decreased granule neuron precursor cell (GNPC proliferation and altered morphogenesis of the cerebellar cortex. Deficits in cerebellar cortical development are symmetric and global even though infection of the CNS results in a non-necrotizing encephalitis characterized by widely scattered foci of virus-infected cells with mononuclear cell infiltrates. These findings suggested that inflammation induced by MCMV infection could underlie deficits in CNS development. We investigated the contribution of host inflammatory responses to abnormal cerebellar development by modulating inflammatory responses in infected mice with glucocorticoids. Treatment of infected animals with glucocorticoids decreased activation of CNS mononuclear cells and expression of inflammatory cytokines (TNF-α, IFN-β and IFNγ in the CNS while minimally impacting CNS virus replication. Glucocorticoid treatment also limited morphogenic abnormalities and normalized the expression of developmentally regulated genes within the cerebellum. Importantly, GNPC proliferation deficits were normalized in MCMV infected mice following glucocorticoid treatment. Our findings argue that host inflammatory responses to MCMV infection contribute to deficits in CNS development in MCMV infected mice and suggest that similar mechanisms of disease could be responsible for the abnormal CNS development in human infants infected in-utero with HCMV.

  20. Multimodal Treatment of Chronic Pain.

    Science.gov (United States)

    Dale, Rebecca; Stacey, Brett

    2016-01-01

    Most patients with chronic pain receive multimodal treatment. There is scant literature to guide us, but when approaching combination pharmacotherapy, the practitioner and patient must weigh the benefits with the side effects; many medications have modest effect yet carry significant side effects that can be additive. Chronic pain often leads to depression, anxiety, and deconditioning, which are targets for treatment. Structured interdisciplinary programs are beneficial but costly. Interventions have their place in the treatment of chronic pain and should be a part of a multidisciplinary treatment plan. Further research is needed to validate many common combination treatments.

  1. Treatment of chronic inflammatory neuropathies

    NARCIS (Netherlands)

    F. Eftimov

    2015-01-01

    This thesis focuses on the efficacy of existing and alternative treatments in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) and explores predictors of treatment response in patients with CIDP treated with corticosteroids. The efficacy of intra

  2. Adverse events of glucocorticoids during treatment of rheumatoid arthritis: lessons from cohort and registry studies.

    Science.gov (United States)

    W J Bijlsma, Johannes; Buttgereit, Frank

    2016-12-01

    Glucocorticoids have now been used for >65 years in the treatment of RA. There is good evidence for their disease-modifying effect, especially in early RA. When used in a dosage of 7.5-10 mg/day, most adverse effects can be handled quite well, although monitoring for and awareness of infections are important. Adverse events may have been overreported, due to bias by indication, but pose an important drawback in the use of these very effective anti-inflammatory and immune-modulatory drugs. Daily dosages >7.5-10 mg and use for a prolonged period (years) of time are associated with a dose-dependent increased mortality. Still, the benefit:risk ratio for low-dosage glucocorticoid in patients with RA is acceptable and in many ways is comparable with other synthetic and biologic DMARDs.

  3. Weight-bearing physical activity, calcium intake, systemic glucocorticoids, chronic inflammation, and body constitution as determinants of lumbar and femoral bone mineral in juvenile chronic arthritis.

    Science.gov (United States)

    Kotaniemi, A; Savolainen, A; Kröger, H; Kautiainen, H; Isomäki, H

    1999-01-01

    The associations between the lumbar and femoral bone mineral and several body constitutional, lifestyle, and disease related variables were studied in 111 children with juvenile chronic arthritis (JCA) by factor and multiple linear regression analyses. In addition to the measurement of bone mineral density (BMD), bone width and bone mineral volumetric density (BMDvol) were determined by dual-x-ray absorptiometry (DXA). Factor analysis of 13 explanatory variables yielded six non-correlating factors, named as body size, physical activity, calcium intake, glucocorticoids, disease duration, and disease activity. These six factors were used as new variables to explain BMD, BMDvol, and bone width by multiple linear regression analyses. These showed body size, physical activity, and calcium intake as significant positive and disease activity and glucocorticoids as significant negative determinants of BMD in JCA. The analyses revealed also considerable differences in the relationships between factors and BM Dvol or bone width.

  4. Chronic glucocorticoids increase hippocampal vulnerability to neurotoxicity under conditions that produce CA3 dendritic retraction but fail to impair spatial recognition memory.

    Science.gov (United States)

    Conrad, Cheryl D; McLaughlin, Katie J; Harman, James S; Foltz, Cainan; Wieczorek, Lindsay; Lightner, Elizabeth; Wright, Ryan L

    2007-08-01

    We previously found that chronic stress conditions producing CA3 dendritic retraction and spatial memory deficits make the hippocampus vulnerable to the neurotoxin ibotenic acid (IBO). The purpose of this study was to determine whether exposure to chronic corticosterone (CORT) under conditions that produce CA3 dendritic retraction would enhance CA3 susceptibility to IBO. Male Sprague Dawley rats were chronically treated for 21 d with CORT in drinking water (400 microg/ml), and half were given daily injections of phenytoin (40 mg/kg), an antiepileptic drug that prevents CA3 dendritic retraction. Three days after treatments stopped, IBO was infused into the CA3 region. Conditions producing CA3 dendritic retraction (CORT and vehicle) exacerbated IBO-induced CA3 damage compared with conditions in which CA3 dendritic retraction was not observed (vehicle and vehicle, vehicle and phenytoin, CORT and phenytoin). Additionally, spatial recognition memory was assessed using the Y-maze, revealing that conditions producing CA3 dendritic retraction failed to impair spatial recognition memory. Furthermore, CORT levels in response to a potentially mild stressor (injection and Y-maze exposure) stayed at basal levels and failed to differ among key groups (vehicle and vehicle, CORT and vehicle, CORT and phenytoin), supporting the interpretations that CORT levels were unlikely to have been elevated during IBO infusion and that the neuroprotective actions of phenytoin were not through CORT alterations. These data are the first to show that conditions with prolonged glucocorticoid elevations leading to structural changes in hippocampal dendritic arbors can make the hippocampus vulnerable to neurotoxic challenges. These findings have significance for many disorders with elevated glucocorticoids that include depression, schizophrenia, Alzheimer's disease, and Cushing's disease.

  5. Chronic inflammation and low-dose glucocorticoid effects on glucose metabolism in premenopausal females with rheumatoid arthritis free of conventional metabolic risk factors.

    Science.gov (United States)

    Penesová, A; Rádiková, Z; Vlček, M; Kerlik, J; Lukáč, J; Rovenský, J; Imrich, R

    2013-01-01

    Chronic systemic inflammation is associated with increased cardiovascular mortality in patients with rheumatoid arthritis (RA). The aim of our study was to investigate association of glucose metabolism and inflammatory markers in a group of patients with rheumatoid arthritis free of other metabolic risk factors. Twenty-two premenopausal RA females (11 patients on low-dose GC (glucocorticoid therapy) and 15 age- and BMI-matched healthy females underwent the oral glucose tolerance test. The insulin sensitivity indices according Matsuda (ISI(MAT)) and Cederholm (ISI(CED)) as well as HOMA2 %S were calculated. Cytokines, lipid profile, non-esterified fatty acids (NEFA) and plasminogen activator inhibitor-1 (PAI-1) were measured in baseline blood samples. Despite elevated interleukin IL-6 and TNF alpha, glucose, insulin and C-peptide responses to oral glucose load as well as ISI(MAT), ISI(CED), PAI-1 and NEFA were comparable in both RA groups and healthy controls. HOMA2 %S correlated with disease activity. In conclusions, low-dose glucocorticoid treatment does not lead to glucose metabolism impairment in RA patients without other metabolic risk factors. Increased cardiovascular mortality and morbidity is probably due to a direct effect of systemic inflammation on myocardium and/or blood vessels.

  6. Short-term glucocorticoid administration in patients with protracted and chronic gout arthritis. Part 2 — comparison of different medication forms efficacy

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    A A Fedorova

    2008-01-01

    Full Text Available Objective. To compare efficacy of different glucocorticoid (GC medication forms in protracted and chronic gout arthritis. Material and methods. 59 pts with tophaceous gout (crystal-verified diagnosis and arthritis of three and more joints lasting more than a months in spite of treatment with sufficient doses of nonsteroidal anti-inflammatory drugs were included. Median age of pts was 56 [48;63], median disease duration — 15,2 years [7,4;20], median swollen joint count at the examination — 8 [5; 11]. The patients were randomized into 2 groups. Methylprednisolone (MP 500 mg/day iv during 2 days and placebo im once was administered in one of them, betamethasone (BM 7 mg im once and placebo iv twice — in the other. Results. Number of pts with full resolution of arthritis, recurrent exacerbation, insufficient arthritis resolution or clinically insignificant response was comparable in both groups. More rapid decrease of pain at moving was achieved during the first 2-3 days after GC administration in pts with full resolution of arthritis (p=0,03 in group receiving MP in comparison with BM. At day 14 joint damage measures did not differ between groups. Conclusion. Efficacy of short-term glucocorticoid administration does not depend on mode of administration and GC medication form (methylprednisolone 500 mg/day iv during 2 days or betamethasone 7 mg im once.

  7. Chronic prenatal ethanol exposure increases glucocorticoid-induced glutamate release in the hippocampus of the near-term foetal guinea pig.

    Science.gov (United States)

    Iqbal, U; Brien, J F; Kapoor, A; Matthews, S G; Reynolds, J N

    2006-11-01

    Exposure to high cortisol concentration can injure the developing brain, possibly via an excitotoxic mechanism involving glutamate (Glu). The present study tested the hypothesis that chronic prenatal ethanol exposure (CPEE) activates the foetal hypothalamic-pituitary-adrenal axis to produce high cortisol exposure in the foetal compartment and alters sensitivity to glucocorticoid-induced Glu release in the foetal hippocampus. Pregnant guinea pigs received daily oral administration of ethanol (4 g/kg maternal body weight/day) or isocaloric-sucrose/pair-feeding from gestational day (GD) 2 until GD 63 (term, approximately GD 68) at which time they were euthanised, 1 h after their final treatment. Adrenocorticotrophic hormone (ACTH) and cortisol concentrations were determined in foetal plasma. Basal and electrically stimulated Glu and gamma-aminobutyric acid (GABA) efflux in the presence or absence of dexamethasone (DEX), a selective glucocorticoid-receptor agonist, were determined ex vivo in foetal hippocampal slices. Glucocorticoid receptor (GR), mineralocorticoid receptor (MR) and N-methyl-D-aspartate (NMDA) receptor NR1 subunit mRNA expression were determined in situ in the hippocampus and dentate gyrus. In the near-term foetus, CPEE increased foetal plasma ACTH and cortisol concentrations. Electrically stimulated glutamate, but not GABA, release was increased in CPEE foetal hippocampal slices. Low DEX concentration (0.3 microM) decreased stimulated glutamate, but not GABA, release in both CPEE and control foetal hippocampal slices. High DEX concentration (3.0 microM) increased basal release of Glu, but not GABA, in CPEE foetal hippocampal slices. GR, but not MR, mRNA expression was elevated in the hippocampus and dentate gyrus, whereas NR1 mRNA expression was increased in the CA1 and CA3 fields of the foetal hippocampus. These data demonstrate that CPEE increases high glucocorticoid concentration-induced Glu release in the foetal hippocampus, presumably as a

  8. A new pathway of glucocorticoid action for asthma treatment through the regulation of PTEN expression

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    Chen Qingge

    2011-04-01

    Full Text Available Abstract Background "Phosphatase and tensin homolog deleted on chromosome 10" (PTEN is mostly considered to be a cancer-related gene, and has been suggested to be a new pathway of pathogenesis of asthma. The purpose of this study was to investigate the effects of the glucocorticoid, dexamethasone, on PTEN regulation. Methods OVA-challenged mice were used as an asthma model to investigate the effect of dexamethasone on PTEN regulation. Immunohistochemistry was used to detect expression levels of PTEN protein in lung tissues. The human A549 cell line was used to explore the possible mechanism of action of dexamethasone on human PTEN regulation in vitro. A luciferase reporter construct under the control of PTEN promoter was used to confirm transcriptional regulation in response to dexamethasone. Results PTEN protein was found to be expressed at low levels in lung tissues in asthmatic mice; but the expression was restored after treatment with dexamethasone. In A549 cells, human PTEN was up-regulated by dexamethasone treatment. The promoter-reporter construct confirmed that dexamethasone could regulate human PTEN transcription. Treatment with the histone deacetylase inhibitor, TSA, could increase PTEN expression in A549 cells, while inhibition of histone acetylase (HAT by anacardic acid attenuated dexamethasone-induced PTEN expression. Conclusions Based on the data a new mechanism is proposed where glucocorticoids treat asthma partly through up-regulation of PTEN expression. The in vitro studies also suggest that the PTEN pathway may be involved in human asthma.

  9. Why glucocorticoid withdrawal may sometimes be as dangerous as the treatment itself

    DEFF Research Database (Denmark)

    Dinsen, Stina; Baslund, Bo; Klose, Marianne;

    2013-01-01

    Glucocorticoid therapy is widely used, but withdrawal from glucocorticoids comes with a potential life-threatening risk of adrenal insufficiency. Recent case reports document that adrenal crisis after glucocorticoid withdrawal remains a serious problem in clinical practice. Partly due to difficul...

  10. Effect and its clinical significance of different dose of glucocorticoids on inflammation mediators in patients with acute exacerbation of chronic obstructive pulmonary diseases

    Institute of Scientific and Technical Information of China (English)

    钟佰强

    2014-01-01

    Objective To explore the effect and its clinical significance of different dose of glucocorticoids on inflammation mediators in patients with acute exacerbation of chronic obstructive pulmonary diseases.Methods 45 patients admitted to our hospitals from March 2007 to March 2011were randomly divided into 3 groups:methylprednisolone40 mg group(methylprednisolone 40mg,iv,qd),meth-

  11. [Pharmacological treatment of chronic pain].

    Science.gov (United States)

    Willimann, Patrick

    2011-09-01

    The pharmacological treatment of chronic pain differs from acute pain management. In chronic non-cancer pain patients pharmacological treatment is only one element of an interdisciplinary approach. Not pain reduction only but gain in physical and social functioning is mandatory for continuation of therapy. The developpement of a strategy is the most important and difficult step toward an individual and sustained pharmacological pain treatment. Simple practical guidelines can help to find an individual therapeutic straight. Outcome parameters have to be determined. Check-ups for discontinuation of the therapy have to be done periodically. Exact documentation of effect and side effects prevents ungrateful and potential dangerous treatments. The WHO ladder remains the cornerstone of pharmacological pain treatment. Further analgesics as antidepressants and anticonvulsants are important in treatment of neuropathic or mixed pain states. Special considerations have to be done in opioid treatment of non-cancer pain regarding the lack of evidence in long term outcome and possible side effects and risks.

  12. Treatment of chronic lymphocytic leukemia.

    Science.gov (United States)

    Ferrajoli, Alessandra; O'Brien, Susan M

    2004-04-01

    Treatment options for patients with chronic lymphocytic leukemia have changed over the past two decades. This article reviews the experience accumulated with the use of alkylating agents alone and in combination; purine analogues alone and in combination and monoclonal antibodies such as rituximab, and alemtuzumab alone and in combination. The results obtained with different treatment strategies are summarized, compared, and reviewed.

  13. Electroacupuncture treatment of chronic insomniacs

    Institute of Scientific and Technical Information of China (English)

    RUAN Jing-wen; WANG Chu-huai; LIAO Xin-xue; YAN Ying-shuo; HU Yue-hua; RAO Zhong-dong; WEN Ming; ZENG Xiao-xiang; LAI Xin-sheng

    2009-01-01

    Background Due to the quick rhythm of life and work pressure, more and more people suffer from sleep quality problems. In this study, we investigated the effect of electroacupuncture on sleep quality of chronic insomniacs and the safety of electroacupuncture therapy.Methods Four courses of electroacupuncture treatment were applied to 47 patients. With pre-treatment and post-treatment self-control statistical method, Pittsburgh sleep quality index (PSQI) scores were used for evaluating sleep quality. Polysomnogram was used for detecting insomniacs' changes in sleep architecture. The safety of electroacupuncture was evaluated by monitoring the self-designed adverse events and side effects during treatment and post-treatment.Results Electroacupuncture considerably improved insomniacs' sleep quality and social function during the daytime.Electroacupuncture had certain repairing effect on the disruption in sleep architecture. At the same time,electroacupuncture prolonged slow wave sleep (SWS) time and relatively rapid eye movement sleep (REM sleep) time.There was no hangover, addiction or decrements in vigilance during the daytime (incidence rate was 0). However,insomnia rebound rate was about 23% within one month.Conclusions These results suggest that electroacupuncture has beneficial effect on sleep quality improvement in the patients with chronic insomnia, which may be associated with repairing sleep architecture, reconstructing sleep continuity,as well as prolonging SWS time and REM sleep time. Electroacupuncture treatment for chronic insomnia is safe.Therefore, electroacupuncture therapy could be a promising avenue of treatment for chronic insomnia.

  14. High-fat diet and glucocorticoid treatment cause hyperglycemia associated with adiponectin receptor alterations

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    Oller do Nascimento Cláudia

    2011-01-01

    Full Text Available Abstract Background Adiponectin is the most abundant plasma protein synthesized for the most part in adipose tissue, and it is an insulin-sensitive hormone, playing a central role in glucose and lipid metabolism. In addition, it increases fatty acid oxidation in the muscle and potentiates insulin inhibition of hepatic gluconeogenesis. Two adiponectin receptors have been identified: AdipoR1 is the major receptor expressed in skeletal muscle, whereas AdipoR2 is mainly expressed in liver. Consumption of high levels of dietary fat is thought to be a major factor in the promotion of obesity and insulin resistance. Excessive levels of cortisol are characterized by the symptoms of abdominal obesity, hypertension, glucose intolerance or diabetes and dyslipidemia; of note, all of these features are shared by the condition of insulin resistance. Although it has been shown that glucocorticoids inhibit adiponectin expression in vitro and in vivo, little is known about the regulation of adiponectin receptors. The link between glucocorticoids and insulin resistance may involve the adiponectin receptors and adrenalectomy might play a role not only in regulate expression and secretion of adiponectin, as well regulate the respective receptors in several tissues. Results Feeding of a high-fat diet increased serum glucose levels and decreased adiponectin and adipoR2 mRNA expression in subcutaneous and retroperitoneal adipose tissues, respectively. Moreover, it increased both adipoR1 and adipoR2 mRNA levels in muscle and adipoR2 protein levels in liver. Adrenalectomy combined with the synthetic glucocorticoid dexamethasone treatment resulted in increased glucose and insulin levels, decreased serum adiponectin levels, reduced adiponectin mRNA in epididymal adipose tissue, reduction of adipoR2 mRNA by 7-fold in muscle and reduced adipoR1 and adipoR2 protein levels in muscle. Adrenalectomy alone increased adiponectin mRNA expression 3-fold in subcutaneous adipose

  15. Treatment of Glucocorticoids Inhibited Early Immune Responses and Impaired Cardiac Repair in Adult Zebrafish.

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    Wei-Chang Huang

    Full Text Available Myocardial injury, such as myocardial infarction (MI, can lead to drastic heart damage. Zebrafish have the extraordinary ability to regenerate their heart after a severe injury. Upon ventricle resection, fibrin clots seal the wound and serve as a matrix for recruiting myeloid-derived phagocytes. Accumulated neutrophils and macrophages not only reduce the risk of infection but also secrete cytokines and growth factors to promote tissue repair. However, the underlying cellular and molecular mechanisms for how immune responses are regulated during the early stages of cardiac repair are still unclear. We investigated the role and programming of early immune responses during zebrafish heart regeneration. We found that zebrafish treated with an anti-inflammatory glucocorticoid had significantly reduced heart regenerative capacities, consistent with findings in other higher vertebrates. Moreover, inhibiting the inflammatory response led to excessive collagen deposition. A microarray approach was used to assess the differential expression profiles between zebrafish hearts with normal or impaired healing. Combining cytokine profiling and immune-staining, our data revealed that impaired heart regeneration could be due to reduced phagocyte recruitment, leading to diminished angiogenesis and cell proliferation post-cardiac injury. Despite their robust regenerative ability, our study revealed that glucocorticoid treatment could effectively hinder cardiac repair in adult zebrafish by interfering with the inflammatory response. Our findings may help to clarify the initiation of cardiac repair, which could be used to develop a therapeutic intervention that may enhance cardiac repair in humans to compensate for the loss of cardiomyocytes after an MI.

  16. Effects of hyperbaric oxygen treatment on glucocorticoid receptor expression in the hipopocampus and on the behavior of rats under chronic restraint stress%高压氧处理对慢性束缚大鼠行为学和海马区糖皮质激素受体的影响

    Institute of Scientific and Technical Information of China (English)

    麦乃铿; 杨晨; 孙瑞佼; 吕艳; 赵津京; 潘树义

    2015-01-01

    Objective To explore the effects of hyperbaric oxygen treatment on chronic stress and glucocorticoid receptor (GR) expression in the hippocampus.Methods A total of 60 male Wistar rats were randomly divided into a restraint group,an HBO (hyperbaric oxygen) group,an HBO-restraint group and a control group using a random number table,each group with 15 animals.All the rats in the restraint and HBO groups were constrained by immobilizing their fore-and hind-limbs on a self-made frame for 3h daily for 21 days,and those in the HBO group received HBO treatment once daily for the same 21 days.The HBO-restraint group was immobilized in the morning and treated with HBO in the afternoon.The control group was reared without any special intervention.On the 1st,11th and 21st day of treatment,rats from the different groups were assessed using the open field test.On the 21st day,all the animals were sacrificed and their brains were harvested to detect GR expression.Results In the open field test on the 11 th day,the restraint group scored (131.0 ± 20.6) in terms of motor level and (26.5 ± 4.6) for exploratory behavior,both significantly higher than before restraint and significantly higher than those in the HBO-restraint group at the same time point.Immunofluorescence assay showed that GR expression in the hippocampus of the restraint group was significantly decreased compared with the control group.There was no significant difference,however,between the HBO-restraint group and the control group.Conclusion Chronic restraint stress induces changes in behavior and GR expression in rats which can be alleviated by hypbaric oxygen treatment.%目的 观察高压氧(HBO)处理和慢性束缚对大鼠行为学及海马区糖皮质激素受体(GR)表达水平的影响,探讨HBO对慢性束缚大鼠的干预作用.方法 将60只雄性Wistar大鼠按随机数字表法分成单纯束缚组、单纯HBO组、HBO联合束缚组和空白对照组,每组15只.单纯束缚组给予行为限制3

  17. Addison disease in patients treated with glucocorticoid therapy.

    LENUS (Irish Health Repository)

    Cronin, C C

    2012-02-03

    Acute adrenal crisis in patients with unrecognized chronic adrenocortical failure is difficult to diagnose and potentially fatal. We describe 2 patients with acute adrenal crisis whose diagnoses were hindered because of concomitant glucocorticoid treatment. Acute adrenal insufficiency is primarily a state of mineralocorticoid deficiency. Prednisolone and prednisone, the most frequently prescribed anti-inflammatory corticosteroid agents, have minimal mineralocorticoid activity. Several conditions that may be treated with pharmacological glucocorticoids are associated with an increased risk of Addison disease. An acute adrenal crisis, against which concurrent glucocorticoid therapy does not confer adequate protection, may develop in such patients.

  18. Interactions between glucocorticoid treatment and cis-regulatory polymorphisms contribute to cellular response phenotypes.

    Directory of Open Access Journals (Sweden)

    Joseph C Maranville

    2011-07-01

    Full Text Available Glucocorticoids (GCs mediate physiological responses to environmental stress and are commonly used as pharmaceuticals. GCs act primarily through the GC receptor (GR, a transcription factor. Despite their clear biomedical importance, little is known about the genetic architecture of variation in GC response. Here we provide an initial assessment of variability in the cellular response to GC treatment by profiling gene expression and protein secretion in 114 EBV-transformed B lymphocytes of African and European ancestry. We found that genetic variation affects the response of nearby genes and exhibits distinctive patterns of genotype-treatment interactions, with genotypic effects evident in either only GC-treated or only control-treated conditions. Using a novel statistical framework, we identified interactions that influence the expression of 26 genes known to play central roles in GC-related pathways (e.g. NQO1, AIRE, and SGK1 and that influence the secretion of IL6.

  19. [Neurosurgical treatment of chronic pain].

    Science.gov (United States)

    Fontaine, D; Blond, S; Mertens, P; Lanteri-Minet, M

    2015-02-01

    Neurosurgical treatment of pain used two kind of techniques: 1) Lesional techniques interrupt the transmission of nociceptive neural input by lesionning the nociceptive pathways (drezotomy, cordotomy, tractotomy…). They are indicated to treat morphine-resistant cancer pain and few cases of selected neuropathic pain. 2) Neuromodulation techniques try to decrease pain by reinforcing inhibitory and/or to limit activatory mechanisms. Chronic electrical stimulation of the nervous system (peripheral nerve stimulation, spinal cord stimulation, motor cortex stimulation…) is used to treat chronic neuropathic pain. Intrathecal infusion of analgesics (morphine, ziconotide…), using implantable pumps, allows to increase their efficacy and to reduce their side effects. These techniques can improve, sometimes dramatically, selected patients with severe and chronic pain, refractory to all other treatments. The quality of the analgesic outcome depends on the relevance of the indications.

  20. A clinical comparative study on treatment of severe newly diagnosed immune thrombocytopenia by recombinant human thrombopoietin combined with glucocorticoid

    Institute of Scientific and Technical Information of China (English)

    顾史洋

    2013-01-01

    Objective To evaluate the efficacy and safety of recombinant human thrombopoietin (rhTPO) combined with glucocorticoid in treatment of severe newly diagnosed primary immune thrombocytopenia (ITP) .Methods From June 2009 to December 2012,24 male patients and 38female patients with the diagnosis of severe primary ITP in our hospital were randomized into trial group (31cases) or control group (31 cases) ,the median age was 50 years (range:21-84 years) .Trial group was treated with rhTPO combined with glucocorticoid,and control group was

  1. Chronic Constipation: Current Treatment Options

    Directory of Open Access Journals (Sweden)

    Louis Wing Cheong Liu

    2011-01-01

    Full Text Available Chronic constipation is a common functional gastrointestinal disorder that affects patients of all ages. In 2007, a consensus group of 10 Canadian gastroenterologists developed a set of recommendations pertaining to the management of chronic constipation and constipation-dominant irritable bowel syndrome. Since then, tegaserod has been withdrawn from the Canadian market. A new, highly selective serotonin receptor subtype 4 agonist, prucalopride, has been examined in several large, randomized, placebo-controlled trials demonstrating its efficacy and safety in the management of patients with chronic constipation. Additional studies evaluating the use of stimulant laxatives, polyethylene glycol and probiotics in the management of chronic constipation have also been published. The present review summarizes the previous recommendations and new evidence supporting different treatment modalities – namely, diet and lifestyle, bulking agents, stool softeners, osmotic and stimulant laxatives, prucalopride and probiotics in the management of chronic constipation. A brief summary of lubiprostone and linaclotide is also presented. The quality of evidence is presented by adopting the Grading of Recommendations, Assessment, Development and Evaluation system. Finally, a management pyramid for patients with chronic constipation is proposed based on the quality of evidence, impact of each modality on constipation and on general health, and their availabilities in Canada.

  2. The Effect of Glucocorticoids on Bone Mass in Patients with Asthma and Chronic obstructive Pulmonary Disease

    Directory of Open Access Journals (Sweden)

    Evrim Karadağ Saygı

    2005-06-01

    Full Text Available Inhaled corticosteroids and bronchodilators have become a key element in the maintenance treatment of bronchial asthma and chronic obstructive pulmanory disease (COPD. It is well known that long-term systemic steroid use causes osteoporosis, whereas inhaled corticosteroids and bronchodilators have been discussed to be cause of such side-affect. The aim of this study was to detect the effect of long term inhaled/oral steroids and bronchodilators on bone mineral density (BMD with asthma and COPD. Fifty-three patients with bronchial asthma (n=44 and COPD (n=9 were enrolled in this study. BMD were measured and risk factors for osteoporosis were detected. BMD measurements of lumbar area of the spine (L2-4, neck of femur and femoral ward’s triangle zone were performed by the dual energy x-ray absorptiometer (LUNAR. 53 patients evaluated in three groups according to treatment type; 26 patients were using inhaled corticosteroids and bronchodilators (group 1, 18 patients were using only bronchodilators (group 2 and 9 patients were using (group 3 oral corticosteroids and bronchodilators. There were significant differences between group 3 and other two groups in terms of BMD, T and Z scores of the lumbar and femoral neck (p0.05. As a result, we suggest that systemic corticosteroids negatively affect bone mineral density more than inhaled corticosteroids in patients with COPD.

  3. Chronic high fat feeding increases anxiety-like behaviour and reduces transcript abundance of glucocorticoid signalling genes in the hippocampus of female rats.

    Science.gov (United States)

    Sivanathan, Shathveekan; Thavartnam, Kabriya; Arif, Shahneen; Elegino, Trisha; McGowan, Patrick O

    2015-06-01

    The consumption of diets high in saturated fats and obesity have been associated with impaired physical and mental health. Previous studies indicate that chronic high fat diet consumption leads to systemic inflammation in humans and non-human animal models. Studies in non-human animals suggest that altered physiological responses to stress are also a consequence of high fat diet consumption. Glucocorticoid signalling mechanisms may link immune and stress-related pathways in the brain, and were shown to be significantly altered in the brains of female rat offspring of mothers exposed to chronic high fat diet during pregnancy and lactation. For adult females, the consequence of chronic high fat diet consumption on these signalling pathways and their relationship to stress-related behaviour is not known. In this study, we examined the effects of chronic consumption of a high fat diet compared to a low fat control diet among adult female Long Evans rats. We found significant differences in weight gain, caloric intake, anxiety-related behaviours, and glucocorticoid-related gene expression over a 10-week exposure period. As expected, rats in the high fat diet group gained the most weight and consumed the greatest number of calories. Rats in the high fat diet group showed significantly greater levels of anxiety-related behaviour in the Light Dark and Open Field tasks compared to rats in the low fat diet group. Rats consuming high fat diet also exhibited reduced transcript abundance in the hippocampus of stress-related mineralocorticoid receptor and glucocorticoid receptor genes, as well as nuclear factor kappa beta gene expression, implicated in inflammatory processes. Together, these data indicate that chronic high fat diet consumption may increase anxiety-like behaviour at least in part via alterations in glucocorticoid signalling mechanisms in limbic brain regions.

  4. Sclerostin-antibody treatment of glucocorticoid-induced osteoporosis maintained bone mass and strength

    Science.gov (United States)

    Jiang, L.; Lay, E. Y.-A.; Zhong, Z.; Ritchie, R. O.; Li, X.; Ke, H.; Lane, N. E.

    2016-01-01

    Summary This study was to determine if antibody against sclerostin (Scl-Ab) could prevent glucocorticoid (GC)-induced osteoporosis in mice. We found that Scl-Ab prevented GC-induced reduction in bone mass and bone strength and that the anabolic effects of Scl-Ab might be partially achieved through the preservation of osteoblast activity through autophagy. Introduction Glucocorticoids (GCs) inhibit bone formation by altering osteoblast and osteocyte cell activity and lifespan. A monoclonal antibody against sclerostin, Scl-Ab, increased bone mass in both preclinical animal and clinical studies in subjects with low bone mass. The objectives of this study were to determine if treatment with the Scl-Ab could prevent loss of bone mass and strength in a mouse model of GC excess and to elucidate if Scl-Ab modulated bone cell activity through autophagy. Methods We generated reporter mice that globally expressed dsRed fused to LC3, a protein marker for autophagosomes, and evaluated the dose-dependent effects of GCs (0, 0.8, 2.8, and 4 mg/kg/day) and Scl-Ab on autophagic osteoblasts, bone mass, and bone strength. Results GC treatment at 2.8 and 4 mg/kg/day of methylprednisolone significantly lowered trabecular bone volume (Tb-BV/TV) at the lumbar vertebrae and distal femurs, cortical bone mass at the mid-shaft femur (FS), and cortical bone strength compared to placebo (PL). In mice treated with GC and Scl-Ab, Tb-BV/TV increased by 60–125 %, apparent bone strength of the lumbar vertebrae by 30–70 %, FS-BV by 10–18 %, and FS-apparent strength by 13–15 %, as compared to GC vehicle-treated mice. GC treatment at 4 mg/kg/ day reduced the number of autophagic osteoblasts by 70 % on the vertebral trabecular bone surface compared to the placebo group (PL, GC 0 mg), and GC + Scl-Ab treatment. Conclusions Treatment with Scl-Ab prevented GC-induced reduction in both trabecular and cortical bone mass and strength and appeared to maintain osteoblast activity through autophagy. PMID

  5. Chronic unpredictable stress exacerbates lipopolysaccharide-induced activation of nuclear factor-kappaB in the frontal cortex and hippocampus via glucocorticoid secretion.

    Science.gov (United States)

    Munhoz, Carolina Demarchi; Lepsch, Lucilia B; Kawamoto, Elisa Mitiko; Malta, Marília Brinati; Lima, Larissa de Sá; Avellar, Maria Christina Werneck; Sapolsky, Robert M; Scavone, Cristoforo

    2006-04-01

    Although the anti-inflammatory actions of glucocorticoids (GCs) are well established in the periphery, these stress hormones can increase inflammation under some circumstances in the brain. The transcription factor nuclear factor-kappaB (NF-kappaB), which is inhibited by GCs, regulates numerous genes central to inflammation. In this study, the effects of stress, GCs, and NMDA receptors on lipopolysaccharide (LPS)-induced activation of NF-kappaB in the brain were investigated. One day after chronic unpredictable stress (CUS), nonstressed and CUS rats were treated with saline or LPS and killed 2 h later. CUS potentiated the increase in LPS-induced activation of NF-kappaB in frontal cortex and hippocampus but not in the hypothalamus. This stress effect was blocked by pretreatment of rats with RU-486, an antagonist of the GC receptor. MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate], an NMDA receptor antagonist, also reduced the effect of LPS in all three brain regions. However, the combined antagonism of both GC and NMDA receptors produced no further reduction in NF-kappaB activation when compared with the effect of each treatment alone. Our results indicate that stress, via GC secretion, can increase LPS-induced NF-kappaB activation in the frontal cortex and hippocampus, agreeing with a growing literature demonstrating proinflammatory effects of GCs.

  6. Treatment of glucocorticoid-induced osteoporosis with alfacalcidol/calcium versus vitamin D/calcium.

    Science.gov (United States)

    Ringe, J D; Cöster, A; Meng, T; Schacht, E; Umbach, R

    1999-10-01

    Vitamin D/calcium substitution is generally regarded as an effective first step treatment for glucocorticoid-induced osteoporosis (GIOP). The aim of our study was to evaluate the efficacy of the active vitamin D metabolite alfacalcidol (1alpha) compared with the native vitamin D(3) in patients with established GIOP with or without vertebral fractures. Patients on long-term corticoid therapy were given either 1 microg alfacalcidol plus 500 mg calcium per day (group A, n = 43) or 1000 IU vitamin D(3) plus 500 mg calcium (group B, n = 42). The two groups were alike in age range, sex ratio, percentages of underlying diseases, average initial bone density values (lumbar spine: mean T-score -3.28 and -3.25, respectively), and rates of vertebral and nonvertebral fractures. During the 3-year study we found a small but significant increase of lumbar spine density in group 1alpha (+2.0%, P back pain (P vitamin D group. We conclude that with the doses used in this trial, alfacalcidol is superior to vitamin D in the treatment of established GIOP.

  7. [Glucocorticoid-induced osteoporosis and rheumatic diseases. Pathogenesis, prevention and treatment].

    Science.gov (United States)

    Di Munno, Ombretta; Delle Sedie, Andrea

    2006-01-01

    Glucocorticoids (GC) are diffusely used to treat a wide variety of inflammatory and autoimmune disorders, including rheumatic diseases. GC-induced osteoporosis (GIO) is the most common and serious side-effect for patients receiving GC. Loss of bone mineral density (BMD) is greatest in the first few months of GC use; fracture (Fx) risk is significantly increased at the spine and hip on doses even as low as 2.5 mg of prednisolone daily; Fx risk increases rapidly from the onset of therapy and, for a given BMD, is higher in GIO than in postmenopausal OP. General measures to reduce bone loss include use of the lowest effective dose; consideration of alternative routes of administration; adequate calcium and vitamin D supplementation. Today, results from large randomised controlled clinical trials provide evidence that bone loss and Fx may be prevented through the use of bone sparing agents (hormone therapy, bisphosphonates, PTH 1-34). Bisphosphonates (alendronate, risedronate) are first-choice therapy for the prevention and treatment of GIO; patients at high risk for Fx, for example those in post-menopausal status or aged > or =65 years and those with a prior fragility Fx, should be advised to start bone-protective therapy at the time of starting GC. Due to the prevalence of GC use, it is imperative that there be a greater awareness of GIO and of therapies that may be offered to patients both for prevention and treatment.

  8. Glucocorticoid-induced osteoporosis and rheumatic diseases. Pathogenesis, prevention and treatment

    Directory of Open Access Journals (Sweden)

    Andrea Delle Sedie

    2011-09-01

    Full Text Available Glucocorticoids (GC are diffusely used to treat a wide variety of inflammatory and autoimmune disorders, including rheumatic diseases. GC-induced osteoporosis (GIO is the most common and serious side-effect for patients receiving GC. Loss of bone mineral density (BMD is greatest in the first few months of GC use; fracture (Fx risk is significantly increased at the spine and hip on doses even as low as 2.5 mg of prednisolone daily; Fx risk increases rapidly from the onset of therapy and, for a given BMD, is higher in GIO than in postmenopausal OP. General measures to reduce bone loss include use of the lowest effective dose; consideration of alternative routes of administration; adequate calcium and vitamin D supplementation. Today, results from large randomised controlled clinical trials provide evidence that bone loss and Fx may be prevented through the use of bone sparing agents (hormone therapy, bisphosphonates, PTH 1-34. Bisphosphonates (alendronate, risedronate are first-choice therapy for the prevention and treatment of GIO; patients at high risk for Fx, for example those in post-menopausal status or aged ³65 years and those with a prior fragility Fx, should be advised to start bone-protective therapy at the time of starting GC. Due to the prevalence of GC use, it is imperative that there be a greater awareness of GIO and of therapies that may be offered to patients both for prevention and treatment

  9. Endoscopic treatment of chronic pancreatitis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Treatment of chronic pancreatitis has been exclusively surgical for a long time. Recently, endoscopic therapy has become widely used as a primary therapeutic option.Initially performed for drainage of pancreatic cysts and pseudocysts, endoscopic treatments were adapted to biliary and pancreatic ducts stenosis. Pancreatic sphincterotomy which allows access to pancreatic ducts was firstly reported. Secondly, endoscopic methods of stenting, dilatation, and stones extraction of the bile ducts were applied to pancreatic ducts. Nevertheless,new improvements were necessary: failures of pancreatic stone extraction justified the development of extra-corporeal shock wave lithotripsy; dilatation of pancreatic stenosis was improved by forage with a new device; moreover endosonography allowed guidance for celiac block, gastro-cystostomy, duodeno-cystostomy and pancreatico-gastrostomy. Although endoscopic treatments are more and more frequently accepted,indications are still debated.

  10. Neurotrophic-priming of glucocorticoid receptor signaling is essential for neuronal plasticity to stress and antidepressant treatment.

    Science.gov (United States)

    Arango-Lievano, Margarita; Lambert, W Marcus; Bath, Kevin G; Garabedian, Michael J; Chao, Moses V; Jeanneteau, Freddy

    2015-12-22

    Neurotrophins and glucocorticoids are robust synaptic modifiers, and deregulation of their activities is a risk factor for developing stress-related disorders. Low levels of brain-derived neurotrophic factor (BDNF) increase the desensitization of glucocorticoid receptors (GR) and vulnerability to stress, whereas higher levels of BDNF facilitate GR-mediated signaling and the response to antidepressants. However, the molecular mechanism underlying neurotrophic-priming of GR function is poorly understood. Here we provide evidence that activation of a TrkB-MAPK pathway, when paired with the deactivation of a GR-protein phosphatase 5 pathway, resulted in sustained GR phosphorylation at BDNF-sensitive sites that is essential for the transcription of neuronal plasticity genes. Genetic strategies that disrupted GR phosphorylation or TrkB signaling in vivo impaired the neuroplasticity to chronic stress and the effects of the antidepressant fluoxetine. Our findings reveal that the coordinated actions of BDNF and glucocorticoids promote neuronal plasticity and that disruption in either pathway could set the stage for the development of stress-induced psychiatric diseases.

  11. Identification of NURR1 as a mediator of MIF signaling during chronic arthritis: effects on glucocorticoid-induced MKP1.

    Science.gov (United States)

    Ralph, Jennifer A; Ahmed, Afsar U; Santos, Leilani L; Clark, Andrew R; McMorrow, Jason; Murphy, Evelyn P; Morand, Eric F

    2010-11-01

    Elucidation of factors regulating glucocorticoid (GC) sensitivity is required for the development of "steroid-sparing" therapies for chronic inflammatory diseases, including rheumatoid arthritis (RA). Accumulating evidence suggests that macrophage migration inhibitory factor (MIF) counterregulates the GC-induction of anti-inflammatory mediators, including mitogen-activated protein kinase phosphatase 1 (MKP1), a critical mitogen-activated protein kinase signaling inhibitor. This observation has yet to be extended to human disease; the molecular mechanisms remain unknown. We investigated NURR1, a GC-responsive transcription factor overexpressed in RA, as a MIF signaling target. We reveal abrogation by recombinant MIF (rMIF) of GC-induced MKP1 expression in RA fibroblast-like synoviocytes (FLS). rMIF enhanced NURR1 expression, artificial NBRE (orphan receptor DNA-binding site) reporter transactivation, and reversed GC-inhibition of NURR1. NURR1 expression was reduced during experimental arthritis in MIF-/- synovium, and silencing MIF reduced RA FLS NURR1 mRNA. Consistent with NBRE identification on the MKP1 gene, MKP1 mRNA was reduced in FLS that ectopically express NURR1, and silencing NURR1 enhanced MKP1 mRNA in RA FLS. rMIF enhanced NBRE binding on the MKP1 gene, and the absence of the NBRE prevented NURR1-repressive effects on basal and GC-induced MKP1 transactivation. This study defines NURR1 as a novel MIF target in chronic inflammation and demonstrates a role for NURR1 in regulating the anti-inflammatory mediator, MKP1. We propose a MIF-NURR1 signaling axis as a regulator of the GC sensitivity of MKP1.

  12. 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

    2012-01-01

    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...... injections administered every other week for a total of three administrations. The evaluation included validated scores. No effect of subcutaneous injections of adalimumab on frozen shoulder symptoms was demonstrated....

  13. Effects of glucocorticoid treatment on focal and systemic bone loss in rheumatoid arthritis.

    Science.gov (United States)

    Di Munno, O; Delle Sedie, A

    2008-07-01

    Rheumatoid arthritis (RA) is characterized by an extensive dysregulation in skeletal homeostasis recognized as 1) focal articular bone erosions, 2) iuxta-articular osteopenia, 3) systemic osteoporosis (OP) and fractures, as is well documented in both cross-sectional and prospective studies. The disease activity, as a consequence of new insights into the complex interaction between bone cells and a variety of cells of the immune system, has emerged as the main responsible for both focal and systemic bone loss. Given this background, the therapeutic approach to RA has become more aggressive, and a more widespread use of low-dose glucocorticoids (GC), recently categorized as disease modifying antirheumatic drugs (DMARD) because of their additional joint sparing effect on the long-term, has also been recommended from the early stages. Addressing the effects of GC on systemic bone loss in RA, GC are considered, in addition to inflammation and inactivity, the major risk factors for OP and fractures. As a consequence, among the most recent recommendations (i.e. dosing, timing, and tapering strategies) for patients receiving GC for more than 3 months, prevention and treatment of GC-induced OP (i.e. calcium, vitamin D, and bisphosphonates) are included. However, innovative GC, characterized by a more favorable risk/benefit profile such as selective GC receptor agonists (SEGRA), are currently in the pipeline. This article reviews the major points of evidence so far available, regarding the effects of GC on focal and systemic bone loss.

  14. Glucocorticoids in the treatment of rheumatoid arthritis: still used after 65 years.

    Science.gov (United States)

    Bijlsma, Johannes W J; Jacobs, Johannes W G

    2014-05-01

    Glucocorticoids (GCs) have been used for over 65 years in the treatment of rheumatoid arthritis (RA). There is by now good evidence for their disease-modifying effects, especially in early RA. When used in a dosage of 5-10 mg, most adverse effects can adequately be monitored, though accurate monitoring and awareness for infections are important. In this paper, the Utrecht and computer-assisted management in early rheumatoid arthritis (CAMERA) studies are discussed; the Utrecht study was the first of these studies in which 10 mg prednisone daily was compared to placebo in patients with early RA. A clear disease-modifying effect was shown. In the CAMERA II study, patients with early RA were treated with a tight-control scheme of climbing dosages of methotrexate plus either 10 mg prednisone daily or placebo. After 2 years, 70% of the patients treated with a tight-control strategy without GCs had no erosions versus 82% of the patients treated with additional prednisone. Remission was reached more often and earlier on in the strategy with prednisone compared to the strategy with placebo.

  15. Growth hormone treatment in boys with Duchenne muscular dystrophy and glucocorticoid-induced growth failure.

    Science.gov (United States)

    Rutter, Meilan M; Collins, James; Rose, Susan R; Woo, Jessica G; Sucharew, Heidi; Sawnani, Hemant; Hor, Kan N; Cripe, Linda H; Wong, Brenda L

    2012-12-01

    This study evaluated efficacy and safety of growth hormone treatment in Duchenne muscular dystrophy boys with glucocorticoid-induced growth failure. We reviewed 39 consecutive boys (average age 11.5 years; 32 ambulatory) treated with growth hormone for 1 year during a four-year period. Boys were on long-term daily deflazacort or prednisone (mean duration 5 ± 2.2 years; dosing regimen prednisone 0.75 mg/kg/day equivalent). Primary outcomes were growth velocity and height-for-age z-scores (height SD) at 1 year. Height velocity increased from 1.3 ± 0.2 to 5.2 ± 0.4 cm/year on growth hormone (pgrowth hormone decline in height SD (-0.5 ± 0.2SD/year) stabilized at height SD -2.9 ± 0.2 on growth hormone (pgrowth hormone and 2.6 ± 0.7 kg/year at 1 year. Motor function decline was similar pre-growth hormone and at 1 year. Cardiopulmonary function was unchanged. Three experienced side effects. In this first comprehensive report of growth hormone in Duchenne muscular dystrophy, growth hormone improved growth at 1 year, without detrimental effects observed on neuromuscular and cardiopulmonary function.

  16. 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)

    2015-01-01

    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 ce

  17. Chronic Prostatitis/Chronic Pelvic Pain Syndrome Diagnosis and Treatment

    Directory of Open Access Journals (Sweden)

    Cem Nedim Yuceturk

    2014-08-01

    Full Text Available Chronic prostatitis is a chronic syndrome that effects men with a wide range of age. The etiology, natural history and appropriate therapy models are still unclear. According to the classification of National Institutes of Health; 4 types of prostatitis were defined; acute bacterial prostatitis (category I, chronic bacterial prostatitis (category II, chronic nonbacterial prostatitis/chronic pelvic pain syndrome (category III and asymptomatic prostatitis (category IV.Since microorganisms can only be isolated from a small percent of patients, empiric treatment is given to the most of the men. Multidisciplinary approach to the patients with suspected chronic prostatitis will help clinicians to play an active role in the treatment and prevent unnecessary medical therapies. [Archives Medical Review Journal 2014; 23(4.000: 691-702

  18. Glucocorticoids in the treatment of asthma in children Los glucocorticoides en el tratamiento del asma en pediatría

    Directory of Open Access Journals (Sweden)

    Olga Francisca Salazar Blanco

    1998-04-01

    Full Text Available Today, asthma is considered an inflammatory disease; steroids could be the drugs of choice for its treatment since they work at different points of the asthmatic reaction, decreasing the infiltration of inflammatory cells, and inhibiting the production of some of them and the release of citokines and other proinflammatory agents; they also diminish mucus secretion in the submucosal glands, improve the response of B2 receptors to bronchodilators and reduce vascular permeability. These and other actions manifest themselves in clinical improvement, less frequent acute crises, hospitalizations and consultations, and lesser deterioration of pulmonary function. Though inhaled corticosteroids are safe and effective drugs in children, they must be used at minimal doses and during the shortest time required by patients. Inadequate use of systemic corticosteroids, either oral or parenteral, can have undesirable effects, some of them irreversible. Corticosteroids neither cure asthma nor reduce its mortality; that is the reason for the active search of other substances or strategies to reduce or block the inflammatory process or the disease itself. El asma se considera hoy una enfermedad inflamatoria para la cual los esteroides podrían ser fármacos de primera elección. Ellos actúan en diferentes puntos de la reacción asmática, disminuyen el infiltrado de células inflamatorias e inhiben la producción de algunas de ellas, así como la liberación de citoquinas y agentes proinflamatorios; reducen la secreción de moco en las glándulas submucosas, mejoran la respuesta de los receptores 82 a los broncodilatadores y controlan la permeabilidad vascular; éstas y otras acciones se traducen en una mejoría clínica de los pacientes que sufren crisis agudas, en disminución del número de hospitalizaciones y consultas y, a largo plazo, en un menor deterioro de la función pulmonar. Los esteroides por vía inhalatoria para el tratamiento del asma son f

  19. Glucocorticoid treatment skews human monocyte differentiation into a hemoglobin-clearance phenotype with enhanced heme-iron recycling and antioxidant capacity.

    Science.gov (United States)

    Vallelian, Florence; Schaer, Christian A; Kaempfer, Theresa; Gehrig, Peter; Duerst, Elena; Schoedon, Gabriele; Schaer, Dominik J

    2010-12-09

    Glucocorticoids are used extensively to treat autoimmune hemolytic anemias. Some beneficial effects of glucocorticoid pulse therapy have also been reported in sickle cell disease and paroxysmal nocturnal hemoglobinuria. Based on established concepts of hemoglobin (Hb) toxicity and physiologic Hb scavenger systems, we evaluated whether glucocorticoids could support an adaptive response to extracellular Hb independently of their immunosuppressive activities. Using global proteome and transcriptome analysis with mass-spectrometry (isobaric tag for relative and absolute quantitation and liquid chromatography-mass spectrometry) and gene-array experiments, we found that glucocorticoid treatment in vitro and in patients on glucocorticoid-pulse therapy polarized monocytes into a M2/alternatively activated phenotype with high Hb-scavenger receptor (CD163) expression and enhanced Hb-clearance and detoxification capability. Monocytes concurrently exposed to the interactive activity of glucocorticoids and extracellular Hb were characterized by high expression of a group of antioxidant enzymes known to be regulated by the conserved oxidative response transcription factor nuclear factor E2-related factor. Further, suppressed transferrin receptor, together with high ferroportin expression, pointed to a shift in iron homeostasis directed toward an increased cellular export of heme-derived iron. Therefore, stimulating Hb-endocytosis by CD163 and enhancing antioxidative homeostasis and iron recycling may be an essential activity of glucocorticoids that helps alleviate the adverse effects of extracellular Hb.

  20. Previous history of chronic stress changes the transcriptional response to glucocorticoid challenge in the dentate gyrus region of the male rat hippocampus.

    Science.gov (United States)

    Datson, Nicole A; van den Oever, Jessica M E; Korobko, Oksana B; Magarinos, Ana Maria; de Kloet, E Ronald; McEwen, Bruce S

    2013-09-01

    Chronic stress is a risk factor for several neuropsychiatric diseases, such as depression and psychosis. In response to stress glucocorticoids (GCs) are secreted that bind to mineralocorticoid and glucocorticoid receptors, ligand-activated transcription factors that regulate the transcription of gene networks in the brain necessary for coping with stress, recovery, and adaptation. Chronic stress particularly affects the dentate gyrus (DG) subregion of the hippocampus, causing several functional and morphological changes with consequences for learning and memory, which are likely adaptive but at the same time make DG neurons more vulnerable to subsequent challenges. The aim of this study was to investigate the transcriptional response of DG neurons to a GC challenge in male rats previously exposed to chronic restraint stress (CRS). An intriguing finding of the current study was that having a history of CRS had profound consequences for the subsequent response to acute GC challenge, differentially affecting the expression of several hundreds of genes in the DG compared with challenged nonstressed control animals. This enduring effect of previous stress exposure suggests that epigenetic processes may be involved. In line with this, CRS indeed affected the expression of several genes involved in chromatin structure and epigenetic processes, including Asf1, Ash1l, Hist1h3f, and Tp63. The data presented here indicate that CRS alters the transcriptional response to a subsequent GC injection. We propose that this altered transcriptional potential forms part of the molecular mechanism underlying the enhanced vulnerability for stress-related disorders like depression caused by chronic stress.

  1. Blunting Autoantigen-induced FOXO3a Protein Phosphorylation and Degradation Is a Novel Pathway of Glucocorticoids for the Treatment of Systemic Lupus Erythematosus.

    Science.gov (United States)

    Lu, Mudan; Xu, Wei; Gao, Bo; Xiong, Sidong

    2016-09-16

    Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease affecting multiple organs. Glucocorticoids (GCs), the potent anti-inflammatory drugs, remain as a cornerstone in the treatment for SLE; nevertheless, their clinical efficacy is compromised by the side effects of long term treatment and resistance. To improve the therapeutic efficacy of GCs in SLE, it is important to further decipher the molecular mechanisms of how GCs exert their anti-inflammatory effects. In this investigation, FOXO3a was identified as a molecule that was down-regulated in the course of SLE. Of interest, GC treatment was found to rescue FOXO3a expression both in SLE mice and in SLE patients. Gain- and loss-of-function studies demonstrated that FOXO3a played a crucial role in GC treatment of SLE via inhibiting inflammatory responses. Further studies showed that the up-regulation of FOXO3a by GCs relied on the suppression of pI3K/AKT-mediated FOXO3a phosphorylation and the arrest of FOXO3a in the nucleus. Finally, our data revealed that FOXO3a was critical for GC-mediated inhibition of NF-κB activity, which might involve its interaction with NF-κB p65 protein. Collectively, these data indicated that FOXO3a played an important role in GC treatment of SLE by suppressing pro-inflammatory response, and targeting FOXO3a might provide a novel therapeutic strategy against SLE.

  2. Disrupted secretory activation of the mammary gland after antenatal glucocorticoid treatment in sheep.

    Science.gov (United States)

    Henderson, Jennifer J; Hartmann, Peter E; Moss, Timothy J M; Doherty, Dorota A; Newnham, John P

    2008-11-01

    Antenatal glucocorticoids are administered to women at risk of preterm delivery to prevent neonatal respiratory morbidity. The effects of exogenous glucocorticoids on the development of lactation are unknown. This study investigated the effects of a single dose of antenatal glucocorticoids on secretory activation in sheep before and after parturition. Pregnant ewes (N=36) were randomised to receive either medroxyprogesterone acetate (MPA) at 118 days of pregnancy and betamethasone at 125 days (BETA group), MPA at 118 days and saline at 125 days (MPA group) or saline at 118 and 125 days (SALINE group). The concentration of lactose, progesterone, cortisol and prolactin in maternal plasma was measured during pregnancy. After term parturition, the concentration of lactose in milk and maternal plasma was measured daily for 5 days. Lambs were weighed at birth and at 5 days of age; milk volume was measured on day 5. The concentration of lactose in maternal plasma increased significantly after betamethasone administration, corresponding to a fall in plasma progesterone. No changes in lactose were observed in MPA or SALINE ewes. Transient decreases in cortisol and increases in prolactin were observed in the BETA group, but not in either the MPA or SALINE group. After parturition, BETA ewes experienced reduced milk yield and lamb weight gain, and delayed increases in milk lactose levels compared with MPA and saline controls. This study demonstrated that, in sheep, antenatal glucocorticoid administration disrupted secretory activation, causing precocious mammary secretion before parturition and compromising postpartum milk production and lamb growth.

  3. Treatment Option Overview (Chronic Myeloproliferative Neoplasms)

    Science.gov (United States)

    ... way to treat some chronic myeloproliferative neoplasms. Platelet apheresis Platelet apheresis is a treatment that uses a special machine ... using interferon alfa or pegylated interferon alpha . Platelet apheresis . A clinical trial of a new treatment. Check ...

  4. Treatment Options for Chronic Myeloproliferative Neoplasms

    Science.gov (United States)

    ... way to treat some chronic myeloproliferative neoplasms. Platelet apheresis Platelet apheresis is a treatment that uses a special machine ... using interferon alfa or pegylated interferon alpha . Platelet apheresis . A clinical trial of a new treatment. Check ...

  5. Implications of combined ovariectomy and glucocorticoid (dexamethasone) treatment on mineral, microarchitectural, biomechanical and matrix properties of rat bone.

    Science.gov (United States)

    Govindarajan, Parameswari; Khassawna, Thaqif; Kampschulte, Marian; Böcker, Wolfgang; Huerter, Britta; Dürselen, Lutz; Faulenbach, Miriam; Heiss, Christian

    2013-12-01

    Osteoporosis is one of the deleterious side effects of long-term glucocorticoid therapy. Since the condition is particularly aggressive in postmenopausal women who are on steroid therapy, in this study we have attempted to analyse the combined effect of glucocorticoid (dexamethasone) treatment and cessation of oestrogen on rat bone. The dual aim was to generate osteoporotic bone status in a short time scale and to characterise the combination of glucocorticoid-postmenopausal osteoporotic conditions. Sprague Dawley rats (N = 42) were grouped randomly into three groups: untreated control, sham-operated and ovariectomized-steroid (OVX-Steroid) rats. Control animals were euthanized with no treatment [Month 0 (M0)], while sham and OVX-Steroid rats were monitored up to 1 month (M1) and 3 months (M3) post laparotomy/post OVX-Steroid treatment. Histology, dual-energy X-ray absorptiometry (DXA), micro-computed tomography (micro-CT), and biomechanical and mRNA expression analysis of collagenous, non-collagenous matrix proteins and osteoclast markers were examined. The study indicated enhanced osteoclastogenesis and significantly lower bone mineral density (BMD) in the OVX-Steroid rats with Z-scores below -2.5, reduced torsional strength, reduced bone volume (BV/TV%), significantly enhanced trabecular separation (Tb.S), and less trabecular number (Tb.N) compared with sham rats. Osteoclast markers, cathepsin K and MMP 9 were upregulated along with Col1α1 and biglycan with no significant expression variation in fibronectin, MMP 14, LRP-5, Car II and TNC. These results show higher bone turnover with enhanced bone resorption accompanied with reduced torsional strength in OVX-Steroid rats; and these changes were attained within a short timeframe. This could be a useful model which mimics human postmenopausal osteoporosis that is associated with steroid therapy and could prove of value both in disease diagnosis and for testing generating and testing biological agents which could

  6. Withdrawal of inhaled glucocorticoids and exacerbations of COPD

    DEFF Research Database (Denmark)

    Magnussen, Helgo; Disse, Bernd; Rodriguez-Roisin, Roberto

    2014-01-01

    BACKGROUND: Treatment with inhaled glucocorticoids in combination with long-acting bronchodilators is recommended in patients with frequent exacerbations of severe chronic obstructive pulmonary disease (COPD). However, the benefit of inhaled glucocorticoids in addition to two long-acting bronchod......BACKGROUND: Treatment with inhaled glucocorticoids in combination with long-acting bronchodilators is recommended in patients with frequent exacerbations of severe chronic obstructive pulmonary disease (COPD). However, the benefit of inhaled glucocorticoids in addition to two long......-acting bronchodilators has not been fully explored. METHODS: In this 12-month, double-blind, parallel-group study, 2485 patients with a history of exacerbation of COPD received triple therapy consisting of tiotropium (at a dose of 18 μg once daily), salmeterol (50 μg twice daily), and the inhaled glucocorticoid...... fluticasone propionate (500 μg twice daily) during a 6-week run-in period. Patients were then randomly assigned to continued triple therapy or withdrawal of fluticasone in three steps over a 12-week period. The primary end point was the time to the first moderate or severe COPD exacerbation. Spirometric...

  7. Interaction of glucocorticoids with macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Werb, Z.; Foley, R.; Munck, A.

    1978-01-01

    The mononuclear phagocyte system plays a central role in mediating host responses in inflammation. Glucocorticoids have anti-inflammatory actions that may be of considerable importance in the therapeutic effects of these agents in chronic inflammation; it is possible that some of these effects are mediated through direct hormonal action on macrophages. Although the site of action of the glucocorticoids on macrophages has not been established, it has been shown that in many other glucocorticoid target systems the effects of glucocorticoids are mediated by specific macromolecular binding proteins, referred to as receptors. In this study we have established that monocytes and macophages contain saturable glucocorticoid-binding proteins, with specificity of binding for cortisol, corticosterone, and related synthetic steroids such as dexamethasone, and that they have dissociation constants for binding within physiological ranges.

  8. Alfacalcidol versus plain vitamin D in the treatment of glucocorticoid/inflammation-induced osteoporosis.

    Science.gov (United States)

    Ringe, Johann D; Faber, Herbert; Fahramand, Parvis; Schacht, Erich

    2005-09-01

    Treatment with plain vitamin D is a nutritional substitute, while the application of alfacalcidol is an active hormonal therapy. Due to strong feedback regulation, plain vitamin D is not activated in the kidney in vitamin-replete patients, while alfacalcidol, having been hydroxylated at position 1, bypasses regulation and increases available amounts of active D-hormone in different target tissues. Nevertheless, a majority of physicians still prescribe plain vitamin D plus calcium as a first-step prevention or even as therapy for glucocorticoid (GC) induced osteoporosis. This article summarizes results of our previous study comparing the therapeutic efficacy of the D-hormone analog alfacalcidol to plain vitamin D in patients with established GC induced osteoporosis with or without vertebral fracture. Patients taking longterm GC therapy were included as well-matched pairs to receive randomly either 1 microg alfacalcidol plus 500 mg calcium per day (group A, n = 103) or 1000 IU vitamin D3 plus 500 mg calcium (group B, n = 101). The mean bone mineral density (BMD) values at baseline for the 2 groups for alfacalcidol and vitamin D3, respectively, were: lumbar spine T score -3.26 and -3.25; femoral neck -2.81 and -2.84. Rates of prevalent vertebral and nonvertebral fractures were not different between groups. In the 3 year study we observed in the alfacalcidol group as compared with the plain vitamin D group, respectively: a 3 year median percentage increase of BMD at the lumbar spine of 2.4% versus -0.8% (p vitamin D group, respectively: a 3 year rate of patients with > or = 1 new vertebral fracture of 9.7% versus 24.8% (risk reduction: 0.61; 95% CI 0.24 to 0.81; p = 0.005); a 3 year rate of patients with > or = 1 new nonvertebral fracture of 15% versus 25% (risk reduction: 0.41; 95% CI -0.06 to 0.68; p = 0.081); a 3 year rate of patients with > or = 1 new fracture of any kind of 19.4% versus 40.6% (risk reduction: 0.52; 95% CI 0.25 to 0.71; p = 0.001). In accordance

  9. Glucocorticoids and the regulation of memory in health and disease.

    Science.gov (United States)

    de Quervain, Dominique J-F; Aerni, Amanda; Schelling, Gustav; Roozendaal, Benno

    2009-08-01

    Over the last decades considerable evidence has accumulated indicating that glucocorticoids - stress hormones released from the adrenal cortex - are crucially involved in the regulation of memory. Specifically, glucocorticoids have been shown to enhance memory consolidation of emotionally arousing experiences, but impair memory retrieval and working memory during emotionally arousing test situations. Furthermore, growing evidence indicates that these different glucocorticoid effects all depend on emotional arousal-induced activation of noradrenergic transmission within the basolateral complex of the amygdala (BLA) and on interactions of the BLA with other brain regions, such as the hippocampus and neocortical regions. Here we review findings from both animal and human experiments and present an integrated perspective of how these opposite glucocorticoid effects might act together to serve adaptive processing of emotionally significant information. Furthermore, as intense emotional memories also play a crucial role in the pathogenesis and symptomatology of anxiety disorders, such as posttraumatic stress disorder (PTSD) or phobias, we discuss to what extent the basic findings on glucocorticoid effects on emotional memory might have implications for the understanding and treatment of these clinical conditions. In this context, we review data suggesting that the administration of glucocorticoids might ameliorate chronic anxiety by reducing retrieval of aversive memories and enhancing fear extinction.

  10. Unilateral adrenal tumor, erectile dysfunction and infertility in a patient with 21-hydroxylase deficiency: effects of glucocorticoid treatment and surgery.

    Science.gov (United States)

    Scaroni, C; Favia, G; Lumachi, F; Opocher, G; Bonanni, G; Mantero, F; Armanini, D

    2003-02-01

    In untreated congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHDS) the presence of adrenal and testicular tumors had been described; however little is known about the effect of the enzymatic defect on fertility in males. We studied a male adult patient affected by 21OHDS for infertility, after a long period of discontinuation of glucocorticoid therapy and then during resumption of treatment and 8 months after monoadrenalectomy. The initial spermatic count revealed azoospermia and testicular needle aspiration showed a cytological picture consistent with prepuberty. The morphofunctional study revealed a right adrenal mass with reduced uptake at radioscan. Treatment was resumed with onset of impotency, which improved after reduction of the dose of glucocorticoids. The patient was monoadrenalectomised and his spermatic count increased. The patient shows that corticosteroid therapy in 21OHDS should be continued lifelong to avoid adrenal hyperplasia with possible areas of autonomy and to allow regular fertility. Impotence during treatment is probably due to a decrease of excessive adrenal androgens while testicular androgen production is still suppressed.

  11. Use of recombinant feline interferon and glucocorticoid in the treatment of feline infectious peritonitis.

    Science.gov (United States)

    Ishida, T; Shibanai, A; Tanaka, S; Uchida, K; Mochizuki, M

    2004-04-01

    A total of 12 clinically ill cats previously diagnosed as feline infectious peritonitis (FIP) were treated with a combination of recombinant feline interferon and glucocorticoid. A complete remission (over 2 years) and a partial remission (2 to 5 months) were observed in four (33.3%) and four (33.3%) cases, respectively. Those that survived for more than 2 years were all older cats (6 to 16 years old) with the effusive form of FIP.

  12. Synapse loss from chronically elevated glucocorticoids: relationship to neuropil volume and cell number in hippocampal area CA3.

    Science.gov (United States)

    Tata, Despina A; Marciano, Veronica A; Anderson, Brenda J

    2006-09-20

    Individuals with clinical disorders associated with elevated plasma glucocorticoids, such as major depressive disorder and Cushing's syndrome, are reported to have smaller hippocampal volume. To understand how the hippocampus responds at the cellular and subcellular levels to glucocorticoids and how such changes are related to volume measures, we have undertaken a comprehensive study of glucocorticoid effects on hippocampal CA3 volume and identified elements in the neuropil including astrocytic volume and cell and synapse number and size. Male Sprague-Dawley rats were injected with corticosterone (40 mg/kg), the primary glucocorticoid in rodents, or vehicle for 60 days. The CA3 was further subdivided so that the two-thirds of CA3 (nearest the dentate gyrus) previously shown to be vulnerable to corticosterone could be analyzed as two separate subfields. Corticosterone had no effect on neuropil volume or glial volume in the proximal subfield but caused a strong tendency for astrocytic processes to make up a larger proportion of the tissue and for volume of tissue made of constituents other than glial cells (primarily neuronal processes) to be smaller in the middle subfield. Within the neuropil, there were no cellular or subcellular profiles that indicated degeneration, suggesting that corticosterone does not cause prolonged damage. Corticosterone did not reduce cell number or cell or nonperforated synapse size but did cause a pronounced loss of synapses. This loss occurred in both subfields and, therefore, was independent of volume loss. Together, the findings suggest that volume measures can underestimate corticosterone effects on neural structure.

  13. Management and treatment of chronic urticaria (CU).

    Science.gov (United States)

    Maurer, M; Church, M K; Gonçalo, M; Sussman, G; Sánchez-Borges, M

    2015-06-01

    Developments increasing our understanding of chronic urticaria have resulted in the simplification and improvement of available treatments. Currently, many treatments target mast cell mediators, but we can now disrupt mast cell activation with the anti-IgE antibody omalizumab, which has markedly advanced the treatment landscape for patients with difficult-to-treat urticaria. Current guidelines provide a framework for the management and treatment of patients with CU but, as each patient is different, knowledge and experience of specialist dermatologists and allergists are key to effective pharmacotherapy. This article reviews the different therapeutic options for patients with chronic spontaneous urticaria (also called chronic idiopathic urticaria) or chronic inducible urticaria and discusses management of special populations or special circumstances related to CU.

  14. [Operative treatment of chronic pleuritis].

    Science.gov (United States)

    Duzhyĭ, I D; Hres'ko, I Ia; Chumak, S O; Elastal, R Z

    2008-09-01

    Basing on the literature data and own experience, grounded on results of follow-up on 2000 patients, suffering an acute pleuritis and performance of more than 200 operative interventions--pleurectomy, the clinic-radiological classification of chronic pleuritis, mostly answering the practical health care necessities, was proposed by the authors.

  15. Computers in the treatment of chronic aphasia.

    Science.gov (United States)

    Katz, Richard C

    2010-02-01

    Computers and related technology can increase the amount of treatment received by adults with chronic aphasia. Computers used in treatment, however, are only valuable to the patient if the intervention is efficacious. Real and potential applications of computer technology are discussed in the context of three roles of computerized aphasia treatment for adults with chronic aphasia. Pertinent studies regarding Phases 1 and 2 are briefly described. The only Phase 3 study of efficacy of computerized aphasia treatment is more fully described and its implications discussed.

  16. Omalizumab in the treatment of chronic urticaria.

    Science.gov (United States)

    Francés, L; Leiva-Salinas, M; Silvestre, J F

    2014-01-01

    Omalizumab is a monoclonal anti-immunoglobulin E antibody currently only approved for use in severe, refractory asthma. In recent years, many authors have reported satisfactory results with omalizumab in patients with difficult-to-treat chronic urticaria. As a result, clinical trials were undertaken to broaden the indication of omalizumab to include chronic urticaria, and the drug was recently cited as a third-line treatment after selective antihistamines at high doses in a consensus document on the treatment of chronic urticaria. In this article our aim is to provide a comprehensive update on the use of omalizumab in the treatment of chronic urticaria. The structure of this biologic agent and its possible mechanisms of actions in this setting will be presented. Treatment strategies and the different dosage regimens used in the series of cases published to date will also be reviewed. Finally, we will discuss the adverse effects that may arise with treatment and the recommended strategies for minimizing the most feared effect, anaphylaxis. Based on the experience of many researchers, omalizumab is emerging as a novel treatment for certain types of spontaneous refractory chronic urticaria and has shown promising results in this setting. The drug has a good safety profile and the main limitation is its high cost.

  17. Chronic migraine--classification, characteristics and treatment

    DEFF Research Database (Denmark)

    Diener, Hans-Christoph; Dodick, David W; Goadsby, Peter J

    2012-01-01

    According to the revised 2nd Edition of the International Classification of Headache Disorders, primary headaches can be categorized as chronic or episodic; chronic migraine is defined as headaches in the absence of medication overuse, occurring on =15 days per month for =3 months, of which...... headaches on =8 days must fulfill the criteria for migraine without aura. Prevalence and incidence data for chronic migraine are still uncertain, owing to the heterogeneous definitions used to identify the condition in population-based studies over the past two decades. Chronic migraine is severely...... disabling and difficult to manage, as affected patients experience substantially more-frequent headaches, comorbid pain and affective disorders, and fewer pain-free intervals, than do those with episodic migraine. Data on the treatment of chronic migraine are scarce because most migraine-prevention trials...

  18. Rituximab treatment for symptomatic chronic ITP

    NARCIS (Netherlands)

    Tamminga, Rienk Y. J.; Bruin, Marrie C. A.

    2006-01-01

    About 20% of the children diagnosed with acute idiopathic thrombocytopenic purpura (ITP) will run a chronic course. Only in a minority of these, platelet-count-enhancing treatments are indicated. Most treatment options are directed at decreasing platelet destruction including corticosteroids, intrav

  19. Treatment of refractory chronic urticaria

    Directory of Open Access Journals (Sweden)

    Aayushi Mehta

    2015-01-01

    Full Text Available Chronic spontaneous urticaria is a distressing disease encountered frequently in clinical practice. The current mainstay of therapy is the use of second-generation, non-sedating antihistamines. However, in patients who do not respond satisfactorily to these agents, a variety of other drugs are used. This article examines the available literature for frequently used agents including systemic corticosteroids, leukotriene receptor antagonists, dapsone, sulfasalazine, hydroxychloroquine, H2 antagonists, methotrexate, cyclosporine A, omalizumab, autologous serum therapy, and mycophenolate mofetil, with an additional focus on publications in Indian literature.

  20. New treatment of chronic hepatitis B

    DEFF Research Database (Denmark)

    Andersen, E.S.; Weis, Nina

    2008-01-01

    Worldwide, 350 million people are infected with chronic hepatitis B. Over the last few years, it has been possible to treat chronic hepatitis B. Treatment very often consists of nucleos(t)ide analogs and in a few cases of pegylated alpha-interferon. In 2007, a new nucleoside analog, Telbivudine......, was approved to treat chronic hepatitis B. In phase II and ongoing phase III studies, Telbivudine has proven more effective than the nucleoside analog, Lamivudine, which was very often used up until recently Udgivelsesdato: 2008/11/24...

  1. Effects of glucocorticoid treatment given in early or late gestation on growth and development in sheep.

    Science.gov (United States)

    Li, S; Sloboda, D M; Moss, T J M; Nitsos, I; Polglase, G R; Doherty, D A; Newnham, J P; Challis, J R G; Braun, T

    2013-04-01

    Antenatal corticosteroids are used to augment fetal lung maturity in human pregnancy. Dexamethasone (DEX) is also used to treat congenital adrenal hyperplasia of the fetus in early pregnancy. We previously reported effects of synthetic corticosteroids given to sheep in early or late gestation on pregnancy length and fetal cortisol levels and glucocorticoids alter plasma insulin-like growth factor (IGF) and insulin-like growth factor binding protein (IGFBP) concentrations in late pregnancy and reduce fetal weight. The effects of administering DEX in early pregnancy on fetal organ weights and betamethasone (BET) given in late gestation on weights of fetal brain regions or organ development have not been reported. We hypothesized that BET or DEX administration at either stage of pregnancy would have deleterious effects on fetal development and associated hormones. In early pregnancy, DEX was administered as four injections at 12-hourly intervals over 48 h commencing at 40-42 days of gestation (dG). There was no consistent effect on fetal weight, or individual fetal organ weights, except in females at 7 months postnatal age. When BET was administered at 104, 111 and 118 dG, the previously reported reduction in total fetal weight was associated with significant reductions in weights of fetal brain, cerebellum, heart, kidney and liver. Fetal plasma insulin, leptin and triiodothyronine were also reduced at different times in fetal and postnatal life. We conclude that at the amounts given, the sheep fetus is sensitive to maternal administration of synthetic glucocorticoid in late gestation, with effects on growth and metabolic hormones that may persist into postnatal life.

  2. [Local invasive treatment of chronic pain].

    Science.gov (United States)

    Medvedeva, L A; Zagorul'ko, O I; Gnezdilov, A V

    2014-01-01

    The literature on methods of invasive local treatment of chronic pain was analyzed. We reviewed 14 publications including meta-analyses and systematic reviews. The use of regional anesthesia conducted by anesthesiologists in pain clinics demonstrated the evidence based efficacy of different types of peridural injections of local anesthetics with steroids in patients with root pain syndromes at cervical and lumbar levels. Therapeutic blockades of the occipital nerve is effective method of treatment of cervicogenic and cluster headache as well as occipital nerve neuralgia. There are clear indications of the efficacy of local injections in primary chronic cephalgia (migraine and headache of tension). The possibility of the abortion of the pain information flow in peripheral nociceptive pathways and, as a consequence, breaking the vicious circle is emphasized. Issues on the efficacy of local injections at trigger points in the treatment of chronic pain are highlighted.

  3. Effects of chronic academic stress on mental state and expression of glucocorticoid receptor α and β isoforms in healthy Japanese medical students.

    Science.gov (United States)

    Kurokawa, Ken; Tanahashi, Toshihito; Murata, Akiho; Akaike, Yoko; Katsuura, Sakurako; Nishida, Kensei; Masuda, Kiyoshi; Kuwano, Yuki; Kawai, Tomoko; Rokutan, Kazuhito

    2011-07-01

    Chronic academic stress responses were assessed by measuring mental state, salivary cortisol levels, and the glucocorticoid receptor (GR) gene expression in healthy Japanese medical students challenging the national medical license examination. Mental states of 17 male and 9 female medical undergraduates, aged 25.0 ± 1.2 years (mean ± SD), were assessed by the State and Trait Anxiety Inventory (STAI) and the Self-Rating Depression Scale (SDS) 2 months before, 2 days before, and 1 month after the examination. At the same time points, saliva and blood were collected. STAI-state scores peaked 2 days before the examination. Scores on STAI-trait and SDS, and salivary cortisol levels were consistently higher during the pre-examination period. One month after the examination, all these measures had significantly decreased to baseline levels. Real-time reverse transcription PCR showed that this chronic anxious state did not change the expression of the functional GRα mRNA isoform in peripheral leukocytes, while it resulted in reduced expression of the GRβ isoform 2 days before the examination. Our results replicate and extend a significant impact of chronic academic stressors on the mental state of healthy Japanese medical students and suggest a possible association of GRβ gene in response to psychological stress.

  4. 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.

    Science.gov (United States)

    Trujillo, Verónica; Durando, Patricia E; Suárez, Marta M

    2016-01-01

    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.

  5. Update on the treatment of chronic urticaria.

    Science.gov (United States)

    Curto-Barredo, L; Silvestre, J F; Giménez-Arnau, A M

    2014-06-01

    Chronic spontaneous urticaria, also known as chronic idiopathic urticaria or simply chronic urticaria, is a common disorder that has a prevalence in the general population that ranges between 0.5% and 1%. This condition negatively affects the patient's quality of life and has considerable impact on direct and indirect health-related costs. Chronic urticaria is difficult to manage. Nonsedating H1 antihistamines are the first line of therapy, but fewer than 50% of patients experience relief at recommended dosages. Although guidelines call for increasing the dosage when response is inadequate, some patients still do not achieve adequate control of symptoms. New treatment alternatives, with proven efficacy under the standards of evidence-based medical practice, must therefore be developed.

  6. The molecular basis for the effectiveness, toxicity, and resistance to glucocorticoids : focus on the treatment of rheumatoid arthritis

    NARCIS (Netherlands)

    Buttgereit, F; Saag, KG; Cutolo, M; da Silva, JAP; Bijlsma, JWJ

    2005-01-01

    Glucocorticoids (GCs) have powerful and potent anti-inflammatory and immunomodulatory effects in rheumatoid arthritis ( RA) and many other diseases. These effects are mediated by up to four different mechanisms of action: cytosolic glucocorticoid receptor (cGCR)-mediated classical genomic and rapid

  7. Neuroendocrine-immune interactions in rheumatoid arthritis: mechanisms of glucocorticoid resistance.

    Science.gov (United States)

    Silverman, Marni N; Sternberg, Esther M

    2008-01-01

    Rheumatoid arthritis (RA) is characterized by chronic inflammation of the synovial membrane, leading to joint destruction. Many autoimmune diseases and disease states of chronic inflammation are accompanied by alterations in the complex interactions between the endocrine, nervous and immune systems. Glucocorticoids, an end product of the hypothalamic-pituitary-adrenal axis, are a mainstay treatment for many autoimmune diseases, including RA, because of their potent anti-inflammatory action. However, about 30% of patients with RA fail to respond to steroid therapy. There are various mechanisms that may contribute to the development of glucocorticoid resistance in inflammatory disorders, which will be the subject of this review. In addition, glucocorticoid resistance may be a contributing factor in the development of inflammatory/autoimmune diseases themselves. Therefore, further elucidation of these mechanisms will reveal new targets for therapeutic intervention in the treatment of RA.

  8. [Systemic glucocorticoid therapy: associated measures].

    Science.gov (United States)

    Sailler, L; Pugnet, G; Arlet, P

    2013-05-01

    Long-term treatment with glucocorticoids results in many adverse effects. Prevention of osteoporosis is well codified, but prevention of other adverse effects is not. If there is some consensus on the prevention of glucocorticoid-induced adverse events, there are also many habits since interventional studies are lacking. A low caloric and low carbohydrate diet as well as a regular physical training are certainly necessary to avoid lipodystrophy, weight gain and diabetes mellitus. Some patients benefit from the repeated intervention of a dietetic or nutrition specialist. Physical training is often neglected though it is efficacious to limit severity of glucocorticoid-induced myopathy and probably to reduce vascular risk. Low sodium intake has no effect on lipodystrophy and its efficacy to prevent hypertension is doubtful. Benzodiazepines may be useful against anxiety, insomnia and nervousness when these symptoms are cumbersome. Anti-ulcer drugs are generally not indicated because glucocorticoids are not ulcerogenic. Hypokaliemia rarely occurs, so we prefer controlling serum potassium level 1 and 3 months after glucocorticoid initiation rather than systematically prescribe potassium supplementation. Patients on glucocorticoids are at increased risk for cardiovascular events. Due to the lack of studies specific to patients on long-term glucocorticoid therapy, the rules for the prescription of statins are the same as in the general population. There is no known prevention for cutaneous atrophy. However, use of adhesive tape should be strictly avoided when skin atrophy is severe. Prevention of infections is developed elsewhere.

  9. [Latex ligation in treatment of chronic hemorrhoids].

    Science.gov (United States)

    Ektov, V N; Somov, K A

    2015-01-01

    We analyzed the results of treatment of 432 patients with chronic hemorrhoids using different variants of latex ligation. New technique including ligation of mucosa and submucosa of low-ampullar rectum providing ligation of hemorrhoidalvessels, lifting and recto-anal repair is developed and suggested. This method is advisable to use in case of chronic internal hemorrhoids stages I and II. The authors recommend simultaneous combined ligation of mucosa of low-ampullar rectum and internal hemorrhoids for stages III and IV. Different variants of latex ligation with external hemorrhoids excision were used in 103 patients. Pointed variants of latex ligation preserve important advantages including mini-invasiveness, simplicity and wide availability, low cost. Good remote results were obtained after these procedures in 87.3% of observations. Suggested tactics extends use of latex ligation and increases its effectiveness in treatment of different stages and forms of chronic hemorrhoids.

  10. Lubiprostone: a novel treatment for chronic constipation.

    Science.gov (United States)

    Lacy, Brian E; Levy, L Campbell

    2008-01-01

    Chronic constipation is highly prevalent, reduces patients' quality of life, and imposes a significant health care burden on society. Lifestyle modifications and over-the-counter agents improve symptoms of constipation in some patients, however many patients have persistent symptoms and require the use of prescription medications. Three prescription medications are currently Food and Drug Administration (FDA) approved and available for the treatment of chronic constipation in adults. This review will focus on lubiprostone, the newest medication available for the treatment of chronic constipation. Lubiprostone is a bicyclic fatty acid metabolite analogue ofprostaglandin E1. It activates specific chloride channels in the gastrointestinal tract to stimulate intestinal fluid secretion, increase gastrointestinal transit, and improve symptoms of constipation. This article will provide a brief overview on chloride channel function in the gastrointestinal tract, describe the structure, function, and pharmacokinetics of lubiprostone, and discuss the safety and efficacy of this new medication.

  11. Chronic hepatitis C: future treatment

    Directory of Open Access Journals (Sweden)

    Wendt A

    2014-01-01

    Full Text Available Astrid Wendt, Xavier Adhoute, Paul Castellani, Valerie Oules, Christelle Ansaldi, Souad Benali, Marc BourlièreDepartment of Hepato-Gastroenterology, Hôpital Saint-Joseph, Marseille, FranceAbstract: The launch of first-generation protease inhibitors (PIs is a major step forward in HCV treatment. However, the major advance is up to now restricted to genotype 1 (GT-1 patients. The development of second-wave and second-generation PIs yields higher antiviral potency through plurigenotypic activity, more convenient daily administration, fewer side effects and, for the second-generation PIs, potential activity against resistance-associated variants. NS5B inhibitors include nucleoside/nucleotide inhibitors (NIs and non-nucleotide inhibitors (NNIs. NIs have high efficacy across all genotypes. Sofosbuvir has highly potent antiviral activity across all genotypes in association with pegylated interferon and ribavirin (PR, thus allowing shortened treatment duration. NS5A inhibitors (NS5A.I have highly potent antiviral activity. It has recently been shown for the first time that NS5A.I in combination with protease inhibitors can cure GT-1b null responders in an interferon-free regimen. Besides, several studies demonstrate that interferon (IFN-free regimens with direct-acting antiviral agent combinations are able to cure a large number of either naïve or treatment-experienced GT-1 patients. Moreover, quadruple regimen with PR is able to cure almost all GT-1 null responders. The development of pan-genotypic direct-acting antiviral agents (NIs or NS5A.I allows new combinations with or without PR that increase the rate of sustained virological response for all patients, even for those with cirrhosis and independently of the genotype. Therefore, the near future of HCV treatment looks promising. The purpose of this article is to provide an overview of the clinical results recently reported for HCV treatment.Keywords: SVR, direct antiviral agents, host

  12. Tumour necrosis factor-α inhibitors are glucocorticoid-sparing in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Nilsson, Anna Christine; Christensen, Anne Friesgaard; Junker, Peter;

    2011-01-01

    Rheumatoid arthritis (RA) is a chronic disease with autoimmune traits of unknown aetiology which primarily affects synovial joints. Glucocorticoids (GCs) are still widely used in RA treatment despite the expanding use of targeted and very efficient agents. The objective of this study was to assess...

  13. Pathogenesis of cigarette smoke-induced chronic obstructive pulmonary disease and therapeutic effects of glucocorticoids and N-acetylcysteine in rats

    Institute of Scientific and Technical Information of China (English)

    徐凌; 蔡柏蔷; 朱元珏

    2004-01-01

    Background T lymphocytes and matrix metalloproteinase (MMP) play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the details of the mechanisms involved are unclear. The aims of this study were to investigate the changes in interferon-γ (IFN-γ), interleukin-4 (IL-4), MMP-9, MMP-12 and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels in a smoke-induced COPD rat model and the therapeutic effects of glucocorticoids and N-acetylcysteine.Methods Male Wistar rats were exposed to cigarette smoke for 3.5 months. Budesonide or N-acetylcysteine was given in the last month. Lung function was measured at the end of the study. IL-4 and IFN-γ levels were then determined in bronchoalveolar lavage fluid and lung tissue samples by enzyme-linked immunosorbent assay. The expression of MMP-9, MMP-12 and TIMP-1 mRNA in lung tissue was determined by RT-PCR. Results In comparison with the control group, rats exposed to smoke had a significant increase in IL-4 and MMP-12 levels and a significant decrease in IFN-γ levels. In addition, the IL-4/ IFN-γ ratio and MMP-12/TIMP-1 ratio were both higher. At the same time, the ratio of forced expiratory volume in 0.3 second to forced vital capacity (FEV0.3/FVC) and dynamic compliance (Cdyn) decreased and expiratory resistance (Re) increased. By measuring pulmonary mean linear intercept and mean alveolar numbers, obvious emphysematous changes were observed in the smoke exposed group. After treatment with budesonide, IL-4 and MMP-12 decreased and IFN-γ increased. The IL-4/IFN-γ ratio returned to normal, though the MMP-12/TIMP-1 ratio remained unchanged. FEV0.3/FVC was significantly higher and Re was significantly lower than that in untreated smoke exposed rats. No significant differences were found in pulmonary mean linear intercept and mean alveolar numbers. After treatment with N-acetylcysteine, IFN-γ increased and the IL-4/IFN-γ ratio decreased. The MMP-12/TIMP-1 ratio remained

  14. Osteoporosis inducida por glucocorticoides Glucocorticoid induced osteoporosis

    Directory of Open Access Journals (Sweden)

    R. Gutiérrez-Polo

    2003-01-01

    . Corticoid-induced osteoporosis is the main adverse event deriving from their systemic and long-term administration, being the most frequent cause of secondary osteoporosis. This implies an important health and socio-economic repercussion due to the complications it causes, such as fragility fractures, above all of vertebral origin, and the resultant functional incapacity. The bone loss is produced early, being greatest in the first few months of glucocorticoid use, in relation fundamentally to daily dose. The pathogenesis of this type of osteoporosis is multifactorial, but the inhibitory effect of corticoids on bone formation can be emphasised. The adequate management of this serious health problem requires an active attitude that is currently suboptimal. It involves similar diagnostic, preventive and therapeutic recommendations available for other, different causes of bone loss, but with certain particularities, especially including those referring to the self-management of corticosteroids. A multidisciplinary strategy is advisable, which has shown its effectiveness, mainly if it is carried out early, from the start of glucocorticoid therapy. Nevertheless, there are many questions to be clarified about aspects relating to therapy with corticosteroids in general, and to the osteoporosis caused by them in particular. What is needed is the evaluation and investigation of new treatments that will improve the effectiveness obtained with those in current use, in order to minimize the adverse consequences that glucocorticoid use has for the health of patients.

  15. Treatment of chronic inflammatory demyelinating polyradiculoneuropathy.

    Science.gov (United States)

    Lehmann, Helmar C; Hughes, Richard A C; Hartung, Hans-Peter

    2013-01-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a sporadically occurring, acquired neuropathic condition of autoimmune origin with chronic progressive or relapsing-remitting disease course. CIDP is a treatable disorder; a variety of immunosuppressive and immunomodulatory agents are available to modify, impede, and even reverse the neurological deficits and sequelae that manifest in the course of the disease. However, in many cases CIDP is not curable. Challenges that remain in the treatment of CIDP patients are well recognized and include a remarkably individual heterogeneity in terms of disease course and treatment response as well as a lack of objective and feasible measures to predict and monitor the responsiveness to the available therapies. In this chapter an overview of the currently used drugs in the treatment of CIDP patients is given and some important and controversial issues that arise in the context of care for CIDP patients are discussed.

  16. Chronic migraine: current concepts and ongoing treatments.

    Science.gov (United States)

    Negro, A; Rocchietti-March, M; Fiorillo, M; Martelletti, P

    2011-12-01

    Migraine is an episodic painful disorder occasionally developing into a chronic form. Such disorder represents one of the most common neurological diseases in clinical practice. Chronicization is often accompanied by the appearance of acute drugs overuse. Chronic migraine (CM) constitutes migraine's natural evolution in its chronic form and involves headache frequency of 15 days/month, with features similar to those of migraine attacks. Medication Overuse Headache (MOH) has been defined as a headache present on > or = 15 days/month, with regular overuse for > 3 months of one or more drugs used for acute and/or symptomatic headache management. Subtypes of MOH attributed to different medications were delineated. Misuse of ergots, triptans, opioids or combination analgesics on > or = 10 days/month was required to make the diagnosis of MOH, while > or = 15 days/month were needed for simple analgesic-overuse headache. CM's low prevalence produces an extremely high disability grade. Therefore, special attention should be paid to both control and reduction of risk factors which might favour the migraine chronicization process and/or the outbreak of MOH. In MOH sufferers, the only treatment of choice is represented by drug withdrawal. Successful detoxification is necessary to ensure improvement in the headache status when treating patients who overuse acute medications. Different procedures have been suggested for withdrawal namely at home, at the hospital, with or without the use of steroids, with re-prophylaxis performed immediately or at the end of the washout period. At the moment we have not a total agreement whether prophylactic treatment should be started before, during, or after discontinuation of the overuse drug. Both drugs have been approved for CM treatment in view of their well-defined resistance to previous prophylaxis drugs. Recently, the PREEMPT clinical program has confirmed onabotulinumtoxinA as an effective, safe, and well-tolerated prophylactic

  17. Sofosbuvir for treatment of chronic hepatitis C.

    Science.gov (United States)

    Kattakuzhy, Sarah; Levy, Rachel; Kottilil, Shyam

    2015-04-01

    Chronic hepatitis C is a leading cause of liver-related morbidity and mortality worldwide. If untreated, chronic hepatitis C can progress to advanced liver fibrosis, cirrhosis, liver failure, hepatocellular carcinoma and death. Until recently, treatment of hepatitis C predominantly constituted an immunomodulatory agent, peg-interferon-alfa and ribavirin. In 2011, the first class of directly acting antiviral agents, HCV NS3/4A serine protease inhibitors, was added to peg-interferon-alfa and ribavirin with increased efficacy. In the past year, an NS5B inhibitor, sofosbuvir, has emerged as a potent agent with pangenotypic efficacy, resulting in the first interferon-free regimen for the treatment of hepatitis C. This review summarizes the data that resulted in regulatory approval of sofosbuvir and highlights the future of hepatitis C therapy with sofosbuvir as the backbone of a highly effective antiviral regimen.

  18. Treatment of Lateral Epicondylitis With Platelet-Rich Plasma, Glucocorticoid, or Saline

    DEFF Research Database (Denmark)

    Krogh, Thøger Persson; Fredberg, Ulrich; Stengaard-Pedersen, Kristian

    2013-01-01

    Lateral epicondylitis (LE) is a common musculoskeletal disorder for which an effective treatment strategy remains unknown.......Lateral epicondylitis (LE) is a common musculoskeletal disorder for which an effective treatment strategy remains unknown....

  19. Glucocorticoid-induced apoptosis and cellular mechanisms of myopathy.

    Science.gov (United States)

    Dirks-Naylor, Amie J; Griffiths, Carrie L

    2009-10-01

    Glucocorticoid-induced myopathy is a common side effect of chronic glucocorticoid therapy. Several mechanisms are currently being examined as ways in which glucocorticoid-induced myopathy occurs. These include apoptotic signaling through mitochondrial-mediated and Fas-mediated apoptosis, the role of the proteosome, the suppression of the IGF-1 signaling, and the role of ceramide in glucocorticoid-induced apoptosis and myopathy. It is difficult to differentiate which mechanism may be the initiating event responsible for the induction of apoptosis; however, all of the mechanisms play a vital role in glucocorticoid-induced myopathy.

  20. Peginterferon Treatment In Children: A Review Of Chronic Hepatitis B And Chronic Hepatitis C Treatment

    Directory of Open Access Journals (Sweden)

    Makbule EREN

    2009-11-01

    Full Text Available Despite of extensive blood product screening and national immunization programs, chronic hepatitis B and C infections continues to be a global problem with high mortality, morbidity and economic impact. Even though acquisition of these infections mostly occurs in childhood, major problems appear in adulthood. Cirrhosis and HCC are two major expected late events related to chronic hepatitis B and C infections. Rarely, children may also face these complications. To avoid these complications and increase the life expectancy in adults treatment of these two type infections should be started in childhood with appropriate patient selection. In contrast to children, adults are luckier in terms of treatment alternatives. They have the chance to use more potent antivirals with higher genetic barrier and pegylated form of interferons. Recently, the use of pegylated interferon and ribavirin combinations has been approved in children in Chronic HCV infection. However, chronic hepatitis B treatment in children is still dependent on the use of one type antiviral drug and conventional interferon. Treatment in early ages with an antiviral agent that has limited genetic barrier may block the chance of treatment or reduce the response rate in adulthood in chronic hepatitis B infection. This burden indicates the necessity of new therapeutic modalities in children. In this term pegylated interferons may be one of the optiones. In this article we aimed to reviewe the efficacy and safety of conventional and pegylated interferons, for the treatment of Hepatitis C and B infections in children.

  1. Short term administration of glucocorticoids in patients with protracted and chronic gout arthritis. Part III – frequency of adverse events

    Directory of Open Access Journals (Sweden)

    A A Fedorova

    2009-01-01

    Full Text Available Objective. To assess frequency of adverse events during short term administration of gluco- corticoid (GC in protracted and chronic gout arthritis. Material and methods. 59 pts with tophaceous gout (crystal-verified diagnosis and arthritis of three and more joints lasting more than a months in spite of treatment with sufficient doses of nonsteroidal anti-inflammatory drugs were included. Median age of pts was 56 [48;63], median disease duration – 15,2 years [7,4;20], median swollen joint count at the examination – 8 [5;11]. The patients were randomized into 2 groups. Methylprednisolone (MP 500 mg/day iv during 2 days and placebo im once was administered in one of them, betamethasone (BM 7 mg im once and placebo iv twice – in the other. Clinical evaluation of inflamed joints was performed every day. Standard laboratory examination and ECG were done before drug administration, at 3rd, 7th, and 14th day of follow up. Immunoreactive insulin level was evaluated before drug administration and at day 14. Blood pressure (BP was measured every day. Results. After first GC administration BP elevated in 28 (47% pts. In pts not having appropriate BP values BP elevated in 73% of cases. Pts with appropriate BP values showed less frequent BP elevation – 38% (p=0,02. In 8 (13% pts at day 3 after GC administration ECG signs of myocardial blood supply deterioration were revealed. Glucose level elevated in 10 (17% pts and after the second BM administration – in 5 (8% pts. Cholesterol level did not significantly change after 14 days of follow up but in 28 (47% pts it increased in comparison with baseline. Trigliceride level significantly decreased at day 14 from 149 [106; 187] to 108 [66,5; 172] mg/dl (p=0,02. 26 (44% pts had face hyperemia, 4 (7% –42 palpitation and 2 (3,4% – bitter taste. Conclusion. Administration of short course of GC in pts with gout requires monitoring of possible adverse events. Antihypertensive therapy providing appropriate BP

  2. [Chronic prostatitis: a new paradigm of treatment].

    Science.gov (United States)

    Bozhedomov, V A

    2016-08-01

    This paper proposes health care recommendations for men with chronic prostatitis (CP) taking into account etiopathogenesis and the clinical presentation of the disease. The proposal is based on the experience of federal and regional clinics of urology and gynecology, respective departments for postgraduate education and on the analysis of scientific literature. It is shown that managing patients with CP requires consideration of factors beyond the traditional practice of urology. The author validates the need to use the modern prostatitis classification UPOINT instead of the traditional NIH NIDDK (1995) to increase the effectiveness of treatment. It is demonstrated that the concurrent use of medications and non-pharmacological treatments aimed at different aspects of the state improve the treatment effectiveness. Indications are refined for medical and non-pharmacological treatments: antibiotics, alpha-blockers, anticholinergic agents, analgesics, antidepressants, herbal remedies, pelvic floor physiotherapy, psychotherapy. The shortcomings and mistakes of existing guidelines/standards are analyzed.

  3. [New treatments for chronic obstructive pulmonary disease].

    Science.gov (United States)

    Miravitlles, Marc

    2005-06-11

    Treatment of chronic obstructive pulmonary disease (COPD) has underwent a very important advance in the last five years. It has been developed a new long-lasting anticholynergic drug, tiotrope bromure, which has been found to improve lung function and exercise capacity and to decrease relapses. Also the combined treatment of long lasting beta 2 adrenergics with inhaled steroids (salmeterol/fluticasone and formoterol/budesonide) has proven similar results. However, the response to these new drugs is not the same in all patients. Individual characteristics such as gravity, degree of bronchial hyperresponsiveness, frequency of relapses, comorbidity, etc will determine the response to several agents. Thus, it is necessary to perform a detailed diagnostic study in COPD patients in order to select the best treatment in an individualized form. In the future, new specific antiinflammatories such as phosphodiesterase 4 inhibitors or agents with a potential action in tissue regeneration could lead to new perspectives, as well as to new questions, in COPD treatment.

  4. Lubiprostone: a novel treatment for chronic constipation

    Directory of Open Access Journals (Sweden)

    Brian E Lacy

    2008-06-01

    Full Text Available Brian E Lacy, L Campbell LevySection of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon NH, USAAbstract: Chronic constipation is highly prevalent, reduces patients’ quality of life, and imposes a significant health care burden on society. Lifestyle modifications and over-the-counter agents improve symptoms of constipation in some patients, however many patients have persistent symptoms and require the use of prescription medications. Three prescription medications are currently Food and Drug Administration (FDA approved and available for the treatment of chronic constipation in adults. This review will focus on lubiprostone, the newest medication available for the treatment of chronic constipation. Lubiprostone is a bicyclic fatty acid metabolite analogue of prostaglandin E1. It activates specific chloride channels in the gastrointestinal tract to stimulate intestinal fluid secretion, increase gastrointestinal transit, and improve symptoms of constipation. This article will provide a brief overview on chloride channel function in the gastrointestinal tract, describe the structure, function, and pharmacokinetics of lubiprostone, and discuss the safety and efficacy of this new medication.Keywords: chloride, chloride channels, constipation, functional bowel disorders, gastrointestinal motility, intestinal secretion, irritable bowel syndrome, lubiprostone

  5. Occurrence of glucocorticoids discharged from a sewage treatment plant in Japan and the effects of clobetasol propionate exposure on the immune responses of common carp (Cyprinus carpio) to bacterial infection.

    Science.gov (United States)

    Nakayama, Kei; Sato, Kentaro; Shibano, Takazumi; Isobe, Tomohiko; Suzuki, Go; Kitamura, Shin-Ichi

    2016-04-01

    The present study evaluated the environmental risks to common carp (Cyprinus carpio) posed by glucocorticoids present in sewage treatment plant (STP) effluent. To gather information on the seasonal variations in glucocorticoid concentration, the authors sampled the effluent of a Japanese STP every other week for 12 mo. Six of 9 selected glucocorticoids were detected in the effluent, with clobetasol propionate and betamethasone 17-valerate detected at the highest concentrations and frequencies. The present study's results indicated that effluent glucocorticoid concentration may depend on water temperature, which is closely related to the removal efficiency of the STP or to seasonal variations in the public's use of glucocorticoids. In a separate experiment, to clarify whether glucocorticoids in environmental water increase susceptibility to bacterial infection in fish, the authors examined the responses to bacterial infection (Aeromonas veronii) of common carp exposed to clobetasol propionate. Clobetasol propionate exposure did not affect bacterial infection-associated mortality. In fish infected with A. veronii but not exposed to clobetasol propionate, head kidney weight and number of leukocytes in the head kidney were significantly increased (p < 0.05), whereas these effects were not observed in infected fish exposed to clobetasol. This suggests that clobetasol propionate alleviated bacterial infection-associated inflammation. Together, these results indicate that susceptibility to bacterial infection in common carp is not affected by exposure to glucocorticoids at environmentally relevant concentrations.

  6. Pharmacology of glucocorticoids in rheumatoid arthritis

    NARCIS (Netherlands)

    Spies, Cornelia M.; Bijlsma, Johannes W. J.; Burmester, Gerd-Ruediger; Buttgereit, Frank

    2010-01-01

    Glucocorticoids (GCs) provide one of the most effective treatments for rheumatoid arthritis (RA); however, their long-term use is marred by undesired side effects. Increased understanding of the mechanisms of glucocorticoid action enables the development of novel drugs, such as SEGRAs or liposomal g

  7. Benefits and risks of low-dose glucocorticoid treatment in the patient with rheumatoid arthritis

    OpenAIRE

    Kavanaugh, Arthur; Wells, Alvin F

    2014-01-01

    Glucocorticosteroids (GCs) have been employed extensively for the treatment of rheumatoid arthritis (RA) and other autoimmune and systemic inflammatory disorders. Their use is supported by extensive literature and their utility is reflected in their incorporation into current treatment guidelines for RA and other conditions. Nevertheless, there is still some concern regarding the long-term use of GCs because of their potential for clinically important adverse events, particularly with an exte...

  8. Glucocorticoids in early rheumatoid arthritis

    NARCIS (Netherlands)

    Everdingen, Amalia A. van

    2002-01-01

    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

  9. Effects of glucocorticoids on mood, memory, and the hippocampus. Treatment and preventive therapy.

    Science.gov (United States)

    Brown, E Sherwood

    2009-10-01

    Corticosteroids, such as prednisone and dexamethasone, are commonly prescribed medications that suppress the immune system and decrease inflammation. Common side effects of long-term treatment with corticosteroids include weight gain, osteoporosis, and diabetes mellitus. This paper reviews the literature on psychiatric and cognitive changes during corticosteroid therapy and potential treatment options. Hypomania and mania are the most common mood changes during acute corticosteroid therapy, although depression has also been reported. However, depression is reported to be more common than mania during long-term treatment with corticosteroids. A decline in declarative and working memory is also reported during corticosteroid therapy. Corticosteroids are associated with changes in the temporal lobe, detected by structural, functional, and spectroscopic imaging. The mood and cognitive symptoms are dose dependent and frequently occur during the first few weeks of therapy. Other risk factors are not well characterized. Controlled trials suggest that lithium and phenytoin can prevent mood symptoms associated with corticosteroids. Lamotrigine and memantine also have been shown to reverse, at least partially, the declarative memory effects of corticosteroids. Uncontrolled trials suggest that antipsychotics, anti-seizure medications, and perhaps some antidepressants can also be useful for normalizing mood changes associated with corticosteroids. Thus, both the symptoms and treatment response are similar to those of bipolar disorder. Moreover, corticosteroid-induced mood and cognitive alterations have been shown to be reversible with dose reduction or discontinuation of treatment.

  10. Omalizumab for the treatment of chronic urticaria.

    Science.gov (United States)

    Zuberbier, Torsten; Maurer, Marcus

    2015-02-01

    Urticaria is a common and often debilitating dermatological condition defined by the sudden appearance of wheals, angioedema or both. It is further classified into specific subtypes based on duration and specific triggers. Awareness and understanding of urticaria are important to ensure a correct initial diagnosis and initiate appropriate guideline-based treatment outlining a stepwise approach. However, in chronic urticaria, approximately 50% of patients are refractory to the first step, the use of licensed doses of second-generation H1-antihistamines. If the second step, an increase in the dose of the second-generation H1-antihistamines, is also not successful, in the third step omalizumab (Xolair™, Novartis Pharma AG(©)/Genentech, Inc.(©)), an anti-IgE therapy, is recommended as an add-on. Of all alternative treatments mentioned in the guidelines, omalizumab is currently the only licensed treatment for H1-antihistamine-refractory chronic spontaneous urticaria, has a favorable risk/benefit ratio and was well tolerated in clinical studies.

  11. Exogenous glucocorticoids and adverse cerebral effects in children

    DEFF Research Database (Denmark)

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

    2011-01-01

    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...

  12. Case report: treatment of chronic osteomyelitis.

    Science.gov (United States)

    Wolfe, Cameron R

    2011-06-01

    Presented is a case of chronic methicillin-resistant Staphylococcus aureus osteomyelitis, which was unsuccessfully treated with multiple courses of debridement and potent antibiotic therapies. Amputation of the patient's lower limb was believed to be the only option remaining. A compassionate access program, with approval from the US Food and Drug Administration and the institutional review board, enabled the patient to undergo a course of treatment with oral fusidic acid (CEM-102). The patient tolerated the drug well, with no significant toxicities noted to date. His infection improved rapidly, his flap healed, he has returned to work part-time, and he continues to take daily suppressive doses of oral CEM-102.

  13. Effects of antenatal dexamethasone treatment on glucocorticoid receptor and calcyon gene expression in the prefrontal cortex of neonatal and adult common marmoset monkeys

    Directory of Open Access Journals (Sweden)

    Feldon Joram

    2010-03-01

    Full Text Available Abstract Background Synthetic glucocorticoids such as dexamethasone (DEX are commonly used to promote fetal lung maturation in at-risk preterm births, but there is emerging evidence of subsequent neurobehavioral abnormalities in these children e.g. problems with inattention/hyperactivity. However, molecular pathways mediating effects of glucocorticoid overexposure on motor and cognitive development are poorly understood. Methods In this study with common marmoset monkeys, we investigated for neonatal and adulthood effects of antenatal DEX treatment on the expression of the corticosteroid receptors and also calcyon, a risk gene for attention-deficit/hyperactivity disorder, in the prefrontal cortex (PFC. Pregnant marmosets were exposed to DEX (5 mg/kg body weight or vehicle during early (days 42-48 or late (days 90-96 stages of the 144-day pregnancy. Results In neonates, relative to controls, glucocorticoid receptor (GR mRNA levels were significantly reduced after the late DEX treatment in the medial, orbital and dorsal PFC and after the early DEX treatment in the dorsal PFC. The early DEX exposure, specifically, resulted in significant reduction in calcyon mRNA expression in the medial, orbital, dorsal and lateral PFC relative to controls. Mineralocorticoid receptor (MR mRNA levels were not significantly affected by DEX treatment. In adults, PFC GR, calcyon, and MR mRNA levels were not significantly affected by early or late prenatal DEX treatment. Conclusion These findings indicate that antenatal DEX treatment could lead to short-term alterations in PFC expression of the GR and calcyon genes, with possible neurodevelopmental functional consequences.

  14. Glucocorticoids enhance prolonged clearance of apoptotic cells by upregulating liver X receptor, peroxisome proliferator-activated receptor-δ and UCP2.

    Science.gov (United States)

    Garabuczi, Éva; Sarang, Zsolt; Szondy, Zsuzsa

    2015-03-01

    Efficient phagocytic clearance of apoptotic cells (efferocytosis) is essential to prevent the development of chronic inflammation and autoimmunity. Glucocorticoids are widely used in the therapy of chronic inflammatory diseases, and increasing evidence suggests that they act partly via enhancing efferocytosis by macrophages. Glucocorticoids were previously shown to promote both protein S- and MFG-E8-dependent efferocytosis. Since previous studies in our laboratory have demonstrated that glucocorticoids induce the expression of retinaldehyde dehydrogenases in macrophages, in the present experiments the possible involvement of retinoids in the glucocorticoid-induced efferocytosis was studied in mouse bone marrow derived macrophages. Here we show that glucocorticoids promote not only short-term, but also long-term clearance of apoptotic cells. Glucocorticoids seem to directly induce the expression of the phagocytosis-related genes MERTK, C1q, UCP2, and the transcription factor C/EBPβ. C/EBPβ contributes to the further induction of the phagocytosis-related genes, and is required for the induction of lipid sensing receptors LXRs, PPARδ, RARα, RXRα and RALDH1, the latter one in an LXR- and RARα-dependent manner. Glucocorticoid-induced enhancement in long-term efferocytosis was dependent on the induction of lipid sensing receptors known to be triggered by the lipid content of the engulfed cells to enhance phagocytic capacity. Retinoids did not affect the glucocorticoid-induced short term phagocytosis of apoptotic cells, but were required for the glucocorticoid-induced enhancement of efferocytosis during prolonged clearance of apoptotic cells by promoting efficient LXR and PPARδ upregulation. Our data indicate that retinoids could be considered as potential promoters of the efficacy of glucocorticoid treatment in inflammatory diseases.

  15. Fluoride in the prevention and treatment of glucocorticoid-induced osteoporosis

    NARCIS (Netherlands)

    Lems, WF; Jacobs, JWG; Bijlsma, JWJ

    2000-01-01

    Since the use of fluoride has been shown to stimulate bone formation and since decreased bone formation is a key feature in the pathogenesis of corticosteroid-induced osteoporosis (CIOP), fluoride is, at least theoretically, attractive for the prevention and treatment of CIOP. In postmenopausal wome

  16. Expectations predict chronic pain treatment outcomes.

    Science.gov (United States)

    Cormier, Stéphanie; Lavigne, Geneviève L; Choinière, Manon; Rainville, Pierre

    2016-02-01

    Accumulating evidence suggests an association between patient pretreatment expectations and numerous health outcomes. However, it remains unclear if and how expectations relate to outcomes after treatments in multidisciplinary pain programs. The present study aims at investigating the predictive association between expectations and clinical outcomes in a large database of chronic pain patients. In this observational cohort study, participants were 2272 patients treated in one of 3 university-affiliated multidisciplinary pain treatment centers. All patients received personalized care, including medical, psychological, and/or physical interventions. Patient expectations regarding pain relief and improvements in quality of life and functioning were measured before the first visit to the pain centers and served as predictor variables. Changes in pain intensity, depressive symptoms, pain interference, and tendency to catastrophize, as well as satisfaction with pain treatment and global impressions of change at 6-month follow-up, were considered as treatment outcomes. Structural equation modeling analyses showed significant positive relationships between expectations and most clinical outcomes, and this association was largely mediated by patients' global impressions of change. Similar patterns of relationships between variables were also observed in various subgroups of patients based on sex, age, pain duration, and pain classification. Such results emphasize the relevance of patient expectations as a determinant of outcomes in multimodal pain treatment programs. Furthermore, the results suggest that superior clinical outcomes are observed in individuals who expect high positive outcomes as a result of treatment.

  17. Surgical treatment of pain in chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    Stefanović Dejan

    2006-01-01

    Full Text Available INTRODUCTION: The principal indication for surgical intervention in chronic pancreatitis is intractable pain. Depending upon the presence of dilated pancreatic ductal system, pancreatic duct drainage procedures and different kinds of pancreatic resections are applied. OBJECTIVE: The objective of the study was to show the most appropriate procedure to gain the most possible benefits in dependence of type of pathohistological process in chronic pancreatitis. METHOD: Our study included 58 patients with intractable pain caused by chronic pancreatitis of alcoholic genesis. The first group consisted of 30 patients with dilated pancreatic ductal system more than 10 mm. The second group involved 28 patients without dilated pancreatic ductal system. Pain relief, weight gain and glucose tolerance were monitored. RESULTS: All patients of Group I (30 underwent latero-lateral pancreaticojejunal - Puestow operation. 80% of patients had no pain after 6 month, 13.6% had rare pain and 2 patients, i.e. 6.4%, who continued to consume alcohol, had strong pain. Group II consisting of 28 patients was without dilated pancreatic ductal system. This group was subjected to various types of pancreatic resections. Whipple procedure (W was done in 6 patients, pylorus preserving Whipple (PPW in 7 cases, and duodenum preserving cephalic pancreatectomy (DPCP was performed in 15 patients. Generally, 89.2% of patients had no pain 6 month after the operation. An average weight gain was 1.9 kg in W group, 2.8 kg in PPW group and 4.1 kg in DPCP group. Insulin-dependent diabetes was recorded in 66.6% in W group, 57.1% in PPW group and 0% in DPCP group. CONCLUSION: According to our opinion, DPCP may be considered the procedure of choice for surgical treatment of pain in chronic pancreatitis in patients without dilatation of pancreas ductal system because of no serious postoperative metabolic consequences.

  18. Chronic care treatment of obese children and adolescents

    DEFF Research Database (Denmark)

    Holm, Jens-Christian; Gamborg, Michael; Bille, Dorthe S

    2011-01-01

    Clinically-relevant protocols for the treatment of childhood obesity are lacking. This study report results for a clinic-based structured treatment program for chronic childhood obesity.......Clinically-relevant protocols for the treatment of childhood obesity are lacking. This study report results for a clinic-based structured treatment program for chronic childhood obesity....

  19. A Meta-analysis of alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis

    Institute of Scientific and Technical Information of China (English)

    杨琳

    2013-01-01

    Objective To assess the efficiency and safety of alendronate for the prevention and treatment of glucocorticoidinduced osteoporosis (GIOP) .Methods The electronic databases of PubMed,EMBASE,Cochrane Library,Web of Science,Chinese BioMedical Literature Database (CBM) and Wanfang Data were searched for all randomized controlled trials (RCT) of alendronate vs.placebo.Two reviewers independently selected trials for inclusion,assessed trial quality using Jadad’s scale and extracted

  20. 糖皮质激素治疗神经囊虫病的荟萃分析%Glucocorticoids for the treatment of neurocysticercosis: a Meta-analysis

    Institute of Scientific and Technical Information of China (English)

    舒志刚; 霍淑平; 梅炳银

    2013-01-01

    Objective To systematically review the efficacy of glucocorticoids in the treatment of neurocysticercosis (NCC) in order to provide the evidence for guiding clinical practice.Methods The Cochrane Library,MEDLINE,EMBASE,Wanfang Database and China National Knowledge Infrastructure (CNKI) were searched.The published time of the literature was from January 1995 to February 2012.All the literatures about glucocorticoid therapies were screened.Two reviewers independently assessed the quality of literatures and extracted data.The included literatures were statistically analyzed using RevMan 5.0 software.Results A total of 63 articles were retrieved,Thirteen effective studies and 1625 patients with NCC were included in the study finally.①Compared the patients treated with placebo drugs (n =213),Glucocorticoids treatment significantly decreased the relapse rate of epilepsy at 6 to 12 months after treatment (OR =0.39,95% CI 0.24 to 0.62,P <0.0001),and improved the image findings (head CT or MRI of the patients revealed that the pathological injury disappeared completely,without or only had a very small residual scarring,calcification,and perilesional edema).The differences were statistically significant (OR =0.40,95% CI 0.20 to 0.80,P =0.009).②As compared of glucocorticoids plus albendazole versus placebo or glucocorticoids plus albendazole,versus glucocorticoids alone in the treatment of NCC,There were no difference in the relapse rate of epilepsy and imaging lesion improvement.③Glucocorticoids plus albendazole may cause abdominal discomfort,skin rashes,headaches,and other adverse reactions as compared with placebo treatment and glucocorticoids alone.The difference were statistically significant (OR0.36,95%CI0.22 to0.64,P<0.0001).Conclusion Glucocorticoidsmayreduce the relapse rate of epilepsy and disease progression during the 6 to 12 months follow-up period.However,it is still small for the sample size of the current evaluation of glucocorticoid efficacy

  1. Topical insulin-like growth factor 1 treatment using gelatin hydrogels for glucocorticoid-resistant sudden sensorineural hearing loss: a prospective clinical trial

    Directory of Open Access Journals (Sweden)

    Teramukai Satoshi

    2010-11-01

    Full Text Available Abstract Background Sudden sensorineural hearing loss (SSHL is a common condition in which patients lose the hearing in one ear within 3 days. Systemic glucocorticoid treatments have been used as standard therapy for SSHL; however, about 20% of patients do not respond. We tested the safety and efficacy of topical insulin-like growth factor 1 (IGF1 application using gelatin hydrogels as a treatment for SSHL. Methods Patients with SSHL that showed no recovery to systemic glucocorticoid administration were recruited. We applied gelatin hydrogels, impregnated with recombinant human IGF1, into the middle ear. The primary outcome measure was the proportion of patients showing hearing improvement 12 weeks after the test treatment. The secondary outcome measures were the proportion of patients showing improvement at 24 weeks and the incidence of adverse events. The null hypothesis was that 33% of patients would show hearing improvement, as was reported for a historical control after hyperbaric oxygen therapy. Results In total, 25 patients received the test treatment at a median of 23 days (range 15-32 after the onset of SSHL, between 2007 and 2009. At 12 weeks after the test treatment, 48% (95% CI 28% to 69%; P = 0.086 of patients showed hearing improvement, and the proportion increased to 56% (95% CI 35% to 76%; P = 0.015 at 24 weeks. No serious adverse events were observed. Conclusions Topical IGF1 application using gelatin hydrogels is well tolerated and may be efficacious for hearing recovery in patients with SSHL that is resistant to systemic glucocorticoids.

  2. Glucocorticoids and central nervous system inflammation.

    Science.gov (United States)

    Dinkel, Klaus; Ogle, William O; Sapolsky, Robert M

    2002-12-01

    Glucocorticoids (GCs) are well known for their anti-inflammatory and immunosuppressive properties in the periphery and are therefore widely and successfully used in the treatment of autoimmune diseases, chronic inflammation, or transplant rejection. This led to the assumption that GCs are uniformly anti-inflammatory in the periphery and the central nervous system (CNS). As a consequence, GCs are also used in the treatment of CNS inflammation. There is abundant evidence that an inflammatory reaction is mounted within the CNS following trauma, stroke, infection, and seizure, which can augment the brain damage. However an increasing number of studies indicate that the concept of GCs being universally immunosuppressive might be oversimplified. This article provides a review of the current literature, showing that under certain circumstances GCs might fail to have anti-inflammatory effects and sometimes even enhance inflammation.

  3. Arthroscopic treatment for chronic lateral epicondylitis

    Directory of Open Access Journals (Sweden)

    Bernardo Barcellos Terra

    2015-08-01

    Full Text Available ABSTRACTOBJECTIVE: To report the clinical and functional results from arthroscopic release of the short radial extensor of the carpus (SREC in patients with chronic lateral epicondylitis that was refractory to conservative treatment. METHODS: Over the period from January 2012 to November 2013, 15 patients underwent arthroscopic treatment. The surgical technique used was the one described by Romeo and Cohen, based on anatomical studies on cadavers. The inclusion criteria were that the patients needed to present lateral epicondylitis and that conservative treatment (analgesics, anti-inflammatory agents, corticoid infiltration or physiotherapy had failed over a period of more than six months. The patients were evaluated based on the elbow functional score of the Mayo Clinic, Nirschl's staging system and a visual analog scale (VAS for pain. RESULTS: A total of 15 patients (9 men and 6 women were included. The mean Mayo elbow functional score after the operation was 95 (ranging from 90 to 100. The pain VAS improved from a mean of 9.2 before the operation to 0.64 after the operation. On Nirschl's scale, the patients presented an improvement from a mean of 6.5 before the operation to approximately one. There were significant differences from before to after the surgery for the three functional scores used ( p 0.05. CONCLUSION: Arthroscopic treatment for lateral epicondylitis was shown to be a safe and effective therapeutic option when appropriately indicated and performed, in refractory cases of chronic lateral epicondylitis. It also allowed excellent viewing of the joint space for diagnosing and treating associated pathological conditions, with a minimally invasive procedure.

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

    DEFF Research Database (Denmark)

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

    2006-01-01

    a pronounced increase in the endocortical bone formation rate (BFR) and a smaller increase in periosteal BFR. The combination of PTH + GC resulted in a partial inhibition of the PTH-induced increase in bone formation. Serum-osteocalcin was increased by 65% in the PTH group and reduced by 39% in the GC group....... 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...

  5. NALP3 inflammasome upregulation and CASP1 cleavage of the glucocorticoid receptor cause glucocorticoid resistance in leukemia cells.

    Science.gov (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

    2015-06-01

    Glucocorticoids 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 cells from 444 patients newly diagnosed with ALL and found significantly higher expression of CASP1 (encoding caspase 1) and its activator NLRP3 in glucocorticoid-resistant leukemia cells, resulting from significantly lower somatic methylation of the CASP1 and NLRP3 promoters. Overexpression of CASP1 resulted in cleavage of the glucocorticoid receptor, diminished the 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 the glucocorticoid transcriptional response suggests that this mechanism could also modify glucocorticoid effects in other diseases.

  6. NALP3 inflammasome up-regulation and CASP1 cleavage of the glucocorticoid receptor causes glucocorticoid resistance in leukemia cells

    Science.gov (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.

    2015-01-01

    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

  7. Effects of glucocorticoids on apoptosis and clearance of apoptotic cells.

    Science.gov (United States)

    McColl, Aisleen; Michlewska, Sylwia; Dransfield, Ian; Rossi, Adriano G

    2007-08-17

    The glucocorticoid (GC) drugs are one of the most commonly prescribed and effective anti-inflammatory agents used for the treatment of many inflammatory disorders through their ability to attenuate phlogistic responses. The glucocorticoid receptor (GCR) primarily mediates GC actions via activation or repression of gene expression. GCs directly induce the expression of proteins displaying anti-inflammatory activities. However, the likely predominant effect of GCs is the repression of multiple inflammatory genes that invariably are overexpressed during nonresolving chronic inflammation. Although most GC actions are mediated through regulation of transcription, rapid nongenomic actions have also been reported. In addition, GCs modulate inflammatory cell survival, inducing apoptosis in immature thymocytes and eosinophils, while delaying constitutive neutrophil apoptosis. Importantly, GCs promote noninflammatory phagocytosis of apoptotic cell targets, a process important for the successful resolution of inflammation. Here, the effects and mechanisms of action of GC on inflammatory cell apoptosis and phagocytosis will be discussed.

  8. Effects of Glucocorticoids on Apoptosis and Clearance of Apoptotic Cells

    Directory of Open Access Journals (Sweden)

    Aisleen McColl

    2007-01-01

    Full Text Available The glucocorticoid (GC drugs are one of the most commonly prescribed and effective anti-inflammatory agents used for the treatment of many inflammatory disorders through their ability to attenuate phlogistic responses. The glucocorticoid receptor (GCR primarily mediates GC actions via activation or repression of gene expression. GCs directly induce the expression of proteins displaying anti-inflammatory activities. However, the likely predominant effect of GCs is the repression of multiple inflammatory genes that invariably are overexpressed during nonresolving chronic inflammation. Although most GC actions are mediated through regulation of transcription, rapid nongenomic actions have also been reported. In addition, GCs modulate inflammatory cell survival, inducing apoptosis in immature thymocytes and eosinophils, while delaying constitutive neutrophil apoptosis. Importantly, GCs promote noninflammatory phagocytosis of apoptotic cell targets, a process important for the successful resolution of inflammation. Here, the effects and mechanisms of action of GC on inflammatory cell apoptosis and phagocytosis will be discussed.

  9. Transrepression function of the glucocorticoid receptor regulates eyelid development and keratinocyte proliferation but is not sufficient to prevent skin chronic inflammation.

    Science.gov (United States)

    Donet, Eva; Bosch, Pilar; Sanchis, Ana; Bayo, Pilar; Ramírez, Angel; Cascallana, José L; Bravo, Ana; Pérez, Paloma

    2008-04-01

    Glucocorticoids (GCs) play a key role in skin homeostasis and stress responses acting through the GC receptor (GR), which modulates gene expression by DNA binding-dependent (transactivation) and -independent (transrepression) mechanisms. To delineate which mechanisms underlie the beneficial and adverse effects mediated by GR in epidermis and other epithelia, we have generated transgenic mice that express a mutant GR (P493R, A494S), which is defective for transactivation but retains transrepression activity, under control of the keratin 5 promoter (K5-GR-TR mice). K5-GR-TR embryos exhibited eyelid opening at birth and corneal defects that resulted in corneal opacity in the adulthood. Transgenic embryos developed normal skin, although epidermal atrophy and focal alopecia was detected in adult mice. GR-mediated transrepression was sufficient to inhibit keratinocyte proliferation induced by acute and chronic phorbol 12-myristate 13-acetate exposure, as demonstrated by morphometric analyses, bromodeoxyuridine incorporation, and repression of keratin 6, a marker of hyperproliferative epidermis. These antiproliferative effects were mediated through negative interference of GR with MAPK/activator protein-1 and nuclear factor-kappaB activities, although these interactions occurred with different kinetics. However, phorbol 12-myristate 13-acetate-induced inflammation was only partially inhibited by GR-TR, which efficiently repressed IL-1beta and MMP-3 genes while weakly repressing IL-6 and TNF-alpha. Our data highlight the relevance of deciphering the mechanisms underlying GR actions on epithelial morphogenesis as well as for its therapeutic use to identify more restricted targets of GC administration.

  10. Treatment of chronic inflammatory demyelinating polyneuropathy.

    Science.gov (United States)

    Kleyman, Inna; Brannagan, Thomas H

    2015-07-01

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is one of the acquired demyelinating neuropathies and is considered to be immune mediated. Diagnosis is typically based on clinical history, neurologic examination, electrophysiologic studies, CSF studies, and pathologic examination. Early diagnosis and treatment is important to prevent irreversible axonal loss and optimize improvement in function. The first-line agents for treatment are intravenous immunoglobulin (IVIg), corticosteroids, and plasmapheresis, which have all been demonstrated to be effective in controlled studies. Studies have not shown a significant difference between these three treatments, and the initial choice of therapy is often based on availability, cost, ease of administration, and side effect profile. If patients do not respond to one of these agents, they may respond to one of the others and sometimes in combination. If the first-line agents are not effective, chemotherapeutic or immunosuppressive agents may be considered. There are limited controlled studies of these modalities, and they are often used in conjunction with a first-line treatment. The majority of patients require long-term therapy to maintain a response and to prevent relapse.

  11. Efficacy of Glucocorticoid Combined With Mecobalamin Treatment in the Treatment of Optic Neuritis%糖皮质激素与甲钴胺联合治疗视神经炎的效果研究

    Institute of Scientific and Technical Information of China (English)

    程笑冬

    2016-01-01

    Objective Glucocorticoid combined with mecobalamin treatment effect in treatment of optic neuritis is to be studied. Methods Chose 55 patients of optic neuritis who were treated in hospital from January 2015 to October 2015 and separated them into two groups according to digits,27 patients in control group were given glucocorticoid treatment only,while 28 patients in study group were given glucocorticoid combined with mecobalamin treatment, and then observed and compared treatment effects between two groups. Results Patients’treatment sensitivity,symptom improvement incidence and treatment efficacy in study group were much higher than counterparts in control group,there was a differential between two groups and such a differential had statistic value(P < 0.05). Conclusion Glucocorticoid combined with mecobalamin treatment is effective in treatment of optic neuritis.%目的:研究糖皮质激素与甲钴胺联合治疗视神经炎的效果。方法研究年度2015年1月~2015年10月纳入视神经炎患者55例,按数字法分两组。糖皮质激素治疗者27例,设对照组;糖皮质激素与甲钴胺联合治疗者28例,设实验组。比较效果。结果两组中实验组敏感度更高,改善率更高,治疗有效率更高,差异具有统计学意义(P <0.05)。结论糖皮质激素与甲钴胺联合治疗视神经炎效果佳。

  12. Short-term, high-dose glucocorticoid treatment does not contribute to reduced bone mineral density in patients with multiple sclerosis

    DEFF Research Database (Denmark)

    Olsson, A; Oturai, Ditte Bang; Sørensen, P S;

    2015-01-01

    BACKGROUND: Patients with multiple sclerosis (MS) are at increased risk of reduced bone mineral density (BMD). A contributing factor might be treatment with high-dose glucocorticoids (GCs). OBJECTIVES: The objective of this paper is to assess bone mass in patients with MS and evaluate the importa......BACKGROUND: Patients with multiple sclerosis (MS) are at increased risk of reduced bone mineral density (BMD). A contributing factor might be treatment with high-dose glucocorticoids (GCs). OBJECTIVES: The objective of this paper is to assess bone mass in patients with MS and evaluate...... the importance of short-term, high-dose GC treatment and other risk factors that affect BMD in patients with MS. METHODS: A total of 260 patients with MS received short-term high-dose GC treatment and had their BMD measured by dual x-ray absorptiometry. BMD was compared to a healthy age-matched reference...... population (Z-scores). Data regarding GCs, age, body mass index (BMI), serum 25(OH)D, disease duration and severity were collected retrospectively and analysed in a multiple linear regression analysis to evaluate the association between each risk factor and BMD. RESULTS: Osteopenia was present in 38...

  13. Diagnosis and treatment of chronic insomnia

    Directory of Open Access Journals (Sweden)

    Saddichha Sahoo

    2010-01-01

    Full Text Available Insomnia is a disorder characterized by inability to sleep or a total lack of sleep, prevalence of which ranges from 10 to 15% among the general population with increased rates seen among older ages, female gender, White population and presence of medical or psychiatric illness. Yet this condition is still under-recognized, under-diagnosed, and under-treated. This article aims to review the operational definitions and management of chronic insomnia. A computerized search on PubMed carried from 1980 to January 2009 led to the summarization of the results. There are several strategies to manage chronic insomnia. To initiate treatment, it is necessary to define it and differentiate it from other co-morbid psychiatric disorders. Non-pharmacologic strategies such as stimulus control therapy and relaxation and cognitive therapies have the best effect sizes followed by sleep restriction, paradoxical intention and sleep hygiene education which have modest to less than modest effect sizes. Among pharmacotherapeutic agents, non-benzodiazepine hypnotics are the first line of management followed by benzodiazepines, amitryptiline and antihistaminics. However, adequate trials of combined behavior therapy and pharmacotherapy are the best course of management.

  14. Advances in glucocorticoid resistance research in chronic airway inflammatory diseases%气道慢性炎症疾病激素抵抗机制的研究进展

    Institute of Scientific and Technical Information of China (English)

    孙云; 陈亚红

    2011-01-01

    Glucocorticoid is widely used in chronic airway inflammatory diseases, however, some patients respond poorly to it. This article summarizes in the advances of glucocorticoid resistance research,including activation of mitogen-activated protein kinase pathways by certain cytokines, increased glucocorticoid receptor-β expression, reduced histone deacetylase-2 activity, regulation of the transcription factors,IL-10 secreting Tregs and IL-10,Th17 and IL-17,and so on.%糖皮质激素广泛应用于气道慢性炎症性疾病,但部分患者对激素治疗疗效较差,存在激素抵抗.关于激素抵抗的分子机制,目前已有许多研究,本文就这一领域的研究进展进行综述,主要包括细胞因子激活丝裂素活化蛋白激酶通路,激素受体β的表达增加,组蛋白去乙酰化酶的活性下降,转录因子的调节,促白介素10分泌细胞和白介素10,T辅助细胞17和白介素17等方面.

  15. Pregabalin for Pain Treatment in Chronic Pancreatitis

    DEFF Research Database (Denmark)

    Olesen, Søren Schou; Bowense, S; Wilder-Smith, Oliver

    2011-01-01

    Intractable pain usually dominates the clinical presentation of chronic pancreatitis (CP). Slowing of electroencephalogram (EEG) rhythmicity has been associated with abnormal cortical pain processing in other chronic pain disorders. The aim of this study was to investigate the spectral distribution...

  16. Pegloticase: in treatment-refractory chronic gout.

    Science.gov (United States)

    Lyseng-Williamson, Katherine A

    2011-11-12

    Intravenous pegloticase offers a novel approach to treating chronic gout refractory to conventional therapy. Pegloticase is a recombinant polyethylene glycol-conjugated form of uricase (a uric acid-specific enzyme lacking in humans) that catalyses the oxidation of uric acid to allantoin. In randomized, placebo-controlled, double-blind, 6-month, phase III trials, intravenous pegloticase 8 mg every 2 or 4 weeks provided sustained reductions in plasma uric acid levels to less than the therapeutic target of 6 mg/dL in a substantial proportion of patients with chronic gout who were refractory to, or intolerant of, conventional urate-lowering therapy. Pegloticase 8 mg every 2 weeks was associated with disease-modifying benefits relative to placebo, as shown by significant improvements from baseline in tophi resolution, frequency of gout flares and tender joint count, and clinically relevant and statistically significant improvements from baseline in health-related quality-of-life parameters related to disability, pain and physical function. Pegloticase 8 mg every 4 weeks was also significantly more effective than placebo with regard to most, but not all, of these endpoints. Preliminary data from an open-label extension of the phase III trials indicate that long-term treatment with pegloticase 8 mg every 2 or 4 weeks may maintain plasma uric acid normalization in patients who experienced a sustained uric acid response during the phase III trials. The most common serious adverse events associated with pegloticase are gout flares, infusion reactions and anaphylaxis. In addition, exacerbation of pre-existing congestive heart failure was reported in 2% of patients receiving pegloticase 8 mg every 2 weeks in the phase III trials.

  17. Reversal of reduced parvalbumin neurons in hippocampus and amygdala of Angelman syndrome model mice by chronic treatment of fluoxetine.

    Science.gov (United States)

    Godavarthi, Swetha K; Sharma, Ankit; Jana, Nihar Ranjan

    2014-08-01

    Angelman syndrome (AS) is a neuropsychiatric disorder characterized by autism, intellectual disability and motor disturbances. The disease is primarily caused by the loss of function of maternally inherited UBE3A. Ube3a maternal-deficient mice recapitulates many essential feature of AS. These AS mice have been shown to be under chronic stress and exhibits anxiety-like behaviour because of defective glucocorticoid receptor signalling. Here, we demonstrate that chronic stress in these mice could lead to down-regulation of parvalbumin-positive interneurons in the hippocampus and basolateral amygdala from early post-natal days. Down-regulation of parvalbumin-positive interneurons number could be because of decrease in the expression of parvalbumin in these neurons. We also find that treatment with fluoxetine, a selective serotonin reuptake inhibitor, results in restoration of impaired glucocorticoid signalling, elevated serum corticosterone level, parvalbumin-positive interneurons and anxiety-like behaviours. Our findings suggest that impaired glucocorticod signalling in hippocampus and amygdala of AS mice is critical for the decrease in parvalbumin interneurons number, emergence of anxiety and other behavioural deficits and highlights the importance of fluoxetine in the recovery of these abnormalities.

  18. VBP15, a glucocorticoid analogue, is effective at reducing allergic lung inflammation in mice.

    Directory of Open Access Journals (Sweden)

    Jesse M Damsker

    Full Text Available Asthma is a chronic inflammatory condition of the lower respiratory tract associated with airway hyperreactivity and mucus obstruction in which a majority of cases are due to an allergic response to environmental allergens. Glucocorticoids such as prednisone have been standard treatment for many inflammatory diseases for the past 60 years. However, despite their effectiveness, long-term treatment is often limited by adverse side effects believed to be caused by glucocorticoid receptor-mediated gene transcription. This has led to the pursuit of compounds that retain the anti-inflammatory properties yet lack the adverse side effects associated with traditional glucocorticoids. We have developed a novel series of steroidal analogues (VBP compounds that have been previously shown to maintain anti-inflammatory properties such as NFκB-inhibition without inducing glucocorticoid receptor-mediated gene transcription. This study was undertaken to determine the effectiveness of the lead compound, VBP15, in a mouse model of allergic lung inflammation. We show that VBP15 is as effective as the traditional glucocorticoid, prednisolone, at reducing three major hallmarks of lung inflammation--NFκB activity, leukocyte degranulation, and pro-inflammatory cytokine release from human bronchial epithelial cells obtained from patients with asthma. Moreover, we found that VBP15 is capable of reducing inflammation of the lung in vivo to an extent similar to that of prednisone. We found that prednisolone--but not VBP15 shortens the tibia in mice upon a 5 week treatment regimen suggesting effective dissociation of side effects from efficacy. These findings suggest that VBP15 may represent a potent and safer alternative to traditional glucocorticoids in the treatment of asthma and other inflammatory diseases.

  19. Treatment strategies for extensive chronic SFA occlusions: indications and results.

    NARCIS (Netherlands)

    Lensvelt, M.M.A.; Reijnen, M.M.P.J.; Wallis de Vries, B.M.; Zeebregts, C.J.A.

    2012-01-01

    Treatment modalities for extensive chronic occlusive disease of the superficial femoral artery (SFA) have changed during the last decades. In this chapter we provide an overview of current treatment modalities for extensive chronic occlusive disease of the SFA. Although the autologous venous conduit

  20. Treatment strategies for extensive chronic SFA occlusions : indications and results

    NARCIS (Netherlands)

    Lensvelt, M. M. A.; Reijnen, M. M. P. J.; De Vries, B. M. Wallis; Zeebregts, C. J.

    2012-01-01

    Treatment modalities for extensive chronic occlusive disease of the superficial femoral artery (SFA) have changed during the last decades. In this chapter we provide an overview of current treatment modalities for extensive chronic occlusive disease of the SFA. Although the autologous venous conduit

  1. Exercício físico previne alterações cardiometabólicas induzidas pelo uso crônico de glicocorticóides Ejercicio físico previene alteraciones cardiometabólicas inducidas por el uso crónico de glucocorticoides Exercise prevents cardiometabolic alterations induced by chronic use of glucocorticoids

    Directory of Open Access Journals (Sweden)

    Carlos Hermano da Justa Pinheiro

    2009-10-01

    exercise on cardiometabolic alterations induced by chronic administration of dexamethasone (Dex - 0.5 mg/kg/day ip in rats. METHODS: Male Wistar rats (n = 24 were divided in four groups: Control group; Trained group; Treated with Dex group and Treated with Dex and trained group. The exercise training (initiated 72 hours after the first dose of Dex was carried out three times a week until the end of the treatment. At the end of this period, the following biochemical assessments were performed: fasting glycemia, oral glucose tolerance test and analysis of the blood lipid profile that included total cholesterol (TC, LDL-c, HDL-c, VLDL-c and triglycerides (TG. The weight of the gastrocnemius muscle, the histopathological analysis of the liver and cardiometabolic indices (TC/HDL-c, LDL-c/HDL-c and TG/HDL-c were also performed. RESULTS: Hyperglycemia, lower glucose tolerance, increased TC, LDL-c, VLDL-c, TG, CT/HDL-c, LDL-c/HDL-c and TG/HDL-c, decreased HDL-c, presence of liver steatosis and muscular hypotrophy were observed in the animals treated with Dex. The exercise training reduced hyperglycemia, improved glucose tolerance, decreased dyslipidemia and prevented liver steatosis, muscular hypotrophy and reduced CT/HDL-c, LDL-c/HDL-c and TG/HDL-c ratios. However, there was no significant effect on HDL-c. CONCLUSION: The aerobic exercise training have a protective effect against the cardiometabolic alterations induced by the chronic use of glucocorticoids.

  2. Serum levels of parathyroid hormone and markers of bone metabolism in patients with rheumatoid arthritis. Relationship to disease activity and glucocorticoid treatment

    DEFF Research Database (Denmark)

    Jensen, Tonny Joran; Hansen, M; Madsen, J C;

    2001-01-01

    OBJECTIVE: To evaluate the influence of inflammatory activity and glucocorticoid (GC) treatment on serum parathyroid hormone (s-PTH) and bone metabolism in patients with rheumatoid arthritis (RA). Furthermore, in patients with active RA, to examine the PTH secretion and Ca2+ set point before...... and after treatment with GC. METHODS: A range of biochemical markers of bone metabolism and calcium homeostasis were measured in 95 patients with definite RA stratified into groups according to disease activity and GC treatment. In a subgroup of 12 patients with active disease, initiating slow...... groups. The levels of urine pyridinoline (Pyr) and s-albumin-corrected calcium (s-AlbCorrCa2+) were elevated in patients with active disease and patients treated with GC. S-PTH and s-phosphate were within normal ranges. S-TAP, s-ICTP, Pyr and s-AlbCorrCa2+ correlated positively with indices of disease...

  3. Treatment of chronic periodontitis decreases serum prohepcidin levels in patients with chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Eduardo Machado Vilela

    2011-01-01

    Full Text Available OBJECTIVE: To determine the impact of periodontal treatment on serum levels of prohepcidin (the prohormone of hepcidin and systemic inflammation markers, as well as correlations among these markers, in patients with chronic periodontitis and chronic kidney disease who were not undergoing dialysis. METHODS: We included 56 chronic periodontitis patients, 36 with chronic kidney disease and 20 without systemic diseases and with normal renal function (control group. Chronic kidney disease was defined as suggested by the clinical practice guidelines in the National Kidney Foundation. Chronic periodontitis was defined through clinical attachment level and by probing pocket depth, according to the American Association of Periodontology. The inflammatory markers ultrasensitive C-reactive protein, interleukin-6, and prohepcidin were evaluated before and 3 months after periodontal treatment. RESULTS: The efficacy of periodontal treatment was confirmed by the improvement in clinical parameters of chronic periodontitis in the control and chronic kidney disease groups. Periodontal treatment resulted in significant reductions in ultrasensitive C-reactive protein, interleukin-6 and serum prohepcidin levels in both groups. Moreover, in multivariate linear regression, the reduction in prohepcidin after periodontal treatment was significantly and independently associated with interleukin-6 levels in the control group. CONCLUSIONS: By inducing a decline in the systemic inflammatory response and a decrease in serum prohepcidin, successful periodontal treatment may represent an important means of ameliorating the inflammatory burden seen in patients with chronic kidney disease.

  4. [Glucocorticoids in rheumatology].

    Science.gov (United States)

    Dziurla, R; Buttgereit, F

    2008-11-01

    Glucocorticoids (GC) are effective drugs which are often used in rheumatology. However, they have a considerable potential for frequent and sometimes serious side effects that restrict their use. Their mechanisms of action are either receptor dependent (specific) or independent (unspecific) on the genomic as well as the non-genomic level. Many adverse effects are predominantly caused by transactivation while the desired effects are mostly mediated by transrepression. Treatment strategies are sub-classified into low, medium, high, very high dose and pulse therapy based on criteria such as dose, indication, duration of treatment and potential risk of adverse events. The musculoskeletal, gastrointestinal, neuro-endocrino-immunological, opthalmological and neuropsychiatric systems are examples where adverse effects may occur.

  5. Chronic heart failure part 2: treatment and management.

    Science.gov (United States)

    Brake, Rebecca; Jones, Ian David

    2017-01-11

    Chronic heart failure is a common and complex clinical syndrome that results from impaired cardiac relaxation or contraction. There have been considerable advances in the management of chronic heart failure; however, the mortality rate remains high. Patients with chronic heart failure may experience multiple debilitating symptoms, such as fatigue, pain, and peripheral oedema. However, breathlessness may be considered the most debilitating symptom. The management of chronic heart failure aims to improve the patient's quality of life by reducing symptoms and supporting the patient to manage their condition. Treatment of patients with chronic heart failure may involve a combination of pharmacological therapy, device implantation and cardiac rehabilitation. This is the second of two articles on chronic heart failure. Part 1 discussed the pathophysiology of chronic heart failure, its causes, assessment, signs and symptoms. Part 2 outlines the treatment and management of patients with the condition, including pharmacological strategies, device implantation, lifestyle modification, cardiac rehabilitation and palliative care.

  6. Primary and secondary prophylaxis to the use of inhaled glucocorticoid in primary health care

    DEFF Research Database (Denmark)

    Nielsen, B.R.; Jorgensen, N.R.; Schwarz, P.

    2008-01-01

    with or without risk factors of osteoporosis. CONCLUSION: More studies are warranted to verify the effects of IGC treatment on bone health and the importance of prophylaxis to prevent osteoporosis in IGC-treated patients before outlining specific recommendations for the management of the disease Udgivelsesdato......OBJECTIVES: To investigate the extent of inhaled glucocorticoid (IGC) treatment in general and to what extent general practitioners (GPs) manage the risk of glucocorticoid-induced osteoporosis. METHOD: A questionnaire was sent to all 3,617 GPs in Denmark. RESULTS: The results are divided...... into criteria for recommending prophylaxis with calcium and vitamin D for patients in actual IGC treatment, routine examinations for osteoporosis before starting asthma or chronic obstructive pulmonary disease (COPD) treatment with IGC, and criteria for starting anti-osteoporotic treatment (bisphosphonates...

  7. Glucocorticoids and inflammation: a double-headed sword in depression? How do neuroendocrine and inflammatory pathways interact during stress to contribute to the pathogenesis of depression?

    Science.gov (United States)

    Horowitz, M A; Zunszain, P A; Anacker, C; Musaelyan, K; Pariante, C M

    2013-01-01

    Both glucocorticoids and inflammation have been implicated in the pathogenesis of depression. There is a large body of literature indicating that hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and glucocorticoid receptor (GR) dysfunction are present in a significant proportion of depressed patients. There is also evidence of increased inflammatory processes in depressed populations, with higher levels of cytokines being a prominent finding - including raised levels of IL-6, and IL-1. These findings appear difficult to reconcile given the well-recognised property of glucocorticoids as prominent anti-inflammatory molecules. There are three potential solutions posed to this dilemma. Firstly, it has been argued that the glucocorticoid system and the inflammatory system exist in balance with one another and chronic stress can disrupt this balance in favour of inflammatory processes at the expense of glucocorticoid signalling. It has also been suggested that glucocorticoids have more complex actions than typically thought, and, in low levels can actually be pro-inflammatory, rather than universally anti-inflammatory. Lastly, it is possible that inflammation and glucocorticoid signalling may act on the same processes and structures without direct interaction to give rise to cumulative damage. Improved understanding of this interaction will allow further progress in determining targets for treatment.

  8. Oriental Medical Treatment of chronic Acalculous Cholecystitis

    Directory of Open Access Journals (Sweden)

    Hae-Yeon Lee

    2004-12-01

    Full Text Available Chronic acalculous cholecystitis gets possession of about 12 to 13 percent of patients with chronic cholecystitis. Pathologically it is characterised by chronic inflammation and thickening of the gallbladder wall but doesn't come across stones. Clinical symptoms are vague and include abdominal discomfort and distension, nausea, flatulence and intolerance of fatty foods. A patient on chronic acalculous cholecystitis diagnosed from his clinical symtoms and abdominal ultrasonogram was treated by Geonbihwan, acupuncture and herbal acupuncture. Satisfactory symptomatic improvement was achieved and findings of abdominal ultrasonogram came also normal.

  9. Effective physical treatment for chronic low back pain.

    Science.gov (United States)

    Maher, C G

    2004-01-01

    It is now feasible to adopt an evidence-based approach when providing physical treatment for patients with chronic LBP. A summary of the efficacy of a range of physical treatments is provided in Table 1. The evidence-based primary care options are exercise, laser, massage, and spinal manipulation; however, the latter three have small or transient effects that limit their value as therapies for chronic LBP. In contrast, exercise produces large reductions in pain and disability, a feature that suggests that exercise should play a major role in the management of chronic LBP. Physical treatments, such as acupuncture, backschool, hydrotherapy, lumbar supports, magnets, TENS, traction, ultrasound, Pilates therapy, Feldenkrais therapy, Alexander technique, and craniosacral therapy are either of unknown value or ineffective and so should not be considered. Outside of primary care, multidisciplinary treatment or functional restoration is effective; however, the high cost probably means that these programs should be reserved for patients who do not respond to cheaper treatment options for chronic LBP. Although there are now effective treatment options for chronic LBP, it needs to be acknowledged that the problem of chronic LBP is far from solved. Though treatments can provide marked improvements in the patient's condition, the available evidence suggests that the typical chronic LBP patient is left with some residual pain and disability. Developing new, more powerful treatments and refining the current group of known effective treatments is the challenge for the future.

  10. Indications and surgical treatment of chronic pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Shao-Liang Han; Jun Chen; Hong-Zhong Zhou; Sheng-Hong Lan; Pei-Chen Zhang; Guan-Bao Zhu

    2008-01-01

    BACKGROUND: Some patients with chronic pancreatitis (CP) may require surgery mainly because of intractable pain, suspicion of malignancy, or complications related to CP. This study aimed to analyze the efifcacy of surgical treatment for patients with CP in terms of pain relief, control of local complications, and pancreatic endocrine/exocrine function. METHODS: Twenty-six patients with CP were treated surgically at our hospital from June 1985 to November 2005. The clinical data of these patients were analyzed retrospectively. RESULTS:  The follow-up time ranged from 8 to 130 months with a median of 60.6 months. No patients were lost to follow-up. All patients had improvement of clinical symptoms such as abdominal pain, steatorrhea and weight loss, to some degree, especially pain relief in patients with good dilation and high pressure of the main pancreatic duct. The endocrine and exocrine functions were not alleviated in all patients, otherwise the impaired glucose tolerance was improved in 8 (30.8%), 15 (57.7%) maintained the same body weight, one (3.8%) had an acute attack of CP, and 2 (7.7%) developed pancreatic carcinoma in the 16th and 28th month postoperatively and died within 3 years after operation for CP. The 1-, 3-, 5-year pain-free rates of CP patients were 96.2%(25/26), 88.5%(23/26) and 84.6%(22/26), respectively. CONCLUSIONS: In selected patients with CP, surgical treatment is a safe procedure and can effectively relieve pain and control local complications;also, it is helpful to improve the quality of life for patients with pancreatitis, and to control the development of this disease.

  11. Current treatment in chronic obstructive pulmonary disease

    Institute of Scientific and Technical Information of China (English)

    李嘉惠

    2008-01-01

    Chronic obstructive pulmonary disease (COPD) is defined by fixed airflow limitation associated with an abnormal pulmonary and systemic inflammatory response of the lungs to cigarette smoke. COPD represents an increasing burden worldwide, reported to be the sixth leading cause of death in 1990 and the fourth in 2000. Discouragingly, it is projected to jump to third place by the year 2020.There is increasing evidence that COPD is a more complex systemic disease than an airway and lung disease. In particular, cachexia, skeletal muscle abnormalities, diabetes, coronary artery disease, heart failure, cancer and pulmonary vascular disease are the most common comorbidities. It is associated with a wide variety of systemic consequences, most notably systemic inflammation. Because COPD patients have in general ahigher cardiovascular risk than the average population, cardiovascular safety in a COPD medication is of critical importance.SINGH et al performed a systematic review and recta-analysis of 17 clinical trials enrolling 14 783 patients treated with inhaled anticholinergic drugs used for the treatment of COPD. Inhaled anticholinergics significantly increased the risk of cardiovascular death, MI, or stroke ( 1.8 % vs 1.2 % for control; RR, 1.58 (95 % CI,1.21 - 2.06); P < 0.001 ). However, UPLIIFT (Understanding the Potential Long-Term Impacts on Function with Tiotropium) , a large, 4-year, placebo controlled clinical trial with tiotropium in approximately 6 000 patients with COPD. The preliminary results of UPLIFT showed that there was no increased risk of stroke with tiotropium bromide compared to placebo.A meta-analysis is always considered less convincing than a large prospective trial designed to assess the outcome of interest. However, COPD is a systemic disease. COPD management needs to focus on four major areas: smoking cessation, pharmacologic therapy, exercise training, and pulmonary rehabilitation. Clinicians and patients should always carefully consider any

  12. Glucocorticoids Inhibit Basal and Hormone-Induced Serotonin Synthesis in Pancreatic Beta Cells

    OpenAIRE

    Moina Hasni Ebou; Amrit Singh-Estivalet; Jean-Marie Launay; Jacques Callebert; François Tronche; Pascal Ferré; Jean-François Gautier; Ghislaine Guillemain; Bernadette Bréant; Bertrand Blondeau; Jean-Pierre Riveline

    2016-01-01

    International audience; Diabetes is a major complication of chronic Glucocorticoids (GCs) treatment. GCs induce insulin resistance and also inhibit insulin secretion from pancreatic beta cells. Yet, a full understanding of this negative regulation remains to be deciphered. In the present study, we investigated whether GCs could inhibit serotonin synthesis in beta cell since this neurotransmitter has been shown to be involved in the regulation of insulin secretion. To this aim, serotonin synth...

  13. Treatment of Vasodilator-resistant Mixed Connective Tissue Disease-associated Pulmonary Arterial Hypertension with Glucocorticoid and Cyclophosphamide.

    Science.gov (United States)

    Sugawara, Eri; Kato, Masaru; Hisada, Ryo; Oku, Kenji; Bohgaki, Toshiyuki; Horita, Tetsuya; Yasuda, Shinsuke; Atsumi, Tatsuya

    2017-01-01

    Pulmonary arterial hypertension (PAH) associated with systemic lupus erythematosus (SLE) or mixed connective tissue disease (MTCD), in contrast to other types of PAH, may respond to immunosuppressive therapy. Most PAH cases with an immunosuppressant response were in the early stages of the disease (WHO functional class III or less). The present case was a 34-year-old woman with MCTD-associated PAH (WHO functional class IV) who was resistant to a combination of three vasodilators. Afterwards, she was treated with glucocorticoid and cyclophosphamide. This case suggested the potential benefit of immunosuppressants in patients with severe MCTD-associated PAH.

  14. The Regulation of Muscle Mass by Endogenous Glucocorticoids

    Directory of Open Access Journals (Sweden)

    Daniel L Marks

    2015-02-01

    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

  15. The regulation of muscle mass by endogenous glucocorticoids.

    Science.gov (United States)

    Braun, Theodore P; Marks, Daniel L

    2015-01-01

    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 profound 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 be discussed.

  16. Diretrizes para prevenção e tratamento da osteoporose induzida por glicocorticoide Guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis

    Directory of Open Access Journals (Sweden)

    Rosa Maria Rodrigues Pereira

    2012-08-01

    Full Text Available Os glicocorticoides (GC são prescritos por praticamente todas as especialidades médicas, e cerca de 0,5% da população geral do Reino Unido utiliza esses medicamentos. Com o aumento da sobrevida dos pacientes com doenças reumatológicas, a morbidade secundária ao uso dessa medicação representa um aspecto importante que deve ser considerado no manejo de nossos pacientes. As incidências de fraturas vertebrais e não vertebrais são elevadas, variando de 30%-50% em pessoas que usam GC por mais de três meses. Assim, a osteoporose e as fraturas por fragilidade devem ser prevenidas e tratadas em todos os pacientes que iniciarão ou que já estejam em uso desses esteroides. Diversas recomendações elaboradas por várias sociedades internacionais têm sido descritas na literatura, porém não há consenso entre elas. Recentemente, o Americam College of Rheumatology publicou novas recomendações, porém elas são fundamentadas na FRAX (WHO Fracture Risk Assessment Tool para analisar o risco de cada indivíduo e, dessa maneira, não podem ser completamente utilizadas pela população brasileira. Dessa forma, a Comissão de Osteoporose e Doenças Osteometabólicas da Sociedade Brasileira de Reumatologia, em conjunto com a Associação Médica Brasileira e a Associação Brasileira de Medicina Física e Reabilitação, implementou as diretrizes brasileiras de osteoporose induzida por glicocorticoide (OPIG, baseando-se na melhor evidência científica disponível e/ou experiência de experts. DESCRIÇÃO DO MÉTODO DE COLETA DE EVIDÊNCIA: A revisão bibliográfica de artigos científicos desta diretriz foi realizada na base de dados MEDLINE. A busca de evidência partiu de cenários clínicos reais, e utilizou as seguintes palavras-chave (MeSH terms: Osteoporosis, Osteoporosis/chemically induced*= (Glucocorticoids= Adrenal Cortex Hormones, Steroids, Glucocorticoids, Glucocorticoids/administration and dosage, Glucocorticoids/therapeutic use

  17. The antidepressant fluoxetine normalizes the nuclear glucocorticoid receptor evoked by psychosocial stress

    Science.gov (United States)

    Mitić, M.; Simić, I.; Djordjević, J.; Radojčić, M. B.; Adžić, M.

    2011-12-01

    Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathophysiology of depression and stress disorders. Glucocorticoids, key regulators of the stress response, exert diverse effects on cellular processes in the hippocampus. Beside non-genomic pathways, glucocorticoid effects are mediated through activation of the glucocorticoid receptor (GR), a ligand activated transcriptional factor that belongs to the nuclear hormone receptor superfamily. We analysed the GR protein levels both in the cytoplasmic and nuclear compartments of the hippocampus of Wistar rats exposed to chronic psychosocial isolation stress upon chronic fluoxetine (FLU) treatment. Under chronic stress, corticosterone levels (CORT) were decreased compared to the control, and treatment with FLU did not change its level in the stressed rats. At the molecular level, FLU normalized the level of nuclear GR protein in the hippocampus of the stressed rats. Discrepancy between normalization of nuclear GR in the hippocampus and lack of normalization of HPA axis activity judged by CORT, suggests that other brain structures such as the amygdale and prefrontal cortex that also regulate HPA axis activity, seem not to be normalized by the FLU treatment used in our study.

  18. Glucocorticoids are ineffective in alcoholic hepatitis

    DEFF Research Database (Denmark)

    Christensen, E; Gluud, C

    1995-01-01

    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...... may be different (beneficial or harmful) in special patient subgroups. These results do not support the routine use of glucocorticoids in patients with alcoholic hepatitis, including those with encephalopathy. Whether other subgroups may benefit needs further investigation using the individual patient...

  19. Glucocorticoids decrease astrocyte numbers by reducing glucocorticoid receptor expression in vitro and in vivo.

    Science.gov (United States)

    Unemura, Kazuhiro; Kume, Toshiaki; Kondo, Minami; Maeda, Yuki; Izumi, Yasuhiko; Akaike, Akinori

    2012-01-01

    Glucocorticoids are stress hormones released from the adrenal cortex and their concentration is controlled by the hypothalamic-pituitary-adrenal axis. In this study, we investigated the effect of glucocorticoids on the number of astrocytes and glucocorticoid receptor (GR) expression in vitro and in vivo. Proliferation of cultured astrocytes was reduced following treatment with corticosterone and dexamethasone for 72 h. Corticosterone and dexamethasone also reduced GR expression in astrocytes. RU486, a GR antagonist, inhibited the reduction in both astrocyte proliferation and GR expression. Furthermore, GR knockdown by siRNA inhibited astrocyte proliferation. We also examined the effect of excessive glucocorticoid release on GR expression and the number of astrocytes in vivo by administering adrenocorticotropic hormone to rats for 14 days. GR expression was reduced in the prefrontal cortex and hippocampus and the number of astrocytes was reduced in the frontal cortex. Overall, our results suggest that glucocorticoids decrease the number of astrocytes by reducing GR expression.

  20. Clinical analysis of glucocorticoid in the treatment of endocrine disorders%糖皮质激素治疗内分泌疾病的临床分析

    Institute of Scientific and Technical Information of China (English)

    葛军

    2015-01-01

    Objective:To explore the clinical effect of glucocorticoid in the treatment of endocrine disorders.Methods:106 patients with endocrine diseases were selected.They were randomly divided into the experimental group and the control group with 54 cases in each.The control group were given conventional treatment,and the experimental group were given glucocorticoids on the basis of the control group,then we observed the therapeutic effect in the two groups.Results:In the experimental group,the total efficiency(98.1%) was significantly higher than that of the control group(79.6%);the satisfaction(98.1%) was significantly higher than that of the control group(79.6%);the adverse reaction rate(3.7%) was significantly lower than that of the control group(14.8%), P<0.05.Conclusion:Glucocorticoid treatment of endocrine disorders can significantly improve the patient's symptoms and improve patient satisfaction,and the safety was good.%目的:探讨糖皮质激素治疗内分泌疾病的临床效果。方法:收治内分泌疾病患者106例,随机分为试验组和对照组各54例,对照组采用常规方法治疗,试验组在对照组的基础上加入糖皮质激素治疗,观察两组的治疗效果。结果:在试验组总有效率(98.1%)明显高于对照组(79.6%),满意度(98.1%)明显高于对照组(79.6%),不良反应率(3.7%)明显低于对照组(14.8%),P<0.05。结论:采用糖皮质激素治疗内分泌疾病可以明显改善患者的症状,提高患者的满意度,安全性好。

  1. Forced Use Treatment of Chronic Hemiparesis

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2002-07-01

    Full Text Available Twelve children (age 1 to 8 years with chronic (>1 year hemiparesis were treated by forced use, or constraint-induced, movement therapy at Tulane University School of Medicine, New Orleans, LA.

  2. Chronic inflammatory demyelinating polyneuropathy after treatment with interferon-alpha.

    Science.gov (United States)

    Hirotani, Makoto; Nakano, Hitoshi; Ura, Shigehisa; Yoshida, Kazuto; Niino, Masaaki; Yabe, Ichiro; Sasaki, Hidenao

    2009-01-01

    Interferon-alpha (IFN-alpha), though widely used for the treatment of chronic viral hepatitis, may be associated with the occurrence of autoimmune disorders. In this case report, a patient with chronic hepatitis C virus infection had chronic inflammatory demyelinating polyneuropathy (CIDP) after the initiation of IFN-alpha therapy. The neurological symptoms of this patient continued to progress even though the treatment with IFN-alpha had been withdrawn; the symptoms improved dramatically following treatment with intravenous immunoglobulin. This case may therefore provide an important clue to understand the immune mechanism of CIDP and IFN-alpha.

  3. Phosphodiesterase 4 inhibitors augment the ability of formoterol to enhance glucocorticoid-dependent gene transcription in human airway epithelial cells: a novel mechanism for the clinical efficacy of roflumilast in severe chronic obstructive pulmonary disease.

    Science.gov (United States)

    Moodley, Thunicia; Wilson, Sylvia M; Joshi, Taruna; Rider, Christopher F; Sharma, Pawan; Yan, Dong; Newton, Robert; Giembycz, Mark A

    2013-04-01

    Post-hoc analysis of two phase III clinical studies found that the phosphodiesterase 4 (PDE4) inhibitor, roflumilast, reduced exacerbation frequency in patients with severe chronic obstructive pulmonary disease (COPD) who were taking inhaled corticosteroids (ICS) concomitantly, whereas patients not taking ICS derived no such benefit. In contrast, in two different trials also performed in patients with severe COPD, roflumilast reduced exacerbation rates in the absence of ICS, indicating that PDE4 inhibition alone is sufficient for therapeutic activity to be realized. Given that roflumilast is recommended as an "add-on" medication to patients with severe disease who will inevitably be taking a long-acting β2-adrenoceptor agonist (LABA)/ICS combination therapy, we tested the hypothesis that roflumilast augments the ability of glucocorticoids to induce genes with anti-inflammatory activity. Using a glucocorticoid response element (GRE) luciferase reporter transfected into human airway epithelial cells [both bronchial epithelium + adenovirus 12 - SV40 hybrid (BEAS-2B) cells and primary cultures], roflumilast enhanced fluticasone propionate-induced GRE-dependent transcription. Roflumilast also produced a sinistral displacement of the concentration-response curves that described the augmentation of GRE-dependent transcription by the LABA formoterol. In BEAS-2B cells and primary airway epithelia, roflumilast interacted with formoterol in a positive cooperative manner to enhance the expression of several glucocorticoid-inducible genes that have anti-inflammatory potential. We suggest that the ability of roflumilast and formoterol to interact in this way supports the concept that these drugs together may impart clinical benefit beyond that achievable by an ICS alone, a PDE4 inhibitor alone, or an ICS/LABA combination therapy. Roflumilast may, therefore, be especially effective in patients with severe COPD.

  4. Glucocorticoid receptor and treatment of psychotic major depression%糖皮质激素受体与重型精神病性抑郁症的治疗

    Institute of Scientific and Technical Information of China (English)

    惠昕; 周彩红; 王明伟

    2005-01-01

    @@ 1 Introduction Psychotic major depression (PMD),which responds poorly to tricyclic anti-depressants, is a distinct syndrome of depression. hy percortisolemia (cortisone hypersecretion), a biological abnormality existing in many patients with PMD, has led to various theoretical and empirical rationales for the potential therapeutic use of anti-glucocorticoid agents in the treatment of depression.

  5. [EFFICIENT TREATMENT OF CHRONIC RESPIRATORY INSUFFICIENCY IN PATIENTS WITH KYPHOSCOLIOSIS].

    Science.gov (United States)

    Tsvetkova, O A; Pal'man, A D; Abdulaeva, G B

    2015-01-01

    We report efficient treatment of chronic respiratory insufficiency in patients with congenital kyphoscoliosis by non-invasive auxiliary ventilation and low-flow oxygen therapy. It proved possible to effectively control severe chronic respiratory insufficiency under conditions of a pulmonological ward without application of means and measures of intensive therapy.

  6. [The use of eurespal for the treatment of chronic laryngitis].

    Science.gov (United States)

    Riabova, M A

    2011-01-01

    The author provides a rationale for the use of eurespal for the treatment of chronic laryngitis based on the pathogenetic concept of pathological condition. The results of a clinical study designed to evaluate the efficiency and safety of eurespal therapy in patients with chronic laryngitis are presented.

  7. Glucocorticoid activity detected by in vivo zebrafish assay and in vitro glucocorticoid receptor bioassay at environmental relevant concentrations.

    Science.gov (United States)

    Chen, Qiyu; Jia, Ai; Snyder, Shane A; Gong, Zhiyuan; Lam, Siew Hong

    2016-02-01

    Glucocorticoids are pharmaceutical contaminants of emerging concern due to their incomplete removal during wastewater treatment, increased presence in aquatic environment and their biological potency. The zebrafish is a popular model for aquatic toxicology and environmental risk assessment. This study aimed to determine if glucocorticoids at environmental concentrations would perturb expression of selected glucocorticoid-responsive genes in zebrafish and to investigate their potentials as an in vivo zebrafish assay in complementing in vitro glucocorticoid receptor bioassay. The relative expression of eleven glucocorticoid-responsive genes in zebrafish larvae and liver of adult male zebrafish exposed to three representative glucocorticoids (dexamethasone, prednisolone and triamcinolone) was determined. The expression of pepck, baiap2 and pxr was up-regulated in zebrafish larvae and the expression of baiap2, pxr and mmp-2 was up-regulated in adult zebrafish exposed to glucocorticoids at concentrations equivalent to total glucocorticoids reported in environmental samples. The responsiveness of the specific genes were sufficiently robust in zebrafish larvae exposed to a complex environmental sample detected with in vitro glucocorticoid activity equivalent to 478 pM dexamethasone (DEX-EQ) and confirmed to contain low concentration (0.2 ng/L or less) of the targeted glucocorticoids, and possibly other glucocorticoid-active compounds. The findings provided in vivo relevance to the in vitro glucocorticoid activity and suggested that the environmental sample can perturb glucocorticoid-responsive genes in its original, or half the diluted, concentration as may be found in the environment. The study demonstrated the important complementary roles of in vivo zebrafish and in vitro bioassays coupled with analytical chemistry in monitoring environmental glucocorticoid contaminants.

  8. Psychological Neuromodulatory Treatments for Young People with Chronic Pain

    Directory of Open Access Journals (Sweden)

    Jordi Miró

    2016-12-01

    Full Text Available The treatment of young people with chronic pain is a complex endeavor. Many of these youth do not obtain adequate relief from available interventions. Psychological neuromodulatory treatments have been shown to have potential benefit for adults with chronic pain. Here, we review and summarize the available information about the efficacy of three promising psychological neuromodulatory treatments—neurofeedback, meditation and hypnosis—when provided to young people with chronic pain. A total of 16 articles were identified and reviewed. The findings from these studies show that hypnotic treatments are effective in reducing pain intensity for a variety of pediatric chronic pain problems, although research suggests variability in outcomes as a function of the specific pain problem treated. There are too few studies evaluating the efficacy of neurofeedback or meditation training in young people with chronic pain to draw firm conclusions regarding their efficacy. However, preliminary data indicate that these treatments could potentially have positive effects on a variety of outcomes (e.g., pain intensity, frequency of pain episodes, physical and psychological function, at least in the short term. Clinical trials are needed to evaluate the effects of neurofeedback and meditation training, and research is needed to identify the moderators of treatment benefits as well as better understand the mechanisms underlying the efficacy of all three of these treatments. The findings from such research could enhance overall treatment efficacy by: (1 providing an empirical basis for better patient-treatment matching; and (2 identifying specific mechanisms that could be targeted with treatment.

  9. Glucocorticoid feedback resistance.

    Science.gov (United States)

    De Kloet, E R; Vreugdenhil, E; Oitzl, M S; Joëls, M

    1997-01-01

    Glucocorticoid feedback resistance can be inherited or locally acquired. The implications of these two forms of resistance for disease are strikingly different. The inherited form is characterized by enhanced adrenocortical function and hypercorticism to compensate for a generalized deficit in the glucocorticoid receptor gene, but these individuals lack symptoms of Cushing's syndrome. By contrast, resistance acquired at the level of the hypothalamic corticotropin-releasing hormone (CRH) neurons is linked to hypercorticism, which is not compensatory but overexposes the rest of the body and the brain to glucocorticoids. This cell-specific glucocorticoid resistance can be acquired by genetically predisposed individuals failing to cope with (early) life events and causes enhanced vulnerability to disease-specific actions of glucocorticoids. (c) 1997, Elsevier Science Inc. (Trends Endocrinol Metab 1997; 8:26-33).

  10. Modern opportunities for the treatment of chronic prostatitis

    Directory of Open Access Journals (Sweden)

    V. A. Bozhedomov

    2016-01-01

    Full Text Available The paper focuses on the recommendations for chronic prostatitis treatment taking into the consideration the peculiarities of the pathogenesis and clinical picture of this disease. The paper demonstrates that the efficient chronic prostatitis treatment requires the new UPOINT prostatitis classification rather than traditional VIN NIDDK (1995 classification. The paper discusses the indications for various drug and non-drug interventions: antibiotics, alpha-blockers, M-cholinolytics, analgesics, antidepressants, phytodrugs, pelviс floor acupuncture and physiotherapy, psychotherapy.

  11. 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.

    2013-01-01

    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. T

  12. Glycyrrhizin treatment for Chronic Hepatitis C

    NARCIS (Netherlands)

    T.G.J. van Rossum (Tekla)

    2000-01-01

    textabstractChronic hepatitis C is a slowly progressive liver disease that may evolve into cirrhosis with its potential complications of liver failure or hepatocellular carcinoma. Current therapy with alpha-interferon is directed at viral clearance, but sustained response is only achieved in 20-40%

  13. CB1 receptor mediates the effects of glucocorticoids on AMPK activity in the hypothalamus.

    Science.gov (United States)

    Scerif, Miski; Füzesi, Tamás; Thomas, Julia D; Kola, Blerina; Grossman, Ashley B; Fekete, Csaba; Korbonits, Márta

    2013-10-01

    AMP-activated protein kinase (AMPK), a regulator of cellular and systemic energy homeostasis, can be influenced by several hormones. Tissue-specific alteration of AMPK activity by glucocorticoids may explain the increase in appetite, the accumulation of lipids in adipose tissues, and the detrimental cardiac effects of Cushing's syndrome. Endocannabinoids are known to mediate the effects of various hormones and to influence AMPK activity. Cannabinoids have central orexigenic and direct peripheral metabolic effects via the cannabinoid receptor type 1 (CB1). In our preliminary experiments, WT mice received implants of a corticosterone-containing pellet to establish a mouse model of Cushing's syndrome. Subsequently, WT and Cb1 (Cnr1)-knockout (CB1-KO) littermates were treated with corticosterone and AMPK activity in the hypothalamus, various adipose tissues, liver and cardiac tissue was measured. Corticosterone-treated CB1-KO mice showed a lack of weight gain and of increase in hypothalamic and hepatic AMPK activity. In adipose tissues, baseline AMPK activity was higher in CB1-KO mice, but a glucocorticoid-induced drop was observed, similar to that observed in WT mice. Cardiac AMPK levels were reduced in CB1-KO mice, but while WT mice showed significantly reduced AMPK activity following glucocorticoid treatment, CB1-KO mice showed a paradoxical increase. Our findings indicate the importance of the CB1 receptor in the central orexigenic effect of glucocorticoid-induced activation of hypothalamic AMPK activity. In the periphery adipose tissues, changes may occur independently of the CB1 receptor, but the receptor appears to alter the responsiveness of the liver and myocardial tissues to glucocorticoids. In conclusion, our data suggest that an intact cannabinoid pathway is required for the full metabolic effects of chronic glucocorticoid excess.

  14. 糖皮质激素治疗乙型肝炎相关肝衰竭的研究进展%Research progress of glucocorticoid treatment for hepatitis B-related liver failure

    Institute of Scientific and Technical Information of China (English)

    孟琳琳; 叶卫江

    2013-01-01

    The pathogenesis of hepatitis B-related liver failure is complicated,and there is no effective treatment at present.Glucocorticoid can inhibit the immune response,reduce the production of inflammatory mediator,and also has strong and rapid effect on anti-endotoxin.At the same time glucocorticoid can stabilize the lysosome membrane,protect the liver cell,and reduce the necrosis of liver cell.Glucocorticoids has been widely used in clinical practice by its unique biological characteristics.In this paper,the research progress of glucocorticoid treatment for hepatitis B-related liver failure is discussed.%乙型肝炎相关肝衰竭发病机制复杂,目前临床上缺乏有效的治疗手段.糖皮质激素具有抑制免疫应答、减少炎症介质的产生,发挥强大而迅速的抗内毒素血症作用,同时还能稳定溶酶体膜、保护肝细胞、减轻肝细胞的坏死.糖皮质激素以其特有的生物学特性已在临床广泛应用.该文对糖皮质激素治疗乙型肝炎相关肝衰竭的现状进行综述.

  15. 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

    2011-01-01

    the groups, while there was a trend towards decreasing bending mechanical properties in the glucocorticoid-2 group. In conclusion, 7 months of glucocorticoid treatment with malnutrition had a significant impact on the cortical microarchitecture of the sheep femur midshaft. These observed changes occurred 3...... months after glucocorticoid cessation, suggesting a delayed effect of glucocorticoid on cortical bone. Thus, changes in cortical bone beyond cancellous bone might further increase fracture risk in patients treated with glucocorticoids. This model might be used as a glucocorticoid-induced osteoporotic...

  16. Recent progress in the discovery of novel glucocorticoid receptor modulators.

    Science.gov (United States)

    Takahashi, Hidenori; Razavi, Hossein; Thomson, David

    2008-01-01

    Glucocorticoids have been used in modern clinical practice for over fifty years. Although they have demonstrated potent anti-inflammatory and immunosuppressive activities, their association with debilitating and life-threatening side effects has been a major drawback. Recent insights into glucocorticoid biology have lent support to the hypothesis that the glucocorticoid anti-inflammatory activities could be dissociated from their adverse side effects. Inspired by these biological findings, the search for dissociated glucocorticoid receptor agonists has intensified. Antag-onists of the glucocorticoid receptor that offer therapeutic benefits for the treatment of diseases such as diabetes have also been pursued. These efforts have been partly focused on the development of tissue, especially liver, selective glucocor-ticoid receptor antagonists, which are thought to have improved safety profiles. This review offers a summary of the research and development activities in this field and covers journal and patent publications from 2003 to March 2006.

  17. Lubiprostone: a novel treatment for chronic constipation

    OpenAIRE

    Lacy, Brian E.; L Campbell Levy

    2008-01-01

    Brian E Lacy, L Campbell LevySection of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon NH, USAAbstract: Chronic constipation is highly prevalent, reduces patients’ quality of life, and imposes a significant health care burden on society. Lifestyle modifications and over-the-counter agents improve symptoms of constipation in some patients, however many patients have persistent symptoms and require the use of prescription medications. Three prescription m...

  18. Current concepts in glucocorticoid resistance.

    Science.gov (United States)

    Yang, Nan; Ray, David W; Matthews, Laura C

    2012-09-01

    Glucocorticoids (GCs) are the most potent anti-inflammatory agents known. A major factor limiting their clinical use is the wide variation in responsiveness to therapy. The high doses of GC required for less responsive patients means a high risk of developing very serious side effects. Variation in sensitivity between individuals can be due to a number of factors. Congenital, generalized GC resistance is very rare, and is due to mutations in the glucocorticoid receptor (GR) gene, the receptor that mediates the cellular effects of GC. A more common problem is acquired GC resistance. This localized, disease-associated GC resistance is a serious therapeutic concern and limits therapeutic response in patients with chronic inflammatory disease. It is now believed that localized resistance can be attributed to changes in the cellular microenvironment, as a consequence of chronic inflammation. Multiple factors have been identified, including alterations in both GR-dependent and -independent signaling downstream of cytokine action, oxidative stress, hypoxia and serum derived factors. The underlying mechanisms are now being elucidated, and are discussed here. Attempts to augment tissue GC sensitivity are predicted to permit safe and effective use of low-dose GC therapy in inflammatory disease.

  19. 老年慢性阻塞性肺病应用抗生素联合糖皮质激素治疗的临床观察%Clinical Observation of Elderly Patients With Chronic Obstructive Pulmonary Disease With Antibiotics Combined With Glucocorticoid Therapy

    Institute of Scientific and Technical Information of China (English)

    米丹; 王敏

    2015-01-01

    Objective To analyze the antibiotic and corticosteroid in the treatment of senile COPD effect. Methods 90 cases of patients with chronic obstructive pulmonary disease patients were randomly divided into twogroups, the control group received antibiotics, observation group was given antibiotics and glucocorticoid treatment, compared two groups of treatment effect. Results The total effective rate of observation group was higher than that of the control group; the two group after treatment, lung function were improved than before treatment, and the observation group improved better than the control group. There was no significant difference between the two groups of adverse reactions. Conclusion Antibiotics and corticosteroid in the treatment of elderly patients with chronic obstructive pulmonary disease in patients with good effect, can effectively improve the lung function, and less adverse reactions.%目的 分析抗生素联合糖皮质激素治疗老年性阻塞性肺病的效果.方法 将90例慢性阻塞性肺病老年患者随机分为两组,对照组予以抗生素治疗,观察组予以抗生素联合糖皮质激素治疗,对比两组治疗效果.结果 观察组治疗总有效率高于对照组;两组治疗后肺功能均比治疗前有所改善,且观察组改善情况优于对照组.两组不良反应无显著差异.结论 抗生素联合糖皮质激素治疗老年慢性阻塞性肺病效果良好,能有效改善患者肺功能,且不良反应较少.

  20. Chronic methadone treatment shows a better cost/benefit ratio than chronic morphine in mice.

    Science.gov (United States)

    Enquist, Johan; Ferwerda, Madeline; Milan-Lobo, Laura; Whistler, Jennifer L

    2012-02-01

    Chronic treatment of pain with opiate drugs can lead to analgesic tolerance and drug dependence. Although all opiate drugs can promote tolerance and dependence in practice, the severity of those unwanted side effects differs depending on the drug used. Although each opiate drug has its own unique set of pharmacological profiles, methadone is the only clinically used opioid drug that produces substantial receptor endocytosis at analgesic doses. Here, we examined whether moderate doses of methadone carry any benefits over chronic use of equianalgesic morphine, the prototypical opioid. Our data show that chronic administration of methadone produces significantly less analgesic tolerance than morphine. Furthermore, we found significantly reduced precipitated withdrawal symptoms after chronic methadone treatment than after chronic morphine treatment. Finally, using a novel animal model with a degrading μ-opioid receptor we showed that, although endocytosis seems to protect against tolerance development, endocytosis followed by receptor degradation produces a rapid onset of analgesic tolerance to methadone. Together, these data indicated that opioid drugs that promote receptor endocytosis and recycling, such as methadone, may be a better choice for chronic pain treatment than morphine and its derivatives that do not.

  1. Treatment in chronic migraine: choice of reabilitation strategies

    Directory of Open Access Journals (Sweden)

    Ioana STANESCU

    2015-12-01

    Full Text Available Migraine is a disabling neurologic condition with a spontaneous clinical evolution into a chronic form. Migraine progression from an episodic into a chronic form is realized through a period of time involving several months or years, during which an increase attack frequency occurs. .According to the International Classification of Headache Disorders (ICHD-3 chronic migraine is a type of primary headache occurring on 15 or more days per month for more than 3 months, in which more than 8 days per month headache meet criteria for migraine with or without aura or respond to specific migraine treatment. The prevalence of chronic migraine is estimated between 1- 3% of general population. Persons with chronic migraine are more likely to suffer from severe disability; chronic migraine has an important socio-economic impact. Diagnostic approach in chronic migraine includes exclusion of a secondary headache disorder and confirmation of a primary episodic headache. When a patient is found to overuse pain medication, diagnosis of both chronic migraine and MOH should be considered. Treating episodic migraine early and managing attack frequency using preventive medication and behavioural interventions will be benefic in reducing the risk of chronicisation. Lifestyle changes are important for avoiding triggers for migraine attacks; treatment of comorbidities is equally important because these conditions exacerbate patient’s tendency to have headaches. The initial relief step for drug abusers always relies in drug withdrawal. For migraine attacks treatment begins with non-pharmacologic interventions (staying in a quiet, dark room, pressure on painful areas, applying cold compresses , simple OTC analgetics (NSAIDs, paracetamol, aspirin, acetaminophen. If these are not effective, triptans are the drugs of choice. Preventive treatment is always recommended in patients with chronic migraine because the high frequency of headache attacks. Treatment should be

  2. [Pathogenesis, diagnosis and treatment of chronic obstructive pulmonary disease in the light of new research].

    Science.gov (United States)

    Płusa, Tadeusz

    2016-12-22

    Accurate number of patients with chronic obtructive pulmonary disease (COPD) is difficult to determine, both in Poland and in the world. Quoted estimates and fragmented with the research indicate that approx. 10% of the world's population may be burdened by this disease. As it turns out, COPD is recognized in 25-45% in non-smokers, suggesting a genetic link. This is confirmed by new data that indicates that further embodiments having genetic polymorphisms associated with the occurrence of the disease. It was further found that the allele GC-1F vitamin D were risk factor for development of COPD. It is emphasized that respiratory epithelial cells directly responsible for the response to inhaled agents. Attention was also drawn to the role of eosinophiles. It has been shown that in patients with COPD with the dominant of eosinophilic faction glucocorticoids work very efficiently, indicating the validity of the division to "responders" and "non-responders" for treatment. As a new biomarker for COPD is proposed irisin, released from skeletal myocytes, which is beneficial to exercise tolerance in patients with COPD.

  3. Treatment of a Case Example with PTSD and Chronic Pain

    Science.gov (United States)

    Shipherd, Jillian C.

    2006-01-01

    This commentary reviews the case of GH, a survivor of a road traffic collision, who has chronic pain and posttraumatic stress disorder (PTSD). The case formulation, assessment strategy, and treatment plan are informed by the relevant experimental literature and empirically supported treatments using a cognitive behavioral perspective. Given this…

  4. Behavioral Neuroadaptation to Alcohol: From Glucocorticoids to Histone Acetylation

    Science.gov (United States)

    Mons, Nicole; Beracochea, Daniel

    2016-01-01

    A prime mechanism that contributes to the development and maintenance of alcoholism is the dysregulation of the hypothalamic–pituitary–adrenal axis activity and the release of glucocorticoids (cortisol in humans and primates, corticosterone in rodents) from the adrenal glands. In the brain, sustained, local elevation of glucocorticoid concentration even long after cessation of chronic alcohol consumption compromises functional integrity of a circuit, including the prefrontal cortex (PFC), the hippocampus (HPC), and the amygdala (AMG). These structures are implicated in learning and memory processes as well as in orchestrating neuroadaptive responses to stress and anxiety responses. Thus, potentiation of anxiety-related neuroadaptation by alcohol is characterized by an abnormally AMG hyperactivity coupled with a hypofunction of the PFC and the HPC. This review describes research on molecular and epigenetic mechanisms by which alcohol causes distinct region-specific adaptive changes in gene expression patterns and ultimately leads to a variety of cognitive and behavioral impairments on prefrontal- and hippocampal-based tasks. Alcohol-induced neuroadaptations involve the dysregulation of numerous signaling cascades, leading to long-term changes in transcriptional profiles of genes, through the actions of transcription factors such as [cAMP response element-binding protein (CREB)] and chromatin remodeling due to posttranslational modifications of histone proteins. We describe the role of prefrontal–HPC–AMG circuit in mediating the effects of acute and chronic alcohol on learning and memory, and region-specific molecular and epigenetic mechanisms involved in this process. This review first discusses the importance of brain region-specific dysregulation of glucocorticoid concentration in the development of alcohol dependence and describes how persistently increased glucocorticoid levels in PFC may be involved in mediating working memory impairments and

  5. Behavioral neuroadaptation to alcohol : from glucocorticoids to histone acetylation

    Directory of Open Access Journals (Sweden)

    Daniel Beracochea

    2016-10-01

    Full Text Available A prime mechanism that contributes to the development and maintenance of alcoholism is the dysregulation of the hypothalamic-pituitary-adrenal (HPA axis activity and the release of glucocorticoids (cortisol in humans and primates, corticosterone in rodents from the adrenal glands. In the brain, sustained, local elevation of glucocorticoid concentration even long after cessation of chronic alcohol consumption compromises functional integrity of a circuit including the prefrontal cortex, the hippocampus and the amygdala. These structures are implicated in learning and memory processes as well as in orchestrating neuroadaptive responses to stress and anxiety responses. Thus, potentiation of anxiety-related neuroadaptation by alcohol is characterized by an abnormally amygdala hyperactivity coupled with a hypofunction of the prefrontal cortex and the hippocampus. This review describes research on molecular and epigenetic mechanisms by which alcohol causes distinct region-specific adaptive changes in gene expression patterns and ultimately, leads to a variety of cognitive and behavioral impairments on prefrontal- and hippocampal-based tasks. Alcohol-induced neuroadaptations involve the dysregulation of numerous signaling cascades, leading to long-term changes in transcriptional profiles of genes, through the actions of transcription factors such as CREB (cAMP response element binding protein and chromatin remodeling due to post-translational modifications of histone proteins. We describe the role of prefrontal-hippocampus-amygdala circuit in mediating the effects of acute and chronic alcohol on learning and memory, and region-specific molecular and epigenetic mechanisms involved in this process. This review first discusses the importance of brain region-specific dysregulation of glucocorticoid concentration in the development of alcohol dependence and describes on how persistently increased glucocorticoid levels in prefrontal cortex may be involved in

  6. Periodontal treatment reduces chronic systemic inflammation in peritoneal dialysis patients.

    Science.gov (United States)

    Siribamrungwong, Monchai; Yothasamutr, Kasemsuk; Puangpanngam, Kutchaporn

    2014-06-01

    Chronic systemic inflammation, a non traditional risk factor of cardiovascular diseases, is associated with increasing mortality in chronic kidney disease, especially peritoneal dialysis patients. Periodontitis is a potential treatable source of systemic inflammation in peritoneal dialysis patients. Clinical periodontal status was evaluated in 32 stable chronic peritoneal dialysis patients by plaque index and periodontal disease index. Hematologic, blood chemical, nutritional, and dialysis-related data as well as highly sensitive C-reactive protein were analyzed before and after periodontal treatment. At baseline, high sensitive C-reactive protein positively correlated with the clinical periodontal status (plaque index; r = 0.57, P chronic systemic inflammation in peritoneal dialysis patients. Treatment of periodontal diseases can improve systemic inflammation, nutritional status and erythropoietin responsiveness in peritoneal dialysis patients.

  7. Endothelial cells of the blood-brain barrier: a target for glucocorticoids and estrogens?

    Science.gov (United States)

    Dietrich, Jean-Bernard

    2004-01-01

    Adhesion molecules are involved in the leukocyte recruitment of leukocytes at the blood-brain barrier. For this reason, it is important to understand how the regulation of their gene expression controls lymphocyte adhesion to endothelial cells in microvessels. Indeed, due to their specificity and diversity, adhesion molecules involved in extravasation play an essential role in the recruitment of activated leukocytes and activation of inflammation. Multiple sclerosis results from a chronic inflammation of the CNS which is mediated by infiltration of inflammatory cells from the immune system. Administration of glucocorticoids is a routine method to control multiple sclerosis since naturally derived or synthetic glucocorticoids are potent immunosuppressive and anti-inflammatory agents. Glucocorticoids also have beneficial effects in stabilizing the blood-brain barrier, as steroid hormones regulate the expression of adhesion molecule genes in endothelial cells. Other hormones such as estrogens modulate many endothelial cell biological activities, among them adhesion to leukocytes. They regulate expression of adhesion molecules genes on endothelial cells and are useful for the treatment of experimental autoimmune encephalomyelitis, the animal model of multiple sclerosis. The effects of glucocorticoids and estrogens on the expression of adhesion molecules on endothelial cells, including microvascular endothelial cells of the blood-brain barrier, are reviewed in this paper, as well as the involvement of these hormones in the therapy of experimental autoimmune encephalomyelitis and multiple sclerosis.

  8. Latin American consensus on guidelines for chronic migraine treatment

    OpenAIRE

    Alex Rodrigo Espinoza Giacomozzi; Alexander Parajeles Vindas; Ariovaldo Alberto da Silva Junior; Carlos Alberto Bordini; Carlos Federico Buonanotte; Celia Aparecida de Paula Roesler; Claudio Manoel Brito; Cristina Perez; Deusvenir de Souza Carvalho; Djacir Dantas Pereira de Macedo; Elcio Juliato Piovesan; Elder Machado Sarmento; Eliana Meire Melhado; Fabiola Dach Eckeli; Fernando Kowacs

    2013-01-01

    Chronic migraine is a condition with significant prevalence all around the world and high socioeconomic impact, and its handling has been challenging neurologists. Developments for understanding its mechanisms and associated conditions, as well as that of new therapies, have been quick and important, a fact which has motivated the Latin American and Brazilian Headache Societies to prepare the present consensus. The treatment of chronic migraine should always be preceded by a careful diagnosis...

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

    Directory of Open Access Journals (Sweden)

    Keith Bruce D

    2008-03-01

    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

  10. Telbivudine: A new treatment for chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Three hundred and fifty million people worldwide are estimated to be chronically infected with hepatitis B virus. 15%-40% of these subjects will develop cirrhosis,liver failure or hepatocellular carcinoma during their life. The treatment of chronic hepatitis B has improved dramatically over the last decade merits to the advent of nucleoside/nucleotide analogues and the use of pegylated interferons. Approved drugs for chronic hepatitis B treatment include: standard interferonalpha 2b, pegylated interferon-alpha 2a, lamivudine,adefovir dipivoxil, and entecavir. Unfortunately, these agents are not effective in all patients and are associated with distinct side effects. Interferons have numerous side effects and nucleoside or nucleotide analogues,which are well tolerated, need to be used for prolonged periods, even indefinitely. However, prolonged treatment with nucleoside or nucleotide analogues is associated with a high rate of resistance. Telbivudine is a novel,orally administered nucleoside analogue for use in the treatment of chronic hepatitis B. In contrast to other nucleoside analogues, Telbivudine has not been associated with inhibition of mammalian DNA polymerase with mitochondrial toxicity. Telbivudine has demonstrated potent activity against hepatitis B with a significantly higher rate of response and superior viral suppression compared with lamivudine, the standard treatment.Telbivudine has been generally well tolerated, with a low adverse effect profile, and at its effective dose, no doselimiting toxicity has been observed. Telbivudine is one of the most potent antiviral agents for chronic hepatitis B virus and was approved by the FDA in late 2006.

  11. Roflumilast: the evidence for its clinical potential in the treatment of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Linda Timm Wagner

    2005-03-01

    Full Text Available Linda Timm Wagner, Charlotte A. KenreighMLC Solutions Ltd, Galena, Ohio, USAIntroduction: Chronic obstructive pulmonary disease (COPD, characterized by a progressive deterioration of lung function caused primarily by the inhalation of toxic substances, is a leading cause of morbidity and mortality worldwide. Current treatment options for the management of its symptoms include the use of bronchodilators and glucocorticoid agents that are not universally beneficial and which are associated with limitations. Phosphodiesterase-4 (PDE4 inhibitors are a novel class of antiinflammatory agents being developed for COPD treatment.Aims: The purpose of this article is to review the clinical potential of roflumilast, a PDE4 inhibitor currently in phase III clinical trials, in the management of patients with COPD.Evidence review: Phase II studies indicate that roflumilast can be given orally once daily. Preliminary evidence from two phase III, randomized, double-blind, placebo-controlled studies suggest that roflumilast improves or stabilizes lung function, as measured by forcedexpiratory volume in 1 s and 6 s (FEV1 and FEV6, forced vital capacity (FVC, and peak expiratory flow (PEF in patients with COPD. Improvements in COPD exacerbation rate were also reported in these trials. Quality of life, as measured by the St George’s Respiratory Questionnaire, also improved with roflumilast treatment. Clinical studies to date suggest that roflumilast is well tolerated.Clinical potential: Current evidence supports the use of roflumilast in the management of COPD as shown by improvements in patients’ symptoms and quality of life, and good tolerability profile. Its once-daily oral dosing regimen is unique among current therapies for COPD. This potential and the place of roflumilast in the stepwise management of the disease need to be confirmed as further evidence is published. Additional evidence will also be welcome to determine if its mechanism of action

  12. Glucocorticoid regulation of brain-derived neurotrophic factor: relevance to hippocampal structural and functional plasticity.

    Science.gov (United States)

    Suri, D; Vaidya, V A

    2013-06-01

    Glucocorticoids serve as key stress response hormones that facilitate stress coping. However, sustained glucocorticoid exposure is associated with adverse consequences on the brain, in particular within the hippocampus. Chronic glucocorticoid exposure evokes neuronal cell damage and dendritic atrophy, reduces hippocampal neurogenesis and impairs synaptic plasticity. Glucocorticoids also alter expression and signaling of the neurotrophin, brain-derived neurotrophic factor (BDNF). Since BDNF is known to promote neuroplasticity, enhance cell survival, increase hippocampal neurogenesis and cellular excitability, it has been hypothesized that specific adverse effects of glucocorticoids may be mediated by attenuating BDNF expression and signaling. The purpose of this review is to summarize the current state of literature examining the influence of glucocorticoids on BDNF, and to address whether specific effects of glucocorticoids arise through perturbation of BDNF signaling. We integrate evidence of glucocorticoid regulation of BDNF at multiple levels, spanning from the well-documented glucocorticoid-induced changes in BDNF mRNA to studies examining alterations in BDNF receptor-mediated signaling. Further, we delineate potential lines of future investigation to address hitherto unexplored aspects of the influence of glucocorticoids on BDNF. Finally, we discuss the current understanding of the contribution of BDNF to the modulation of structural and functional plasticity by glucocorticoids, in particular in the context of the hippocampus. Understanding the mechanistic crosstalk between glucocorticoids and BDNF holds promise for the identification of potential therapeutic targets for disorders associated with the dysfunction of stress hormone pathways.

  13. The operative treatment of chronic calcaneal paratenonitis.

    Science.gov (United States)

    Kvist, H; Kvist, M

    1980-08-01

    The conservative management of chronic calcaneal paratenonitis is time-consuming and often unsatisfactory. A new, safe and simple technique is described. The crural fascia on both sides of the tendon is incised and left open, adhesions around the tendon are trimmed away, the strongly hypertrophied portions of the paratenon are removed and mobilisation is begun immediately after operation. Between 1961 and 1978 201 such operations were performed on 182 patients 62 of whom were top-ranking Finnish athletes. Only five patients were not athletes. The results, including early return to full activity, were excellent in 169, good in 25 and poor in seven cases. After operation one of the patients gained an Olympic gold medal; others have attained international prominence.

  14. Craniosacral Therapy for the Treatment of Chronic Neck Pain

    OpenAIRE

    2016-01-01

    Objectives: With growing evidence for the effectiveness of craniosacral therapy (CST) for pain management, the efficacy of CST remains unclear. This study therefore aimed at investigating CST in comparison with sham treatment in chronic nonspecific neck pain patients. Materials and Methods: A total of 54 blinded patients were randomized into either 8 weekly units of CST or light-touch sham treatment. Outcomes were assessed before and after treatment (week 8) and again 3 months later (week 20)...

  15. Non-pharmacological treatment of chronic widespread musculoskeletal pain.

    Science.gov (United States)

    Hassett, Afton L; Williams, David A

    2011-04-01

    Individuals with chronic widespread pain, including those with fibromyalgia, pose a particular challenge to treatment, given the modest effectiveness of pharmacological agents for this condition. The growing consensus indicates that the best approach to treatment involves the combination of pharmacological and non-pharmacological interventions. Several non-pharmacological interventions, particularly exercise and cognitive-behavioural therapy (CBT), have garnered good evidence of effectiveness as stand-alone, adjunctive treatments for patients with chronic pain. In this article, evidenced-based, non-pharmacological management techniques for chronic widespread pain are described by using two broad categories, exercise and CBT. The evidence for decreasing pain, improving functioning and changing secondary symptoms is highlighted. Lastly, the methods by which exercise and CBT can be combined for a multi-component approach, which is consistent with the current evidence-based guidelines of several American and European medical societies, are addressed.

  16. 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

    mechanical properties in the glucocorticoid-2. In conclusion, 7 months glucocorticoid treatment with malnutrition had significant impact on cortical microarchitecture of sheep femur midshaft. These changes occurred particularly 3 months after the glucocorticoid cessation suggesting a delayed effect......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...

  17. Chronic proctalgia and chronic pelvic pain syndromes: New etiologic insights and treatment options

    Institute of Scientific and Technical Information of China (English)

    Giuseppe Chiarioni; Corrado Asteria; William E Whitehead

    2011-01-01

    This systematic review addresses the pathophysiology, diagnostic evaluation, and treatment of several chronic pain syndromes affecting the pelvic organs: chronic proctalgia, coccygodynia, pudendal neuralgia, and chronic pelvic pain. Chronic or recurrent pain in the anal canal, rectum, or other pelvic organs occurs in 7% to 24% of the population and is associated with impaired quality of life and high health care costs. However, these pain syndromes are poorly understood, with little research evidence available to guide their diagnosis and treatment. This situation appears to be changing: A recently published large randomized, controlled trial by our group comparing biofeedback, electrogalvanic stimulation, and massage for the treatment of chronic proctalgia has shown success rates of 85% for biofeedback when patients are selected based on physical examination evidence of tenderness in response to traction on the levator ani muscle-a physical sign suggestive of striated muscle tension. Excessive tension (spasm) in the striated muscles of the pelvic floor appears to be common to most of the pelvic pain syndromes. This suggests the possibility that similar approaches to diagnostic assessment and treatment may improve outcomes in other pelvic pain disorders.

  18. Nutritional support treatment for severe chronic hepatitis and posthepatitic cirrhosis.

    Science.gov (United States)

    Qin, Huimin; Li, Hongtao; Xing, Mingyou; Wu, Chunming; Li, Guojun; Song, Jianxin

    2006-01-01

    The therapeutic effectiveness of nutritional support in the treatment of severe chronic hepatitis and posthepatitic cirrhosis was evaluated. 143 patients with severe chronic hepatitis and 83 with posthepatitic cirrhosis were evaluated with SGA for assessing the nutritional status before the treatment. Patients with severe chronic hepatitis were divided into three groups: group A subject to enteral nutrition (EN) and parenteral nutrition (PN), group B subject to comprehensive treatment (CT)+PN; group C subject to CT+EN. The patients with posthepatitic cirrhosis were divided into two groups: group D receiving CT and group E receiving CT+PN+EN. The function of liver and kidney and nutritional status were monitored to assess the therapy in 6 weeks. The results showed before treatment, over 90 % patients had moderate to severe malnutrition. After nutritional support, the liver function (ALT, T-bil) and nutritional status (TP, TC) in group A was improved significantly as compared with that in groups B and C (Pcirrhosis had malnutrition to varying degrees. The nutritional support treatment could obviously improve the nutritional status of these patients, and was helpful to ameliorate the liver function of the patients with severe chronic hepatitis. Among the methods of nutritional support treatment, PN combined with EN had the best effectiveness.

  19. The regulation of muscle mass by endogenous glucocorticoids

    OpenAIRE

    2015-01-01

    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 mobilizatio...

  20. Pegylated interferons in the treatment of chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    张福奎

    2003-01-01

    Purpose To review the efficacy and safety of pegylated interferons (peginterferons) in the treatment of chronic hepatitis C.Data sources An English language literature search (MEDLINE 1988-2001) was performed and a total of 19 original articles related to the issue were selected.Data extraction After careful review of the selected papers, the meaningful results and conclusions were extracted using scientific criteria. The papers reviewed pertained mainly to the efficacy and safety profiles of peginterferons in the treatment of chronic hepatitis C.

  1. [Intermittent thrombolytic treatment. Results during severe, chronic arterial diseases].

    Science.gov (United States)

    Fiessinger, J N; Aiach, M; Lagneau, P; Cormier, J M; Housset, E

    1975-04-20

    38 patients with severe chronic arteritis of the lower limbs were treated with streptokinase intermittently. All had been refused for surgical operation. One patient died, 4 others had early interruption of treatment. Eleven of the 38 patients had efficient thrombolysis confirmed by arteriography. The facts confirm the possibility of thrombolysis during chronic arterial disease. The fact that the aggravation was recent was favourable factor in prognosis. The eleven patients improved, had severe aggravation of symptomes for less than 2 months. Thus thrombolytic treatment has a place of choice in the treatment of severe arterial disease where surgery is impossible, or dangerous, owing to the uncertain state of the vascular bed below the lesion. Efficacious, it permits reconstructive surgery in cases where it had been at first refused. The use of intermittent treatment, apart from advantages of confort and cost, seems to increase the efficacy of treatment.

  2. [Treatment's initiation in chronic inflammatory demyelinating polyradiculopathy (CIDP)].

    Science.gov (United States)

    Uzenot, D; Azulay, J-P; Pouget, J

    2007-09-01

    Treatment's initiation in chronic inflammatory demyelinating polyradiculopathy (CIDP) remains a difficult medical decision. Only plasma exchanges, intravenous immunoglobulins (IVIg) and corticosteroids are proven effective treatments. Immunosuppressors are actually not first-line treatments in CIDP. Particular CIDP forms are associated with different response to treatments: pure motor CIDP should be treated by IVIg, and corticosteroids should only carefully be used in Lewis-Sumner syndrome. Otherwise, IVIg are first-line treatment in diabetic patients. Patients must be informed of side's effects and expected clinical effects. Early treatment was actually not proved to prevent axonal damages in CIDP patients, and waiting seems to be the best therapeutic option in poorly symptomatic patients. Recently, clinical guidelines were proposed to help clinician in this treatment choice, but there is no consensus about the best dose, duration or administration way to CIDP treatments. Further studies should be performed to clarify these points and to determine immunosuppressor agents place in treatment strategy.

  3. 耳后注射糖皮质激素治疗突发性聋的研究进展%The progress of glucocorticoids via postauricular injection in treatment of sudden hearing loss

    Institute of Scientific and Technical Information of China (English)

    陈爱平

    2016-01-01

    Corticosteroids are commonly accepted and recommended for treating sudden hearing loss.In recent years,postauricular delivery attracts attention due to the advantage of high drug concentration in cochlear and minimal side-effects.This article reviews the published literature related the application of glucocorticoids via postauricular injection in treatment of sudden hearing loss and its animal experiments,speculates the possible pathway that drugs enter inner ear,and put forward the idea of treating facial nerve diseases via postauricular injection.

  4. Psychosomatic group treatment helps women with chronic pelvic pain.

    Science.gov (United States)

    Albert, H

    1999-12-01

    This study evaluates group treatment for women suffering from chronic pelvic pain. The concept of group treatment was based on psychosomatic and physio-therapeutical principles and on cognitive and operant behavioral therapy. Each group was composed of up to six women suffering from chronic pelvic pain, and two physiotherapists. Each group treatment session lasted 2.5 h per week for a period of 10 weeks. The women completed questionnaires and pain drawings four times during the treatment period from the beginning of the period till 15 months later. During 13 group treatment periods 53 women accomplished the treatment. Before the treatment the women had experienced pain for an average period of 5 years and 9 months (ranging from 6 months to 22 years). The women's descriptions of the changes derived from group treatment were analyzed according to the Grounded Theory Method. A methodical triangulation of quantitative and qualitative data as well as analyzes of the drawings were applied. One year after the end of the treatment, 39% of the women were pain-free. The average level of pain measured according to the Visual Analog Scale was reduced from 2.8 to 0.9 (p Theory Analysis a model of the development process was elaborated. The process begins with the development of self-knowledge, followed by the woman assuming self responsibility for her own life and performing self-activeness. During the process the woman increases her feeling of self-control and personal mastery of her emotions. The women's pain drawings improved, resulting in more detailed drawings, the color intensity abating, the extent of pains declining, and the outlines blurring. In conclusion this kind of group treatment brings the women relief from their pain thus reducing the use of the National Health Service by women suffering from chronic pelvic pain. The women also experience a positive psychological development. This method of treatment, in which a synergetic combination of physical and

  5. Latin American consensus on guidelines for chronic migraine treatment

    Directory of Open Access Journals (Sweden)

    Alex Rodrigo Espinoza Giacomozzi

    2013-07-01

    Full Text Available Chronic migraine is a condition with significant prevalence all around the world and high socioeconomic impact, and its handling has been challenging neurologists. Developments for understanding its mechanisms and associated conditions, as well as that of new therapies, have been quick and important, a fact which has motivated the Latin American and Brazilian Headache Societies to prepare the present consensus. The treatment of chronic migraine should always be preceded by a careful diagnosis review; the detection of possible worsening factors and associated conditions; the stratification of seriousness/impossibility to treat; and monitoring establishment, with a pain diary. The present consensus deals with pharmacological and nonpharmacological forms of treatment to be used in chronic migraine.

  6. Gabapentin and pregabalin for the treatment of chronic pruritus.

    Science.gov (United States)

    Matsuda, Kazuki M; Sharma, Divya; Schonfeld, Ariel R; Kwatra, Shawn G

    2016-09-01

    Chronic pruritus is a distressing symptom that is often refractory to treatment. Patients frequently fail topical therapies and oral over-the-counter antihistamines, prompting the clinician to consider alternative therapies such as neuroactive agents. Herein, the use of gabapentin and pregabalin, 2 medications well known for treating neuropathic pain and epilepsy that are occasionally used for relieving chronic pruritus is explored. The findings from original sources published to date to evaluate the use of gabapentin and pregabalin as antipruritic agents are explored. They are found to be promising alternative treatments for the relief of several forms of chronic pruritus, particularly uremic pruritus and neuropathic or neurogenic itch, in patients who fail conservative therapies.

  7. Glucocorticoids decrease Treg cell numbers in lungs of allergic mice.

    Science.gov (United States)

    Olsen, P C; Kitoko, J Z; Ferreira, T P; de-Azevedo, C T; Arantes, A C; Martins, Μ A

    2015-01-15

    Glucocorticoids have been the hallmark anti-inflammatory drug used to treat asthma. It has been shown that glucocorticoids ameliorate asthma by increasing numbers and activity of Tregs, in contrast recent data show that glucocorticoid might have an opposite effect on Treg cells from normal mice. Since Tregs are target cells that act on the resolution of asthma, the aim of this study was to elucidate the effect of glucocorticoid treatment on lung Tregs in mouse models of asthma. Allergen challenged mice were treated with either oral dexamethasone or nebulized budesonide. Broncoalveolar lavage and airway hyperresponsiveness were evaluated after allergenic challenge. Lung, thymic and lymph node cells were phenotyped on Treg through flow cytometry. Lung cytokine secretion was detected by ELISA. Although dexamethasone inhibited airway inflammation and hyperresponsiveness, improving resolution, we have found that both dexamethasone and budesonide induce a reduction of Treg numbers on lungs and lymphoid organs of allergen challenged mice. The reduction of lung Treg levels was independent of mice strain or type of allergen challenge. Our study also indicates that both glucocorticoids do not increase Treg activity through production of IL-10. Glucocorticoid systemic or localized treatment induced thymic atrophy. Taken together, our results demonstrate that glucocorticoids decrease Treg numbers and activity in different asthma mouse models, probably by reducing thymic production of T cells. Therefore, it is possible that glucocorticoids do not have beneficial effects on lung populations of Treg cells from asthmatic patients.

  8. Nutritional Support Treatment for Severe Chronic Hepatitis and Posthepatitic Cirrhosis

    Institute of Scientific and Technical Information of China (English)

    QIN Huimin; LI Hongtao; XING Mingyou; WU Chunming; LI Guojun; SONG Jianxin

    2006-01-01

    The therapeutic effectiveness of nutritional support in the treatment of severe chronic hepatitis and posthepatitic cirrhosis was evaluated. 143 patients with severe chronic hepatitis and 83 with posthepatitic cirrhosis were evaluated with SGA for assessing the nutritional status before the treatment. Patients with severe chronic hepatitis were divided into three groups: group A subject to enteral nutrition (EN) and parenteral nutrition (PN), group B subject to comprehensive treatment (CT) +PN; group C subject to CT+ EN. The patients with posthepatitic cirrhosis were divided into two groups: group D receiving CT and group E receiving CT+PN+EN. The function of liver and kidney and nutritional status were monitored to assess the therapy in 6 weeks. The results showed before treatment, over 90 % patients had moderate to severe malnutrition. After nutritional support, the liver function (ALT, T-biil) and nutritional status (TP, TC) in group A was improved significantly as compared with that in groups B and C (P<0.05). Compared with group D,the values of TP and Alb were increased significantly in group E (P<0.05), but the levels of ALT, AST and T-bil had no obvious change. It was suggested that most patients with severe chronic hepatitis or posthepatitic cirrhosis had malnutrition to varying degrees. The nutritional support treatment could obviously improve the nutritional status of these patients, and was helpful to ameliorate the liver function of the patients with severe chronic hepatitis. Among the methods of nutritional support treatment, PN combined with EN had the best effectiveness.

  9. The effect of Ginkgo biloba extract treatment in the Bcl-2 expression by osteoblasts in the femoral trabecular bone of Wistar rats with glucocorticoid-induced osteoporosis

    Directory of Open Access Journals (Sweden)

    Leda M.F. Lucinda

    2014-06-01

    Full Text Available Evaluate the effect of the extract of Ginkgo biloba L., Ginkgoaceae (EGb in the Bcl-2 expression by osteoblasts in the femoral trabecular bone of Wistar rats with glucocorticoid-induced osteoporosis. Rats were divided into five groups: osteoporosis; EGb1 (28 mg/kg; EGb2 (56 mg/kg; alendronate (0.2 mg/animal and control. The treatments were conducted for 20 or 30 days. The Bcl-2 expression by osteoblasts cells was evaluated in the femoral trabecular bone. The control group was compared with the osteoporosis-induced group (Student's t-test. The other groups were analyzed by ANOVA test followed by Tukey's test (p < 0.05. The percentage of Bcl-2 expression was reduced, when the control group (17.95 ± 3.45 20 days; 21.11 ± 3.43 30 days was compared with the osteoporosis group (10.64 ± 3.30 20 days; 9.72 ± 2.84 30 days. Nevertheless, this percentage increased in the EGb2 group (18.58 ± 3.41 20 days; 16.51 ± 1.80 30 days when compared to the osteoporosis group. The EGb increased the expression of the anti-apoptotic protein, suggesting a decrease in osteoblast apoptosis.

  10. Alitretinoin for the treatment of severe chronic hand eczema

    Directory of Open Access Journals (Sweden)

    King T

    2014-11-01

    Full Text Available Thomas King, John McKenna, Anton B Alexandroff Department of Dermatology, University Hospitals of Leicester, Leicester Royal Infirmary, Leicester, UK Abstract: Chronic hand eczema is a common and often debilitating condition. Alitretinoin, a 9-cis-retinoic acid and pan-retinoic acid agonist, is a new and effective systemic treatment for chronic hand eczema, which provides another treatment option. A “clear” or “almost clear” response can be achieved in up to half of patients within a 24-week course of treatment. Even higher rates of remission can be obtained with a longer duration of treatment. Alitretinoin has a favorable overall profile of adverse effects; however, female patients who are at risk of becoming pregnant should follow a strict pregnancy-prevention program due to the teratogenic effects of this drug. Keywords: dermatitis, toctino, CTCL

  11. Laparoscopic antireflux surgery vs esomeprazole treatment for chronic GERD

    DEFF Research Database (Denmark)

    Galmiche, Jean-Paul; Hatlebakk, Jan; Attwood, Stephen;

    2011-01-01

    Context Gastroesophageal reflux disease (GERD) is a chronic, relapsing disease with symptoms that have negative effects on daily life. Two treatment options are long-term medication or surgery. Objective To evaluate optimized esomeprazole therapy vs standardized laparoscopic antireflux surgery (L...

  12. Anagrelide treatment in 52 patients with chronic myeloproliferative diseases

    DEFF Research Database (Denmark)

    Penninga, E; Jensen, B A; Hansen, P B

    2004-01-01

    In this retrospective multi-centre study, we report our experience with anagrelide in the treatment of thrombocytosis in patients with chronic myeloproliferative diseases. Our study included 52 patients (age 20-78 years). The initial anagrelide dose was, in general, 0.5 mg once daily and mean...

  13. Interferon alpha for treatment of chronic myeloid leukemia

    DEFF Research Database (Denmark)

    Simonsson, Bengt; Hjorth-Hansen, Henrik; Bjerrum, Ole Weis;

    2011-01-01

    Treatment of chronic myeloid leukemia (CML) with interferon-alpha (IFN-α) was introduced in the early 1980s. Several clinical trials showed a survival advantage for patients treated with IFN-α compared to conventional chemotherapy. Some patients achieved longstanding complete cytogenetic remissions...

  14. Interferon alpha for treatment of chronic myeloid leukemia

    DEFF Research Database (Denmark)

    Simonsson, Bengt; Hjorth-Hansen, Henrik; Bjerrum, Ole Weis;

    2011-01-01

    Treatment of chronic myeloid leukemia (CML) with interferon-alpha (IFN-a) was introduced in the early 1980s. Several clinical trials showed a survival advantage for patients treated with IFN-a compared to conventional chemotherapy. Some patients achieved longstanding complete cytogenetic remissions...

  15. TREATMENT OF CHRONIC HEART FAILURE: FOCUS ON METOPROLOL SUCCINATE

    Directory of Open Access Journals (Sweden)

    O. D. Ostroumova

    2015-12-01

    Full Text Available Advantages of metoprolol succinate in patients with chronic heart failure (CHF are covered. Results of MERIT-HF study are taken as the main evidences. Patterns of the metoprolol succinate use in the treatment of different categories of patients with CHF (women, the elderly , severe CHF forms, CHF with concomitant hypertension or diabetes are considered.

  16. Methylphenidate in Treatment of ADHD and Comorbid Chronic Tic Disorder

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2007-07-01

    Full Text Available The safety and efficacy of immediate-release methylphenidate (MPH-IR for the treatment of attention deficit hyperactivity disorder (ADHD in children (ages 6-12 years with Tourette's syndrome (96% or chronic motor tic disorder (4% were evaluated at State University of New York, Stony Brook.

  17. Correlates of Improvement in Multidisciplinary Treatment of Chronic Pain.

    Science.gov (United States)

    Jensen, Mark P.; And Others

    1994-01-01

    Chronic pain patients (n=94) completed measures of physical and psychological functioning, health care utilization, pain beliefs, and use of pain coping strategies at admission and three to six months after inpatient pain treatment. Improved functioning and decreased health care use were associated with changes in both beliefs and cognitive coping…

  18. Treatment of Chronic Anger Through Cognitive and Relaxation Controls

    Science.gov (United States)

    Novaco, Raymond W.

    1976-01-01

    The study examined the extent to which cognitive self-control processes and relaxation techniques could be therapeutically applied to chronic anger problems. The cognitive treatment was implemented by self-instruction procedures. The cognitive coping procedures involved the use of self-statements for the management of anger and cognitive…

  19. Intravenous immunoglobulin treatment in chronic inflammatory demyelinating polyneuropathy

    NARCIS (Netherlands)

    P.A. van Doorn (Pieter)

    1990-01-01

    textabstractPatients with a chronic inflammatory demyelinating polyneuropathy (CIDP) may respond to treatment with corticosteroids and to plasmapheresis, which was demonstrated in controlled clinical studies. In an uncontrolled study it was found that 13/17 CIDP patients had a rapid and clinical imp

  20. Advances in surgical treatment of chronic subdural hematoma

    Institute of Scientific and Technical Information of China (English)

    张作洪; 刘建雄

    2003-01-01

    @@ Chronic subdural hematoma (CSDH) represents one of the most frequent types of intracranial hemorrhage. Management of the patients with CSDH has been evolved through a vast variety of methods and techniques. Although there is general agreement that surgical therapy is usually the preferred treatment, there are few other neurosurgical conditions that spark such strong discussions and differences of opinion concerning the optimal surgical technique.1,2 In this paper, we review advances in surgical treatment of CSDH.

  1. Glucocorticoid Mechanisms of Functional Connectivity Changes in Stress-Related Neuropsychiatric Disorders.

    Science.gov (United States)

    Hall, Baila S; Moda, Rachel N; Liston, Conor

    2015-01-01

    Stress-especially chronic, uncontrollable stress-is an important risk factor for many neuropsychiatric disorders. The underlying mechanisms are complex and multifactorial, but they involve correlated changes in structural and functional measures of neuronal connectivity within cortical microcircuits and across neuroanatomically distributed brain networks. Here, we review evidence from animal models and human neuroimaging studies implicating stress-associated changes in functional connectivity in the pathogenesis of PTSD, depression, and other neuropsychiatric conditions. Changes in fMRI measures of corticocortical connectivity across distributed networks may be caused by specific structural alterations that have been observed in the prefrontal cortex, hippocampus, and other vulnerable brain regions. These effects are mediated in part by glucocorticoids, which are released from the adrenal gland in response to a stressor and also oscillate in synchrony with diurnal rhythms. Recent work indicates that circadian glucocorticoid oscillations act to balance synapse formation and pruning after learning and during development, and chronic stress disrupts this balance. We conclude by considering how disrupted glucocorticoid oscillations may contribute to the pathophysiology of depression and PTSD in vulnerable individuals, and how circadian rhythm disturbances may affect non-psychiatric populations, including frequent travelers, shift workers, and patients undergoing treatment for autoimmune disorders.

  2. Glucocorticoid mechanisms of functional connectivity changes in stress-related neuropsychiatric disorders

    Directory of Open Access Journals (Sweden)

    Baila S. Hall

    2015-01-01

    Full Text Available Stress—especially chronic, uncontrollable stress—is an important risk factor for many neuropsychiatric disorders. The underlying mechanisms are complex and multifactorial, but they involve correlated changes in structural and functional measures of neuronal connectivity within cortical microcircuits and across neuroanatomically distributed brain networks. Here, we review evidence from animal models and human neuroimaging studies implicating stress-associated changes in functional connectivity in the pathogenesis of PTSD, depression, and other neuropsychiatric conditions. Changes in fMRI measures of corticocortical connectivity across distributed networks may be caused by specific structural alterations that have been observed in the prefrontal cortex, hippocampus, and other vulnerable brain regions. These effects are mediated in part by glucocorticoids, which are released from the adrenal gland in response to a stressor and also oscillate in synchrony with diurnal rhythms. Recent work indicates that circadian glucocorticoid oscillations act to balance synapse formation and pruning after learning and during development, and chronic stress disrupts this balance. We conclude by considering how disrupted glucocorticoid oscillations may contribute to the pathophysiology of depression and PTSD in vulnerable individuals, and how circadian rhythm disturbances may affect non-psychiatric populations, including frequent travelers, shift workers, and patients undergoing treatment for autoimmune disorders.

  3. Glucocorticoid mechanisms of functional connectivity changes in stress-related neuropsychiatric disorders

    Science.gov (United States)

    Hall, Baila S.; Moda, Rachel N.; Liston, Conor

    2014-01-01

    Stress—especially chronic, uncontrollable stress—is an important risk factor for many neuropsychiatric disorders. The underlying mechanisms are complex and multifactorial, but they involve correlated changes in structural and functional measures of neuronal connectivity within cortical microcircuits and across neuroanatomically distributed brain networks. Here, we review evidence from animal models and human neuroimaging studies implicating stress-associated changes in functional connectivity in the pathogenesis of PTSD, depression, and other neuropsychiatric conditions. Changes in fMRI measures of corticocortical connectivity across distributed networks may be caused by specific structural alterations that have been observed in the prefrontal cortex, hippocampus, and other vulnerable brain regions. These effects are mediated in part by glucocorticoids, which are released from the adrenal gland in response to a stressor and also oscillate in synchrony with diurnal rhythms. Recent work indicates that circadian glucocorticoid oscillations act to balance synapse formation and pruning after learning and during development, and chronic stress disrupts this balance. We conclude by considering how disrupted glucocorticoid oscillations may contribute to the pathophysiology of depression and PTSD in vulnerable individuals, and how circadian rhythm disturbances may affect non-psychiatric populations, including frequent travelers, shift workers, and patients undergoing treatment for autoimmune disorders. PMID:25729760

  4. Chronic Pain: Symptoms, Diagnosis, & Treatment | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... of this page please turn Javascript on. Feature: Chronic Pain Chronic Pain: Symptoms, Diagnosis, & Treatment Past Issues / Spring 2011 Table of Contents Symptoms Chronic pain is often defined as any pain lasting ...

  5. Safety of interferon treatment for chronic HCV hepatitis

    Institute of Scientific and Technical Information of China (English)

    D Festi; L Sandri; G Mazzella; E Roda; T Sacco; T Staniscia; S Capodicasa; A Vestito; A Colecchia

    2004-01-01

    Hepatitis C is a major cause of liver-related morbidity and mortality worldwide, In fact, chronic hepatitis C is considered as one of the primary causes of chronic liver disease, cirhosis and hepatocellular carcinoma, and is the most common reason for liver transplantation. The primary objectives for the treatment of HCV-related chronic hepatitis is to eradicate infection and prevent progression of the disease. The treatment has evolved from the use of α-interferon (TFNα)alone to the combination of IFNα plus ribavirin, with a significant improvement in the overall efficacy, and to the newer PEG-IFNs which have further increased the virological response, used either alone or in combination with ribavirin.Despite these positive results, in terms of efficacy, concerns are related to the safety and adverse events. Many patients must reduce the dose of PEG-IFN or ribavirin, others must stop the treatment and a variable percentage of subjects are not suitable owing to intolerance toward drugs. IFNβ represents a potential therapeutic alternative for the treatment of chronic viral hepatitis and in some countries it plays an important role in therapeutic protocols. Aim of the present paper was to review available data on the safety of IFNβ treatment in HCV-related chronic hepatitis.The rates of treatment discontinuation and/or dose modification due to the appearance of severe side effects during IFNβ are generally low and in several clinical studies no requirements for treatment discontinuation and/or dose modifications have been reported. The most frequent side effects experienced during IFNβ treatment are flu-like syndromes, fever, fatigue and injection-site reactions. No differences in terms of side-effect frequency and severity between responders and non-responders have been reported.A more recent study, performed to compare IFNβ alone or in combination with ribavirin, confirmed the good safety profile of both treatments. Similar trends of adverse event

  6. Sarcoidosis and chronic hepatitis C: treatment with prednisone and colchicine*

    Science.gov (United States)

    Pereira, Eduardo Guimarães; Guimarães, Tais Ferreira; Bottino, Caroline Bertolini; D’Acri, Antonio Macedo; Lima, Ricardo Barbosa; Martins, Carlos José

    2016-01-01

    Sarcoidosis is a disease which still has uncertain etiology. Possible environmental causes are cited in the literature, like organic and inorganic particles and infectious agents. Recent studies have demonstrated the occurrence of sarcoidosis in patients with chronic C hepatitis; however, this association remains without statistical or causal evidence. In this report a case of sarcoidosis associated with chronic hepatitis C will be described, with subcutaneous lesions, considered rare, and good response to treatment with colchicine and prednisone. The hepatitis C virus was isolated in sarcoid tissue and the association between the two diseases will be discussed. PMID:27192527

  7. New Chronic Pain Treatments in the Outpatient Setting: Review Article.

    Science.gov (United States)

    Grandhe, R; Souzdalnitski, D; Gritsenko, K

    2016-05-01

    Chronic pain is an issue encountered by many health care providers in their routine clinical practice. In addition to generalized patient suffering, this condition has significant clinical, psychological, and socioeconomic impact due to its widespread occurrence. The landscape of chronic pain management has been changing rapidly with an array of treatment innovations, better understanding of established therapies, and care coordination across specialties. In this article, we have reviewed emerging new modalities as well as transformation of established therapies by interventional, pharmacologic, rehabilitative, psychological, complimentary, and interdisciplinary approaches.

  8. Exogenous glucocorticoids and adverse cerebral effects in children

    DEFF Research Database (Denmark)

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

    2011-01-01

    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...

  9. Glucocorticoid-related genetic susceptibility for Alzheimer's disease.

    Science.gov (United States)

    de Quervain, Dominique J-F; Poirier, Raphael; Wollmer, M Axel; Grimaldi, Luigi M E; Tsolaki, Magdalini; Streffer, Johannes R; Hock, Christoph; Nitsch, Roger M; Mohajeri, M Hasan; Papassotiropoulos, Andreas

    2004-01-01

    Because glucocorticoid excess increases neuronal vulnerability, genetic variations in the glucocorticoid system may be related to the risk for Alzheimer's disease (AD). We analyzed single-nucleotide polymorphisms in 10 glucocorticoid-related genes in a population of 814 AD patients and unrelated control subjects. Set-association analysis revealed that a rare haplotype in the 5' regulatory region of the gene encoding 11beta-hydroxysteroid dehydrogenase type 1 (HSD11B1) was associated with a 6-fold increased risk for sporadic AD. Results of a reporter-gene assay indicated that the rare risk-associated haplotype altered HSD11B1 transcription. HSD11B1 controls tissue levels of biologically active glucocorticoids and thereby influences neuronal vulnerability. Our results indicate that a functional variation in the glucocorticoid system increases the risk for AD, which may have important implications for the diagnosis and treatment of this disease.

  10. Macrophage migration inhibitory factor polymorphisms do not predict therapeutic response to glucocorticoids or to tumour necrosis factor α‐neutralising treatments in rheumatoid arthritis

    Science.gov (United States)

    Radstake, Timothy R D J; Fransen, Jaap; Toonen, Erik J M; Coenen, Marieke J H; Eijsbouts, Agnes E; Donn, Rachelle; van den Hoogen, Frank H J; van Riel, Piet L C M

    2007-01-01

    Background Macrophage migration inhibitory factor (MIF) is an inflammatory mediator associated with RA severity. In various diseases, MIF polymorphisms are associated with clinical response glucocorticoid (GC) treatment. It is unclear whether MIF polymorphisms determine GC response in rheumatoid arthritis (RA) and to other RA treatments. Therefore, the question of whether two functional variants in MIF are associated with the response to tumour necrosis factor (TNF)α‐neutralising and GC treatments in RA was investigated. Methods Data from two cohorts of an RA registry were used. For patients who started with TNFα‐neutralising (infliximab) or GC treatment, courses with a duration of at least 3 months were included and response to TNFα blockers or GC was calculated according to the European League Against Rheumatism response criteria. MIF −173G→C genotyping was achieved using an assay‐on‐demand allelic discrimination assay, and alleles of the CATT repeat element were identified using a fluorescently labelled PCR primer and capillary electrophoresis. Logistic‐regression modelling was used for the statistical analysis. Results In total, 192 courses of oral prednisone or methylprednisolone injections in 98 patients with RA and 90 patients with RA who were on TNFα‐neutralising treatments were documented. In all, 27% of the patients with RA were found to be heterozygous for seven CATT repeats (CATT7) and 31% were heterozygous for −173C. Respectively, 4% and 6% of the patients with RA were homozygous for the MIF CATT7 repeat or the MIF −173C allele. Carrier status and homozygosity for CATT7 repeat and the MIF −173C allele were not associated with response to GC (odds ratios (ORs) close to 1) or to TNFα‐neutralising treatment (ORs close to 2). Conclusion The MIF‐CATT7 repeat and the MIF−173G→C functional variant are not strongly associated with a decreased clinical response to TNFα‐neutralising or GC treatment in RA. PMID:17456524

  11. Clinicopathological study in treatment of chronic hepatitis with hyperbaricoxygenation

    Institute of Scientific and Technical Information of China (English)

    Wei Liu; Xiang Lü; Xiao Gang Zheng; Wei Zhao; Chan Luo

    2000-01-01

    AIM To probe into the feasibility and theoretic basis for the treatment of chronic hepatitis with hyperbaricoxygenation (HBO).METHODS Sixty cases of chronic hepatitis were randomly distributed into an experimental group (n=30)and a control group (n =30). The experimental group was treated with HBO for 6 courses. The controlgroup was treated with commonly used drugs in clinic for 60 days. The function and blood stream graph ofliver were examined and the liver biopsies were made before and after treatment. The routine paraffin slidesof liver tissue were cut, stained with HE, and observed under optical microscope. The ultrathin slides fromparaformaldehyde and glutaraldehyde fixed liver tissue were cut, stained with lead citrate, and observedunder transmission electric microscope. The HBsAg and HBcAg in the experimental group were detected bythe ABC immunohistochemical method before and after treatment.RESULTS In the experimental group the ALT, SB, γ-GT, AKP, IgG and IgM in blood (P0.05) in the liver, and the expression ofHBsAg and HBcAg in the liver was not lowered (P<0.05) after the treatment with HBO.CONCLUSION The treatment with HBO for chronic hepatitis was effective and recommendable.

  12. Treatment of chronic rhinosinusitis with pressure-pulsed corticosteroid inhalation.

    Science.gov (United States)

    Goektas, Oender; Lau, Larissa; Olze, Heidi

    2013-08-01

    Chronic rhinosinusitis may cause olfactory dysfunction and affects quality of life in patients. In a prospective study we investigated the effect of topical application of corticosteroids through pressure-pulsed inhalation as treatment option of chronic rhinosinusitis with olfactory disorder. Patients with sinonasal olfactory disorder according to the European Position Paper on Rhinosinusitis and Nasal Polyps (EP3OS) were allocated to the new nasal inhalation therapy or a systemic corticosteroid therapy, each receiving a corticosteroid course of 12 days. 18 patients received topical corticosteroid pressure-pulsed inhalation (AMSA, Schumacher, Dausenau) and 15 systemic corticosteroid. Olfactory function was measured before and after treatment using the Threshold Discrimination Identification score (TDI score) and visual analogue scales. Lund Mackay score (LMS) was measured before starting treatment. Olfactory function (OF) increased from 17.5 ± 6.4 to 21 ± 7.9 TDI points (p treatment after 2 months. In the follow-up period of 6 months, the mean TDI score dropped to 20.0 ± 9.2 points (p = 0.01). There was no correlation between LMS and TDI. Treatment of chronic rhinosinusitis with pressure-pulsed inhalation was demonstrated to be effective. Multicenter investigations with large participant numbers are needed.

  13. 激素性股骨头坏死成脂分化学说及治疗现状%Glucocorticoids-induced osteonecrosis of the femoral head:adipogenic differentiation and treatment progress

    Institute of Scientific and Technical Information of China (English)

    刘彬; 李刚; 许波; 刘国岩

    2014-01-01

    BACKGROUND:Glucocorticoids may induce local bone trabecular and bone marrow necrosis, femoral head col apse and deformation, thus resulting in hip dysfunction. However the pathological mechanisms and treatment of glucocorticoids-induced osteonecrosis of the femoral head remain unclear, and the pathogenesis mechanisms are controversial. The current studies focus on the understanding of the pathological mechanisms. OBJECTIVE:To summary the research progress of adipogenic differentiation theory of glucocorticoids-induced osteonecrosis of the femoral head and the treatment. METHODS:The first author searched literature from CNKI and PubMed database from 1988 to 2010, by using the key words is“Glucocorticoids, osteonecrosis of femoral head, bone marrow stromal stem cells, adipogenic differentiation, differentiation factors, treatment, choices”in English, and“glucocorticoids induced osteonecrosis of femoral head, adipogenic differentiation, treatment, research progress”in Chinese. Articles regarding the adipogenic differentiation theory of glucocorticoids-induced osteonecrosis of the femoral head and the treatment were included. RESULTS AND CONCLUSION:A total of 112 literatures were screened out, according to inclusion and exclusion criteria for literature screening, 54 articles were included. Modern researches emphasize the celland molecular biology level, and show that the biological base of glucocorticoids-induced osteonecrosis of the femoral head is abnormal adipogenic differentiation of bone cells, glucocorticoids cause the variations of adipogenic differentiation factors, leading to adipogenic differentiation of bone marrow stromal cells. But glucocorticoids affects multiple differentiation factors, it may cause great error in the evaluation of the pathogenesis of glucocorticoids-induced osteonecrosis of the femoral head purely from one factor. The abuse of glucocorticoids is the leading cause for the osteonecrosis of femoral head. Further studies are

  14. Blockade of glucocorticoid receptors with ORG 34116 does not normalize stress-induced symptoms in male tree shrews.

    Science.gov (United States)

    Van Kampen, Marja; De Kloet, E Ronald; Flügge, Gabriele; Fuchs, Eberhard

    2002-12-20

    Glucocorticoid receptors play an important role in the regulation of the activity of the hypothalamo-pituitary-adrenal axis, and are thought to be involved in the pathophysiology of depressive disorders. The present study investigated the effect of the specific glucocorticoid receptor antagonist ORG 34116 (a substituted 11,21 bisarylsteroid compound) in the tree shrew (Tupaia belangeri) chronic psychosocial stress model, an established animal model for depressive disorders. Animals were stressed for 10 days before treatment with ORG 34116 started (25 mg/kg p.o. for 28 days). Stress induced a decrease in body weight, which just failed significance, whereas ORG 34116 did not affect body weight in stress and control animals. ORG 34116 enhanced the stress-induced increase in the concentration of urinary-free cortisol, although no differences between the different experimental groups existed during the last week of treatment. In stressed animals, ORG 34116 did not affect marking behavior, but decreased locomotor activity. Post mortem analysis of 5-HT(1A) receptors revealed a decreased affinity of 3[H]-8-OH-DPAT (3[H]-8-hydroxy-2-[di-n-propylamino]tetralin) binding sites in the hippocampus of animals treated with the glucocorticoid receptor antagonist. In conclusion, under our experimental conditions, the glucocorticoid receptor antagonist ORG 34116 did not normalize the depressive-like symptoms in the psychosocial stress model of male tree shrews. This finding, however, does not exclude that specific central, neuroendocrine and behavioral features are affected by the compound.

  15. Challenges in the treatment of chronic inflammatory demyelinating polyradiculoneuropathy.

    Science.gov (United States)

    Guimarães-Costa, R; Iancu Ferfoglia, R; Viala, K; Léger, J-M

    2014-10-01

    Chronic idiopathic demyelinating polyradiculoneuropathy (CIDP) is a rare disease, the most frequent one within the spectrum of the so-called "chronic immune-mediated neuropathies". Challenges in the treatment of CIDP firstly concern its diagnosis, which may be difficult, mainly for the atypical forms. Secondly, challenges encompass the choice of the first-line treatment, such as corticosteroids, intravenous immunoglobulins (IVIg), and plasma exchanges (PE) that have been proven as efficacious by several randomized controlled trials (RCT). Recent reports have focused on both different regimens of corticosteroids, and the occurrence of relapses following treatment with either corticosteroids or IVIg. These data may be helpful for the choice of the first-line treatment and may result in changing the guidelines for treatment of CIDP in clinical practice. The third and more difficult challenge is to manage long-term treatment for CIDP, since no immunomodulatory treatment has to date been proven as efficacious in this situation. Lastly, challenges in the treatment concern the choice of the best outcome measure for CIDP in RCT and clinical practice. The aim of this article is to overview the results of the more recently reported published trials for CIDP, and to give some insights for the current and future management of CIDP.

  16. Patient-reported treatment burden of chronic immune thrombocytopenia therapies

    Directory of Open Access Journals (Sweden)

    Brown T

    2012-03-01

    Full Text Available Abstract Background Chronic immune thrombocytopenia (ITP is a debilitating autoimmune disorder that causes a reduction in blood platelets and increased risk of bleeding. ITP is currently managed with various pharmacologic therapies and splenectomy. This study was conducted to assess patient perceived and reported treatment side effects, as well as the perceived burden or bother, and need to reduce or stop treatment, associated with these side effects among adult patients with chronic ITP. Methods A Web-enabled survey was administered to members of a US-based ITP patient support group. Patients reported demographic and clinical characteristics, ITP treatments' side effects for treatments received since diagnosed, level of bother (or distress, and need to reduce or stop treatment, associated with side effects. Current and past exposure was assessed for five specific treatment types: corticosteroids (CS, intravenous immunoglobulin (IVIg, anti-D immunoglobulin (anti-D, rituximab (RT, and splenectomy (SPL, as well as for other patient-referenced therapies (captured as "other". Results The survey was completed by 589 patients; 78% female, 89% white, mean age 48 years (SD = 14.71, and 68% reported a typical low platelet count of P P P P Conclusions Current ITP treatments, particularly corticosteroids, are associated with multiple bothersome side effects that may lead to patients stopping or reducing therapy. Open, informed and complete communication between clinician and patient regarding both the benefits and the side effects of ITP treatment may better prepare patients for their prescribed regimens.

  17. Antiviral Treatment among Pregnant Women with Chronic Hepatitis B

    OpenAIRE

    Lin Fan; Kwame Owusu-Edusei; Schillie, Sarah F.; Murphy, Trudy V.

    2014-01-01

    Objective. To describe the antiviral treatment patterns for chronic hepatitis B (CHB) among pregnant and nonpregnant women. Methods. Using 2011 MarketScan claims, we calculated the rates of antiviral treatment among women (aged 10–50 years) with CHB. We described the pattern of antiviral treatment during pregnancy and ≥1 month after delivery. Results. We identified 6274 women with CHB during 2011. Among these, 64 of 507 (12.6%) pregnant women and 1151 of 5767 (20.0%) nonpregnant women receiv...

  18. The surgical treatment of chronic recurrent hematogenous osteomyelitis in children

    Directory of Open Access Journals (Sweden)

    Sukhrob Zayniev

    2013-04-01

    Full Text Available The results of surgical treatment of 178 patients with chronic recurrent osteomyelitis of the tube bones have been analyzed. It has been proposed the tactic of surgical treatment consisting of the tear of tissues for a distance of the diaphysis of the affected bone, cautious periosteum exfoliation from the bone, longitudinal osteotomy, sequestrnecrectomy with full restoration structure of intramedullary canal along the whole length, lavage and ultrasound cavitation with antiseptic solution. The performed surgical tactic secured the most radical sanation of the osteomyelitic focus and improved the treatment results of this severe pathology.

  19. Subjective experiences of clozapine treatment by patients with chronic schizophrenia.

    Science.gov (United States)

    Waserman, J; Criollo, M

    2000-05-01

    A 37-item survey covering a variety of somatopsychic domains was constructed to explore patients' subjective response to treatment with clozapine. The survey was administered to 130 patients with diagnoses of chronic schizophrenic or schizoaffective disorders who were on a stable clozapine regimen. The majority reported improvement in their level of satisfaction, quality of life, compliance with treatment, thinking, mood, and alertness. Most patients reported worsening in nocturnal salivation, and smaller numbers reported worsening in various gastrointestinal and urinary symptoms and weight gain. This general health survey highlights the patients' positive regard for clozapine, despite adverse bodily experiences. Subjective reports are a useful component of outcome measures of drug treatment.

  20. Glucocorticoid Regulation of the Vitamin D Receptor

    Science.gov (United States)

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

    2010-01-01

    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

  1. INFRARED DIODE LASER RETINAL TREATMENT FOR CHRONIC HEADACHE

    Directory of Open Access Journals (Sweden)

    Subba Rao

    2013-12-01

    Full Text Available ABSTRACT: Nearly 60 to 70 crores of people all over the world are suffering from various types of chronic headache. This is one of the commonest medical problems. To get relief from headache various medical treatments are used with little success. The aim of our study is to give permanent treatment to chronic headache patients by using infrared diode laser selective retinal photocoagulati on. NIDEK infrared diode laser with NIDEK SL40 slit - lamp and NIDEK digital fundus camera for retinal evaluation, MAINSTER 135D lens for laser beam focusing and retinal examination and TOPCON non - contact tonometer for intra ocular pressure measurements are used. Diode laser is chosen because of its deep penetration into all the layers of retina and choroid. 500 cases of chronic headache were studied. Laser photocoagulation was given in selective areas of retina in 2 to 3 sessions with 15 days interval. 10 to 60 years age group were studied. 90% of patients who got laser treatment are relieved from their headache in severity and in frequency. 80% of patients needed 2 sittings and 20% of patients needed 3 sittings. 70% of patients got relief from headache by fi rst sitting itself. 50% of patients are not only relieved from their headaches but also noticed visual clarity improvement. Retinal ischaemia is one of the main cause for ocular pain and headache. Laser treatment will improve circulation by reducing ischae mia thereby relieves ocular pain and headache

  2. Treatment of Chronic Plantar Fasciitis With Percutaneous Latticed Plantar Fasciotomy.

    Science.gov (United States)

    Yanbin, Xu; Haikun, Chu; Xiaofeng, Ji; Wanshan, Yang; Shuangping, Liu

    2015-01-01

    Plantar fasciitis, the most common cause of pain in the inferior heel, accounts for 11% to 15% of all foot symptoms requiring professional care among adults. The present study reports the results of a minimally invasive surgical treatment of chronic plantar fasciitis. All patients with plantar fasciitis who had undergone percutaneous latticed plantar fasciotomy at 3 clinical sites from March 2008 to March 2009 were included in the present study. The follow-up evaluations for this treatment were conducted using the Mayo clinical scoring system. We investigated 17 patients with recalcitrant chronic plantar fasciitis who had undergone this treatment within a follow-up period of ≥13 months. All procedures were performed in the clinic with the patient under local anesthesia. No wound infections or blood vessel or nerve damage occurred. At a mean follow-up period of 16.0 ± 2.29 (range 13 to 21) months, significant improvement was seen in the preoperative mean Mayo score (from 12.06 ± 2.54 to 89.76 ± 4.28, p plantar fasciitis with percutaneous latticed plantar fasciotomy could be a promising treatment option for patients with recalcitrant chronic plantar fasciitis.

  3. Update of Inpatient Treatment for Refractory Chronic Daily Headache.

    Science.gov (United States)

    Lai, Tzu-Hsien; Wang, Shuu-Jiun

    2016-01-01

    Chronic daily headache (CDH) is a group of headache disorders, in which headaches occur daily or near-daily (>15 days per month) and last for more than 3 months. Important CDH subtypes include chronic migraine, chronic tension-type headache, hemicrania continua, and new daily persistent headache. Other headaches with shorter durations (<4 h/day) are usually not included in CDH. Common comorbidities of CDH are medication overuse headache and various psychiatric disorders, such as depression and anxiety. Indications of inpatient treatment for CDH patients include poor responses to outpatient management, need for detoxification for overuse of specific medications (particularly opioids and barbiturates), and severe psychiatric comorbidities. Inpatient treatment usually involves stopping acute pain, preventing future attacks, and detoxifying medication overuse if present. Multidisciplinary integrated care that includes medical staff from different disciplines (e.g., psychiatry, clinical psychology, and physical therapy) has been recommended. The outcomes of inpatient treatment are satisfactory in terms of decreasing headache intensity or frequency, withdrawal from medication overuse, reducing disability, and improving life quality, although long-term relapse is not uncommon. In conclusion, inpatient treatment may be useful for select patients with refractory CDH and should be incorporated in a holistic headache care program.

  4. Chronic pain: the burden of disease and treatment innovations

    Directory of Open Access Journals (Sweden)

    S. Monti

    2015-10-01

    Full Text Available Musculoskeletal conditions are the most frequent cause of chronic pain and affect around 1 in 5 adults in Europe. When chronic pain occurs, it becomes disease itself, with substantial clinical, social and economic impact. Effi cacy and tolerability problems are encountered with all therapeutic strategies available to treat musculoskeletal pain. This often limits effective analgesia and patients’ long term compliance, with the result that chronic pain is persistently underestimated and undertreated. Tapentadol is a novel, centrally acting analgesic that has been recently commercialized for the treatment of chronic pain. This new molecule, by combining two distinct mechanisms of action, μ-opioid receptor agonism (MOR and noradrenaline reuptake inhibition (NRI, introduces a new pharmacological class called MOR-NRI. Several studies demonstrated promising results in the management of both nociceptive and neuropathic pain and good tolerability profi le, particularly concerning side effects, compared to traditional opioids. This novel analgesic represents a possible therapeutic option also in the rheumatologic fi eld, particularly in the treatment of osteoarthritis and low back pain.

  5. 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

    2012-10-01

    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

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

    Science.gov (United States)

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

    2012-06-01

    In this study, 18 female skeletally mature sheep were randomly allocated into three groups of six each. Group 1 (glucocorticoid-1) received prednisolone treatment (0.60 mg/kg/day, five times weekly) for 7 months. Group 2 (glucocorticoid-2) received the same treatment regime followed by observation 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 the groups, while there was a trend towards decreasing bending mechanical properties in the glucocorticoid-2 group. In conclusion, 7 months of glucocorticoid treatment with malnutrition had a significant impact on the cortical microarchitecture of the sheep femur midshaft. These observed changes occurred 3 months after glucocorticoid cessation, suggesting a delayed effect of glucocorticoid on cortical bone. Thus, changes in cortical bone beyond cancellous bone might further increase fracture risk in patients treated with glucocorticoids. This model might be used as a glucocorticoid-induced osteoporotic model for orthopaedic biomaterial, joint prosthesis and medical device researches.

  7. Antiviral treatment for chronic hepatitis B virus infection--immune modulation or viral suppression?

    NARCIS (Netherlands)

    E.H.C.J. Buster (Erik); H.L.A. Janssen (Harry)

    2006-01-01

    textabstractThe availability of nucleoside analogues has broadened treatment options for chronic hepatitis B virus (HBV ) infection. Registered treatment for chronic hepatitis B currently consists of (pegylated) interferon, lamivudine and adefovir, while entecavir is expected to be

  8. Development of glucocorticoid receptor regulation in the rat forebrain: Implications for adverse effects of glucocorticoids in preterm infants

    Science.gov (United States)

    Glucocorticoids are the consensus treatment to avoid respiratory distress in preterm infants but there is accumulating evidence that these agents evoke long-term neurobehavioral deficits. Earlier, we showed that the developing rat forebrain is far more sensitive to glucocorticoi...

  9. Role of ofatumumab in treatment of chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Veliz M

    2011-05-01

    Full Text Available Marays Veliz, Javier Pinilla-IbarzH Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USAAbstract: The management of chronic lymphocytic leukemia (CLL has dramatically improved in the past decade with the addition of anti-CD20 monoclonal antibodies to the treatment armamentarium. Ofatumumab is a novel anti-CD20 monoclonal antibody recently approved in the US and Europe for the treatment of CLL refractory to alemtuzumab and fludarabine. Preclinical data showed improved complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity compared with rituximab. Clinical studies have shown single-agent activity for ofatumumab in CLL and in other low-grade non-Hodgkin's lymphomas. Combination studies are being conducted to enhance the therapeutic efficacy of ofatumumab. This paper reviews some of the key clinical studies that led to approval of ofatumumab, and future directions.Keywords: ofatumumab, chronic lymphocytic leukemia, efficacy, safety

  10. Glucocorticoids and insulin both modulate caloric intake through actions on the brain.

    Science.gov (United States)

    Dallman, Mary F; Warne, James P; Foster, Michelle T; Pecoraro, Norman C

    2007-09-01

    Glucocorticoids act primarily in a feed-forward fashion on brain to activate CNS pathways that implement wanting appropriate to physiological needs. Thus, depending on the available conditions, elevated glucocorticoids may augment the behavioural want to run, fight or feed. Although glucocorticoids stimulate intake of chow, fat and sucrose, insulin appears to sculpt calorie-associated desires toward foods high in fat, acting through hepatic branch afferents of the vagus nerve. Both conditions of reduced food allowance and chronic stress excite glucocorticoid-augmented central neural networks that may lead toward ultimate abdominal obesity.

  11. AMELOTEX IN THE TREATMENT OF CHRONIC BACK PAIN SYNDROMES

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    Irina Yuryevna Suvorova

    2010-01-01

    Full Text Available Recently there has been a considerable increase in the number of patients with lingering recurrent and chronic pain syndromes of various origin. Forty-one patients with dorsopathies were examined. Two types of pain were identified; these were vertebrogenic and nonvertebrogenic pains. The appropriateness of this identification was confirmed by instrumental studies. Treatment was performed using a selective nonsteroidal antiinflammatory drug (Amelotex. Pain syndrome relief was noted during the therapy

  12. Chronic Generalized Parodontitis. Part II. Modern Treatment and Prevention Techniques

    OpenAIRE

    Lukinykh L.M.; Kruglova N.V.

    2011-01-01

    To optimize a therapeutic process due to technological development in dentistry there have appeared new progressive technologies that allow improving life quality of patients with periodontal inflammatory diseases. Modern techniques of a complex etiopathogenic treatment of periodontal inflammatory diseases including conservative, orthopedic, orthodontic and surgical measures have been presented. There has been proved the use of preparations of systemic and local effect to treat chronic ge...

  13. Treatment of severe chronic hypotonic hyponatremia: a new treatment model

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    Antonio Burgio

    2013-03-01

    Full Text Available Recommended treatment of severe hypotonic hyponatremia is based on the infusion of 3% sodium chloride solution, with a daily correction rate below 10 mEq/L of sodium concentration, according to the Adrogué and Madias formula that includes the current desired change in sodium concentrations. However, such treatment needs close monitoring of the rate of infusion and does not take into account the body weight or age of the patient. This may result in hypercorrection and neurological damage. We made an inverse calculation using the same algorithms of the Adrogué and Madias formula to estimate the number of vials of sodium chloride needed to reach a correction rate of the serum sodium concentration below 0.4 mEq/h, taking into account the body weight and age of the patient. Three tables have been produced, each containing the number of vials to be infused, according to the patient’s age and body weight, the serum sodium concentration, and the rate of correction over 24 h to avoid the risk of brain damage. We propose a new practical model to calculate the need of sodium chloride infusate to safely correct the hyponatremia. The tables make treatment easier to manage in daily clinical practice in a wide range of patient ages and body weights.

  14. Glucocorticoid hypersensitivity as a rare but potentially fatal side effect of paediatric asthma treatment: a case report

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    Lehmann Sylvia

    2008-06-01

    Full Text Available Abstract Introduction Immediate-type hypersensitivity to glucocorticosteroids is rare but well known among allergists. Surprisingly, very few reports of glucocorticosteroid hypersensitivity in children exist although glucocorticosteroid treatment is particularly common in this age group. Case presentation We report the case of a 2-year-old boy who developed generalized urticaria, facial angio-oedema, nausea and severe dyspnoea after intravenous application of prednisolone-21-hydrogen succinate. Skin prick testing with prednisolone-21-hydrogen succinate elicited a positive result; no reactions were observed to prednisone, betamethasone or dexamethasone. While fluorescence enzyme immunoassay analysis revealed no specific IgE antibodies against prednisolone-21-hydrogen succinate, CD63-based basophil activation testing with the culprit drug prednisolone-21-hydrogen succinate was positive. In contrast, additional incubation of basophils with prednisone, betamethasone and dexamethasone did not elicit any significant response. Hence, we performed an oral provocation test with betamethasone and a titrated intravenous dexamethasone challenge. As both drugs were tolerated without any complications they were recommended for future treatment. Conclusion In a child with confirmed immediate-type hypersensitivity to glucocorticosteroids, it is still not possible to predict which glucocorticosteroid might be tolerated by solely relying on clinical history or results of skin and in vitro testing. Therefore, incremental glucocorticosteroid challenges under standardized clinical conditions remain necessary in order to facilitate a patient-tailored emergency treatment and to avoid severe reactions to glucocorticosteroids in these patients.

  15. Diagnosis and treatment of chronic acquired demyelinating polyneuropathies.

    Science.gov (United States)

    Latov, Norman

    2014-08-01

    Chronic neuropathies are operationally classified as primarily demyelinating or axonal, on the basis of electrodiagnostic or pathological criteria. Demyelinating neuropathies are further classified as hereditary or acquired-this distinction is important, because the acquired neuropathies are immune-mediated and, thus, amenable to treatment. The acquired chronic demyelinating neuropathies include chronic inflammatory demyelinating polyneuropathy (CIDP), neuropathy associated with monoclonal IgM antibodies to myelin-associated glycoprotein (MAG; anti-MAG neuropathy), multifocal motor neuropathy (MMN), and POEMS syndrome. They have characteristic--though overlapping--clinical presentations, are mediated by distinct immune mechanisms, and respond to different therapies. CIDP is the default diagnosis if the neuropathy is demyelinating and no other cause is found. Anti-MAG neuropathy is diagnosed on the basis of the presence of anti-MAG antibodies, MMN is characterized by multifocal weakness and motor conduction blocks, and POEMS syndrome is associated with IgG or IgA λ-type monoclonal gammopathy and osteosclerotic myeloma. The correct diagnosis, however, can be difficult to make in patients with atypical or overlapping presentations, or nondefinitive laboratory studies. First-line treatments include intravenous immunoglobulin (IVIg), corticosteroids or plasmapheresis for CIDP; IVIg for MMN; rituximab for anti-MAG neuropathy; and irradiation or chemotherapy for POEMS syndrome. A correct diagnosis is required for choosing the appropriate treatment, with the aim of preventing progressive neuropathy.

  16. Blocking glucocorticoid receptors at adolescent age prevents enhanced freezing between repeated cue-exposures after conditioned fear in adult mice raised under chronic early life stress

    NARCIS (Netherlands)

    Arp, J.M.; ter Horst, J.P.; Loi, M.; den Blaauwen, J.; Bangert, E.L.; Fernández, G.; Joëls, M.; Oitzl, M.S.; Krugers, H.J.

    2016-01-01

    Early life adversity can have long-lasting impact on learning and memory processes and increase the risk to develop stress-related psychopathologies later in life. In this study we investigated i) how chronic early life stress (ELS) - elicited by limited nesting and bedding material from postnatal d

  17. Blocking glucocorticoid receptors at adolescent age prevents enhanced freezing between repeated cue-exposures after conditioned fear in adult mice raised under chronic early life stress

    NARCIS (Netherlands)

    Arp, J.M.; Horst, J.P. ter; Loi, M.; Blaauwen, J. den; Bangert, E.; Fernandez, G.S.E.; Joels, M.; Oitzl, M.S.; Krugers, H.J.

    2016-01-01

    Early life adversity can have long-lasting impact on learning and memory processes and increase the risk to develop stress-related psychopathologies later in life. In this study we investigated (i) how chronic early life stress (ELS) - elicited by limited nesting and bedding material from postnatal

  18. Is exercise an alternative treatment for chronic insomnia?

    Directory of Open Access Journals (Sweden)

    Giselle Soares Passos

    Full Text Available The purposes of this systematic/critical review are: 1 to identify studies on the effects of exercise on chronic insomnia and sleep complaints in middle-aged and older adults and to compare the results of exercise with those obtained with hypnotic medications and 2 to discuss potential mechanisms by which exercise could promote sleep in insomniac patients. We identified studies from 1983 through 2011 using MEDLINE, SCOPUS and Web of Science. For systematic analyses, only studies assessing the chronic effects of exercise on sleep in people with sleep complaints or chronic insomnia were considered. We used the following keywords when searching for articles: insomnia, sleep, sleep complaints, exercise and physical activity. For a critical review, studies were selected on the effects of exercise and possible mechanisms that may explain the effects of exercise on insomnia. We identified five studies that met our inclusion criteria for systematic review. Exercise training is effective at decreasing sleep complaints and insomnia. Aerobic exercise has been more extensively studied, and its effects are similar to those observed after hypnotic medication use. Mechanisms are proposed to explain the effects of exercise on insomnia. There is additional documented evidence on the antidepressant and anti-anxiety effects of exercise. Exercise is effective to decrease sleep complaints and to treat chronic insomnia. Exercise presented similar results when compared with hypnotics; however, prospective studies comparing the effects of exercise with medical and non-medical treatments are warranted before including exercise as a first-line treatment for chronic insomnia are necessary.

  19. Treatment of Chronic Migraine with Focus on Botulinum Neurotoxins

    Directory of Open Access Journals (Sweden)

    Sara M. Schaefer

    2015-07-01

    Full Text Available Migraine is the most common neurological disorder, and contributes to disability and large healthcare costs in the United States and the world. The treatment of migraine until recently has focused on medications, both abortive and prophylactic, but treatment of chronic migraine has been revolutionized with the introduction of botulinum toxin injection therapy. In this review, we explore the current understanding of migraine pathophysiology, and the evolution of the use of botulinum toxin therapy including proposed pathophysiological mechanisms through animal data. We also discuss the similarities and differences between three injection techniques.

  20. How to Do in Persistent Diarrhea of Children?: Concepts and Treatments of Chronic Diarrhea

    OpenAIRE

    Lee, Kun Song; Kang, Dong Soo; Yu, JeeSuk; Chang, Young Pyo; Park, Woo Sung

    2012-01-01

    Chronic diarrhea is defined as passing watery stools that lasts for more than 2 weeks. Persistent diarrhea belongs to chronic diarrhea and is a chronic episode of diarrhea of infectious etiology. The etiology of chronic diarrhea is varied. It is important to consider the child's age and clinical manifestations with alarm signals for an application of proper treatments to children with chronic diarrhea. Vicious cycle is present in chronic diarrhea and nutritional rehabilitation can break the v...

  1. Defining conditions where long-term glucocorticoid treatment has an acceptably low level of harm to facilitate implementation of existing recommendations

    DEFF Research Database (Denmark)

    Strehl, Cindy; Bijlsma, Johannes W J; de Wit, Maarten;

    2016-01-01

    of patients at long-term dosages of ≤5 mg prednisone equivalent per day, whereas at dosages of >10 mg/day the risk of harm is elevated. At dosages between >5 and ≤10 mg/day, patient-specific characteristics (protective and risk factors) determine the risk of harm. The level of harm of glucocorticoids depends...

  2. HDL cholesterol response to GH replacement is associated with common cholesteryl ester transfer protein gene variation (-629C > A) and modified by glucocorticoid treatment

    NARCIS (Netherlands)

    Dullaart, Robin P. F.; van den Berg, Gerrit; van der Knaap, Aafke M.; Dijck-Brouwer, Janneke; Dallinga-Thie, Geesje M.; Zelissen, Peter M. J.; Sluiter, Wim J.; van Beek, Andre P.

    2010-01-01

    Objective: GH replacement lowers total cholesterol and low-density lipoprotein cholesterol (LDL-C) in GH-deficient adults, but effects on high-density lipoprotein (HDL) cholesterol (HDL-C) are variable. Both GH and glucocorticoids decrease cholesteryl ester transfer protein (CETP) activity, which is

  3. Treatment of chronic osteomyelitis with one-stage allograft

    Institute of Scientific and Technical Information of China (English)

    LU Wei-ju; LI Bin; BAO Ni-rong; QIAN Hong-bo; ZENG Xiao-feng; XU Bin; CHEN Yong; ZHAO Jian-ning

    2006-01-01

    Objective: To avoid disadvantages of two-stage cancellus bone autograft, we investigated the feasibility of one-stage allograft for reconstructing the bone defect resulting from debridement of chronic osteomyelitis in limbs.Methods: Between Feb. 1999 and Apr. 2004, 35 cases of chronic osteomyelitis (8 cases of nonunion )underwent one-stage allograft after debridement in our hospital.Results: Thirty-five cases were followed up for an average period of 28 months (range, 13 to 55 months), in which 32 cases (91.43%) were found no infection, and 3cases (8.57 %) were confirmed recurrence of infection.Four out of 8 cases of bone nonunion healed in 9.5 months on average (range, 3 to 12 months), and another case also acquired union after redebridement and autograft of ilium due to infection recurrence 35 days after surgery.Renonunion occurred in 3 cases, 2 out of whom healed after secondary operation with autograft. One case of renonunion and 2 cases of infection recurrence refused further treatment.Conclusions: A high rate of infection arrest can be attained when one-stage allograft is used to reconstruct the bone defect of chronic osteomyelitis after debridement in limbs. Therefore, chronic osteomyelitis should not be regarded as a contraindication to one-stage allogeneic bone grafting. Renonuion, however, achieves a relatively high rate, especially in cases of segmental bone defect.

  4. Neuropsychiatric findings in Cushing syndrome and exogenous glucocorticoid administration.

    Science.gov (United States)

    Starkman, Monica N

    2013-09-01

    This article reviews the neuropsychiatric presentations elicited by spontaneous hypercortisolism and exogenous supraphysiologic glucocorticoids. Patients with Cushing disease and syndrome develop a depressive syndrome: irritable and depressed mood, decreased libido, disrupted sleep and cognitive decrements. Exogenous short-term glucocorticoid administration may elicit a hypomanic syndrome with mood, sleep and cognitive disruptions. Treatment options are discussed. Brain imaging and neuropsychological studies indicate elevated cortisol and other glucocorticoids are especially deleterious to hippocampus and frontal lobe. The research findings also shed light on neuropsychiatric abnormalities in conditions that have substantial subgroups exhibiting elevated and dysregulated cortisol: aging, major depressive disorder and Alzheimer's disease.

  5. Neurobehavioral response to increased treatment dosage in chronic, severe aphasia

    Directory of Open Access Journals (Sweden)

    Jennifer L Mozeiko

    2014-04-01

    •\tIncreased activation in S2’s bilateral inferior frontal gyrus following the second treatment session indicates that a second Treatment Period can influence continued neuroplastic change in severe, chronic aphasia. •\tS1 appears to show the most activation following Treatment Period I. It is possible that his greater lesion volume or site did not allow for benefit from a second dose to the same degree as S2. •\tActivation changes (or lack thereof in both cases corresponded with performance on the naming task in the scanner, reflecting the effect of treatment. •\tFor S2, neuroimaging supported the behavioral results which favor a second dose of ILAT. For S1, behavioral results, particularly in his consistent increases on the BNT, are not supported by either the behavioral results in the scanner or the BOLD response.

  6. [Subcutaneous immunoglobulin. Treatment in chronic inflammatory demyelinating polyradiculo-neuropathy].

    Science.gov (United States)

    Nogués, Martín A; Varela, Francisco J; Seminario, Gisela; Insúa, María C; Bezrodnik, Liliana

    2016-01-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired disease that may affect nerve roots and peripheral nerves. Despite its low incidence, diagnosis is particularly important because there are different effective treatments. Human immunoglobulin is one of the mainstays of the treatment. Although there are few studies up to date, subcutaneous immunoglobulin (IgSC) has been proposed as an alternative to intravenous administration with similar efficacy. We present three cases with definite CIDP, classified according to the European Federation of Neurological Societies / Peripheral Nerve, Society (EFNS /PNS) criteria in which was used SCIgG as a treatment after success with the intravenous route. The Overall Neuropathy Limitations Scale (ONLS) was used to estimate the changes in the muscular strength before and after treatment.

  7. Antioxidant Phytochemicals for the Prevention and Treatment of Chronic Diseases

    Directory of Open Access Journals (Sweden)

    Yu-Jie Zhang

    2015-11-01

    Full Text Available Overproduction of oxidants (reactive oxygen species and reactive nitrogen species in the human body is responsible for the pathogenesis of some diseases. The scavenging of these oxidants is thought to be an effective measure to depress the level of oxidative stress of organisms. It has been reported that intake of vegetables and fruits is inversely associated with the risk of many chronic diseases, and antioxidant phytochemicals in vegetables and fruits are considered to be responsible for these health benefits. Antioxidant phytochemicals can be found in many foods and medicinal plants, and play an important role in the prevention and treatment of chronic diseases caused by oxidative stress. They often possess strong antioxidant and free radical scavenging abilities, as well as anti-inflammatory action, which are also the basis of other bioactivities and health benefits, such as anticancer, anti-aging, and protective action for cardiovascular diseases, diabetes mellitus, obesity and neurodegenerative diseases. This review summarizes recent progress on the health benefits of antioxidant phytochemicals, and discusses their potential mechanisms in the prevention and treatment of chronic diseases.

  8. Medium-Level Laser in Chronic Tinnitus Treatment

    Directory of Open Access Journals (Sweden)

    K. Dejakum

    2013-01-01

    Full Text Available The purpose of this study was to evaluate the effect of medium-level laser therapy in chronic tinnitus treatment. In a prospective double-blind placebo-controlled trial, either active laser (450 mW, 830 nm combined Ga-Al-As diode laser or placebo irradiation was applied through the external acoustic meatus of the affected ear towards the cochlea. Fourty-eight patients with chronic tinnitus were studied. The main outcome was measured using the Goebel tinnitus questionnaire, visual analogue scales measuring the perceived loudness of tinnitus, the annoyance associated with tinnitus, and the degree of attention paid to tinnitus as well as psycho-acoustical matches of tinnitus pitch and loudness. The results did show only very moderate temporary improvement of tinnitus. Moreover, no statistically relevant differences between laser and placebo group could be found. We conclude that medium-level laser therapy cannot be regarded as an effective treatment of chronic tinnitus in our therapy regime considering the limited number of patients included in our study.

  9. 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.

  10. Targeted treatment for chronic lymphocytic leukemia: clinical potential of obinutuzumab

    Directory of Open Access Journals (Sweden)

    Smolej L

    2014-12-01

    Full Text Available Lukáš Smolej 4th Department of Internal Medicine – Hematology, University Hospital Hradec Králové and Charles University in Prague, Faculty of Medicine in Hradec Králové, Hradec Králové, Czech Republic Abstract: Introduction of targeted agents revolutionized the treatment of chronic lymphocytic leukemia (CLL in the past decade. Addition of chimeric monoclonal anti-CD20 antibody rituximab to chemotherapy significantly improved efficacy including overall survival (OS in untreated fit patients; humanized anti-CD52 antibody alemtuzumab and fully human anti-CD20 antibody ofatumumab lead to improvement in refractory disease. Novel small molecule inhibitors such as ibrutinib and idelalisib demonstrated excellent activity and were very recently licensed in relapsed/refractory CLL. Obinutuzumab (GA101 is the newest monoclonal antibody approved for the treatment of CLL. This novel, glycoengineered, type II humanized anti-CD20 antibody is characterized by enhanced antibody-dependent cellular cytotoxicity and direct induction of cell death compared to type I antibodies. Combination of obinutuzumab and chlorambucil yielded significantly better OS in comparison to chlorambucil monotherapy in untreated comorbid patients. These results led to approval of obinuzutumab for the treatment of CLL. Numerous clinical trials combining obinutuzumab with other cytotoxic drugs and novel small molecules are currently under way. This review focuses on the role of obinutuzumab in the treatment of CLL. Keywords: chronic lymphocytic leukemia, anti-CD20 antibodies, chlorambucil, rituximab, ofatumumab, obinutuzumab, overall survival

  11. Managing chronic thromboembolic pulmonary hypertension: pharmacological treatment options

    Directory of Open Access Journals (Sweden)

    I. M. Lang

    2009-03-01

    Full Text Available Chronic thromboembolic pulmonary hypertension (CTEPH is a life-threatening condition in which organised thrombi obstruct the pulmonary vessels, causing increased pulmonary vascular resistance, progressive pulmonary hypertension (PH and right heart failure. The treatment of choice is pulmonary endarterectomy, which restores pulmonary haemodynamics with acceptable periprocedural mortality rates in the majority of suitable patients. However, CTEPH may be inoperable owing to surgically inaccessible thrombi or comorbid diseases that confer an unacceptably high risk. Pharmacotherapies, although not yet approved, may be useful in this situation or for treating residual or recurrent PH following surgery. Vasodilator drugs for PH are attracting growing interest as potential treatments for CTEPH because this disease has recently been labelled as a "dual" pulmonary vascular disorder: major vessel obstruction and remodelling is combined with a small vessel arteriopathy that is histologically indistinguishable from the classical pulmonary arteriopathy observed in pulmonary arterial hypertension. Of three completed randomised controlled trials in patients with CTEPH, only one was powered to detect a treatment effect. The BENEFIT trial employed the dual endothelin-receptor antagonist bosentan. Although haemodynamics improved significantly, the second component of the primary end-point, exercise capacity, was not met. More evidence is required to resolve whether vasodilator treatments are beneficial for inoperable chronic thromboembolic pulmonary hypertension.

  12. Emerging biologics for the treatment of chronic rhinosinusitis.

    Science.gov (United States)

    Pauwels, Bauke; Jonstam, Karin; Bachert, Claus

    2015-03-01

    Chronic rhinosinusitis (CRS) is a prevalent chronic inflammatory disease of the nasal and paranasal cavities and is known to seriously impair quality of life in affected patients. CRS appears to be a heterogeneous group of diseases with different inflammatory and remodeling patterns, suggesting that not only different clinical phenotypes but also pathophysiological endotypes occur. CRS with nasal polyps (CRSwNP) is considered a more severe phenotype, especially when associated with comorbid asthma, as patients having this condition often do not respond to conventional treatment, including topical and systemic corticosteroids or surgery. Recently, studies with biologic agents have shown various effects in severe airway disease; specifically in Th2-biased CRSwNP, these effects were very promising. The greatest challenge for the future is to define the different endotypes of CRSwNP using easily accessible biomarkers to select the patients who have the best chance of a positive therapeutic response to innovative approaches.

  13. TREATMENT OF CHRONIC BRONCHITIS WITH FIFTY-YING-ACUPUNCTURE THERAPY

    Institute of Scientific and Technical Information of China (English)

    袁民

    2001-01-01

    Objective: To observe the clinical effect of Fifty-ying acupuncture therapy for treatment of chronic bronchitis, and to explore its underlying mechanisms. Methods: A total of 36 out- and in-patients with chronic bronchitis including 10 cases of asthma were subjected into this study. Among them, 20 cases were qi-deficiency type and 16 qi-yin-deficiency with phlegm-clamp type. The changes of symptoms, T-lymphocyte subgroups of CD3+, CD4+, CD8+,CD4+/CD8+, soluble interleuki-2 receptor ( SIL-2R), interleukin-6(IL-6), IgG, IgA and IgM before and after treatment were observed and detected using monoclonal indirect fluorescence method, enzyme linked immunosorbent assay (ELISA) and nephelometry respectively. Results: (1)The effective rate of qi-dificiency type was 100% and that of qi-yin-deficiency with phlegm-damp type 87.5%. (2) After acupuncture treatment, in qi-deficiency type patients, serum IgG, IgA and IgM contents increased significantly (P< 0. 001) in comparison with pre-treatment and in qi-yin-deficiency with phlegm-damp type patients, IgG level lowered obviously. Serum SIL-2R and CD4+/CD8+ decreased obviously(P<0.01, 0.001), CD3+, CD4+ and CD8+ increased evidently (P<0.01). Conclusion: The Fifty-ying acupuncture therapy can better clinical symptoms of chronic bronchitis patients through its resultant up-regulation of the immune system function.

  14. [Pharmacological treatment of stable chronic obstructive pulmonary disease].

    Science.gov (United States)

    Allain, Yves-Marie; Giraud, Frédérique; Huchon, Gérard; Roche, Nicolas

    2009-03-01

    The pharmacological treatment of chronic obstructive pulmonary disease (COPD) can significantly improve quality of life by reducing exacerbations, dyspnea and exercise intolerance, thereby limiting the degree of handicap and improving daily activities. Recently, large randomised trials showed that some treatments can alter the decline in FEV1, which was previously only accessible to smoking cessation, and maybe reduce mortality. Bronchodilators are the first-line pharmacological treatment of COPD. Their clinical efficacy cannot be predicted by the inconstant changes in FEV(1.) Their main mechanism of action is the reduction in lung hyperinflation. Theophylline has a lower efficacy/tolerance ratio than inhaled bronchodilators. In symptomatic patients with FEV1 regeneration are also being studied. Medications must be associated with non-pharmacological measures (including help towards smoking cessation, education, exercise training...). Systemic manifestations of COPD must also be taken into account.

  15. Antiviral treatment for chronic hepatitis B in renaltransplant patients

    Institute of Scientific and Technical Information of China (English)

    Ezequiel Ridruejo

    2015-01-01

    Chronic hepatitis B infection is frequent in renaltransplant patients. It negatively impacts long termoutcomes reducing graft and patient survival. Currentguidelines clearly define who needs treatment, whento start, what is the first line therapy, how to monitortreatment response, when to stop, and how patientsmust be controlled for its safety. There is some datashowing a favorable safety and efficacy profile ofnucleos(t)ide analogue (NUC) treatment in the renaltransplant setting. Entecavir, a drug without majorsigns of nephrotoxicity, appears to be the first optionfor NUC na?ve patients and tenofovir remains thepreferred choice for patients with previous resistanceto lamivudine or any other NUC. Renal transplantrecipients under antiHBV therapy should be monitoredfor its efficacy against HBV but also for its safety witha close renal monitoring. Studies including a largenumber of patients with long term treatment and followup are still needed to better demonstrate the safetyand efficacy of newer NUCs in this population.

  16. Antiviral Treatment among Pregnant Women with Chronic Hepatitis B

    Directory of Open Access Journals (Sweden)

    Lin Fan

    2014-01-01

    Full Text Available Objective. To describe the antiviral treatment patterns for chronic hepatitis B (CHB among pregnant and nonpregnant women. Methods. Using 2011 MarketScan claims, we calculated the rates of antiviral treatment among women (aged 10–50 years with CHB. We described the pattern of antiviral treatment during pregnancy and ≥1 month after delivery. Results. We identified 6274 women with CHB during 2011. Among these, 64 of 507 (12.6% pregnant women and 1151 of 5767 (20.0% nonpregnant women received antiviral treatment (P < 0.01. Pregnant women were most commonly prescribed tenofovir (73.4% and lamivudine (21.9%; nonpregnant women were most commonly prescribed tenofovir (50.2% and entecavir (41.3% (P < 0.01. Among 48 treated pregnant women with an identifiable delivery date, 16 (33.3% were prescribed an antiviral before pregnancy and continued treatment for at least one month after delivery; 14 (29.2% started treatment during the third trimester and continued at least one month after delivery. Conclusion. Among this insured population, pregnant women with CHB received an antiviral significantly less often than nonpregnant women. The most common antiviral prescribed for pregnant women was tenofovir. These data provide a baseline for assessing changes in treatment patterns with anticipated increased use of antivirals to prevent breakthrough perinatal hepatitis B virus infection.

  17. Antiviral Treatment among Pregnant Women with Chronic Hepatitis B

    Science.gov (United States)

    Fan, Lin; Owusu-Edusei, Kwame; Schillie, Sarah F.; Murphy, Trudy V.

    2014-01-01

    Objective. To describe the antiviral treatment patterns for chronic hepatitis B (CHB) among pregnant and nonpregnant women. Methods. Using 2011 MarketScan claims, we calculated the rates of antiviral treatment among women (aged 10–50 years) with CHB. We described the pattern of antiviral treatment during pregnancy and ≥1 month after delivery. Results. We identified 6274 women with CHB during 2011. Among these, 64 of 507 (12.6%) pregnant women and 1151 of 5767 (20.0%) nonpregnant women received antiviral treatment (P < 0.01). Pregnant women were most commonly prescribed tenofovir (73.4%) and lamivudine (21.9%); nonpregnant women were most commonly prescribed tenofovir (50.2%) and entecavir (41.3%) (P < 0.01). Among 48 treated pregnant women with an identifiable delivery date, 16 (33.3%) were prescribed an antiviral before pregnancy and continued treatment for at least one month after delivery; 14 (29.2%) started treatment during the third trimester and continued at least one month after delivery. Conclusion. Among this insured population, pregnant women with CHB received an antiviral significantly less often than nonpregnant women. The most common antiviral prescribed for pregnant women was tenofovir. These data provide a baseline for assessing changes in treatment patterns with anticipated increased use of antivirals to prevent breakthrough perinatal hepatitis B virus infection. PMID:25548510

  18. Update on the Pharmacological Treatment of Chronic Migraine.

    Science.gov (United States)

    Sun-Edelstein, Christina; Rapoport, Alan M

    2016-01-01

    Chronic migraine (CM) is a common and disabling disorder that remains underdiagnosed and poorly treated. Significant unmet therapeutic needs add to the burden of this disorder; even when CM is recognized, effective treatment options are limited and randomized controlled trials supporting the use of various preventive medications are sparse. In this review, we discuss the available options for CM treatment. Currently the only FDA-approved treatment for CM prevention is onabotulinumtoxinA. Two double-blind studies have demonstrated the efficacy of topiramate for CM prevention, but it is not FDA-approved for this indication. Treatments in development for migraine will also be reviewed. Advancements in the understanding of migraine pathogenesis have identified new targets for both acute and preventive treatment and have engendered the development of targeted and mechanism-based therapies. The need for more effective treatment for CM patients, which has long since been identified, is now being addressed. Several of the emerging treatments for migraine prevention are under investigation specifically for CM or high-frequency episodic migraine.

  19. Lamivudine treatment for decompensated cirrhosis resulting from chronic hepatitis B.

    Science.gov (United States)

    Villeneuve, J P; Condreay, L D; Willems, B; Pomier-Layrargues, G; Fenyves, D; Bilodeau, M; Leduc, R; Peltekian, K; Wong, F; Margulies, M; Heathcote, E J

    2000-01-01

    The prognosis of decompensated cirrhosis resulting from chronic hepatitis B is poor, and the benefits of treatment with interferon are outweighed by serious side effects and by the risk of fatal exacerbation of disease activity. Lamivudine rapidly reduces hepatitis B virus (HBV)-DNA in serum to undetectable levels. We have treated 35 patients with chronic hepatitis B and decompensated cirrhosis with lamivudine 100 mg or 150 mg orally once daily. Pretreatment, all were positive for HBV-DNA in serum. Ten had Child-Pugh class B and 25 had Child-Pugh class C liver disease. Seven patients underwent liver transplantation within 6 months of treatment initiation, 5 patients died within 6 months, and 23 patients were treated for at least 6 months (mean = 19 months). In a majority of these 23 cases, there was a slow but marked improvement in liver function, which was most apparent after 9 months of treatment, with a decrease in serum bilirubin from 67 +/- 13 to 30 +/- 4 micromol/L (P decompensated HBV cirrhosis, but the long-term benefits remain uncertain.

  20. Treatment Preferences for CAM in Children with Chronic Pain

    Directory of Open Access Journals (Sweden)

    Jennie C. I. Tsao

    2007-01-01

    Full Text Available CAM therapies have become increasingly popular in pediatric populations. Yet, little is known about children's preferences for CAM. This study examined treatment preferences in chronic pediatric pain patients offered a choice of CAM therapies for their pain. Participants were 129 children (94 girls (mean age = 14.5 years ± 2.4; range = 8–18 years presenting at a multidisciplinary, tertiary clinic specializing in pediatric chronic pain. Bivariate and multivariate analyses were used to examine the relationships between CAM treatment preferences and patient's sociodemographic and clinical characteristics, as well as their self-reported level of functioning. Over 60% of patients elected to try at least one CAM approach for pain. The most popular CAM therapies were biofeedback, yoga and hypnosis; the least popular were art therapy and energy healing, with craniosacral, acupuncture and massage being intermediate. Patients with a diagnosis of fibromyalgia (80% were the most likely to try CAM versus those with other pain diagnoses. In multivariate analyses, pain duration emerged as a significant predictor of CAM preferences. For mind-based approaches (i.e. hypnosis, biofeedback and art therapy, pain duration and limitations in family activities were both significant predictors. When given a choice of CAM therapies, this sample of children with chronic pain, irrespective of pain diagnosis, preferred non-invasive approaches that enhanced relaxation and increased somatic control. Longer duration of pain and greater impairment in functioning, particularly during family activities increased the likelihood that such patients agreed to engage in CAM treatments, especially those that were categorized as mind-based modalities.

  1. Treatment Preferences for CAM in children with chronic pain.

    Science.gov (United States)

    Tsao, Jennie C I; Meldrum, Marcia; Kim, Su C; Jacob, Margaret C; Zeltzer, Lonnie K

    2007-09-01

    CAM therapies have become increasingly popular in pediatric populations. Yet, little is known about children's preferences for CAM. This study examined treatment preferences in chronic pediatric pain patients offered a choice of CAM therapies for their pain. Participants were 129 children (94 girls) (mean age = 14.5 years +/- 2.4; range = 8-18 years) presenting at a multidisciplinary, tertiary clinic specializing in pediatric chronic pain. Bivariate and multivariate analyses were used to examine the relationships between CAM treatment preferences and patient's sociodemographic and clinical characteristics, as well as their self-reported level of functioning. Over 60% of patients elected to try at least one CAM approach for pain. The most popular CAM therapies were biofeedback, yoga and hypnosis; the least popular were art therapy and energy healing, with craniosacral, acupuncture and massage being intermediate. Patients with a diagnosis of fibromyalgia (80%) were the most likely to try CAM versus those with other pain diagnoses. In multivariate analyses, pain duration emerged as a significant predictor of CAM preferences. For mind-based approaches (i.e. hypnosis, biofeedback and art therapy), pain duration and limitations in family activities were both significant predictors. When given a choice of CAM therapies, this sample of children with chronic pain, irrespective of pain diagnosis, preferred non-invasive approaches that enhanced relaxation and increased somatic control. Longer duration of pain and greater impairment in functioning, particularly during family activities increased the likelihood that such patients agreed to engage in CAM treatments, especially those that were categorized as mind-based modalities.

  2. Clinical Study on Treatment of Chronic Renal Failure with Shenshuailing

    Institute of Scientific and Technical Information of China (English)

    鞠建伟; 郭亚玲; 梁延平; 孙世宁; 杨建华; 杨素云

    2001-01-01

    The therapeutic effects of Shenshuailing Kou Fu Ye (SKFY肾衰灵口服液, the Oral Liquid for Renal Failure) and Shenshuailing Guan Chang Ye (SGCY肾衰灵灌肠液, the Enema for Renal Failure) were evaluated in treatment of chronic renal failure, with coateg aldehyde oxystarch as the controls. The changes in the clinical symptoms, serum creatinine, blood urea nitrogen and creatinine clearance rate were observed. The total effective rate in the former was 90.46%, and the latter 60.43%.

  3. 糖皮质激素治疗突发性耳聋的临床效果观察%Clinical effect of glucocorticoid in the treatment of sudden deafness

    Institute of Scientific and Technical Information of China (English)

    刘富月

    2016-01-01

    目的:研究分析糖皮质激素治疗突发性耳聋的临床效果。方法:选取在我院治疗的突发性耳聋患者80例(2014年5月~2015年5月)。将其动态随机化分2组,研究组和对照组各40例。对照组患者给予非激素常规治疗,研究组患者在常规治疗的基础上给予糖皮质激素进行治疗,对比两组患者突发性耳聋的临床疗效。结果:研究组患者治愈率为27.50%,总有效率为87.50%,与对照组患者对比存在明显差异(P<0.05)。结论:采用糖皮质激素对突发性耳聋患者进行治疗的效果显著,能有效改善患者听力情况,在临床上可以广泛应用。%Objective:To study the clinical effect of glucocorticoid in the treatment of sudden deafness.Methods:80 cases of sudden deafness were randomly divided into study group and control group,40 cases in each group.The study group was treated with glucocorticoids.Results:the cure rate and total effective rate of the study group were significantly different from that of the control group(P<0.05).Conclusion:glucocorticoid is effective in the treatment of sudden deafness.

  4. Approach to the Treatment of Chronic Metabolic Acidosis in CKD.

    Science.gov (United States)

    Raphael, Kalani L

    2016-04-01

    Chronic metabolic acidosis is not uncommon in patients with chronic kidney disease (CKD). Clinical practice guidelines suggest that clinicians administer alkali to maintain serum bicarbonate level at a minimum of 22 mEq/L to prevent the effects of acidosis on bone demineralization and protein catabolism. Small interventional studies support the notion that correcting acidosis slows CKD progression as well. Furthermore, alkaline therapy in persons with CKD and normal bicarbonate levels may also preserve kidney function. Observational studies suggest that targeting a serum bicarbonate level near 28 mEq/L may improve clinical outcomes above and beyond targeting a value ≥ 22 mEq/L, yet values > 26 mEq/L have been reported to be associated with incident heart failure and mortality in the CRIC (Chronic Renal Insufficiency Cohort) Study. Furthermore, correcting acidosis may provoke vascular calcification. This teaching case discusses several uncertainties regarding the management of acidosis in CKD, such as when to initiate alkali treatment, potential side effects of alkali, and the optimum serum bicarbonate level based on current evidence in CKD. Suggestions regarding the maximum sodium bicarbonate dose to administer to patients with CKD to achieve the target serum bicarbonate concentration are offered.

  5. 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.

    1978-01-01

    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.

  6. My treatment approach to chronic hepatitis C virus.

    Science.gov (United States)

    Shiffman, Mitchell L; Long, April G; James, Amy; Alexander, Phillip

    2014-07-01

    The treatment of chronic hepatitis C virus (HCV) is evolving rapidly. In 2014, the standard of care and new backbone of HCV treatment is the polymerase inhibitor sofosbuvir (SOF). Our treatment approach in patients with HCV genotype 1 is 12 weeks of SOF, peginterferon (PEGINF), and ribavirin (RBV). In patients with cirrhosis or extrahepatic manifestations of HCV who cannot tolerate PEGINF, we use 12 weeks of SOF and simeprevir. The latter is less costly and more effective than SOF and RBV for 24 weeks. Our treatment approach in all patients with genotype 2 is SOF and RBV for 12 weeks. Hepatitis C virus genotype 3 is now the most costly and difficult to cure. Our approach to treatment-naive patients with genotype 3 is SOF and RBV for 24 weeks. In patients who have previously undergone PEGINF and RBV treatment, we use PEGINF, SOF, and RBV for 12 weeks, which is equally if not more effective and less costly than SOF and RBV for 24 weeks. Patients with cirrhosis who cannot tolerate PEGINF should be treated for 24 weeks with SOF and RBV, although the sustained virologic response is suboptimal.

  7. Adalimumab treatment for severe recalcitrant chronic plaque psoriasis.

    LENUS (Irish Health Repository)

    Ryan, C

    2012-02-01

    AIM: To assess the efficacy and safety profile of adalimumab in patients with severe, recalcitrant chronic plaque psoriasis, and to assess short-term overlapping of other systemic treatment with adalimumab to prevent flaring of disease. METHODS: This was a retrospective study comprising 39 patients with chronic plaque psoriasis treated with adalimumab between October 2005 and January 2008. All had failed treatment with other systemic agents, including biological therapies in 59% of patients. Patients were started on adalimumab 40 mg weekly or fortnightly, as clinically indicated. Severity of psoriasis was assessed by the Psoriasis Area and Severity Index (PASI). Therapeutic response was assessed by 75% improvement on PASI (PASI 75). All adverse events were recorded. RESULTS: Results were analysed separately for those treated with adalimumab only and those on combination treatment. PASI 75 was achieved in 38% (8 of 21 patients at week 16), 62% (13 of 21 patients) at week 24, 69% (9 of 13 patients) at week 48% and 71% (5 of 7 patients) at week 72 in the adalimumab-only group, compared with 56% (5 of 9 patients) at week 16, 50% (4 of 8 patients) at week 24, 80% (4 of 5 patients) at week 48% and 67% (2 of 3 patients) at week 72 in the combined group. Of the 39 patients, 15 (38%) achieved a PASI of 0 at some point in their treatment. Adalimumab was well tolerated; 38% of patients experienced side-effects, which were generally mild. CONCLUSION: Adalimumab was effective in a group of patients with psoriasis refractory to other systemic therapies, including biological treatments, and was well tolerated.

  8. The glucocorticoid/aggression relationship in animals and humans: an analysis sensitive to behavioral characteristics, glucocorticoid secretion patterns, and neural mechanisms.

    Science.gov (United States)

    Haller, József

    2014-01-01

    Glucocorticoids control a wide array of biological processes from glucose homeostasis to neuronal function. The mechanisms mediating their effects are similarly varied and include rapid and transient nongenomic effects on calcium trafficking, various neurotransmitter receptors, and other membrane/cytoplasmic proteins, as well as slowly developing but durable genomic effects that are mediated by a large number of glucocorticoid-sensitive genes that are affected after variable lag-times. Given this complexity, we suggest that the aggression/glucocorticoid relationship cannot be reduced to the simple "stimulation/inhibition" question. Here, we review the effects of glucocorticoids on aggression by taking into account the complexities of glucocorticoid actions. Acute and chronic effects were differentiated because these are mediated by different mechanisms. The effects of chronic increases and decreases in glucocorticoid production were discussed separately, because the activation of mechanisms that are not normally activated and the loss of normal functions should not be confounded. Findings in healthy/normal subjects and those obtained in subjects that show abnormal forms of behavior or psychopathologies were also differentiated, because the effects of glucocorticoids are indirect, and largely depend on the properties of neurons they act upon, which are altered in subjects with psychopathologies. In addition, the conditions of glucocorticoid measurements were also thoroughly evaluated. Although the role of glucocorticoids in aggression is perceived as controversial by many investigators, a detailed analysis that is sensitive to glucocorticoid and behavioral measure as well as to the mediating mechanism suggests that this role is rather clear-cut; moreover, there is a marked similarity between animal and human findings.

  9. Treatments for chronic myeloid leukemia: a qualitative systematic review

    Directory of Open Access Journals (Sweden)

    Ferdin

    2012-08-01

    Full Text Available Roxanne Ferdinand,1 Stephen A Mitchell,2 Sarah Batson,2 Indra Tumur11Pfizer, Tadworth, UK; 2Abacus International, Bicester, UKBackground: Chronic myeloid leukemia (CML is a myeloproliferative disorder of blood stem cells. The tyrosine kinase inhibitor (TKI imatinib was the first targeted therapy licensed for patients with chronic-phase CML, and its introduction was associated with substantial improvements in response and survival compared with previous therapies. Clinical trial data are now available for the second-generation TKIs (nilotinib, dasatinib, and bosutinib in the first-, second-, and third-line settings. A qualitative systematic review was conducted to qualitatively compare the clinical effectiveness, safety, and effect on quality of life of TKIs for the management of chronic-, accelerated-, or blast-phase CML patients.Methods: Included studies were identified through a search of electronic databases in September 2011, relevant conference proceedings and the grey literature.Results: In the first-line setting, the long-term efficacy (up to 8 years of imatinib has been confirmed in a single randomized controlled trial (International Randomized Study of Interferon [IRIS]. All second-generation TKIs reported lower rates of transformation, and comparable or superior complete cytogenetic response (CCyR, major molecular response (MMR, and complete molecular response rates compared with imatinib by 2-year follow-up. Each of the second-generation TKIs was associated with a distinct adverse-event profile. Bosutinib was the only second-generation TKI to report quality-of-life data (no significant difference compared with imatinib treatment. Data in the second- and third-line setting confirmed the efficacy of the second-generation TKIs in either imatinib-resistant or -intolerant patients, as measured by CCyR and MMR rates.Conclusion: Data from first-line randomized controlled trials reporting up to 2-year follow-up indicate superior response

  10. Treatment of 35 Cases of Chronic Prostatitis by Comprehensive Therapies

    Institute of Scientific and Technical Information of China (English)

    DU Han-qiang; ZHU Shao-ying

    2005-01-01

    目的:运用微波射频并TDP加电针治疗慢性前列腺炎疗效观察.方法:采用大连产WE2102-3型射频治疗机并TDP加电针治疗慢性前列腺炎35例,每次治疗40 min,15次为1个疗程,共2~3个疗程.结果:痊愈12例,显效10例,占有效8例,无效5例,总有效率62.9%.结论:体外微波射频合并TDP加电针治疗慢性前列腺炎是一种有效方法,能促进慢性前列腺炎的康复.%Purpose: To observe the therapeutic effect of radio-frequency current therapy and TDP plus electroacupuncture in treating chronic prostatitis. Methods: The WE2102-3 type radio-frequency current apparatus made in Dalian and TDP plus electroacupuncture were adopted to treat 35 cases of chronic prostatitis, each treatment lasted 40 min, and 15 times made up a course of treatment, 2-3 courses in all. Results: Twelve cases was cured, 10 cases was remarkably effective, 8 cases was effective, 5 cases got no effect, with the total effective rate being 62.9%. Conclusion: The radio-frequency current therapy and TDP plus electro-acupuncture had a better effect on chronic prostatitis.

  11. Hydrogen peroxide-induced oxidative damage in peripheral blood lymphocytes from rats chronically treated with corticosterone: The protective effect of oxytocin treatment.

    Science.gov (United States)

    Stanić, Dušanka; Plećaš-Solarović, Bosiljka; Petrović, Jelena; Bogavac-Stanojević, Nataša; Sopić, Miron; Kotur-Stevuljević, Jelena; Ignjatović, Svetlana; Pešić, Vesna

    2016-08-25

    Contemporary lifestyle is commonly associated with chronic stress, an environmental factor contributing to development of various psychological and somatic disorders. Increased levels of glucocorticoids, observed in the chronic stress, induce the production of reactive oxygen species leading to genotoxicity. The aim of this study was to investigate whether chronic administration of oxytocin (OXY) 10 IU/400 μL/day, s.c., for 14 days, a hormone presumed to exert antioxidant effect, may prevent DNA damage in the comet assay of peripheral blood lymphocytes of Wistar rats treated chronically with corticosterone (CORT) 100 mg/L ad libitum, per os, for 21 days, as well as, to influence some plasma oxidative stress parameters, i.e. levels of total lipid hydroperoxide (LOOH), and malondialdehyde (MDA), and the activity of antioxidative enzyme superoxide dismutase (SOD). Even though there was no reduction in overall number of damaged cells after oxytocin treatment only, the marked increase in total comet score (TCS) after incubation with H2O2 in CORT group compared to controls, was absent in the CORT + OXY experimental group. Furthermore, significant decrease of highly damaged cells compared to corticosterone group was noted. Chronic oxytocin administration thus protected lymphocytes from high intensity damage that leads to cellular death. In addition, treatment with OXY along with CORT, significantly decreased concentration of LOOH in plasma, and increased SOD compared to CORT treatment only. This finding corresponds well with current reports on beneficial effects of OXY in conditions of HPA axis hyperactivity, and supports the hypothesis of OXY-mediated antioxidant action.

  12. Chronic Cluster Headache with an Atypical Presentation and Treatment Response

    Directory of Open Access Journals (Sweden)

    Telma Santos

    2016-01-01

    Full Text Available The management of cluster headache (CH may be challenging. We report a 50-year-old male with recurrent attacks of dull and severe unilateral periorbital pain, lasting 30–45 minutes, twice a day, exclusively during sleep, and accompanied by ipsilateral rhinorrhea and lacrimation. The pain switched sides within every attack. CH treatment was initiated but the patient maintained recurrence rates compatible with chronic CH, even after increasing verapamil to 460 mg/day. Afterwards we decided to add lithium (800 mg/day. With this treatment the severity and recurrence of CH substantially decreased, despite the patient’s autonomous decision to take lithium only during the acute phase of the cluster. The exclusively alternating location and the excellent response to short cycles of lithium represent two unique features of CH.

  13. Diagnosis and treatment of chronic cerebrovascular disease, use of pentoxifylline

    Directory of Open Access Journals (Sweden)

    V. A. Parfenov

    2016-01-01

    Full Text Available Chronic cerebrovascular disease (CCVD is one of the most common  iagnoses in Russian neurology, by which is meant vascular cognitive impairment (VCI in modern foreign literature. There are data available in the literature on the diagnosis and treatment of CCVD (VCI. Theresults of the author’s studies show that CCVD often masks other diseases (anxiety and depressive disorders, primary headache, peripheral vestibulopathy, and Alzheimer's disease that are unfortunately poorly diagnosed in our country, so patients do not receive effective treatment. To modify risk factors for stroke (smoking and alcohol cessation, sufficient exercise, to normalize blood pressure (the use of antihypertensivemedications, to reduce blood cholesterol levels (statins, to perform antithrombotic therapy (antiplatelet agents and anticoagulants, and to use cognitive enhancers are of key importance when treating patients with CCVD (VCI. There are data on the use of pentoxifylline in patients with CCVD, vascular dementia.

  14. Extracorporeal shock wave treatment for chronic lateral epicondylitis (tennis elbow).

    Science.gov (United States)

    Ho, C

    2007-01-01

    (1) Electrohydraulic, electromagnetic, or piezoelectric devices are used to translate energy into acoustic waves during extracorporeal shock wave treatment (ESWT) for chronic lateral epicondylitis (CLE) of the elbow (elbow tendonitis or tennis elbow). These waves may help to accelerate the healing process via an unknown mechanism. (2) Results from randomized controlled trials have been conflicting. Half of the studies showed statistically significant improvement in pain in the treatment group, and half of the studies had data showing no benefit over placebo for any measured outcomes. (3) Limited evidence shows that ESWT is cheaper than arthroscopic surgery, open surgery, and other conservative therapies, such as steroid infiltrations and physiotherapy, that continue for more than six weeks. (4) The lack of convincing evidence regarding its effectiveness does not support the use of ESWT for CLE.

  15. Treatment of Chronic Myelomonocytic Leukemia with 5-Azacytidine: Case Reports

    Directory of Open Access Journals (Sweden)

    Peter Rohon

    2012-01-01

    Full Text Available Epigenetic therapy with hypomethylating agent (5-azacytidine; AZA is common in the management of specific subtypes of myelodysplastic syndrome (MDS, but there are only few studies in chronic myelomonocytic leukemia (CMML patients. In this paper our experience with 3 CMML patients treated with AZA is described. In one patient transfusion independency was observed after 4 treatment cycles; in one case a partial response was recorded, but a progression to acute myeloid leukemia (AML after 13 AZA cycles has appeared. In one patient, AZA in reduced dosage was administered as a bridging treatment before allogeneic stem cell transplantation (ASCT, but in the control bone marrow aspirate (before ASCT a progression to AML was recorded. Future studies are mandatory for evaluation of new molecular and clinical features which could predict the efficiency of hypomethylating agents in CMML therapy with respect to overall survival, event-free survival, quality-adjusted life year, and pharmacoeconomy.

  16. Ecological System Influences in the Treatment of Pediatric Chronic Pain

    Directory of Open Access Journals (Sweden)

    Deirdre E Logan

    2012-01-01

    Full Text Available Family, school and the peer network each shape the chronic pain experience of the individual child, and each of these contexts also represents a domain of functioning often impaired by chronic pain. The goal of the present article is to summarize what is known about these bidirectional influences between children with pain and the social systems that surround them. Case reports that illustrate these complex, transactional forces and their ultimate impact on the child’s pain-related functioning are included. A case involving siblings participating in an intensive interdisciplinary program for functional restoration and pain rehabilitation highlights how parents change through this treatment approach and how this change is vital to the child’s outcomes. Another case involving a child undergoing intensive interdisciplinary treatment illustrates how school avoidance can be treated in the context of pain rehabilitation, resulting in successful return to the regular school environment. Finally, an acceptance and commitment therapy-focused group intervention for children with sickle cell disease and their parents demonstrates the benefits of peer contact as an element of the therapeutic intervention.

  17. Ecological system influences in the treatment of pediatric chronic pain.

    Science.gov (United States)

    Logan, Deirdre E; Engle, Lisa B; Feinstein, Amanda B; Sieberg, Christine B; Sparling, Penny; Cohen, Lindsey L; Conroy, Caitlin; Driesman, Dana; Masuda, Akihiko

    2012-01-01

    Family, school and the peer network each shape the chronic pain experience of the individual child, and each of these contexts also represents a domain of functioning often impaired by chronic pain. The goal of the present article is to summarize what is known about these bidirectional influences between children with pain and the social systems that surround them. Case reports that illustrate these complex, transactional forces and their ultimate impact on the child's pain-related functioning are included. A case involving siblings participating in an intensive interdisciplinary program for functional restoration and pain rehabilitation highlights how parents change through this treatment approach and how this change is vital to the child's outcomes. Another case involving a child undergoing intensive interdisciplinary treatment illustrates how school avoidance can be treated in the context of pain rehabilitation, resulting in successful return to the regular school environment. Finally, an acceptance and commitment therapy-focused group intervention for children with sickle cell disease and their parents demonstrates the benefits of peer contact as an element of the therapeutic intervention.

  18. Rituximab for the treatment of patients with chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    M Gentile

    2010-03-01

    Full Text Available M Gentile, E Vigna, C Mazzone, E Lucia, AG Recchia, L Morabito2, MG Bisconte, C Gentile, F Morabito1UOC di Ematologia, Azienda Ospedaliera di Cosenza, Italy; 2Servicio de Hematología y Hemoterapia, Hospital Universitario de Canarias, La Laguna, Tenerife, SpainAbstract: Chronic lymphocytic leukemia (CLL is a lymphoproliferative disorder that originates from antigen-experienced B lymphocytes that do not die and hence accumulate due to external survival signals or undergo apoptosis and are replenished by proliferating precursors. These neoplastic lymphocytes exhibit a characteristic immunophenotype of CD5+/CD19+/CD20+/HLA-DR+/CD23+/sIgdim. Thus, the CD20 antigen has been an appealing target for therapy. The introduction of the monoclonal antibody rituximab (anti-CD20 enabled an outstanding advance in CLL treatment. The introduction of this monoclonal antibody into chemotherapy regimens has dramatically improved complete response rates and progression-free survival in patients with both untreated and relapsed CLL. Although only preliminary data from phase III confirmatory trials have been reported, the FCR regimen, which combines fludarabine and cyclophosphamide with rituximab, is currently the most effective treatment regimen for CLL patients, and has also been demonstrated to significantly improve overall survival . The success of rituximab and the identification of other CLL lymphocyte surface antigens have spurred the development of a multitude of monoclonal antibodies targeting distinct proteins and epitopes in an attempt to target CLL cells more effectively.Keywords: rituximab, chronic lymphocytic leukemia, chemotherapy

  19. Extrahepatic complications of chronic cholestasis: current diagnosis and treatment.

    Science.gov (United States)

    Prelipcean, Cristina Cijevschi; Mihai, Cătălina; Gogălniceanu, P; Mihai, B

    2012-01-01

    Pruritus, fatigue and osteoporosis are the main symptoms of the extra hepatic manifestations of chronic cholestasis that affect patients' quality of life. Pruritus affects more often female patients, varies as intensity during a day and for longer period of time, typically can be localized on the palms of hands and soles of feet or can be generalized. Pruritus can be treated with anions resines exchange--cholestiramine, the pregnanne X receptor agonist Rifampicine, Naltrexone. Liver transplantation can be considered if severe pruritus remains refractory to all medical treatments. Fatigue is the most disabling complain in chronic colestasis. No specific therapies are available for fatigue and liver transplantation doesn't improve it. Osteoporosis and the risk of fractures are more severe with the duration and severity of hepatic disease. For treatment are recommended regular physical exercise, vitamin D and Ca supplimentation and bisphosphonates (Alendronate 70 mg/week) in severe cases. Only patients with atherosclerotic risk and hyperlipemia can be treated with statines. Fat soluble vitamin supplementation can be administrated only in symptomatic and proved vitamin deficiency.

  20. The negative bone effects of the disease and of chronic corticosteroid treatment in premenopausal women affected by rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    A. Fassio

    2016-09-01

    Full Text Available Osteoporosis is a well-known extra-articular complication in rheumatoid arthritis (RA. The chronic corticosteroid treatment, the functional impairment associated with RA and the disease itself appear to be the most relevant determinants. Most of the previous studies involved postmenopausal women, in whom the estrogenic deficiency might amplify the negative effect towards bone of both RA and corticosteroid therapy. We decided to evaluate bone health in a cohort of premenopausal RA patients. The study population includes 47 premenopausal women attending our outpatient clinic for RA and twice as many healthy age-matched control women selected from the hospital personnel. The bone density at the spine and femoral neck were significantly lower in patients with RA as compared with controls. When spine bone mineral density (BMD values were adjusted for the cumulative glucocorticoid (GC dose alone and for the cumulative GC dose plus body mass index (BMI the mean differences between two groups decreased but they remained statistically significant. We found no difference when the spine BMD was adjusted for cumulative GC dose, BMI and health assessment questionnaire. The difference in femoral neck BMD remained statistically significant also after all the same adjustments. In conclusion, our study shows that a BMD deficiency is frequent also in premenopausal women affected by RA, especially at femoral site and that the main determinants of this bone loss are not only the disease-related weight loss, corticosteroid therapy and functional impairment, but also the systemic effects of the disease itself.

  1. Tolloid-like 1 is negatively regulated by stress and glucocorticoids.

    Science.gov (United States)

    Tamura, Goichiro; Olson, Dawne; Miron, Joel; Clark, Timothy G

    2005-12-14

    Glucocorticoids affect a variety of tissues to enable the organism to adapt to the stress. Hippocampal neurons contain glucocorticoid receptors and respond to elevated glucocorticoid levels by down-regulating the HPA axis. Chronically, however, stress is deleterious to hippocampal neurons. Chronically elevated levels of glucocorticoids result in a decrease in the number of dendritic spines, reduced axonal growth and synaptogenesis, and decreased neurogenesis in the hippocampus. Tolloid-like 1 (Tll-1) is a metalloprotease that potentiates the activity of the bone morphogenetic proteins (BMPs). Neurogenesis in the hippocampus of both developing and adult mammals requires BMPs. In this study, we demonstrate that Tll-1 expression is increased in mice that have increased neurogenesis. The Tll-1 promoter contains glucocorticoid response elements which are capable of binding to purified glucocorticoid receptor. Glucocorticoids decrease Tll-1 expression in vitro. Finally, prenatal stress leads to a decrease in Tll-1 mRNA expression in the hippocampus of adult female mice that is not observed in adult male mice indicating that Tll-1 expression is differentially regulated in males and females. The results of this study indicate that Tll-1 is responsive to glucocorticoids and this mechanism might influence neurogenesis in the hippocampus.

  2. Surgical strategies in the treatment of chronic pancreatitis

    Science.gov (United States)

    Zhao, Xin; Cui, Naiqiang; Wang, Ximo; Cui, Yunfeng

    2017-01-01

    Abstract Background: Chronic pancreatitis (CP) is a common and frequently occurring disease. Pancreaticoduodenectomy (PD), pylorus-preserving pancreaticoduodenectomy (PPPD), and duodenum-preserving pancreatic head resection (DPPHR) are important treatment options for patients with chronic pancreatitis. The Beger and Frey procedures are 2 main duodenum-preserving techniques in duodenum-preserving pancreatic head resection (DPPHR) strategies. We conducted this systematic review and meta-analysis to compare the clinical efficacy of DPPHR versus PD, the Beger procedure versus PD, the Frey procedure versus PD, and the Beger procedure versus the Frey procedure in the treatment of pancreatitis. The optimal surgical option for chronic pancreatitis is still under debate. The aim of this systematic review and meta-analysis was to evaluate the clinical efficacy of different surgical strategies for chronic pancreatitis. Methods: Five databases (PubMed, Medline, SinoMed, Embase, and Cochrane Library) were searched with the limitations of human subjects and randomized controlled trials (RCTs) text. Data were extracted by 2 of the coauthors independently and analyzed using the RevMan statistical software, version 5.3. Weighted mean differences (WMDs), risk ratios (RRs), and 95% confidence intervals (CIs) were calculated. Cochrane Collaboration's Risk of Bias Tool was used to assess the risk of bias. Results: Seven studies involving a total of 385 patients who underwent the surgical treatments were assessed. The methodological quality of the trials ranged from low to moderate and included PD (n = 134) and DPPHR (n = 251 [Beger procedure = 100; Frey procedure = 109; Beger or Frey procedure = 42]). There were no significant differences between DPPHR and PD in post-operation mortality (RR = 2.89, 95% CI = 0.31–26.87, P = 0.36), pain relief (RR = 1.09, 95% CI = 0.94–1.25, P = 0.26), exocrine insufficiency (follow-up time > 60 months

  3. Treatment of chronic immune-mediated neuropathies: chronic inflammatory demyelinating polyradiculoneuropathy, multifocal motor neuropathy, and the Lewis-Sumner syndrome.

    Science.gov (United States)

    Sederholm, Benson H

    2010-09-01

    Current treatment approaches for the management of chronic immune-mediated peripheral neuropathies are reviewed, including chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN), and the Lewis-Sumner syndrome (LSS). A summary of existing evidence for commonly used treatment modalities, such as corticosteroids, intravenous immune globulin (IVIG), and plasma exchange is provided. Evidence for the use of additional immunosuppressant and immunomodulatory agents is also reviewed.

  4. Current progress in the treatment of chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Alexandra Alexopoulou; George V Papatheodoridis

    2012-01-01

    Over the last decade,the standard of care for the treatment of chronic hepatitis C has been the combination of pegylated-interferon-alfa (PEG-IFN) and ribavirin (RBV)which results in sustained virological response (SVR)rates of 75%-85% in patients with genotypes 2 or 3 but only of 40%-50% in patients with genotype 1.Currently,there are rapid and continuous developments of numerous new agents against hepatitis C virus (HCV),which are the focus of this review.Boceprevir and telaprevir,two first-generation NS3/4A HCV protease inhibitors,have been recently licensed in several countries around the world to be used in combination with PEGIFN and RBV for the treatment of genotype 1 patients.Boceprevir or telaprevir based triple regimens,compared with the PEG-IFN/RBV combination,improve the SVR rates by 25%-31% in treatment-naive genotype 1 patients,by 40%-64% in prior relapsers,by 33%-45% in prior partial responders and by 24%-28% in prior null responders.At the same time,the application of response-guided treatment algorithms according to the on-treatment virological response results in shortening of the total therapy duration to only 24 wk in 45%-55% of treatment-naive patients.There are,however,several challenges with the use of the new triple combinations in genotype 1 patients,such as the need for immediate results of HCV RNA testing using sensitive quantitative assays,new and more frequent adverse events (anemia and dysgeusia for boceprevir; pruritus,rash and anemia for telaprevir),new drug interactions and increasing difficulties in compliance.Moreover,the SVR rates are still poor in very difficult to treat subgroups of genotype 1 patients,such as null responders with cirrhosis,while there is no benefit for patients who cannot tolerate PEGIFN/RBV or who are infected with non-1 HCV genotype.Many newer anti-HCV agents of different classes and numerous combinations are currently under evaluation with encouraging results.Preliminary data

  5. [Treatment options for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)].

    Science.gov (United States)

    Kuntzer, T

    2006-04-01

    Limits of treatment in chronic inflammatory demyelinating poly(radiculo)neuropathies (CIDP) patients are better known thanks to recent Cochrane reviews. (1) Randomized controlled trials have only focused on short-term effects, but most patients need long-term therapy, (2) There are three proven effective treatments available (prednisone; intravenous immunoglobulin or IVIg and plasma exchange or PE) which are useful in more than 60 p. 100 of patients, (3) New open studies indicated possible efficacy for mycophenolate, rituximab, etanercept, ciclosporine and interferons, and (4) Whether CIDP variants need specific treatment is still unknown. Many CIDP patients need treatment for years. The fear of side effects during long-term steroid treatment, the high costs of IVIg, the necessity for specialized equipment and the invasive nature of PE, are important factors determining the choice for one of these treatments. In most up-to-date treatment options, patients are initially treated with IVIg at a dosage of 2 g/kg administered for 25 days, clinical improvement can be judged within 10 days. The percentage of patients responding seems to be approximately 70 percent, with a very high chance (approximately 85 percent) that repeated administration of IVIg will be necessary, explaining why most neurologists add an immunosuppressive drug at this stage, but there is no consensus concerning the best drug to be used. Combinations of drugs are most likely to be useful in the next future, using IVIg, prednisone, and a immunosuppressor agent, such as mycophenolate, rituximab, etanercept, or ciclosporine. General measures to rehabilitate patients and to manage symptoms like fatigue and other residual findings are important.

  6. Profile of omalizumab in the treatment of chronic spontaneous urticaria

    Directory of Open Access Journals (Sweden)

    Labrador-Horrillo M

    2015-08-01

    Full Text Available Moises Labrador-Horrillo,1 Marta Ferrer2 1Allergy Section, Internal Medicine Department, Vall d’Hebron Hospital, Universitat Autònoma de Barcelona, Barcelona, 2Department of Allergy and Clinical Immunology, Clínica Universidad de Navarra, IDISNA, Instituto de Investigación de Navarra, Pamplona, Spain Abstract: Chronic spontaneous urticaria (CSU is a disease with significant morbidity and relative prevalence that has important effects on the quality of life (QoL of those who suffer from it. Omalizumab is a recombinant humanized anti-immunoglobulin E (IgE antibody that binds to the Cε3 domain of the IgE heavy chain and prevents it from binding to its high-affinity receptor FcεRI. It has been largely studied in the field of asthma and is currently approved for the treatment of both adult and pediatric (children; >6-year-old patients. In addition, in recent, well-controlled clinical trials in patients with CSU resistant to antihistamines, add-on therapy with subcutaneous omalizumab significantly reduced the severity of itching, and the number and size of hives, and increased patients’ health-related QoL and the proportion of days free from angioedema compared with placebo, with an excellent tolerance. Thus, omalizumab is an effective and well-tolerated add-on therapy for patients with CSU who are symptomatic despite background therapy with H1 antihistamines. In this review, we cover the following points: epidemiology, pathogenesis, assessment of activity, impact on QoL, and treatment of CSU, and finally, we focus on omalizumab in the treatment of CSU including the pharmacokinetic properties and mechanism of action, and use in pregnant women, nursing infants, and children. Keywords: omalizumab, chronic spontaneous urticaria, antihistamines, subcutaneous administration, add-on therapy

  7. Chronic lymphocytic leukemia: treatment options for patients with refractory disease.

    Science.gov (United States)

    Motta, Marina; Wierda, William G; Ferrajoli, Alessandra

    2009-09-01

    Patients with purine analogue-refractory chronic lymphocytic leukemia (CLL) have short survival and limited treatment options. Defining the best salvage strategies for this population is challenging, because limited data are available from clinical trials, and because studies have enrolled mixed populations (patients with recurrent and refractory disease or patients with refractory disease and Richter transformation). Moreover, patients with refractory CLL have a high incidence of unfavorable molecular and clinical features, such as high-risk genomic profiles, unmutated immunoglobulin heavy-chain genes, expression of zeta-chain-associated protein kinase 70, and bulky lymphadenopathies. These patients are also severely immunosuppressed because of the underlying disease and the treatments received, and experience a high rate of infectious complications that pose an additional difficulty in selecting treatment. Despite these challenges, in parallel with better characterizations of the biologic features of refractory CLL, the number of available treatment modalities for this population has increased. Several chemoimmunotherapy combinations have been developed, and novel agents with a different mechanism of action are being investigated in clinical trials. Furthermore, allogeneic stem cell transplantation with nonmyeloablative conditioning regimens is a therapeutic strategy that is increasingly offered to patients with refractory CLL.

  8. Targeted treatment for chronic lymphocytic leukemia: clinical potential of obinutuzumab.

    Science.gov (United States)

    Smolej, Lukáš

    2015-01-01

    Introduction of targeted agents revolutionized the treatment of chronic lymphocytic leukemia (CLL) in the past decade. Addition of chimeric monoclonal anti-CD20 antibody rituximab to chemotherapy significantly improved efficacy including overall survival (OS) in untreated fit patients; humanized anti-CD52 antibody alemtuzumab and fully human anti-CD20 antibody ofatumumab lead to improvement in refractory disease. Novel small molecule inhibitors such as ibrutinib and idelalisib demonstrated excellent activity and were very recently licensed in relapsed/refractory CLL. Obinutuzumab (GA101) is the newest monoclonal antibody approved for the treatment of CLL. This novel, glycoengineered, type II humanized anti-CD20 antibody is characterized by enhanced antibody-dependent cellular cytotoxicity and direct induction of cell death compared to type I antibodies. Combination of obinutuzumab and chlorambucil yielded significantly better OS in comparison to chlorambucil monotherapy in untreated comorbid patients. These results led to approval of obinuzutumab for the treatment of CLL. Numerous clinical trials combining obinutuzumab with other cytotoxic drugs and novel small molecules are currently under way. This review focuses on the role of obinutuzumab in the treatment of CLL.

  9. Interferon-induced thyroiditis during treatment of chronic hepatitis C.

    Science.gov (United States)

    Kozielewicz, Dorota; Halota, Waldemar

    2012-01-01

    Thyroid function disorders affect between 5% and 15% of patients treated with IFNα and RBV for chronic hepatitis C. Women and patients with thyroid peroxidase antibodies (TPOAb) found before the treatment are at risk of developing the disorders (46.1% vs. 5.4%). The spectrum of IFNα-induced thyroiditis (IIT) includes two groups. Disorders with an autoimmune background are: presence of thyroid autoantibodies without clinical disease, Hashimoto's disease and Graves' disease. The second group comprises diseases caused by the direct toxic effect of IFNα on the thyroid gland, i.e. destructive thyroiditis and non-autoimmune hypothyroidism. Thyroid diseases are not an absolute contraindication for IFNα and RBV therapy. In patients diagnosed with thyroid dysfunction, before the antiviral therapy it is necessary to achieve euthyreosis. Thyroid function disorders may occur at any moment of the therapy. The earliest have been observed in the 4th week of treatment, and the latest 12 months after its termination. During the therapy, in order to diagnose IIT early, it is recommended to determine TSH level every 2-3 months depending on the presence of TPOAb before the treatment. The diagnosis and treatment of thyroid function disorders should be conducted in co-operation with an endocrinologist.

  10. Clinical Observation of the Clinical Effects of Inhaling Glucocorticoid in Treatment of Stable COPD%吸入糖皮质激素在稳定期COPD中的临床疗效观察

    Institute of Scientific and Technical Information of China (English)

    孙茹

    2013-01-01

    Objective:To observed the clinical effects of inhaling glucocorticoid in treatment of stable COPD. Method:To analyze the clinical effects of the on the basis of conventional treatment of inhaling budesonide(Observation group)or the basis of conventional treatment(Control group)for treatment of 80 patients with stable COPD in our hospital from April 2010 to June 2012. Result:After treatment,the lung function,dyspnea score,quality of life score and 6-MWD in the observation group were significantly better than those in the control group. Conclusion:The inhaling glucocorticoid in treatment of stable COPD is efficacy. It is worthy to be popularized.%  目的:观察吸入糖皮质激素治疗稳定期COPD中的临床疗效。方法:选择本院2010年4月-2012年6月收治的80例稳定期COPD患者,随机分为观察组和对照组,观察组40例,在常规治疗的基础上给予吸入布地奈德,对照组40例行常规治疗,比较分析两组疗效。结果:治疗后,观察组患者肺功能、呼吸困难评分、生活质量评分和6-MWD情况都显著地优于对照组患者。结论:吸入糖皮质激素治疗稳定期COPD疗效可靠,值得临床推广。

  11. Glucocorticoid influence on prognosis of idiopathic sudden sensorineural hearing loss

    Directory of Open Access Journals (Sweden)

    Eduardo Amaro Bogaz

    2014-06-01

    Full Text Available INTRODUCTION: Idiopathic Sudden Sensorineural Hearing Loss (ISSHL is defined when a loss of at least 30 dB occurs in over 3 continuous frequencies, in up to 72 hours, of which etiology is not established, despite adequate investigation. Different types of treatment regimens have been proposed, but only glucocorticoids have shown some evidence of benefit in the literature. OBJECTIVE: To analyze whether the type of treatment or time of treatment with glucocorticoids have any influence on hearing recovery in ISSHL. METHODS: Observational retrospective cohort study. One hundred twenty-seven patients with ISSHL, treated at outpatient clinics between the years 2000 and 2010, were studied. We evaluated the prognostic correlation of the type of treatment and time to treatment with glucocorticoids and ISSHL. RESULTS: The absolute hearing gain and the relative hearing gain was as follows: 23.6 dB and 37.2%. Complete recovery was observed in 15.7% of patients, significant recovery in 27.6% and recovery in 57.5%. CONCLUSION: In this study, there was no difference between the use and nonuse of glucocorticoids in hearing improvement. However, when started within seven days after onset, the use of glucocorticoids was a factor of better prognosis.

  12. Glucocorticoid-induced osteoporosis: 2013 update.

    Science.gov (United States)

    Mazzantini, M; Di Munno, O

    2014-01-01

    Glucocorticoids are the most common cause of secondary osteoporosis leading to the so-called glucocorticoid-induced osteoporosis (GIO). A treatment with 10 mg/d of prednisone or equivalent for more than 3 months leads to a 7-fold increase in hip fractures and a 17-fold increase in vertebral fractures. The difference between bone quantity and quality in GIO makes bone mineral density measurements inadequate to detect patients at risk of fracture. The adverse effects of glucocorticoids on the skeleton derive from a direct impact on bone cells with a severe impairment of mechanical competence. Crucial to prevention of GIO is early timing of intervention. The World Health Organization has adopted a fracture prevention algorithm (FRAX) intended to estimate fracture risk in GIO. The American College of Rhematology modified its prevention and treatment guidelines taking into account the individual risk of fracture calculated in GIO on the basis of the FRAX algorithm. Recently, also a joint Guideline Working Group of the International Osteoporosis Foundation (IOF) and the European Calcified Tissue Society (ECTS) published a framework for the development of national guidelines for the management of GIO. Bisphosphonates are the first-line drugs to treat GIO; teriparatide counteracts several fundamental pathophysiologic aspects of GIO; denosumab is useful in patients with renal failure and in potentially pregnant young women. Vertebroplasty and kyphoplasty may be less beneficial in GIO than in primary involutional osteoporosis.

  13. [NON-ONCOLOGIC CHRONIC PAIN TREATMENT WITH OPIATES].

    Science.gov (United States)

    Molas Ferrer, Glòria; Castellà Kastner, Montse; Lombraña Mencia, María

    2014-09-01

    Non-oncologic chronic pain is a very common symptom. It causes great impact on daily activities of people who suffer it. The incidence of this type of pain is rising due to the increase in life expectancy. The most affected population is geriatric population. Back pain, osteoarthritic pain and neuropathic pain are the most prevalent types of non-oncologic chronic pain. Opiates, among other analgesic drugs, are used to alleviate this type of pain. Opiates are divided into minor opiates (tramadol, codeine) and major opiates (morphine, fentanyl, oxycodone, methadone). Opiates are very effective to treat pain, but they also have important adverse effects that we must know and try to prevent. One of these adverse effects is the opiates ability to cause dependence, tolerance, addiction and other aberrant behaviors. Terminology of these concepts is sometimes confusing. It is necessary to be careful and control the patient periodically in order to avoid these aberrant behaviors. However, if health professionals take precautions to prevent these behaviors, the risk is considerably reduced. Controlling patients on opiate treatment is essential to achieve a correct use if these drugs.

  14. Treatment of chronic venous leg ulcers by platelet gel.

    Science.gov (United States)

    Ficarelli, Elena; Bernuzzi, Gino; Tognetti, Elena; Bussolati, Ovidio; Zucchi, Alfredo; Adorni, Daniela; De Panfilis, Giuseppe

    2008-07-01

    Chronic venous leg ulcers (CVLU) are chronic wounds, associated with long-standing venous hypertension, which have a poor prognosis for healing. In the process of wound healing the first step is represented by platelet aggregation and subsequent release of growth factors and other mediators, which play a key role in the repair response. Platelet gel (PG), a hemocomponent obtained by mixing platelets, thrombin, and calcium, is able, when applied topically, to release platelet mediators that likely favor CVLU healing. However, unstandardized protocols have been described in studies utilizing PG for the regeneration of a number of tissues, including CVLU; the relative clinical outcomes were hence highly variable. In our experience the topical use of PG, together with the strict adherence to the principles of good wound care, quickly promoted increased granulation tissue, followed by a complete CVLU epithelization. Although further studies and trials are needed to establish the major outcome affecting rules for optimal indications, preparation, and use of PG for CVLU treatment, PG can be undoubtedly considered a useful tool, able to improve the management of CVLU.

  15. Surgical and Endoscopic Treatment of Pain in Chronic Pancreatitis : A Multidisciplinary Update

    NARCIS (Netherlands)

    Issa, Y.; van Santvoort, H. C.; van Goor, H.; Cahen, D. L.; Bruno, M. J.; Boermeester, M. A.

    2013-01-01

    Chronic pancreatitis is an inflammatory disease of the pancreas with abdominal pain as the most prominent symptom. Adequate treatment of patients with chronic pancreatitis remains a major challenge, mainly because of the lack of evidence-based treatment protocols. The primary goal of treatment is to

  16. Treatment of younger patients with chronic lymphocytic leukemia.

    Science.gov (United States)

    Ferrajoli, Alessandra

    2010-01-01

    Younger patients (defined as patients younger than 50-55 years of age) represent a small group of newly diagnosed patients with chronic lymphocytic leukemia, accounting only for 10% to 20% of newly diagnosed cases. However, once these patients become symptomatic and require treatment, their life expectancy is significantly reduced. Therapeutic approaches for younger patients should be directed at improving survival by achieving a complete remission and, where possible, eradicating minimal residual disease. Chemoimmunotherapy combinations carry the highest response rates and are commonly offered to younger patients. Additional strategies that should be considered for younger patients include early referral for stem-cell transplantation and clinical trials of consolidation therapy to eliminate minimal residual disease.

  17. Chronic perineal pain: current pathophysiological aspects, diagnostic approaches and treatment.

    Science.gov (United States)

    Andromanakos, Nikolaos P; Kouraklis, Grigorios; Alkiviadis, Kostakis

    2011-01-01

    Chronic perineal pain is the anorectal and perineal pain without underlying organic disease, anorectal or endopelvic, which has been excluded by careful physical examination, radiological and endoscopic investigations. A variety of neuromuscular disorders of the pelvic floor lead to the different pathological conditions such as anorectal incontinence, urinary incontinence and constipation of obstructed defecation, sexual dysfunction and pain syndromes. The most common functional disorders of the pelvic floor muscles, accompanied by perineal pain are levator ani syndrome, proctalgia fugax, myofascial syndrome and coccygodynia. In the diagnosis of these syndromes, contributing to a thorough history, physical examination, selected specialized investigations and the exclusion of organic disease with proctalgia is carried out. Accurate diagnosis of the syndromes helps in choosing an appropriate treatment and in avoiding unnecessary and ineffective surgical procedures, which often are performed in an attempt to alleviate the patient's symptoms.

  18. Chronic radiation proctopathy:A practical review of endoscopic treatment

    Institute of Scientific and Technical Information of China (English)

    Luciano Lenz; Rachel Rohr; Frank Nakao; Ermelindo Libera; Angelo Ferrari

    2016-01-01

    Chronic radiation proctopathy(CRP) is a troublesome complication of pelvic radiotherapy. The most common presentation is rectal bleeding. CRP symptoms interfere with daily activities and decrease quality of life. Rectal bleeding management in patients with CRP represents a conundrum for practitioners. Medical therapy is ineffective in general and surgical approach has a high morbidmortality. Endoscopy has a role in the diagnosis,staging and treatment of this disease. Currently available endoscopic modalities are formalin,potassium titanyl phosphate laser,neodymium:yttrium-aluminum-garnet laser,argon laser,bipolar electrocoagulation(BiCAP),heater probe,band ligation,cryotherapy,radiofrequency ablation and argon plasma coagulation(APC). Among these options,APC is the most promising.

  19. Evaluation of glycopyrrolate in the treatment of chronic drooling

    Directory of Open Access Journals (Sweden)

    Reddihough DS

    2011-05-01

    Full Text Available DS Reddihough1,2,3, SM Reid2,3, C Plover11Royal Children's Hospital, Melbourne, VIC, Australia; 2Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, VIC, Australia; 3University of Melbourne, Melbourne, VIC, AustraliaAbstract: Drooling is a major problem for children and adults with cerebral palsy and other neurological conditions. Medication is a major treatment option for these individuals. The focus of this review is to review glycopyrrolate, one of the frequently used medications for poor saliva control. Glycopyrrolate is a quaternary ammonium compound structurally related to atropine. The pharmacology, mode of action and pharmocokinetics are discussed, efficacy studies are reviewed, and safety and tolerability are described. Mention is made of the limited amount of information that is available on patient satisfaction and quality of life. Glycopyrrolate has an important place in the treatment of chronic drooling and possible uses for this medication are described. Further research would be helpful comparing glycopyrrolate with other anticholinergic medication and alternative treatments for drooling including botulinum toxins and surgical procedures.Keywords: dribbling, poor saliva control, cerebral palsy, Parkinson Disease

  20. Profile of omalizumab in the treatment of chronic spontaneous urticaria.

    Science.gov (United States)

    Labrador-Horrillo, Moises; Ferrer, Marta

    2015-01-01

    Chronic spontaneous urticaria (CSU) is a disease with significant morbidity and relative prevalence that has important effects on the quality of life (QoL) of those who suffer from it. Omalizumab is a recombinant humanized anti-immunoglobulin E (IgE) antibody that binds to the Cε3 domain of the IgE heavy chain and prevents it from binding to its high-affinity receptor FcεRI. It has been largely studied in the field of asthma and is currently approved for the treatment of both adult and pediatric (children; >6-year-old) patients. In addition, in recent, well-controlled clinical trials in patients with CSU resistant to antihistamines, add-on therapy with subcutaneous omalizumab significantly reduced the severity of itching, and the number and size of hives, and increased patients' health-related QoL and the proportion of days free from angioedema compared with placebo, with an excellent tolerance. Thus, omalizumab is an effective and well-tolerated add-on therapy for patients with CSU who are symptomatic despite background therapy with H1 antihistamines. In this review, we cover the following points: epidemiology, pathogenesis, assessment of activity, impact on QoL, and treatment of CSU, and finally, we focus on omalizumab in the treatment of CSU including the pharmacokinetic properties and mechanism of action, and use in pregnant women, nursing infants, and children.

  1. 慢性咽炎及慢性扁桃体炎的治疗%Treatment of Chronic Pharyngitis and Chronic Tonsillitis

    Institute of Scientific and Technical Information of China (English)

    李健; 吴合

    2003-01-01

    Objective To illustrate the proper treatment of chronic pharyngitis and chronic tonsilli-tis. Methods To recover the immune functions of the patients. Result Chronic pharyngitis and chronictonsillitis could be radically cured by restoring the immune functions of the patients. Conlcusion Thekey etiology of the chronic pharyngitis and chronic tonsillitis is the abnormal immune functions of the patients and the key treatment is to restore the immune functions of the patients.

  2. Outcome of long-term heroin-assisted treatment offered to chronic, treatment-resistant heroin addicts in the Netherlands

    NARCIS (Netherlands)

    P. Blanken; V.M. Hendriks; J.M. van Ree; W. van den Brink

    2010-01-01

    Aims To describe 4-year treatment retention and treatment response among chronic, treatment-resistant heroin-dependent patients offered long-term heroin-assisted treatment (HAT) in the Netherlands. Design Observational cohort study. Setting and intervention Out-patient treatment in specialized heroi

  3. Hippocampal neuronal nitric oxide synthase mediates the stress-related depressive behaviors of glucocorticoids by downregulating glucocorticoid receptor.

    Science.gov (United States)

    Zhou, Qi-Gang; Zhu, Li-Juan; Chen, Chen; Wu, Hai-Yin; Luo, Chun-Xia; Chang, Lei; Zhu, Dong-Ya

    2011-05-25

    The molecular mechanisms underlying the behavioral effects of glucocorticoids are poorly understood. We report here that hippocampal neuronal nitric oxide synthase (nNOS) is a crucial mediator. Chronic mild stress and glucocorticoids exposures caused hippocampal nNOS overexpression via activating mineralocorticoid receptor. In turn, hippocampal nNOS-derived nitric oxide (NO) significantly downregulated local glucocorticoid receptor expression through both soluble guanylate cyclase (sGC)/cGMP and peroxynitrite (ONOO(-))/extracellular signal-regulated kinase signal pathways, and therefore elevated hypothalamic corticotrophin-releasing factor, a peptide that governs the hypothalamic-pituitary-adrenal axis. More importantly, nNOS deletion or intrahippocampal nNOS inhibition and NO-cGMP signaling blockade (using NO scavenger or sGC inhibitor) prevented the corticosterone-induced behavioral modifications, suggesting that hippocampal nNOS is necessary for the role of glucocorticoids in mediating depressive behaviors. In addition, directly delivering ONOO(-) donor into hippocampus caused depressive-like behaviors. Our findings reveal a role of hippocampal nNOS in regulating the behavioral effects of glucocorticoids.

  4. SURGICAL TREATMENT OF PAIN IN CHRONIC PANCREATITIS:STUDIES OF 111 PATIENTS

    Institute of Scientific and Technical Information of China (English)

    D. Guinier; P. Mathieu; B. Heyd; G. Mantion

    2004-01-01

    Objective Evaluation of the efficacy of pancreatic resections for the treatment of chronic pains during chronic pancreatitis. Methods Retrospective study of inpatients for chronic pancreatitis between 1982 to 2000. Purpose of admission, morphological changes, treatments and results were evaluated. Results 142 patients were admitted for chronic pancreatitis. 111 patients suffered from chronic pains, due to morphological changes such as pseudocysts, inflammatory masses in the head, dilated pancreatic ducts, biliary or duodenal compressions. Denervations were never efficient, pancreatic resections achieved relief of pain in up to 75% of cases and drainages were efficient in 52% of cases. Conclusions Pancreatic resections during chronic pancreatitis seem to be the most efficient treatment of chronic pains. New techniques such as duodenum-preserving head resection or total pancreatectomy with islet autotransplantation should improve these results.

  5. Alitretinoin for the treatment of severe chronic hand eczema.

    Science.gov (United States)

    Paulden, M; Rodgers, M; Griffin, S; Slack, R; Duffy, S; Ingram, J R; Woolacott, N; Sculpher, M

    2010-05-01

    This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of alitretinoin for the treatment of adults with severe chronic hand eczema refractory to topical steroid treatment in accordance with the licensed indication, based upon the evidence submission from Basilea Pharmaceuticals Ltd to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The clinical evidence came from a single placebo-controlled randomised controlled trial of daily treatment with alitretinoin for 12-24 weeks, with follow-up for a further 24 weeks, in patients with severe chronic hand eczema (CHE) unresponsive to topical steroids. A statistically significantly greater proportion of patients using alitretinoin achieved the primary end point of clear or almost clear hands by week 24 than did those with placebo. Dose-dependent headache was the most commonly reported adverse event in patients treated with alitretinoin. Serious adverse events were rare, but alitretinoin was associated with increases in both total cholesterol and triglycerides, which has implications for risks of future cardiovascular events. The manufacturer submitted a de novo decision analytic model to estimate, over a time horizon of 3 years, the cost-effectiveness of alitretinoin versus the other relevant comparators identified by NICE. In response to the points of clarification put to it by the ERG regarding the initial submission, the manufacturer provided additional evidence and a revised decision analytic model with a 'placebo' arm. In the manufacturer's original submission to NICE, the base-case incremental cost-effectiveness ratios (ICERs) reported for alitretinoin were 8614 pounds per quality-adjusted life-year (QALY) versus ciclosporin, -469 pounds per QALY versus psoralen + UVA (with alitretinoin dominant) and 10,612 pounds per QALY versus azathioprine. These ICERs decreased as the time

  6. Obinutuzumab for the treatment of chronic lymphocytic leukemia.

    Science.gov (United States)

    Rogers, K A; Jones, J A

    2014-06-01

    Obinutuzumab is a novel therapeutic anti-CD20 monoclonal antibody recently approved by the United States Food and Drug Administration (FDA) for use in combination with chlorambucil as first-line treatment of chronic lymphocytic leukemia (CLL). It is distinguished from other anti-B-lymphocyte antigen CD20 (anti-CD20) therapeutic antibodies in current clinical use by its type II properties and glycoengineered Fc region. In vitro these unique properties translate into higher rates of antibody-dependent cytotoxicity and direct cell death compared to rituximab, and obinutuzumab demonstrates improved efficacy in human lymphoma xenograft models and whole blood lymphocyte depletion assays. FDA approval was based upon results from a randomized phase III trial comparing treatment with single-agent chlorambucil to the combination of chlorambucil and either rituximab or obinutuzu-mab. The obinutuzumab arm resulted in higher rates of complete remission and significant improvements in progression-free survival versus either comparator regimen. The majority of patients in the obinutuzumab and chlorambucil arm finished all six planned treatment cycles, and therapy was well tolerated. Toxicities of obinutuzumab are similar to those of other anti-CD20 antibodies, although infusion-related reactions and neutropenia appear to be more common. This trial establishes chemoimmunotherapy with obinutuzumab and chlorambucil as an attractive treatment option for CLL patients, particularly those with comorbid medical illnesses or advanced age. Obinutuzumab remains under study in combination with both chemotherapy and novel agents for CLL and non-Hodgkin's lymphoma, where it is expected to find additional clinical applications.

  7. Thalidomide for the treatment of chronic refractory pruritus.

    Science.gov (United States)

    Sharma, Divya; Kwatra, Shawn G

    2016-02-01

    Pruritus is a common and often times difficult to treat symptom in many dermatologic and systemic diseases. For pruritus with an inflammatory or autoimmune origin, therapies such as topical corticosteroids and antihistamines are often initiated. However, in the case that these and additional systemic therapies are ineffective, thalidomide, an immunomodulator and neuromodulator, may be a useful alternative treatment. Considerable relief of chronic pruritus has been demonstrated with thalidomide in case reports, case series, and controlled trials. Double-blind controlled studies demonstrated thalidomide's efficacy as an antipruritic agent in patients with uremic pruritus, primary biliary cirrhosis, and prurigo nodularis. In case reports, case series, and open-label trials, thalidomide significantly reduced pruritus associated with conditions such as actinic prurigo and paraneoplastic pruritus. Because of variations in study design and evaluation of antipruritic effect, it is difficult to fully understand thalidomide's role based on the evidence described to date in the medical literature. In this review, we provide an overview of the reported findings and evaluate thalidomide's utility in managing refractory pruritus in the context of its adverse risk profile. We propose that thalidomide can be an alternative or combination antipruritic treatment for patients who do not obtain enough relief from conservative therapy.

  8. Lenalidomide in the Treatment of Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Agostino Cortelezzi

    2012-01-01

    Full Text Available The application of nucleoside analogue-based chemotherapy and immunotherapy with rituximab or alemtuzumab has increased both response rate and survival in patients with Chronic Lymphocytic Leukemia (CLL. However, because none of these therapies is curative, sequential therapeutic regimens are required. The majority of patients with relapsed or refractory CLL carry poor prognostic factors and show shorter overall survival and resistance to standard treatment. Numerous drugs have recently been approved for CLL therapy and many novel agents are under clinical investigation. The role of the tumor microenvironment and of immune dysfunction in CLL have allowed to enlarge the therapeutic armamentarium for CLL patients. This article will provide a comprehensive summary regarding mechanism of action, efficacy and safety of lenalidomide in CLL patients. Relevant clinical trials using lenalidomide alone or in combinations are discussed. Lenalidomide shows good activity also in relapsed/refractory or treatment-naive CLL patients. Definitive data from ongoing studies are needed to validate overall and progression-free survival. The toxicity profile might limit lenalidomide use because it can result in serious side effects, but largely controlled by gradual dose escalation. Further understanding of the exact mechanism of action in CLL will allow more efficacious use of lenalidomide alone or in combination regimens.

  9. Glucocorticoids reduce phobic fear in humans.

    Science.gov (United States)

    Soravia, Leila M; Heinrichs, Markus; Aerni, Amanda; Maroni, Caroline; Schelling, Gustav; Ehlert, Ulrike; Roozendaal, Benno; de Quervain, Dominique J-F

    2006-04-04

    Phobias are characterized by excessive fear, cued by the presence or anticipation of a fearful situation. Whereas it is well established that glucocorticoids are released in fearful situations, it is not known whether these hormones, in turn, modulate perceived fear. As extensive evidence indicates that elevated glucocorticoid levels impair the retrieval of emotionally arousing information, they might also inhibit retrieval of fear memory associated with phobia and, thereby, reduce phobic fear. Here, we investigated whether acutely administrated glucocorticoids reduced phobic fear in two double-blind, placebo-controlled studies in 40 subjects with social phobia and 20 subjects with spider phobia. In the social phobia study, cortisone (25 mg) administered orally 1 h before a socio-evaluative stressor significantly reduced self-reported fear during the anticipation, exposure, and recovery phase of the stressor. Moreover, the stress-induced release of cortisol in placebo-treated subjects correlated negatively with fear ratings, suggesting that endogenously released cortisol in the context of a phobic situation buffers fear symptoms. In the spider phobia study, repeated oral administration of cortisol (10 mg), but not placebo, 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 2 days after the last cortisol administration, suggesting that cortisol may also have facilitated the extinction of phobic fear. Cortisol treatment did not reduce general, phobia-unrelated anxiety. In conclusion, the present findings in two distinct types of phobias indicate that glucocorticoid administration reduces phobic fear.

  10. The depressogenic-like effect of acute and chronic treatment with dexamethasone and its influence on the activity of antidepressant drugs in the forced swim test in adult mice.

    Science.gov (United States)

    Wróbel, Andrzej; Serefko, Anna; Wlaź, Piotr; Poleszak, Ewa

    2014-10-01

    There is a close relationship between chronic stress, glucocorticoids and depression. Psychiatric and cognitive symptoms resembling major depression have been observed in patients experiencing elevated glucocorticoid levels, and a high percentage of people suffering from depression have undergone a stressful event/events prior to the onset of this mental disorder. In our study, we investigated whether acute and chronic treatment of dexamethasone induces depression-like behavior in mice and if dexamethasone therapy influences the activity of antidepressant drugs with diverse modes of action. The antidepressant-like effect was assessed by the forced swim test in adult mice. The depressogenic-like activity of dexamethasone turned out to be dose-dependent: only the highest tested dose of the glucocorticoid (i.e., 64μg/kg) given as a single injection increased immobility time, whereas 16μg/kg/day of dexamethasone (but not 4μg/kg/day) administered repeatedly induced a significant alteration in animal behavior. These depressogenic doses of dexamethasone (i.e., 64μg/kg and 16μg/kg/day for an acute and repeated administration, respectively) diminished the antidepressant potential of the therapeutic doses of imipramine (10mg/kg), amitriptyline (10mg/kg), tianeptine (25mg/kg), mianserin (10mg/kg), citalopram (15mg/kg) and moclobemide (25mg/kg). Two main findings of our study should be particularly underlined: (1) both single and repeated administration of dexamethasone evoked a depression-like behavior of mice, (2) both single and repeated administration of dexamethasone were able to modify the activity of the antidepressant agents from various pharmacological groups, which may lead to a considerable reduction in the efficacy of pharmacotherapy prescribed for patients with mood disorders.

  11. Fatigue and gene expression in human leukocytes: increased NF-κB and decreased glucocorticoid signaling in breast cancer survivors with persistent fatigue.

    Science.gov (United States)

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

    2011-01-01

    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.

  12. Chronic fluoxetine treatment increases daytime melatonin synthesis in the rodent

    Directory of Open Access Journals (Sweden)

    Gillian W Reierson

    2009-09-01

    Full Text Available Gillian W Reierson, Claudio A Mastronardi, Julio Licinio, Ma-Li WongCenter on Pharmacogenomics, Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USAAbstract: Circadian rhythm disturbances can occur as part of the clinical symptoms of major depressive disorder and have been found to resolve with antidepressant therapy. The pineal gland is relevant to circadian rhythms as it secretes the hormone melatonin following activation of the cyclic adenosine monophosphate (cAMP signaling cascade and of arylalkylamine N-acetyltransferase (AA-NAT, the rate-limiting enzyme for its synthesis. Cyclic AMP is synthesized by adenylate cyclases (AC and degraded by phosphodiesterases (PDEs. Little is known about the contribution of the PDE system to antidepressant-induced alterations in pineal cAMP signaling and melatonin synthesis. In the present study we used enzyme immunoassay to measure plasma melatonin levels and pineal cAMP levels and as well as quantitative real-time polymerase chain reaction to measure pineal expression of PDE, AC, and AA-NAT genes in rats chronically treated with the prototypic antidepressant fluoxetine. We found elevated melatonin synthesis with increased pineal AA-NAT gene expression and daytime plasma melatonin levels and downregulated cAMP signaling with increased PDE and unchanged AC pineal gene expression, and decreased content of pineal cAMP. We conclude that chronic fluoxetine treatment increases daytime plasma melatonin and pineal AA-NAT gene expression despite downregulated pineal cAMP signaling in the rodent.Keywords: antidepressant, melatonin, pineal, nucleotides, cyclic, phosphodiesterase, rat

  13. Oral Calcidiol Is More Effective Than Cholecalciferol Supplementation to Reach Adequate 25(OH)D Levels in Patients with Autoimmune Diseases Chronically Treated with Low Doses of Glucocorticoids: A “Real-Life” Study

    Science.gov (United States)

    Ortego-Jurado, Miguel; Callejas-Rubio, José-Luis; Ríos-Fernández, Raquel; González-Moreno, Juan; González Ramírez, Amanda Rocío; González-Gay, Miguel A.; Ortego-Centeno, Norberto

    2015-01-01

    Glucocorticoids (GCs) are the cornerstone of the therapy in many autoimmune and inflammatory diseases. However, it is well known that their use is a double edged sword, as their beneficial effects are associated almost universally with unwanted effects, as, for example glucocorticoid-induced osteoporosis (GIO). Over the last years, several clinical practice guidelines emphasize the need of preventing bone mass loss and reduce the incidence of fractures associated with GC use. Calcium and vitamin D supplementation, as adjunctive therapy, are included in all the practice guidelines. However, no standard vitamin D dose has been established. Several studies with postmenopausal women show that maintaining the levels above 30–33 ng/mL help improve the response to bisphosphonates. It is unknown if the response is the same in GIO, but in the clinical practice the levels are maintained at around the same values. In this study we demonstrate that patients with autoimmune diseases, undergoing glucocorticoid therapy, often present suboptimal 25(OH)D levels. Patients with higher body mass index and those receiving higher doses of glucocorticoids are at increased risk of having lower levels of 25(OH)D. In these patients, calcidiol supplementations are more effective than cholecalciferol to reach adequate 25(OH)D levels. PMID:26124976

  14. Oral Calcidiol Is More Effective Than Cholecalciferol Supplementation to Reach Adequate 25(OHD Levels in Patients with Autoimmune Diseases Chronically Treated with Low Doses of Glucocorticoids: A “Real-Life” Study

    Directory of Open Access Journals (Sweden)

    Miguel Ortego-Jurado

    2015-01-01

    Full Text Available Glucocorticoids (GCs are the cornerstone of the therapy in many autoimmune and inflammatory diseases. However, it is well known that their use is a double edged sword, as their beneficial effects are associated almost universally with unwanted effects, as, for example glucocorticoid-induced osteoporosis (GIO. Over the last years, several clinical practice guidelines emphasize the need of preventing bone mass loss and reduce the incidence of fractures associated with GC use. Calcium and vitamin D supplementation, as adjunctive therapy, are included in all the practice guidelines. However, no standard vitamin D dose has been established. Several studies with postmenopausal women show that maintaining the levels above 30–33 ng/mL help improve the response to bisphosphonates. It is unknown if the response is the same in GIO, but in the clinical practice the levels are maintained at around the same values. In this study we demonstrate that patients with autoimmune diseases, undergoing glucocorticoid therapy, often present suboptimal 25(OHD levels. Patients with higher body mass index and those receiving higher doses of glucocorticoids are at increased risk of having lower levels of 25(OHD. In these patients, calcidiol supplementations are more effective than cholecalciferol to reach adequate 25(OHD levels.

  15. Progress on Clinical Study of Acupuncture Treatment for Chronic Pelvic Inflammation

    Institute of Scientific and Technical Information of China (English)

    ZHAO Wen-jie; HUANG Guo-qi

    2008-01-01

    @@ Chronic pelvic inflammation is mostly caused byincomplete treatment of acute pelvic inflammation orby transference from pathologic condition due to poorbody constitution, including chronic endometritis,chronic salpingo-oophoritis and chronic inflammationof connective tissue, and is a commonly andfrequently encountered disease in the gynecologydepartment. Due to long duration, intractablecondition and high recurrent rate, it is also acommonly encountered reason to induce heterotopicpregnancy, sterility, pelvic pain and pelvic adhesivediseases. In the investigative study on the domesticliterature about acupuncture treatment of chronicpelvic inflammation in the recent five years, theauthor hopes to summarize the information forreference in the clinical treatment and to point outsome issues existing in the current clinical study.

  16. Instructions for producing a mouse model of glucocorticoid-induced osteoporosis

    DEFF Research Database (Denmark)

    Thiele, S.; Baschant, U.; Rauch, A.

    2014-01-01

    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 com...

  17. Analysis of the Treatment of Glucocorticoid-induced Osteonecrosis With Traditional Chinese Medicine(TCM)in Proteomics%中药治疗激素性骨坏死的蛋白质组学分析

    Institute of Scientific and Technical Information of China (English)

    吴鹏飞

    2015-01-01

    Objective Using the mechanism of traditional Chinese medicine treatment,according to the research of the proteomic approach,to study of hormone osteonecrosis of pathology,to provide some references for the clinical treatment of glucocorticoid-induced osteonecrosis. Methods Established two rats models groups,one control group with common hormone osteonecrosis and TCM treatment of glucocorticoid-induced osteonecrosis,another control group with blank. After four weeks,identified model based on bone morphology method after the success of the confirmation from rat bone tissue protein samples,used proteomics analysis method according to the data and map for further research. Results Analyzed three groups of rats bone tissue total protein molecular anatomy atlas peptide and protein fingerprint by proteomic. There were obvious difference among three kinds of protein. Conclusion AnticoagulatingⅡB heavy chain of protein,lecithin glutathione oxygen enzyme and enzyme E2 ubiquitin play important regulatory role in the incidence of glucocorticoid-induced osteonecrosis and influence the treatment results of traditional Chinese medicine treatment of glucocorticoid-induced osteonecrosis.%目的:利用中药治疗机理,根据蛋白质组学的研究方法对激素性骨坏死的病理进行研究,为临床治疗激素性骨坏死提供一些参考。方法建立常用激素性骨坏死和中医治疗激素性骨坏死的大鼠模型对照组,并设立一组空白对照组,4周后根据骨形态学方法鉴定模型,确认成功后提取大鼠骨组织蛋白质样品,运用蛋白质组学分析方法,针对得到的数据和图谱进行进一步的研究。结果三组大鼠骨组织总蛋白质分子的解剖图谱和蛋白质肽指纹图谱通过蛋白质组学分析发现,有三种蛋白质存在明显差异。结论在激素性骨坏死发病中发挥作用的阻凝蛋白重链ⅡB、磷脂谷胱甘肽过氧分酶及泛素化酶E2,亦影响了中药对激

  18. Craniosacral Therapy for the Treatment of Chronic Neck Pain

    Science.gov (United States)

    Lauche, Romy; Cramer, Holger; Rampp, Thomas; Saha, Felix J.; Ostermann, Thomas; Dobos, Gustav

    2016-01-01

    Objectives: With growing evidence for the effectiveness of craniosacral therapy (CST) for pain management, the efficacy of CST remains unclear. This study therefore aimed at investigating CST in comparison with sham treatment in chronic nonspecific neck pain patients. Materials and Methods: A total of 54 blinded patients were randomized into either 8 weekly units of CST or light-touch sham treatment. Outcomes were assessed before and after treatment (week 8) and again 3 months later (week 20). The primary outcome was the pain intensity on a visual analog scale at week 8; secondary outcomes included pain on movement, pressure pain sensitivity, functional disability, health-related quality of life, well-being, anxiety, depression, stress perception, pain acceptance, body awareness, patients’ global impression of improvement, and safety. Results: In comparison with sham, CST patients reported significant and clinically relevant effects on pain intensity at week 8 (−21 mm group difference; 95% confidence interval, −32.6 to −9.4; P=0.001; d=1.02) and at week 20 (−16.8 mm group difference; 95% confidence interval, −27.5 to −6.1; P=0.003; d=0.88). Minimal clinically important differences in pain intensity at week 20 were reported by 78% within the CST group, whereas 48% even had substantial clinical benefit. Significant between-group differences at week 20 were also found for pain on movement, functional disability, physical quality of life, anxiety and patients’ global improvement. Pressure pain sensitivity and body awareness were significantly improved only at week 8. No serious adverse events were reported. Discussion: CST was both specifically effective and safe in reducing neck pain intensity and may improve functional disability and the quality of life up to 3 months after intervention. PMID:26340656

  19. Effects of sulfasalazine treatment on serum immunoglobulin levels in children with juvenile chronic arthritis

    NARCIS (Netherlands)

    van Rossum, MAJ; Fiselier, TJW; Franssen, MJAN; ten Cate, R; van Suijlekom-Smit, LWA; Wulffraat, NM; van Luijk, WHJ; Oostveen, JCM; Kuis, W; Dijkmans, BAC; van Soesbergen, RM

    2001-01-01

    This article describes the effects of sulfasalazine (SSZ) treatment on serum immunoglobulin (Ig) levels in 6 children with oligoarticular- or polyarticular onset juvenile chronic arthritis (JCA). None of the children who developed dysimmunoglobulinemia during treatment showed clinical symptoms of th

  20. Antiviral treatment for chronic hepatitis C in patients with human immunodeficiency virus

    DEFF Research Database (Denmark)

    Iorio, Alfonso; Marchesini, Emanuela; Awad, Tahany;

    2010-01-01

    Antiviral treatment for chronic hepatitis C may be less effective if patients are co-infected with human immunodeficiency virus (HIV).......Antiviral treatment for chronic hepatitis C may be less effective if patients are co-infected with human immunodeficiency virus (HIV)....

  1. Analysis of the effect of glucocorticoid on the treatment of severe Mycoplasma pneumoniae pneumonia%糖皮质激素对重症肺炎支原体肺炎的治疗效果分析

    Institute of Scientific and Technical Information of China (English)

    何宇霞

    2016-01-01

    Objective:To investigate the effect of glucocorticoid in the treatment of severe Mycoplasma pneumoniae pneumonia. Methods:Clinical data were reviewed in our hospital in January 2010 ~ 2015 December 160 cases of severe mycoplasma pneumonia pneumonia patients, according to random number table method, divided into the treatment group(n=80) and control group(n=80), patients in control group received azithromycin was given conventional treatment, patients in the treatment group in the control group on the basis of be glucocorticoid treatment, compared two groups of patients with clinical curative effect. Results:Two groups of patients compared patients in the treatment group were cough time, cooling time, length of hospital stay were significantly shorter than that of the control group (P<0.05);the clinical therapeutic effect of two groups of patients compared treatment effective rate is 95% (76 cases) and the control of patients in the treatment group the effective rate was 70.00% (56 cases) and treatment effective rate was significantly higher than that of the control group (P < 0.05). Conclusion:In patients with severe pneumonia mycoplasma pneumonia be glucocorticoid combined with azithromycin treatment, not only can relieve clinical symptoms, but also can shorten the patient's clinical treatment time, to improve the treatment effect of patients, it is worth wide clinical application and promotion.%目的:探讨糖皮质激素治疗重症肺炎支原体肺炎的效果。方法:回顾我院2010年1月~2015年12月收治的160例重症肺炎支原体肺炎患者的临床资料,按照随机数字表法分为治疗组(n=80)和对照组(n=80),对照组予以阿奇霉素进行常规治疗,治疗组在对照组基础上予以糖皮质激素进行治疗,比较两组临床治疗效果。结果:治疗组咳嗽时间、退热时间、住院时间均明显短于对照组(P<0.05);两组临床治疗效果比较,治疗组治疗有效率为95.00%

  2. Correlation between pre-treatment quasispecies complexity and treatment outcome in chronic HCV genotype 3a.

    LENUS (Irish Health Repository)

    Moreau, Isabelle

    2012-02-03

    Pre-treatment HCV quasispecies complexity and diversity may predict response to interferon based anti-viral therapy. The objective of this study was to retrospectively (1) examine temporal changes in quasispecies prior to the start of therapy and (2) investigate extensively quasispecies evolution in a group of 10 chronically infected patients with genotype 3a, treated with pegylated alpha2a-Interferon and ribavirin. The degree of sequence heterogeneity within the hypervariable region 1 was assessed by analyzing 20-30 individual clones in serial serum samples. Genetic parameters, including amino acid Shannon entropy, Hamming distance and genetic distance were calculated for each sample. Treatment outcome was divided into (1) sustained virological responders (SVR) and (2) treatment failure (TF). Our results indicate, (1) quasispecies complexity and diversity are lower in the SVR group, (2) quasispecies vary temporally and (3) genetic heterogeneity at baseline can be use to predict treatment outcome. We discuss the results from the perspective of replicative homeostasis.

  3. The mechanisms of the relationship between glucocorticoids and cardiovascular diseases

    Institute of Scientific and Technical Information of China (English)

    Ejder Kardesoglu; Zafer Isilak; Omer Uz; Turgay Celik

    2010-01-01

    @@ To the editor: We have enjoyed reading an original article by Ji et al,1 entitled Influence of drug treatment on glucocorticoid receptor levels in patients with coronary heart disease, published in a recent issue of the Chinese Medical Journal. Herein, 80 patients with coronary artery disease were divided into four groups according to given drugs, and glucocorticoid (GC) receptor protein levels in peripheral blood lymphocytes were investigated before and I month after treatment in each group. In groups receiving beta blocker and nifedipine, increased levels were observed. They proposed that these increased levels might account for antiinflammatory effects of these drugs.

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

    Directory of Open Access Journals (Sweden)

    Dore RK

    2013-05-01

    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

  5. Stress-induced increases in brainstem amino acid levels are prevented by chronic sodium hydrosulfide treatment.

    Science.gov (United States)

    Warenycia, M W; Kombian, S B; Reiffenstein, R J

    1990-01-01

    Neurotransmitter amino acid levels were measured in select brain regions of rats and mice after chronic treatment with sublethal doses of sodium hydrosulfide (NaHS). Brainstem aspartate, glutamate, glutamine, taurine and GABA levels increased in chronically but not acutely saline-treated rats. These increases may have been due to stress from frequent handling, and were prevented by chronic NaHS treatment (7.5 mg/kg ip every 8 hr for 3 consecutive days). In contrast, aspartate, glutamate and glutamine increased in female but not in male ICR mouse brainstems after once daily treatment with 7.0 mg/kg NaHS for 5 consecutive days. These effects of NaHS may indicate chronic low level H2S neurotoxicity. Differences between chronic and acute treatments, female and male responses, and treatment paradigms may complicate interpretations of such toxicity studies.

  6. Diagnosis and treatment of acute and chronic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    1978-01-01

    The Cancergram covers both acute and chronic leukemia in all of its forms (acute lymphocytic, acute monocytic, acute or sub-acute granulocytic, chronic granulocytic, chronic lymphocytic, chronic monocytic, plasma cell, stem cell, and hairy cell). Other neoplastic conditions of the reticuloendothelial system, lymphatic system, spleen, multiple myeloma, macroglobulinemia and other monoclonal gammopathies are excluded, and will be coveted by other Cancergrams now under development. This Cancergram includes abstracts concerning all clinical aspects of the disease, such as diagnosis and staging, supportive care, evaluation, and therapy. Animal models, tissue culture experiments, carcinogenesis and other pre-clinical studies are generally excluded, except for those considered to have direct clinical relevance.

  7. TRPV1 and TRPM8 in Treatment of Chronic Cough

    Directory of Open Access Journals (Sweden)

    Eva Millqvist

    2016-07-01

    Full Text Available Chronic cough is common in the population, and among some there is no evident medical explanation for the symptoms. Such a refractory or idiopathic cough is now often regarded as a neuropathic disease due to dysfunctional airway ion channels, though the knowledge in this field is still limited. Persistent coughing and a cough reflex easily triggered by irritating stimuli, often in combination with perceived dyspnea, are characteristics of this disease. The patients have impaired quality of life and often reduced work capacity, followed by social and economic consequences. Despite the large number of individuals suffering from such a persisting cough, there is an unmet clinical need for effective cough medicines. The cough treatment available today often has little or no effect. Adverse effects mostly follow centrally acting cough drugs comprised of morphine and codeine, which demands the physician’s awareness. The possibilities of modulating airway transient receptor potential (TRP ion channels may indicate new ways to treat the persistent cough “without a reason”. The TRP ion channel vanilloid 1 (TRPV1 and the TRP melastin 8 (TRPM8 appear as two candidates in the search for cough therapy, both as single targets and in reciprocal interaction.

  8. TRPV1 and TRPM8 in Treatment of Chronic Cough.

    Science.gov (United States)

    Millqvist, Eva

    2016-07-28

    Chronic cough is common in the population, and among some there is no evident medical explanation for the symptoms. Such a refractory or idiopathic cough is now often regarded as a neuropathic disease due to dysfunctional airway ion channels, though the knowledge in this field is still limited. Persistent coughing and a cough reflex easily triggered by irritating stimuli, often in combination with perceived dyspnea, are characteristics of this disease. The patients have impaired quality of life and often reduced work capacity, followed by social and economic consequences. Despite the large number of individuals suffering from such a persisting cough, there is an unmet clinical need for effective cough medicines. The cough treatment available today often has little or no effect. Adverse effects mostly follow centrally acting cough drugs comprised of morphine and codeine, which demands the physician's awareness. The possibilities of modulating airway transient receptor potential (TRP) ion channels may indicate new ways to treat the persistent cough "without a reason". The TRP ion channel vanilloid 1 (TRPV1) and the TRP melastin 8 (TRPM8) appear as two candidates in the search for cough therapy, both as single targets and in reciprocal interaction.

  9. Advances in the treatment of chronic myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Morley Kimberly

    2011-08-01

    Full Text Available Abstract Although imatinib is firmly established as an effective therapy for newly diagnosed patients with chronic myeloid leukemia (CML, the field continues to advance on several fronts. In this minireview we cover recent results of second generation tyrosine kinase inhibitors in newly diagnosed patients, investigate the state of strategies to discontinue therapy and report on new small molecule inhibitors to tackle resistant disease, focusing on agents that target the T315I mutant of BCR-ABL. As a result of these advances, standard of care in frontline therapy has started to gravitate toward dasatinib and nilotinib, although more observation is needed to fully support this. Stopping therapy altogether remains a matter of clinical trials, and more must be learned about the mechanisms underlying the persistence of leukemic cells with treatment. However, there is good news for patients with the T315I mutation, as effective drugs such as ponatinib are on their way to regulatory approval. Despite these promising data, accelerated or blastic phase disease remains a challenge, possibly due to BCR-ABL-independent resistance.

  10. Treatment and Prevention of Common Complications of Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Sheikh Salahuddin Ahmed

    2014-01-01

    Full Text Available Chronic kidney disease (CKD is a worldwide public health problem with an increasing incidence and prevalence. Outcomes of CKD include not only complications of decreased kidney function and cardiovascular disease but also kidney failure causing increased morbidity and mortality. Unfortunately, CKD is often undetected and undertreated because of its insidious onset, variable progression, and length of time to overt kidney failure. Diabetes is now the leading cause of CKD requiring renal replacement therapy in many parts of the world, and its prevalence is increasing disproportionately in the developing countries. This review article outlines the current recommendations from various clinical guidelines and research studies for treatment, prevention and delaying the progression of both CKD and its common complications such as hypertension, anemia, renal osteodystrophy, electrolyte and acid-base imbalance, and hyperlipidemia. Recommendations for nutrition in CKD and measures adopted for early diabetic kidney disease to prevent further progression have also been reviewed. There is strong evidence that early detection and management of CKD can prevent or reduce disease progression, decrease complications and improve outcomes. Evidence supports that achieving optimal glucose control, blood pressure, reduction in albuminuria with a multifactorial intervention slows the progression of CKD. Angiotensin-converting enzyme inhibitors and angiotensin-II receptor antagonists are most effective because of their unique ability to decrease proteinuria, a factor important for the progression of CKD.

  11. Emerging drugs for the treatment of chronic obstructive pulmonary disease.

    Science.gov (United States)

    Malhotra, Samir; Man, S F Paul; Sin, Don D

    2006-05-01

    By 2020 chronic obstructive pulmonary disease (COPD) will be the third leading cause of mortality and fifth leading cause of morbidity. Research over the past two decades has shed important insights on the pathobiology of COPD, leading to the development of novel drugs. In the past, symptomatic treatment with bronchodilators was the predominant focus of COPD management. With increased awareness of the importance of airway inflammation in COPD progression, there has been a shift in emphasis to drugs that attack various targets in the inflammatory cascade. These drugs include phosphodiesterase 4 inhibitors, leukotriene modifiers and TNF antagonists, which are poised to enter the COPD market in the very near future. Tyrosine kinase antagonists, inhibitors of NF-kappaB, neutrophil elastase inhibitors, chemokine antagonists, mucolytics and novel antibiotics are being evaluated for possible effectiveness in COPD. Many of these drugs may enter the COPD market within the next decade. This paper reviews the molecular rationale for these emerging drugs and their potential efficacy in COPD.

  12. Catheter venography and endovascular treatment of chronic cerebrospinal venous insufficiency.

    Science.gov (United States)

    Mandato, Kenneth; Englander, Meridith; Keating, Lawrence; Vachon, Jason; Siskin, Gary P

    2012-06-01

    Multiple sclerosis (MS) is a disorder characterized by damage to the myelin sheath insulation of nerve cells of the brain and spinal cord affecting nerve impulses which can lead to numerous physical and cognitive disabilities. The disease, which affects over 500,000 people in the United States alone, is widely believed to be an autoimmune condition potentially triggered by an antecedant event such as a viral infection, environmental factors, a genetic defect or a combination of each. Chronic cerebrospinal venous insufficiency (CCSVI) is a condition characterized by abnormal venous drainage from the central nervous system that has been theorized to have a possible role in the pathogenesis and symptomatology of MS (1). A significant amount of attention has been given to this theory as a possible explanation for the etiology of symptoms related to MS patients suffering from this disease. The work of Dr. Zamboni, et al, who reported that treating the venous stenoses causing CCSVI with angioplasty resulting in significant improvement in the symptoms and quality of life of patients with MS (2) has led to further interest in this theory and potential treatment. The article presented describes endovascular techniques employed to diagnose and treat patients with MS and CCSVI.

  13. Inflammation in Parkinson's disease: role of glucocorticoids.

    Science.gov (United States)

    Herrero, María-Trinidad; Estrada, Cristina; Maatouk, Layal; Vyas, Sheela

    2015-01-01

    Chronic inflammation is a major characteristic feature of Parkinson's disease (PD). Studies in PD patients show evidence of augmented levels of potent pro-inflammatory molecules e.g., TNF-α, iNOS, IL-1β whereas in experimental Parkinsonism it has been consistently demonstrated that dopaminergic neurons are particularly vulnerable to activated glia releasing these toxic factors. Recent genetic studies point to the role of immune system in the etiology of PD, thus in combination with environmental factors, both peripheral and CNS-mediated immune responses could play important roles in onset and progression of PD. Whereas microglia, astrocytes and infiltrating T cells are known to mediate chronic inflammation, the roles of other immune-competent cells are less well understood. Inflammation is a tightly controlled process. One major effector system of regulation is HPA axis. Glucocorticoids (GCs) released from adrenal glands upon stimulation of HPA axis, in response to either cell injury or presence of pathogen, activate their receptor, GR. GR regulates inflammation both through direct transcriptional action on target genes and by indirectly inhibiting transcriptional activities of transcriptional factors such as NF-κB, AP-1 or interferon regulatory factors. In PD patients, the HPA axis is unbalanced and the cortisol levels are significantly increased, implying a deregulation of GR function in immune cells. In experimental Parkinsonism, the activation of microglial GR has a crucial effect in diminishing microglial cell activation and reducing dopaminergic degeneration. Moreover, GCs are also known to regulate human brain vasculature as well as blood brain barrier (BBB) permeability, any dysfunction in their actions may influence infiltration of cytotoxic molecules resulting in increased vulnerability of dopamine neurons in PD. Overall, deregulation of glucocorticoid receptor actions is likely important in dopamine neuron degeneration through establishment of chronic

  14. 局部和全身应用糖皮质激素治疗突发性耳聋的Meta分析%Local and systemic glucocorticoid treatment for sudden hearing loss: a Meta-analysis

    Institute of Scientific and Technical Information of China (English)

    刘文; 陈鸿雁; 钟朝晖

    2012-01-01

    Objective:To assess the efficacy and safety of glucocorticoid in treating sudden hearing loss with local and systemic ways. Methods:The data base of PubMed, OVID, CBM,CNKI, VIP, Wanfang were systematically retrieved and the literatures associated with local and systemic glucocorticoid in the treatment of sudden hearing loss between 1971 and 2011 were collected. Literatures were screened according to the pre-established inclusion and exclusion standards and the quality was evaluated strictly by using the Cochrane Handbook 5.0. The data were extracted and analyzed by using RevMan 5.0 Meta-analysis software. Results: Among all the qualified literatures, 7 articles were randomized controlled trials. Meta analysis results showed that the odds ratio (OR) of the total effective rate within two groups was 2.01 and 95% confident interval(CI) was between 1.31 and 3.08. Regarding the influence of blood sugar, the statistical results showed that the value of x2 was 3.592 and the value of P was greater than 0.05. Contusions; Although there is no significant difference of the adverse effects between local and systemic glucocorticoid treatment, the local glucocorticoid for sudden deafness is more effective than the systemic administration. It can be preferred in clinical treatment.%目的:利用Meta分析方法比较国内外局部和全身应用糖皮质激素治疗突发性耳聋(Sudden hearing loss,SHL)的疗效,并探讨其安全性.方法:电子检索PubMed、OVID、CBM、CNKI、维普、万方数据库,系统地收集1971-2011年局部和全身给药治疗SHL的相关文献.根据预先制定的纳入和排除标准筛选文献,Cochrane Handbook 5.0严格评价纳入文献质量,提取数据,RevMan 5.0软件进行Meta分析.结果:纳入文献7篇,均为随机对照试验.Meta分析结果显示:局部给药组与全身给药组总有效率的比值比(Odds ratio,OR)为2.01,95%可信区间(Confident interval,CI)为1.31-3.08.关于2种途径给药对

  15. Temporal variability of glucocorticoid receptor activity is functionally important for the therapeutic action of fluoxetine in the hippocampus.

    Science.gov (United States)

    Lee, M-S; Kim, Y-H; Park, W-S; Park, O-K; Kwon, S-H; Hong, K S; Rhim, H; Shim, I; Morita, K; Wong, D L; Patel, P D; Lyons, D M; Schatzberg, A F; Her, S

    2016-02-01

    Previous studies have shown inconsistent results regarding the actions of antidepressants on glucocorticoid receptor (GR) signalling. To resolve these inconsistencies, we used a lentiviral-based reporter system to directly monitor rat hippocampal GR activity during stress adaptation. Temporal GR activation was induced significantly by acute stress, as demonstrated by an increase in the intra-individual variability of the acute stress group compared with the variability of the non-stress group. However, the increased intra-individual variability was dampened by exposure to chronic stress, which was partly restored by fluoxetine treatment without affecting glucocorticoid secretion. Immobility in the forced-swim test was negatively correlated with the intra-individual variability, but was not correlated with the quantitative GR activity during fluoxetine therapy; this highlights the temporal variability in the neurobiological links between GR signalling and the therapeutic action of fluoxetine. Furthermore, we demonstrated sequential phosphorylation between GR (S224) and (S232) following fluoxetine treatment, showing a molecular basis for hormone-independent nuclear translocation and transcriptional enhancement. Collectively, these results suggest a neurobiological mechanism by which fluoxetine treatment confers resilience to the chronic stress-mediated attenuation of hypothalamic-pituitary-adrenal axis activity.

  16. The Comparison of The Efficacy of Three Different Treatment Protocols on The Type 3 Chronic Prostatitis (Chronic Pelvic Pain Syndrome

    Directory of Open Access Journals (Sweden)

    Fikret Erdemir

    2010-05-01

    Full Text Available  Aim: In this study, the effect of three different treatment protocols on the type 3 chronic prostatitis was evaluated. In addition to our knowledge, the comparative studies which related CPPS are limited in Turkish literature. Material and Methods: Between January 2004 and December 2008 a total of 87 male patients with diagnosed of type 3 chronic prostatitis, were evaluated in our clinic. According to treatment protocols patients with type 3 chronic prostatitis, were randomized into three groups as fallows group 1; antibiotic+antiinflammatory+ α-blocker, group 2; α-blocker and group 3; antibiotic+antiinflammatory. Pretreatment and post treatment results were compared. Results: The mean age of all patients was 34.14±7.68 years. The mean age of the patients was 34.13±7.39 years, 34.76±7.99 years, and 33.72±8.25 years in group 1, group 2 and group 3, respectively (p>0.05. While the improvement rates after treatment was detected 68% in group 1, these rates were found as 35.3% and 52% in group 2 and group 3, respectively.This difference was statitistically significant in combined group when  compared to other groups (p=0.047. Conclusion:Although alternative treatment researches have still been continue in type 3 chronic prostatitis which consist of 90-95% of all prostatitis. It is seen that combined treatment is beneficial. However, studies in larger, randomized and controlled series are needed to prove the effect of treatment on type 3 chronic prostatitis.

  17. Induction of neuroserpin expression in rat frontal cortex after chronic antidepressant treatment and electroconvulsive treatment.

    Science.gov (United States)

    Tanaka, Satoshi; Yamada, Misa; Kitahara, Sari; Higuchi, Teruhiko; Honda, Kazuo; Kamijima, Kunitoshi; Yamada, Mitsuhiko

    2006-02-01

    Using expressed sequence tag (EST) analysis, we previously identified certain molecular machinery that mediates antidepressant effects. To date, several partial cDNA fragments, termed antidepressant-related genes (ADRGs), have been isolated as ESTs from rat brain. In the present study, we identified two of the ADRGs to be rat neuroserpin. Using real-time quantitative PCR, we demonstrated increased neuroserpin mRNA expression in rat frontal cortex after chronic treatment with several classes of antidepressants, including imipramine, fluoxetine, sertraline, and venlafaxine. Electroconvulsive treatment (ECT), another therapeutic treatment for depression, also increased neuroserpin expression in rat frontal cortex. Neuroserpin is a serine protease inhibitor that is implicated in the regulation of synaptic plasticity, neuronal migration, and axogenesis in the central nervous system. In conclusion, our results support the hypothesis that neuroserpin-mediated plastic changes in frontal cortex may underlie the therapeutic action of antidepressants and ECT.

  18. Recognizing Family Dynamics in the Treatment of Chronic Fatigue Syndrome

    Science.gov (United States)

    Sperry, Len

    2012-01-01

    Chronic fatigue syndrome (CFS) is an increasingly common chronic medical condition that affects not only patients but also their families. Because family dynamics, particularly the family life cycle, can and does influence the disease process, those providing counseling to CFS patients and their families would do well to recognize these dynamics.…

  19. Fatigue in chronic kidney disease: Definition, assessment and treatment.

    Science.gov (United States)

    Zalai, Dora; Bohra, Miqdad

    2016-01-01

    Chronic fatigue--an overwhelming subjective feeling of mental or physical exhaustion--impacts patients' everyday functioning and quality of life, delays recovery after hemodialysis, and increases mortality. There are a number of factors that may perpetuate clinically significant fatigue among individuals with chronic kidney disease, including sleep disorders, depression, sedentary lifestyle, anemia, and chronic inflammation. Some of these factors (i.e., anemia and inflammation) are in the forefront of clinical attention, whereas the other contributing factors often remain unrecognized. This article provides a pragmatic overview of the definition, assessment, maintaining factors, and management of fatigue in chronic kidney disease. Given that chronic fatigue is a major determinant of patients' quality of life, nurses can bring about a fundamental improvement in patients' well-being if they recognize the most common fatigue-perpetuating factors and facilitate fatigue management interventions.

  20. Controlled trials of antibiotic treatment in patients with post-treatment chronic Lyme disease.

    Science.gov (United States)

    Klempner, Mark S

    2002-01-01

    Some patients have persistence of profound fatigue, myalgias, arthralgias without arthritis, dysesthesia/paresthesia, and mood and memory disturbances after standard courses of antibiotic treatment for Lyme disease. This constellation of symptoms has been variously referred to as "chronic Lyme disease," "post-Lyme disease syndrome," and "post-treatment chronic Lyme disease." Persistent symptoms have been reported in patients who are seropositive for IgG antibodies against Borrelia burgdorferi as well as in patients who are seronegative. The cause or causes of persistent symptoms in these patients have not been clearly defined and are controversial. Because of the temporal association of these symptoms with infection with B. burgdorferi, some patients have been treated with prolonged courses of antibiotics. Case reports and uncontrolled trials have reported the efficacy of prolonged antibiotic therapy, often with relapse of the symptoms after discontinuation of therapy. To date, only one randomized, placebo-controlled, double-blind trial of antibiotic therapy for these patients has been published. An abstract of a second placebo-controlled trial of antibiotic therapy in a smaller cohort has also been presented. This paper will describe this patient population in detail and will review the clinical, microbiological, and selected biochemical and immunologic parameters and their responses to antibiotic treatment in the setting of a controlled trial.

  1. Different approaches in the treatment of obstructive pulmonary diseases.

    Science.gov (United States)

    Kabir, Eva Rahman; Morshed, Nabila

    2015-10-05

    Advances in drug formulation, inhalation device design and disease management are generating new opportunities for patients suffering from obstructive pulmonary diseases. This article provides a comprehensive review of the different promising pulmonary drug delivery technologies in the treatment of obstructive pulmonary diseases, particularly with regard to the treatment of asthma and chronic pulmonary diseases (COPD), which are increasing day by day due to increasing environmental pollution and its harmful and toxic contaminants. In the recent years, a better knowledge has been gained regarding the mechanism of action of glucocorticoids and how they suppress the chronic inflammation. New etiology has been brought into light regarding the inactivity of glucocorticoids in some patients having asthma and COPDs even though the inflammatory genes are triggered by similar molecules in both the diseases. This new knowledge has given a new platform to improve glucocorticoids and their resistance also how other combination therapy can be used for these diseases. It has also led to the quest for improving and developing other alternatives such as anti-leukotriene agents, muscarinic inhibitors, combination therapy, as well as biologic immune-modulators in the treatment of the different pulmonary diseases. Several new combinations of glucocorticoids are available in the global market for the use in pulmonary diseases especially asthma although their availability fluctuates between continents. There has been several studies done regarding the variation of effectiveness of the different inhaled glucocorticoids and hence it is important to take into consideration the different delivery systems and the methods which are used to treat the patients.

  2. Treatment of a case of refractory feline chronic gingivostomatitis with feline recombinant interferon omega.

    Science.gov (United States)

    Southerden, P; Gorrel, C

    2007-02-01

    Chronic gingivostomatitis is a common debilitating disease in cats, which is often refractory to medical and surgical treatment. An eight-year-old, neutered female domestic shorthair cat with a history of gingivitis was presented with chronic gingivostomatitis. Initial treatment by extraction of all premolars and molars was unsuccessful. However, the condition resolved within six weeks of treatment with feline recombinant interferon omega (Virbagen; Virbac).

  3. Examining influential factors in providers’ chronic pain treatment decisions: a comparison of physicians and medical students

    OpenAIRE

    2015-01-01

    Background Chronic pain treatment guidelines are unclear and conflicting, which contributes to inconsistent pain care. In order to improve pain care, it is important to understand the various factors that providers rely on to make treatment decisions. The purpose of this study was to examine factors that reportedly influence providers’ chronic pain treatment decisions. A secondary aim was to examine differences across participant training level. Methods Eighty-five participants (35 medical st...

  4. Cholesterol deregulation induced by chronic corticosterone (CORT) stress in pectoralis major of broiler chickens.

    Science.gov (United States)

    Duan, Yujing; Fu, Wenyan; Wang, Song; Ni, Yingdong; Zhao, Ruqian

    2014-10-01

    Chronic endogenous glucocorticoid (GC) excess in mammals is associated with metabolic dysfunction and dyslipidemia that are characterized by increased plasma triglyceride and total cholesterol (Tch) levels. However, the effects of chronic GC administration on cholesterol metabolism, particularly in muscle tissues of broiler chickens, are unknown. In this study, broiler chickens were treated chronically with vehicle (CON) or corticosterone (CORT) for 2 weeks. Chronic CORT treatment significantly increased Tch levels in pectoralis major muscle (PMC) (p0.05). Western blot results showed that the levels of total GR (p=0.08) tended to be increased and nuclear GR protein (pchickens by increasing cholesterol synthesis and uptake.

  5. The role of glucocorticoid receptor (GR) polymorphisms in human erythropoiesis.

    Science.gov (United States)

    Varricchio, Lilian; Migliaccio, Anna Rita

    2014-01-01

    Glucocorticoids are endogenous steroid hormones that regulate several biological functions including proliferation, differentiation and apoptosis in numerous cell types in response to stress. Synthetic glucocorticoids, such as dexamethasone (Dex) are used to treat a variety of diseases ranging from allergy to depression. Glucocorticoids exert their effects by passively entering into cells and binding to a specific Glucocorticoid Receptor (GR) present in the cytoplasm. Once activated by its ligand, GR may elicit cytoplasmic (mainly suppression of p53), and nuclear (regulation of transcription of GR responsive genes), responses. Human GR is highly polymorphic and may encode > 260 different isoforms. This polymorphism is emerging as the leading cause for the variability of phenotype and response to glucocorticoid therapy observed in human populations. Studies in mice and clinical observations indicate that GR controls also the response to erythroid stress. This knowledge has been exploited in-vivo by using synthetic GR agonists for treatment of the erythropoietin-refractory congenic Diamond Blackfan Anemia and in-vitro to develop culture conditions that may theoretically generate red cells in numbers sufficient for transfusion. However, the effect exerted by GR polymorphism on the variability of the phenotype of genetic and acquired erythroid disorders observed in the human population is still poorly appreciated. This review will summarize current knowledge on the biological activity of GR and of its polymorphism in non-hematopoietic diseases and discuss the implications of these observations for erythropoiesis.

  6. Glucocorticoid-induced osteoporosis: an update on effects and management.

    Science.gov (United States)

    Buehring, Bjoern; Viswanathan, Ravi; Binkley, Neil; Busse, William

    2013-11-01

    Glucocorticoids remain a cornerstone of guideline-based management of persistent asthma and allergic diseases. Glucocorticoid-induced osteoporosis (GIO) is the most common iatrogenic cause of secondary osteoporosis and an issue of concern for physicians treating patients with inhaled or oral glucocorticoids either continuously or intermittently. Patients with GIO experience fragility fractures at better dual-energy x-ray absorptiometry T-scores than those with postmenopausal or age-related osteoporosis. This might be explained, at least in part, by the effects of glucocorticoids not only on osteoclasts but also on osteoblasts and osteocytes. Effective options to detect and manage GIO exist, and a management algorithm has been published by the American College of Rheumatology to provide treatment guidance for clinicians. This review will summarize GIO epidemiology and pathophysiology and assess the role of inhaled and oral glucocorticoids in asthmatic adults and children, with particular emphasis on the effect of such therapies on bone health. Lastly, we will review the American College of Rheumatology GIO guidelines and discuss diagnostic and therapeutic strategies to mitigate the risk of GIO and fragility fractures.

  7. Azithromycin buccal patch in treatment of chronic periodontitis

    Science.gov (United States)

    Latif, Sajith Abdul; Vandana, K. L.; Thimmashetty, J.; Dalvi, Priyanka Jairaj

    2016-01-01

    Aim: This study aims to explore the clinical, microbiological, and biochemical impact of azithromycin (AZM) buccal patch in chronic generalized patients as a monotherapy as well as an adjunct to nonsurgical therapy. Materials and Methods: A parallel design was used forty periodontitis patients were randomly allocated into five groups, namely Group 1 scaling root planing (SRP) alone, Group 2 (SRP + AZM patch group), Group 3 (SRP + AZM tablet group), Group 4 (AZM patch monotherapy), and Group 5 (AZM tablet as monotherapy). Plaque index, gingival bleeding index, modified gingival index, probing pocket depth (PPD), and clinical attachment level (CAL) were assessed at baseline and 21 and 90 days. Subgingival pooled plaque sample was collected to assess periodontopathogens like Porphyromonas gingivalis and Prevotella intermedia (Pi) by anaerobic culture method. Tumor necrosis factor alpha (TNF-α) was also evaluated at baseline and 21 days. Periodontal maintenance was performed in Group 1 until 90th day, and clinical parameter was assessed at the end of 90th day. Results: SRP + AZM tablets showed greater reduction in clinical parameters (P < 0.05) AZM as monotherapy did not offer clinical benefits over SRP. Baseline data were compared at the end, i.e., 90th day a significant reduction in plaque scores, gingival bleeding, and PPD was observed however no significant gain in the clinical attachment was observed. Conclusion: The monotherapy resulted in no improvement of periodontal parameters, microbial parameters, and TNF-α level. It is safe to use AZM + SRP as a mode of nonsurgical treatment in periodontitis patients. PMID:27127325

  8. Mathematical modeling of genesis and treatment of chronic myeloid leukemia.

    Science.gov (United States)

    Horn, Matthias; Loeffler, Markus; Roeder, Ingo

    2008-01-01

    Chronic myeloid leukemia (CML) is a clonal hematopoietic disorder induced by translocation of chromosomes 9 and 22, resulting in an overproduction of myeloid blood cells. CML-specific characteristics include a latency time of several years, a period of coexistence of malignant and normal cells and an eventual dominance of the malignant clone. Different drug therapies are available, most notably imatinib, which inhibits the oncogenic BCR-ABL1 tyrosine kinase. Although the chromosomal aberration causing CML is well known, the resulting dynamic effects on the system behavior are not sufficiently understood yet. Here, we apply an already established mathematical model of hematopoietic stem cell organization. Based on parameter estimates for normal hematopoiesis, we systematically explore the changes in these parameters necessary to reproduce CML-specific characteristics regarding emergence and course of disease as well as a variety of qualitative and quantitative clinical data on CML treatment. Our results indicate that 1 or more of the following mechanisms are compatible with the induction of a dominant clone in the proposed model: a retarded differentiation process, a reduced turnover time or a defective cell-microenvironment interaction of the neoplastic cells. However, in order to explain the massive overproduction of malignant cells, an unregulated and abnormal activation of leukemia stem cells into cycle has to be assumed additionally. Based on our simulation results we conclude that CML dynamics can most appropriately be explained by a modulation of the cell-microenvironment interactions of leukemia stem cells, including both the process of stem cell silencing and activation into cycle.

  9. Diagnosis and Treatment of Infective Endocarditis in Chronic Hemodialysis Patients

    Institute of Scientific and Technical Information of China (English)

    Jian-ling Tao; Xue-mei Li; Xue-wang Li; Jie Ma; Guang-li Ge; Li-meng Chen; Hang Li; Bao-tong Zhou; Yang Sun; Wen-ling Ye; Qi Miao

    2010-01-01

    Objective To analyze the clinical features of hemodialysis patients complicated by infective endo-carditis.Methods The clinical features of six such patients admitted to Peking Union Medical College Hos-pital during the year 1990 to 2009 were analyzed. All of them were diagnosed based on Chinese Children Diagnostic Criteria for Infective Endocarditis.Results The average age of the six patients was 52.3±19.3 years old. Four were males. Vascular ac-cesses at the onset of infective endocarditis were as follows: permanent catheters in three, temporary cathe-ters in two, and arteriovenous fistula in one. Three were found with mitral valve involvement, two with aor-tic valve involvement, and one with both. Five vegetations were found by transthoraeic echocardiography, and one by transesophageal echocardiography. Four had positive blood culture results. The catheters were all removed. Four of the patients were improved by antibiotics treatment, in which two were still on hemodialy-sis in the following 14-24 months and the other two were lost to follow-up. One patient received surgery, but died of heart failure after further hemodialysis for three months. One was well on maintenance hemodi-alysis for three months after surgery.Conclusions Infective endocarditis should be suspected when hemodialysis patients suffer from long-term fever, for which prompt blood culture and transthoracic echocardiography confirmation could be performed. Transesophageal echocardiography could be considered even when transthoracic echocardiogra-phy produces negative findings. With catheters removed, full course of appropriate sensitive antibiotics and surgery if indicated could improve the outcome of chronic hemodialysis patients complicated by infective endocarditis.

  10. Pain volatility and prescription opioid addiction treatment outcomes in patients with chronic pain.

    Science.gov (United States)

    Worley, Matthew J; Heinzerling, Keith G; Shoptaw, Steven; Ling, Walter

    2015-12-01

    The combination of prescription opioid dependence and chronic pain is increasingly prevalent and hazardous to public health. Variability in pain may explain poor prescription opioid addiction treatment outcomes in persons with chronic pain. This study examined pain trajectories and pain volatility in patients with chronic pain receiving treatment for prescription opioid addiction. We conducted secondary analyses of adults with chronic pain (n = 149) who received buprenorphine/naloxone (BUP/NLX) and counseling for 12 weeks in an outpatient, multisite clinical trial. Good treatment outcome was defined as urine-verified abstinence from opioids at treatment endpoint (Week 12) and during at least 2 of the previous 3 weeks. Pain severity significantly declined over time during treatment (b = -0.36, p treatment outcome (odds ratio = 0.55, p treatment provides observational support for the analgesic effects of BUP/NLX in patients with chronic pain and opioid dependence. Patients with greater volatility in subjective pain during treatment have increased risk of returning to opioid use by the conclusion of an intensive treatment with BUP/NLX and counseling. Future research should examine underlying mechanisms of pain volatility and identify related therapeutic targets to optimize interventions for prescription opioid addiction and co-occurring chronic pain.

  11. Glucocorticoids increase impairments in learning and memory due to elevated amyloid precursor protein expression and neuronal apoptosis in 12-month old mice.

    Science.gov (United States)

    Li, Wei-Zu; Li, Wei-Ping; Yao, Yu-You; Zhang, Wen; Yin, Yan-Yan; Wu, Guo-Cui; Gong, Hui-Ling

    2010-02-25

    Alzheimer's disease is a chronic neurodegenerative disorder marked by a progressive loss of memory and cognitive function. Stress level glucocorticoids are correlated with dementia progression in patients with Alzheimer's disease. In this study, twelve month old male mice were chronically treated for 21 days with stress-level dexamethasone (5mg/kg). We investigated the pathological consequences of dexamethasone administration on learning and memory impairments, amyloid precursor protein processing and neuronal cell apoptosis in 12-month old male mice. Our results indicate that dexamethasone can induce learning and memory impairments, neuronal cell apoptosis, and mRNA levels of the amyloid precursor protein, beta-secretase and caspase-3 are selectively increased after dexamethasone administration. Immunohistochemistry demonstrated that amyloid precursor protein, caspase-3 and cytochrome c in the cortex and CA1, CA3 regions of the hippocampus are significantly increased in 12-month old male mice. Furthermore, dexamethasone treatment induced cortex and hippocampus neuron apoptosis as well as increasing the activity of caspase-9 and caspase-3. These findings suggest that high levels of glucocorticoids, found in Alzheimer's disease, are not merely a consequence of the disease process but rather play a central role in the development and progression of Alzheimer's disease. Stress management or pharmacological reduction of glucocorticoids warrant additional consideration of the regimen used in Alzheimer's disease therapies.

  12. Nutrition treatment of deficiency and malnutrition in chronic pancreatitis: a review.

    LENUS (Irish Health Repository)

    Duggan, SN

    2010-08-01

    Chronic pancreatitis results in exocrine and endocrine dysfunction, affecting normal digestion and absorption of nutrients. In individuals with chronic pancreatitis, nutrition status may be further affected by poor dietary intake, often related to alcoholism. However, some deficiencies may be overlooked, potentially leading to nutrition-related problems with bone health and fatigue. The aim of this article is to describe the deficiencies that occur and to propose an evidence-based algorithm for the nutrition assessment and treatment of patients with chronic pancreatitis.

  13. Suppression of glucocorticoid secretion enhances cholinergic transmission in rat hippocampus.

    Science.gov (United States)

    Mizoguchi, Kazushige; Shoji, Hirotaka; Ikeda, Ryuji; Tanaka, Yayoi; Maruyama, Wakako; Tabira, Takeshi

    2008-08-15

    We previously demonstrated that suppression of glucocorticoid secretion by adrenalectomy (ADX) impaired prefrontal cortex-sensitive working memory, but not reference memory. Since the cholinergic system in the hippocampus is also involved in these memories, we examined the effects of glucocorticoid suppression on cholinergic transmission in the rat hippocampus. A microdialysis study revealed that ADX did not affect the basal acetylcholine release, but enhanced the KCl-evoked response. This enhanced response was reversed by the corticosterone replacement treatment. The extracellular choline concentrations increased under both basal and KCl-stimulated conditions in the ADX rats, and these increases were also reversed by the corticosterone replacement. These results indicate that suppression of glucocorticoid secretion enhances cholinergic transmission in the hippocampus in response to stimuli. It is possible that this enhanced cholinergic transmission may not contribute to the ADX-induced working memory impairment, but it may be involved in maintenance of reference memory.

  14. TCM Treatment for Two Cases of Chronic and Intractable Eczema

    Institute of Scientific and Technical Information of China (English)

    He Kuanqi; Zhu Hanting

    2008-01-01

    @@ The author treated 2 cases of chronic and intractable eczema,who were once treated by western drugs without good results,with Chinese medicine and obtained satisfactory therapeutic effects.Now it is reported as follows.

  15. [New pharmaceuticals in treatment of chronic dust bronchitis].

    Science.gov (United States)

    Kosarev, V V; Vakurova, N V; Babanov, S A

    2007-01-01

    The study was dedicated to the assessment of the therapeutic possibilities provided by erespal (fenspirid) as a new class of pharmaceuticals inhibiting the inflammatory process, in patients with chronic dust bronchitis.

  16. Treatment with Tacrolimus and Sirolimus Reveals No Additional Adverse Effects on Human Islets In Vitro Compared to Each Drug Alone but They Are Reduced by Adding Glucocorticoids

    Directory of Open Access Journals (Sweden)

    Kristine Kloster-Jensen

    2016-01-01

    Full Text Available Tacrolimus and sirolimus are important immunosuppressive drugs used in human islet transplantation; however, they are linked to detrimental effects on islets and reduction of long-term graft function. Few studies investigate the direct effects of these drugs combined in parallel with single drug exposure. Human islets were treated with or without tacrolimus (30 μg/L, sirolimus (30 μg/L, or a combination thereof for 24 hrs. Islet function as well as apoptosis was assessed by glucose-stimulated insulin secretion (GSIS and Cell Death ELISA. Proinflammatory cytokines were analysed by qRT-PCR and Bio-Plex. Islets exposed to the combination of sirolimus and tacrolimus were treated with or without methylprednisolone (1000 μg/L and the expression of the proinflammatory cytokines was investigated. We found the following: (i No additive reduction in function and viability in islets existed when tacrolimus and sirolimus were combined compared to the single drug. (ii Increased expression of proinflammatory cytokines mRNA and protein levels in islets took place. (iii Methylprednisolone significantly decreased the proinflammatory response in islets induced by the drug combination. Although human islets are prone to direct toxic effect of tacrolimus and sirolimus, we found no additive effects of the drug combination. Short-term exposure of glucocorticoids could effectively reduce the proinflammatory response in human islets induced by the combination of tacrolimus and sirolimus.

  17. Treatment of 68 Cases of Chronic Prostatitis with Acupuncture

    Institute of Scientific and Technical Information of China (English)

    康振财; 刘海珊; 聂世聪

    2009-01-01

    @@ Chronic prostatitis (CPT) is a common prevalent disease in urology department,which always occurs in people aged 20-40 years.It can cause complex clinical symptoms,with a low cure rate and high recurrence.It has a certain relationship with sterility and cause great pressure on patients.The author treated 68 cases of chronic prostatitis by acupuncture in recent years.It is now reported is as follows.

  18. Influence of glucocorticoids and growth hormone on insulin sensitivity in humans.

    Science.gov (United States)

    Yuen, K C J; Chong, L E; Riddle, M C

    2013-06-01

    The seminal concept proposed by Sir Harold Himsworth more than 75 years ago that a large number of patients with diabetes were 'insulin insensitive', now termed insulin resistance, has now expanded to include several endocrine syndromes, namely those of glucocorticoid excess, and growth hormone excess and deficiency. Synthetic glucocorticoids are increasingly used to treat a wide variety of chronic diseases, whereas the beneficial effects of recombinant growth hormone replacement therapy in children and adults with growth hormone deficiency have now been well-recognized for over 25 years. However, clinical and experimental studies have established that increased circulating levels of glucocorticoids and growth hormone can also lead to worsening of insulin resistance, glucose intolerance, overt diabetes mellitus and cardiovascular disease. Improved understanding of the physiological 24-h rhythmicity of glucocorticoid and growth hormone secretion and its influence on the dawn phenomenon and the Staub-Trauggot effect has therefore led to renewed interest in studies on the mechanisms of insulin resistance induced by exogenous administration of glucocorticoids and growth hormone in humans. In this review, we describe the physiological events that result from the presence of resistance to insulin action at the level of skeletal muscle, adipose tissue, and liver, describe the known mechanisms of glucocorticoid- and growth hormone-mediated insulin resistance, and provide an update of the contributions of glucocorticoids and growth hormone to understanding the pathophysiology of insulin resistance and its effects on several endocrine syndromes.

  19. Brief report: Glucocorticoid receptor polymorphism affects transrepression but not transactivation

    NARCIS (Netherlands)

    E.L.T. van den Akker (Erica); H. Russcher (Henk); E.F.C. van Rossum (Liesbeth); A.O. Brinkmann (Albert); F.H. de Jong (Frank); A.C.S. Hokken-Koelega (Anita); H.A.P. Pols (Huib); J.W. Koper (Jan); S.W.J. Lamberts (Steven)

    2006-01-01

    textabstractContext: Glucocorticoids (GCs) are extensively used in the treatment of inflammatory and autoimmune diseases. Their beneficial effects are thought to be mediated by GC transrepression on gene expression. However, their use is limited by serious adverse effects, presumably mediated by GC

  20. Melatonin Treatment in Individuals with Intellectual Disability and Chronic Insomnia: A Randomized Placebo-Controlled Study

    Science.gov (United States)

    Braam, W.; Didden, R.; Smits, M.; Curfs, L.

    2008-01-01

    Background: While several small-number or open-label studies suggest that melatonin improves sleep in individuals with intellectual disabilities (ID) with chronic sleep disturbance, a larger randomized control trial is necessary to validate these promising results. Methods: The effectiveness of melatonin for the treatment of chronic sleep…

  1. The rise and fall of new treatment options for chronic hepatitis C

    NARCIS (Netherlands)

    van Soest, H.

    2011-01-01

    Hepatitis C virus (HCV) is a leading cause of chronic liver disease. It is a life-shortening disease associated with liver cirrhosis and hepatocellular carcinoma. The main goal of treatment for chronic hepatitis C (CHC) is to prevent liver-related morbidity and mortality. In this thesis, new treatme

  2. Treatment of Chronic Phantom Limb Pain Using a Trauma-Focused Psychological Approach

    Directory of Open Access Journals (Sweden)

    C de Roos

    2010-01-01

    Full Text Available BACKGROUND: Chronic phantom limb pain (PLP is a disabling chronic pain syndrome for which regular pain treatment is seldom effective. Pain memories resulting from long-lasting preamputation pain or pain flashbacks, which are part of a traumatic memory, are reported to be powerful elicitors of PLP.

  3. A Unified, Transdiagnostic Treatment for Adolescents with Chronic Pain and Comorbid Anxiety and Depression

    Science.gov (United States)

    Allen, Laura B.; Tsao, Jennie C. I.; Seidman, Laura C.; Ehrenreich-May, Jill; Zeltzer, Lonnie K.

    2012-01-01

    Chronic pain disorders represent a significant public health concern, particularly for children and adolescents. High rates of comorbid anxiety and unipolar mood disorders often complicate psychological interventions for chronic pain. Unified treatment approaches, based on emotion regulation skills, are applicable to a broad range of emotional…

  4. Extracorporeal shockwave therapy in the treatment of chronic diabetic foot ulcers

    DEFF Research Database (Denmark)

    Jeppesen, S M; Yderstraede, K B; Rasmussen, B S B

    2016-01-01

    OBJECTIVE: To investigate the efficacy of extracorporeal shockwave therapy (ESWT) on healing chronic diabetic foot ulcers (DFU). METHOD: Patients with chronic DFUs were randomised (1:1) to receive a series of six ESWT treatments over 3 weeks in combination with standard care or standard care alone...

  5. Glucocorticoids and nervous system plasticity

    Institute of Scientific and Technical Information of China (English)

    Kathryn M Madalena; Jessica K Lerch

    2016-01-01

    Glucocorticoid and glucocorticoid receptor (GC/GR) interactions alter numerous aspects of neuronal function. These consequences (e.g., anti-inlfammatoryvs. pro-inlfammatory) can vary depending on the duration of GC exposure or central nervous system (CNS) injury model. In this review we discuss how GC/GR interactions impact neuronal recovery after a central or peripheral nerve injury and discuss how GC exposure duration can produce divergent CNS neuronal growth responses. Finally we consider how new ifndings on gender speciifc immune cell responses after a nerve injury could intersect with GC/GR interactions to impact pain processing.

  6. Researching of cardos activity for chronic heart failure treatment in case of concomitant chronic kidney disease (stage V, conventional hemodialysis

    Directory of Open Access Journals (Sweden)

    Chepurina N.G.

    2011-06-01

    Full Text Available Aim: comparative investigation of cardos (antibodies to angiotensin II receptor subtype 1 (AT., C-terminal fragment, diovan (Valsartan or both drug combination effects (changing of clinical picture, physical exertion tolerance and quality of life for treatment chronic heart failure (CHF patients. Methods. 12-month open-label randomized research was performed. CHF patients (NYHA Class l-ll, n=30 with concomitant chronic kidney disease (stage V, conventional hemodialysis were randomized (10 patients in each group for 6-month treatment by cardos (group I, average dose 1,8g/day, diovan (group II, average dose 80mg/dayorboth drug combination (group III, cardos 1,8g/day and diovan 80mg/day. CHD basic treatment was prescribed for all patients. In a 6-month drug crossover between groups I and I was performed, group III was divided into 2 subgroups (subgroup IIIA— cardos, subgroup NIB — diovan followed by next 6-month treatment. Results. Long-term treatment by cardos has improved functional class (NYHA of CHF patients with concomitant chronic kidney disease (stage V, conventional hemodialysis. cardos, diovan and both drug combination have demonstrated improvement of physical exertion tolerance, quality of life and patient clinical status during 6-min walking test. Conclusion. Cardos and diovan have shown the same efficacy. Cardos can be used as real alternative in case of ARA administration necessity

  7. The Role of the Glucocorticoids in Developing Resilience to Stress and Addiction

    Directory of Open Access Journals (Sweden)

    Subhashini eSrinivasan

    2013-08-01

    Full Text Available There is emerging evidence that individuals have the capacity to learn to be resilient by developing protective mechanisms that prevent them from the maladaptive effects of stress that can contribute to addiction. The emerging field of the neuroscience of resilience is beginning to uncover the circuits and molecules that protect against stress-related neuropsychiatric diseases, such as addiction. Glucocorticoids (GCs are important regulators of basal and stress-related homeostasis in all higher organisms and influence a wide array of genes in almost every organ and tissue. Glucocorticoids, therefore, are ideally situated to either promote or prevent adaptation to stress. In this review, we will focus on the role of GCs in the HPA axis and extra-hypothalamic regions in regulating basal and chronic stress responses. GCs interact with a large number of neurotransmitter and neuropeptide systems that are associated with the development of addiction. Additionally, the review will focus on two pathways the orexinergic and cholinergic neurotransmission and highlight their role in stress and addiction. We will provide examples of interactions between GCs and these wherever studied. GCs play a key role in promoting the development of resilience or susceptibility associated with the development of stress-induced addiction and represent important pharmacotherapeutic targets that can reduce the impact of a maladapted stress system for the treatment of stress-induced addiction.

  8. Culture-directed topical antibiotic treatment for chronic rhinosinusitis

    Science.gov (United States)

    Davis, Greg E.

    2016-01-01

    Background: Topical antibiotics, delivered optimally as high-volume culture-directed sinus irrigations, are being increasingly used for recalcitrant chronic rhinosinusitis (CRS). Their impact on subjective and objective outcome measures, however, is still unclear. Objective: To assess if the use of topical antibiotics in recalcitrant CRS is associated with improved 20-Item Sino-Nasal Outcome Test and Lund-Kennedy endoscopic scores, and to determine the negative posttreatment culture “control” rate. Methods: Patients were included in the study if they met diagnostic criteria for CRS, received high-volume topical antibiotic sinus irrigations twice daily for 1 month, between December 2009 and May 2015, and had undergone endoscopic sinus surgery. The primary outcome was the 20-Item Sino-Nasal Outcome Test score. Secondary outcomes were the Lund-Kennedy endoscopic score and a negative posttreatment culture “control” rate. Paired t-tests were used to compare pre- and posttreatment scores. Patients with cystic fibrosis were analyzed separately. Results: Of the 58 patients included, 47% had nasal polyposis, 57% had asthma, 16% had aspirin sensitivity, and 55% had environmental allergies. The median Lund-Mackay computed tomography score was 11 (interquartile range, 6–16), and the median time to follow-up was 8 weeks (interquartile range, 6–10 weeks). The 20-Item Sino-Nasal Outcome Test scores improved from pre- to posttreatment period, although this was not significant mean 1.5 [confidence interval {CI} 1.3, 1.7] to mean 1.3 [CI 1.1, 1.6]; p = 0.16). Lund-Kennedy endoscopic scores, however, significantly improved from pre- to posttreatment (mean 4.9 [CI 4.3, 5.6] to mean 4.1 [CI 3.5, 4.7]; p = 0.05). Of the 47 patients with complete culture data, 72% had negative posttreatment culture results, defined as “controlled.” Only one patient discontinued treatment, related to discomfort from irrigations. Conclusion: In patients with recalcitrant CRS, the use of

  9. Efficacy of medical therapy in treatment of chronic rhinosinusitis.

    Science.gov (United States)

    Young, Lee C; Stow, Nicholas W; Zhou, Lifeng; Douglas, Richard G

    2012-01-01

    Uncomplicated chronic rhinosinusitis (CRS) is generally treated with medical therapy initially and surgery is contemplated only after medical therapy has failed. However, there is considerable variation in the medical treatment regimens used and studies defining their efficacy are few. The aim of this study was to determine the proportion of patients treated medically who responded sufficiently well so that surgery was not required. Subgroup analysis to identify clinical features that predicted a favorable response to medical therapy was also performed. Eighty patients referred to the Otorhinolaryngology Clinic at North Shore Hospital were treated with a standardized medical therapy protocol (oral prednisone for 3 weeks, oral antibiotics and ongoing saline lavage and intranasal budesonide spray). Symptom scores were collected before and after medical therapy. Clinical features such as presence of polyps, asthma, and aspirin hypersensitivity were recorded. Failure of medical therapy was defined as the persistence of significant CRS symptoms, and those patients who failed medical therapy were offered surgery. Follow-up data were available for 72 (90%) patients. Of this group, 52.5%, (95% CI, 42.7%, 62.2%) failed to respond adequately to medical therapy and were offered surgery. The remaining patients (37.5%) were successfully treated with medical therapy and did not require surgery at the time of follow-up. The premedical therapy symptom scores were significantly higher than the postmedical therapy symptom scores (p < 0.01). The symptom scores of those patients postmedical therapy who proceeded to have surgery were significantly higher than the group who responded well to maximum medical therapy (MMT) and did not require surgery (p < 0.0001). There were no significant differences in the proportion of patients with asthma, aspirin sensitivity, or polyps between the groups failing or not failing MMT. In approximately one-third of patients with CRS, medical therapy

  10. Effectiveness of psychotherapeutic, pharmacological, and combined treatments for chronic depression: a systematic review (METACHRON

    Directory of Open Access Journals (Sweden)

    von Wolff Alessa

    2010-11-01

    Full Text Available Abstract Background Chronic depressions represent a substantial part of depressive disorders and are associated with severe consequences. Several studies were performed addressing the effectiveness of psychotherapeutic, pharmacological, and combined treatments for chronic depressions. Yet, a systematic review comparing the effectiveness of multiple treatment options and considering all subtypes of chronic depressions is still missing. Methods/Design Aim of this project is to summarize empirical evidence on efficacy and effectiveness of treatments for chronic depression by means of a systematic review. The primary objectives of the study are to examine, which interventions are effective; to examine, if any differences in effectiveness between active treatment options exist; and to find possible treatment effect modifiers. Psychotherapeutic, pharmacological, and combined treatments will be considered as experimental interventions and no treatment, wait-list, psychological/pharmacological placebo, treatment as usual, and other active treatments will be seen as comparators. The population of patients will include adults with chronic major depression, dysthymia, double depression, or recurrent depression without complete remission between episodes. Outcomes of the analyses are depressive symptoms, associated consequences, adverse events, and study discontinuation. Only randomized controlled trials will be considered. Discussion Given the high prevalence and serious consequences of chronic depression and a considerable amount of existing primary studies addressing the effectiveness of different treatments the present systematic review may be of high relevance. Special attention will be given to the use of current methodological standards. Findings are likely to provide crucial information that may help clinicians to choose the appropriate treatment for chronically depressed patients.

  11. Glucocorticoid-induced osteoporosis: 2013 update

    Directory of Open Access Journals (Sweden)

    M. Mazzantini

    2014-07-01

    Full Text Available Glucocorticoids are the most common cause of secondary osteoporosis leading to the so-called glucocorticoidinduced osteoporosis (GIO. A treatment with 10 mg/d of prednisone or equivalent for more than 3 months leads to a 7-fold increase in hip fractures and a 17-fold increase in vertebral fractures. The difference between bone quantity and quality in GIO makes bone mineral density measurements inadequate to detect patients at risk of fracture. The adverse effects of glucocorticoids on the skeleton derive from a direct impact on bone cells with a severe impairment of mechanical competence. Crucial to prevention of GIO is early timing of intervention. The World Health Organization has adopted a fracture prevention algorithm (FRAX intended to estimate fracture risk in GIO. The American College of Rhematology modified its prevention and treatment guidelines taking into account the individual risk of fracture calculated in GIO on the basis of the FRAX algorithm. Recently, also a joint Guideline Working Group of the International Osteoporosis Foundation (IOF and the European Calcified Tissue Society (ECTS published a framework for the development of national guidelines for the management of GIO. Bisphosphonates are the first-line drugs to treat GIO; teriparatide counteracts several fundamental pathophysiologic aspects of GIO; denosumab is useful in patients with renal failure and in potentially pregnant young women. Vertebroplasty and kyphoplasty may be less beneficial in GIO than in primary involutional osteoporosis.

  12. Chronic pain relief after the exposure of nitrous oxide during dental treatment: longitudinal retrospective study

    Directory of Open Access Journals (Sweden)

    Francisco Moreira Mattos Júnior

    2015-07-01

    Full Text Available The objective was to investigate the effect of nitrous/oxygen in chronic pain. Seventy-seven chronic pain patients referred to dental treatment with conscious sedation with nitrous oxide/oxygen had their records included in this research. Data were collected regarding the location and intensity of pain by the visual analogue scale before and after the treatment. Statistical analysis was performed comparing pre- and post-treatment findings. It was observed a remarkable decrease in the prevalence of pain in this sample (only 18 patients still had chronic pain, p < 0.001 and in its intensity (p < 0.001. Patients that needed fewer sessions received higher proportions of nitrous oxide/oxygen. Nitrous oxide may be a tool to be used in the treatment of chronic pain, and future prospective studies are necessary to understand the underlying mechanisms and the effect of nitrous oxide/oxygen in patients according to the pain diagnosis and other characteristics.

  13. Treatment of patients with refractory chronic lymphocytic leukemia with alemtuzumab, alone or in combination with fludarabine

    Directory of Open Access Journals (Sweden)

    E. V. Kataeva

    2014-07-01

    Full Text Available In present study the immediate and long-term therapy results of 14 patients with refractory chronic lymphocytic leukemia (CLL are analyzed. Treatment program included alemtuzumab alone or in combination with fludarabine.

  14. Treatment of patients with refractory chronic lymphocytic leukemia with alemtuzumab, alone or in combination with fludarabine

    Directory of Open Access Journals (Sweden)

    E. V. Kataeva

    2011-01-01

    Full Text Available In present study the immediate and long-term therapy results of 14 patients with refractory chronic lymphocytic leukemia (CLL are analyzed. Treatment program included alemtuzumab alone or in combination with fludarabine.

  15. Correlation between pre-treatment quasispecies complexity and treatment outcome in chronic HCV genotype 3a

    Directory of Open Access Journals (Sweden)

    Kenny-Walsh Elizabeth

    2008-07-01

    Full Text Available Abstract Pre-treatment HCV quasispecies complexity and diversity may predict response to interferon based anti-viral therapy. The objective of this study was to retrospectively (1 examine temporal changes in quasispecies prior to the start of therapy and (2 investigate extensively quasispecies evolution in a group of 10 chronically infected patients with genotype 3a, treated with pegylated α2a-Interferon and ribavirin. The degree of sequence heterogeneity within the hypervariable region 1 was assessed by analyzing 20–30 individual clones in serial serum samples. Genetic parameters, including amino acid Shannon entropy, Hamming distance and genetic distance were calculated for each sample. Treatment outcome was divided into (1 sustained virological responders (SVR and (2 treatment failure (TF. Our results indicate, (1 quasispecies complexity and diversity are lower in the SVR group, (2 quasispecies vary temporally and (3 genetic heterogeneity at baseline can be use to predict treatment outcome. We discuss the results from the perspective of replicative homeostasis.

  16. Chronic Urticaria: Indian Context—Challenges and Treatment Options

    Directory of Open Access Journals (Sweden)

    Sujoy Khan

    2013-01-01

    Full Text Available Urticaria is a common condition that occurs in both children and adults. Most cases have no specific allergic trigger and the aetiology of urticaria remains idiopathic and occasionally spontaneous in nature. Inappropriate advice such as avoidance of foods (milk, egg, prawn, and brinjal is common place in certain sections of India mostly by nonspecialists that should not be routinely recommended. It is important to look for physical urticarias such as pressure urticaria in chronic cases, which may be present either alone or in combination with other causes. Autoimmune causes for chronic urticaria have been found to play an important role in a significant proportion of patients. Long-acting nonsedating antihistamines at higher than the standard doses is safe and effective. Quality of life is affected adversely in patients with chronic symptomatic urticaria and some may require multidisciplinary management.

  17. [Gel Metrogil Denta photopheresis use in comprehensive treatment of patients with chronic generalized parodontitis].

    Science.gov (United States)

    Prikuls, V F; Gerasimenko, M Iu; Moskovets, O N; Skovorod'ko, S N

    2008-01-01

    115 patients with chronic generalized parodontitis of middle or severe degree were examined and for them special treatment was developed with laser therapy and photophoresis use. The application of mentioned above physical and pharmacological methods in comprehensive treatment let to shorten the course of treatment and prolong the remission time.

  18. [EXPERIENCE OF SEVERE CHRONIC VENOUS INSUFFICIENCY OF THE LOWER EXTREMITIES TREATMENT].

    Science.gov (United States)

    Ponomarenko, A V

    2015-06-01

    The results of treatment of 246 patients on different forms of chronic venous insufficiency of the lower extremities were presented. The leading diagnostic criterion when choosing tactics consider patients ultrasound duplex scanning with color mapping. Patients in the presence of large ulcers basic treatment is autodermoplasty. The complex treatment include pharmacotherapy, the use of elastic compression hosiery.

  19. Developing an enforceable "right to treatment" theory for the chronically mentally disabled in the community.

    Science.gov (United States)

    Nordwind, B L

    1982-01-01

    Historical developments, mental health approaches, and applicable legal authorities are examined in arguing a legal basis for pursuing greater treatment benefits for chronically mentally disabled persons in the community. Mental health lawyers have traditionally been concerned with patients' right to treatment while in the hospital. Lawyers are called on to examine the plight of (and to extend advocacy for) the chronically mentally disabled in the community.

  20. Effect of non-surgical periodontal treatment on chronic kidney disease patients

    OpenAIRE

    Hilana Paula Carillo Artese; Celso Oliveira de Sousa; Ronir Raggio Luiz; Carmelo Sansone; Maria Cynésia Medeiros Barros Torres

    2010-01-01

    Chronic kidney disease (CKD) is a debilitating systemic condition. Our working hypothesis is that CKD predialysis patients with periodontitis would respond poorly to periodontal treatment owing to immunologic compromise. Twenty-one predialysis patients (group 1) and 19 individuals without clinical evidence of kidney disease (group 2) with chronic periodontitis were subjected to non-surgical periodontal treatment with no antibiotics. Clinical periodontal and systemic parameters were evaluated ...

  1. HSV gene transfer in the treatment of chronic pain

    Institute of Scientific and Technical Information of China (English)

    David J. Fink; Marina Mata

    2008-01-01

    It has proven difficult to use systemic administration of small molecules to selectively modulate nociception. Over the past decade, we and others have developed non-replicating herpes simplex virus (HSV)-based vectors to treat chronic pain. Subcutaneous inoculation of an HSV vector effectively transduces sensory neurons in the dorsal root ganglion; release of transgene-coded inhibitory neurotransmitters or anti-inflammatory peptides reduces pain-related behaviors in rodent models of chronic inflammatory and neuro-pathic pain. A phase 1 trial of this therapy in patients is set to begin soon.

  2. Resolution of chronic severe refractory thrombocytopenia after treatment of hypothyroidism

    Science.gov (United States)

    Bowles, K M; Turner, G E; Wimperis, J Z

    2004-01-01

    The case of a 52 year old woman with chronic severe refractory thrombocytopenia is presented. Over a three year period, her platelet count was persistently less than 20 × 109/litre (normal range, 150–400). She required repeated hospital admission for management of bleeding and received multiple blood transfusions. She was given repeated courses of steroids, immunosuppression, immunoglobulin, and splenectomy, without success, in an attempt to stop the chronic blood loss. Eventually, she was found to be profoundly hypothyroid. On correction of her thyroid deficiency the platelet count returned to the normal range and all bleeding stopped. The platelet count remains in the normal range three years later. PMID:15333667

  3. Bone density threshold and other predictors of vertebral fracture in patients receiving oral glucocorticoid therapy.

    NARCIS (Netherlands)

    Staa, T.P. van; Laan, R.F.J.M.; Barton, I.P.; Cohen, S.; Reid, D.M.; Cooper, C.

    2003-01-01

    OBJECTIVE: To evaluate predictors of vertebral fractures, including a threshold for bone mineral density (BMD), in patients receiving oral glucocorticoids (GCs). METHODS: Data were obtained from 2 randomized clinical trials (prevention and treatment trials of risedronate) using similar methods, but

  4. Glucocorticoid regulates TrkB protein levels via c-Cbl dependent ubiquitination: a decrease in c-Cbl mRNA in the prefrontal cortex of suicide subjects.

    Science.gov (United States)

    Pandya, Chirayu; Kutiyanawalla, Ammar; Turecki, Gustavo; Pillai, Anilkumar

    2014-07-01

    Brain derived neurotrophic factor (BDNF) signaling through its receptor TrkB plays a crucial role in neurodevelopment and plasticity. Stress and glucocorticoids have been shown to alter TrkB signaling in neurons, and defects in TrkB expression have been reported in the prefrontal cortex of suicide subjects. Glucocorticoid treatment has been shown to induce deleterious effects on the neuronal maturation. However, the mechanisms involved in the regulation of TrkB by glucocorticoid during neurodevelopment are not clear. Here we show that acute corticosterone exposure induced posttranslational upregulation of TrkB in primary cortical neurons (days in vitro 4, DIV4), which was blocked by the proteasome inhibitors. Acute corticosterone-induced increase in TrkB protein levels was dependent on glucocorticoid receptor (GR). At the cellular level, ubiquitin E3 ligase c-Cbl mediates TrkB stabilization and corticosterone-induced TrkB levels. Moreover, the tyrosine kinase binding domain in c-Cbl plays a critical role in corticosterone-induced TrkB levels. Chronic treatment of neurons with corticosterone induced significant decreases in both TrkB and c-Cbl protein levels. Acute corticosterone treatment failed to induce any significant change in TrkB and c-Cbl protein levels in mature neurons (DIV 12), where as chronic corticosterone exposure reduced TrkB levels. Under an in vivo condition, chronic corticosterone exposure induced down-regulation of c-Cbl in mouse frontal cortex and hippocampus. Importantly, we demonstrate for the first time a significant decrease in c-Cbl mRNA levels in the prefrontal cortex of suicide subjects indicating the possible role of c-Cbl in the pathophysiology of suicidal behavior. Thus, ubiquitin-proteasome-mediated TrkB regulation may be an important mechanism for improving BDNF signaling and maintaining neuroplasticity in stress-related neuropsychiatric disorders.

  5. Clinical and economic profile of prucalopride in the treatment of chronic constipation in women

    Directory of Open Access Journals (Sweden)

    Vincenzo Stanghellini

    2012-09-01

    Full Text Available Chronic constipation is a common disorder, especially in women. Options available for different subgroups of constipation are limited and in most cases unsatisfactory. The most severe forms of chronic constipation often require the use of laxatives in high doses or the use of invasive therapies. The introduction of a new drug, such as prucalopride, active in promoting intestinal transit, can help to improve the therapy of patients with chronic idiopathic constipation who have not found relief from previous treatment with laxatives. In this review, after a brief discussion of pathophysiology and pharmacotherapy of chronic constipation, we evaluate the pharmacological profile, therapeutic and cost of prucalopride, recently authorized in the EU countries and also available in Italy for the treatment of chronic constipation in women who did not benefit from the use of laxatives

  6. Glucocorticoid programming of intrauterine development.

    Science.gov (United States)

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

    2016-07-01

    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.

  7. OBSERVATION ON THE THERAPEUTIC EFFECT OF ELECTROACUPUNCTURE TREATMENT FOR SIMPLE CHRONIC RHINITIS

    Institute of Scientific and Technical Information of China (English)

    WEN Biling; ZHOU Shuang; YANG Yihong

    2002-01-01

    @@ Simple chronic rhinitis is a reversible chronic inflammatory disorder of nasal mucosa caused by various factors, it is a frequently encountered disorder with clinical manifestations of increased nasal secretion, intermittent alternative nasal obstruction, frequent ( respiratory ) anosmia and rhinophonia while speaking. In severe cases, it may manifest as hypocathexis, hypomnesis, fatigue, headache, head distress, insomnia, etc.that considerably hinder the patient's work or study. In the last 10 years, the authors have chiefly applied electroacupuncture (EA) to treatment of 38 cases of chronic rhinitis and the therapeutic effects are satisfactory. The following is the report of the treatment.

  8. Guideline on prevention and treatment of chronic hepatitis B in China (2005)

    Institute of Scientific and Technical Information of China (English)

    Chinese Society of Hepatology,Chinese Medical Asso

    2007-01-01

    @@ Chronic hepatitis B is one of the most common epidemic diseases in China and has become a major health issue.To help standardize the prevention,diagnosis,and treatment of chronic hepatitis B,the Guideline on prevention and treatment of chronic hepatitis B (abbr.Guideline) was created by a group of appropriate experts belonging to the Society of Hepatology and the Society of Infectious Disease,the Chinese Medical Association according to the principles of evidence-based medicine using the latest clinical research data.

  9. 糖皮质激素鼓室给药治疗突发性聋的现况分析%Current State of Intratympanic Glucocorticoids Treatment for Sudden Sensorineural Hearing Loss

    Institute of Scientific and Technical Information of China (English)

    刘璐; 钟时勋

    2015-01-01

    突发性聋是耳鼻喉科常见的急症,目前临床上全身使用糖皮质激素治疗突发性聋获得较为肯定的疗效,但全身使用糖皮质激素的禁忌症及可能引起严重的不良反应,使得糖皮质激素鼓室给药治疗突发性聋逐渐得到应用并成为广泛关注的热点。本文将对糖皮质激素鼓室给药的疗效进行评估,以及对其临床运用的现况进行阐述。%Sudden sensorineural hearing loss is a common emergency in otolaryngology. Currently, systemic glucocorti⁃coids is a commonly used treatment with certain efficacies, but concerns over potentially serious adverse reactions as contraindi⁃cations remain. Hence intratympanic glucocorticoids injection for sudden sensorineural hearing loss has gradually attracted at⁃tention. This article evaluates the efficacy of this treatment in sudden sensorineural hearing loss, and elaborates on its clinical application.

  10. Effects of Glucocorticoids on TCM diagnosis and treatment of Patients with Systemic Lupus Erythematosus%糖皮质激素对中医诊治SLE影响的思考

    Institute of Scientific and Technical Information of China (English)

    孙小钧; 高永翔

    2015-01-01

    糖皮质激素对中医诊治SLE有影响。针对患者常出现多脏腑病位、多症状表现、虚实夹杂、寒热互结的病机病性改变的复杂病情,对此类病人的辨证论治应注意:辨病论治与辨证论治相结合,四诊合参,注重辨别患者体质。%Glucocorticoid has affected TCM diagnosis and treatment of SLE. This kind of diseases Often affect many viscera, appear multiple symptoms, mingled with excess and deficiency syndromes, mixed cold and heat syndromes. Those lead complex changes in disease pathogenesis. Diagnosing and treating such patients, should pay attention to: treatment and diagnosis based on differentiation of disease and Syndrome , Synthesis of the four diagnostic methods,the important of Physical Discrimination of patients.

  11. Clinical Experience in TCM Treatment of Chronic Cervicitis

    Institute of Scientific and Technical Information of China (English)

    周宜强; 范宏宇

    2002-01-01

    @@ Chronic cervicitis is a common disease in the female reproductive system, which may be the inducing factor for carcinoma of uterine cervix. It is clinically manifested by sticky and foul leukorrhagia, contact hemorrhage, pain in the lower limbs or lumbosacral region, dysmenorrhea and infertility.

  12. Imaging and Treatment of Chronic Midportion Achilles Tendinopathy

    NARCIS (Netherlands)

    R.J. de Vos (Robert-Jan)

    2010-01-01

    textabstractIntroduction: It is estimated that 30-50% of sports injuries are caused by tendon disorders. Chronic midportion Achilles tendinopathy is a frequent problem, particularly occurring in athletes but also affecting inactive people. Diagnosis is made based on clinical findings and currently t

  13. Diagnostic efficiency and treatment strategy in chronic axonal polyneuropathy

    NARCIS (Netherlands)

    Vrancken, A.F.J.E.

    2007-01-01

    Polyneuropathy is a common peripheral nerve disorder that often has a well known cause such as diabetes, chronic renal disease, alcohol abuse, vitamin deficiency, hypothyroidism, or use of toxic medication. Elderly people are more often affected, but the differentiation from signs of normal ageing c

  14. Chronic hepatitis C: This and the new era of treatment

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    Over the last years it has started a real revolution in thetreatment of chronic hepatitis C. This occurred for theavailability of direct-acting antiviral agents that allowto reach sustained virologic response in approximately90% of cases. In the near future further progress willbe achieved with the use of pan-genotypic drugs withhigh efficacy but without side effects.

  15. Mexiletine for treatment of chronic painful diabetic neuropathy

    DEFF Research Database (Denmark)

    Dejgard, A; Kastrup, J; Petersen, P

    1988-01-01

    Sixteen of nineteen patients completed a randomised double-blind crossover trial to assess the effect of oral mexiletine (10 mg/kg bodyweight daily) on the symptoms and signs of chronic painful diabetic neuropathy. The median age of the sixteen patients was 50 years (range 30-64). Assessment...

  16. Anemia in chronic heart failure : etiology and treatment options

    NARCIS (Netherlands)

    Westenbrink, B. Daan; de Boer, Rudolf A.; Voors, Adriaan A.; van Gilst, Wiek H.; van Veldhuisen, Dirk J.

    2008-01-01

    Purpose of review Anemia is common in patients with chronic heart failure, and is related to increased morbidity and mortality. The etiology of anemia in heart failure is complex and still not fully resolved. The review will describe current advances in the understanding of the pathophysiology of an

  17. Local Treatment of Chronic Wounds in Patients With Peripheral Vascular Disease, Chronic Venous Insufficiency, and Diabetes

    NARCIS (Netherlands)

    Ruettermann, Mike; Maier-Hasselmann, Andreas; Nink-Grebe, Brigitte; Burckhardt, Marion

    2013-01-01

    Background: A chronic wound is defined as an area where the skin is not intact that fails to heal within eight weeks. Such wounds usually develop on the lower limbs as a complication of diabetes, venous insufficiency, or inadequate arterial perfusion. Most of the roughly 45 000 limb amputations perf

  18. Forkhead box A3 mediates glucocorticoid receptor function in adipose tissue.

    Science.gov (United States)

    Ma, Xinran; Xu, Lingyan; Mueller, Elisabetta

    2016-03-22

    Glucocorticoids (GCs) are widely prescribed anti-inflammatory agents, but their chronic use leads to undesirable side effects such as excessive expansion of adipose tissue. We have recently shown that the forkhead box protein A3 (Foxa3) is a calorie-hoarding factor that regulates the selective enlargement of epididymal fat depots and suppresses energy expenditure in a nutritional- and age-dependent manner. It has been demonstrated that Foxa3 levels are elevated in adipose depots in response to high-fat diet regimens and during the aging process; however no studies to date have elucidated the mechanisms that control Foxa3's expression in fat. Given the established effects of GCs in increasing visceral adiposity and in reducing thermogenesis, we assessed the existence of a possible link between GCs and Foxa3. Computational prediction analysis combined with molecular studies revealed that Foxa3 is regulated by the glucocorticoid receptor (GR) in preadipocytes, adipocytes, and adipose tissues and is required to facilitate the binding of the GR to its target gene promoters in fat depots. Analysis of the long-term effects of dexamethasone treatment in mice revealed that Foxa3 ablation protects mice specifically against fat accretion but not against other pathological side effects elicited by this synthetic GC in tissues such as liver, muscle, and spleen. In conclusion our studies provide the first demonstration, to our knowledge, that Foxa3 is a direct target of GC action in adipose tissues and point to a role of Foxa3 as a mediator of the side effects induced in fat tissues by chronic treatment with synthetic steroids.

  19. Treatment of chronic depression with sulpiride: evidence of efficacy in placebo-controlled single case studies.

    Science.gov (United States)

    Maier, W; Benkert, O

    1994-08-01

    Systematic variation of treatment (alternating active drug and placebo in four treatment periods) in individual patients is proposed to collect preliminary evidence for a therapeutic effect of sulpiride in chronic depression; the ARIMA model is applied to evaluate the intervention effects of the tentatively effective treatment in single subjects. Ten single cases of chronic depression with a diagnosis of major depression or dysthymia were selected and seven of these provided evidence for beneficial effects of sulpiride with regard to treating the symptoms of depression and anxiety. However, the drug effects were intraindividually not always replicable. The results obtained with these single cases positively support the recommendation to perform regular randomized placebo-controlled trials with sulpiride in chronic depression. Simultaneously, these single case investigations reveal a lack of temporal stability of treatment response and inconsistencies of response with regard to different treatment targets in individual patients.

  20. Long-term opioid treatment of chronic nonmalignant pain: unproven efficacy and neglected safety?

    Directory of Open Access Journals (Sweden)

    Kissin I

    2013-07-01

    Full Text Available Igor Kissin Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Background: For the past 30 years, opioids have been used to treat chronic nonmalignant pain. This study tests the following hypotheses: (1 there is no strong evidence-based foundation for the conclusion that long-term opioid treatment of chronic nonmalignant pain is effective; and (2 the main problem associated with the safety of such treatment – assessment of the risk of addiction – has been neglected. Methods: Scientometric analysis of the articles representing clinical research in this area was performed to assess (1 the quality of presented evidence (type of study; and (2 the duration of the treatment phase. The sufficiency of representation of addiction was assessed by counting the number of articles that represent (1 editorials; (2 articles in the top specialty journals; and (3 articles with titles clearly indicating that the addiction-related safety is involved (topic-in-title articles. Results: Not a single randomized controlled trial with opioid treatment lasting >3 months was found. All studies with a duration of opioid treatment ≥6 months (n = 16 were conducted without a proper control group. Such studies cannot provide the consistent good-quality evidence necessary for a strong clinical recommendation. There were profound differences in the number of addiction articles related specifically to chronic nonmalignant pain patients and to opioid addiction in general. An inadequate number of chronic pain-related publications were observed with all three types of counted articles: editorials, articles in the top specialty journals, and topic-in-title articles. Conclusion: There is no strong evidence-based foundation for the conclusion that long-term opioid treatment of chronic nonmalignant pain is effective. The above identified signs indicating neglect of addiction associated with the

  1. Treatment of a chronic Scedosporium apiospermum vertebral osteomyelitis. Case report.

    Science.gov (United States)

    German, John W; Kellie, Susan M; Pai, Manjunath P; Turner, Paul T

    2004-12-15

    Scedosporium apiospermum is a rare cause of fungal vertebral osteomyelitis that may result in chronic infection requiring multiple surgical interventions and long-term medical therapy. This case is the seventh one reported in the literature and is the first to include salvage surgery of a previous major spinal reconstruction. This report is also the first to describe the use of the new antifungal agent voriconazole. In treating this case of chronic vertebral osteomyelitis, several principles are emphasized from both the surgical and medical perspectives. From a surgical perspective, the use of salvage surgery, temporary avoidance of spinal instrumentation, and an appropriate choice of graft materials are emphasized. From a medical perspective, confirmation of the diagnosis, the need for long-term antifungal therapy, the need for long-term patient compliance, and the use of the new antifungal agent voriconazole are emphasized. Application of these principles has led to an adequate 2-year outcome.

  2. EXPERIENCE IN LOCAL IMMUNOCORRECTION IN TREATMENT OF CHRONIC WOUNDS

    Directory of Open Access Journals (Sweden)

    I. A. Novikova

    2010-01-01

    Full Text Available At present time, immunotyping of lymphocyte subpopulations is an obligatory test, if an acquired immunodeficiency state is suspected, e.g., in chronic recurrent furunculosis. However, the data obtained are sometimes difficult to interprete, due to of insignificant and or multidirectional changes of parameters determined in the patients undergoing immunological testing. In present study, some basic features of immune status were examined in the patients with chronic recurrent furunculosis, being in remission state. A detailed analysis of separate immunological indices is presented, taking into account duration of the disease, periodicity of recurrencies, and individual clinical features of furunculosis. Dynamics of immunological test values in the course of disease and upon clinical exacerbations were subject to special analysis. Altered relationships between lymphocyte subpopulation are described in patients with furunculosis.

  3. TRPV1 and TRPM8 in Treatment of Chronic Cough

    OpenAIRE

    Eva Millqvist

    2016-01-01

    Chronic cough is common in the population, and among some there is no evident medical explanation for the symptoms. Such a refractory or idiopathic cough is now often regarded as a neuropathic disease due to dysfunctional airway ion channels, though the knowledge in this field is still limited. Persistent coughing and a cough reflex easily triggered by irritating stimuli, often in combination with perceived dyspnea, are characteristics of this disease. The patients have impaired quality of li...

  4. Obinutuzumab treatment in the elderly patient with chronic lymphocytic leukemia

    OpenAIRE

    Seiter K; Mamorska-Dyga A

    2015-01-01

    Karen Seiter, Aleksandra Mamorska-DygaDepartment of Medicine, Division of Hematology/Oncology, New York Medical College, Valhalla, NY, USA Abstract: Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults in Western countries. Fludarabine-based regimens demonstrate higher response rates in younger patients but have a significant risk of infection and are thus poorly tolerated by older, frail patients. Anti-CD20 monoclonal antibodies have added to the efficacy of chemotherapy ...

  5. Karyotypic findings in chronic myeloid leukemia cases undergoing treatment

    OpenAIRE

    Anupam Kaur; Simran Preet Kaur; Amarjit Singh; Jai Rup Singh

    2012-01-01

    Background: Chronic myeloid leukemia (CML) is a clonal myeloproliferative expansion of primitive hematopoietic progenitor cells. Materials and Methods: In the present study, CML samples were collected from various hospitals in Amritsar, Jalandhar and Ludhiana. Results: Chromosomal alterations seen in peripheral blood lymphocytes of these treated and untreated cases of CML were satellite associations, double minutes, random loss, gain of C group chromosomes and presence of marker chr...

  6. Endomorphins as agents for the treatment of chronic inflammatory disease.

    Science.gov (United States)

    Jessop, David S

    2006-01-01

    Endomorphin (EM)-1 and EM-2 are tetrapeptides located within the mammalian central nervous system and immune tissues, with high affinity and specificity for micro-opioid receptors. Most of the literature has focused on the analgesic properties of EM-1 and EM-2 in animal models of neuropathic or neurogenic pain, but there is persuasive evidence emerging that EMs can also exert potent anti-inflammatory effects in both acute and chronic peripheral inflammation. The purpose of this review is to present and evaluate the evidence for anti-inflammatory properties of EM-1 and EM-2 with a view to their potential for use in chronic human inflammatory disease. Distribution of EMs within the immune system and functional roles as immunomodulatory agents are summarized and discussed. Possible milestones to be met revolve around issues of peptide stability, biodegradability problems and optimal route and method of delivery. The potential for delivery of a low-cost drug with both peripheral anti-inflammatory and analgesic properties, effective in low doses, and targeted to the site of inflammation, should focus our attention on further development of EMs as potent therapeutic agents in chronic inflammation.

  7. Repetitive prenatal glucocorticoids increase lung endothelial nitric oxide synthase expression in ovine fetuses delivered at term.

    Science.gov (United States)

    Grover, T R; Ackerman, K G; Le Cras, T D; Jobe, A H; Abman, S H

    2000-07-01

    Antenatal administration of glucocorticoids has been shown to improve postnatal lung function after preterm birth in the ovine fetus. Mechanisms of steroid-induced lung maturation include increased surfactant production and altered parenchymal lung structure. Whether steroid treatment also affects lung vascular function is unclear. Because nitric oxide contributes to the fall in pulmonary vascular resistance at birth, we hypothesized that the improvement of postnatal lung function of preterm lambs after treatment with prenatal glucocorticoids may be in part caused by an increase in endothelial nitric oxide synthase (eNOS) activity. To determine whether glucocorticoid treatment increases lung eNOS expression, we measured eNOS protein content by Western blot analysis of distal lung homogenates and immunostaining of formalin-fixed lungs from ovine fetuses delivered at preterm and term gestation after prenatal administration of glucocorticoids. Treatment protocols were followed in which ewes were treated with intramuscular betamethasone (0.5 mg/kg) at single or multiple doses at weekly intervals, and fetuses were delivered at 125, 135, or 145 d gestation. All groups were compared with saline-treated controls. Western blot analysis of whole lung homogenates demonstrated a 4-fold increase in eNOS protein content in lambs treated with repetitive doses of glucocorticoids and delivery at term (145 d; p preterm ages (125 and 135 d). Immunostaining showed eNOS predominantly in the vascular endothelium in all vessel sizes. Pattern of staining was not altered by treatment with antenatal glucocorticoids. We conclude that maternal treatment with glucocorticoids increases lung eNOS content after multiple doses and delivery at term gestation. We speculate that antenatal glucocorticoids may up-regulate eNOS but that the timing and duration of steroid administration appears to be critical to this response.

  8. Cognitive-behavioral treatments for chronic pain: what works for whom?

    Science.gov (United States)

    Vlaeyen, Johan W S; Morley, Stephen

    2005-01-01

    Since the introduction of behavioral medicine in the early 70s, cognitive-behavioral treatment interventions for chronic pain have expanded considerably. It is now well established that these interventions are effective in reducing the enormous suffering that patients with chronic pain have to bear. In addition, these interventions have potential economic benefits in that they appear to be cost-effective as well. Despite these achievements, there is still room for improvement. First, there is a substantial proportion of patients who do not appear to benefit from treatment interventions available. Second, although the effect sizes of most cognitive-behavioral treatments for chronic pain are comparable to those in psychopathology, they are quite modest. Third, there is little evidence for differential outcomes for different treatment methods. Fourth, there still is relatively little known about the specific biobehavioral mechanisms that lead to chronic pain and pain disability. One direction is to better match treatment programs to patients' characteristics. This can be done according to an "Aptitude X Treatment Interaction" framework, or from the perspective of the Moderator-Mediator distinction. In this introduction to the special series on what works for whom in cognitive-behavioral treatments for chronic pain, we review existing knowledge concerning both moderating and mediating variables in cognitive-behavioral treatments for chronic pain. We further argue in favor of theory-driven research as the only way to define specific a priori hypotheses about which patient-treatment interactions to expect. We also argue that replicated single-participant studies, with appropriate statistics, are likely to enhance new developments in this clinical research area.

  9. Physical exercise as non-pharmacological treatment of chronic pain: Why and when.

    Science.gov (United States)

    Ambrose, Kirsten R; Golightly, Yvonne M

    2015-02-01

    Chronic pain broadly encompasses both objectively defined conditions and idiopathic conditions that lack physical findings. Despite variance in origin or pathogenesis, these conditions are similarly characterized by chronic pain, poor physical function, mobility limitations, depression, anxiety, and sleep disturbance, and they are treated alone or in combination by pharmacologic and non-pharmacologic approaches, such as physical activity (aerobic conditioning, muscle strengthening, flexibility training, and movement therapies). Physical activity improves general health, disease risk, and progression of chronic illnesses such as cardiovascular disease, type 2 diabetes, and obesity. When applied to chronic pain conditions within appropriate parameters (frequency, duration, and intensity), physical activity significantly improves pain and related symptoms. For chronic pain, strict guidelines for physical activity are lacking, but frequent movement is preferable to sedentary behavior. This gives considerable freedom in prescribing physical activity treatments, which are most successful when tailored individually, progressed slowly, and account for physical limitations, psychosocial needs, and available resources.

  10. Erythropoietin treatment does not compromise cardiovascular function in chronic renal failure

    DEFF Research Database (Denmark)

    Haedersdal, C; Mehlsen, J; Stenver, Doris Irene

    1994-01-01

    The anemia in patients with chronic renal failure can be corrected through treatment with recombinant human erythropoietin treatment. This correction is associated with changes in the rheologic variables, which could explain the changes in hemodynamics found by many investigators. The authors have...... followed up 11 patients with chronic renal failure on hemodialysis before and during six months of therapy with erythropoietin. The measurements were made before treatment, after four months of therapy, and after six months of therapy. The measurements included hematocrit, osmotic resistance of the red...

  11. Pamidronate treatment of chronic noninfectious inflammatory lesions of the mandible in children.

    Science.gov (United States)

    Compeyrot-Lacassagne, Sandrine; Rosenberg, Alan M; Babyn, Paul; Laxer, Ronald M

    2007-07-01

    Noninfectious inflammatory lesions of the mandible occur in chronic recurrent multifocal osteomyelitis (CRMO). Diffuse sclerosing osteomyelitis of the mandible (DSOM) is a condition thought to be a localized form of CRMO. Recently, bisphosphonate therapy, and particularly intravenous pamidronate, has been proposed as a treatment for patients with both CRMO and DSOM who do not improve with nonsteroidal antiinflammatory drug treatment. We report our experience using pamidronate in 2 children with chronic noninfectious osteomyelitis affecting the mandible. We describe the clinical and radiographic features and the treatment, side effects, and clinical and radiographic responses. Our experience suggests that pamidronate is an effective second-line therapy.

  12. Chronic dihydroergotoxine treatment affects the number of dopamine recognition sites in rat striatum

    Energy Technology Data Exchange (ETDEWEB)

    Battaini, F.; Govoni, S.; Rius, R.A.; Spano, P.F.; Trabucchi, M.

    1984-06-01

    Ergot derivatives have been proposed to have ameliorative effects in various pathological conditions where dopaminergic transmission is believed to be impaired, namely Parkinson's disease, amenorrhea-galactorrhea syndrome, and in the treatment of behavioural disturbances of the elderly. To get more insight into a possible involvement of a direct action of ergot derivatives on dopamine receptors we studied the effect of acute and chronic dihydroergotoxine (DHT) treatment on 3H-Spiroperidol and 3H-N-Propylnorapomorphine (3H-NPA) binding to rat striatal membrane preparations. The results are in favor of an interaction of ergot derivatives with dopamine recognition sites both after acute and chronic treatment.

  13. Clinical Studies on Treatment of Chronic Prostatitis with Acupuncture and Mild Moxibustion

    Institute of Scientific and Technical Information of China (English)

    Yu Yang; Kang Jingli; Duan Shumin

    2005-01-01

    To observe the therapeutic effect of acupuncture and mild moxibustion on chronic prostatitis and to probe into the mechanism of the therapy. Two hundred patients with chronic prostatitis were randomly divided into two groups so as to observe respectively the changes in clinical symptoms, count of WBC and lecithin corpuscles in succus prostaticus, prostatic capcules and internal echo, tenderness and elasticity of prostate by palpation before and after treatment. After treatment, a remarkable improvement was found in clinical symptoms, succus prostaticus test and ultrasonic examination in the treatment group with a statistically significant difference (P<0.05) as compared to the control group. The treatment of chronic prostatitis with acupuncture and mild moxibustion can remove the stagnation of succus prostaticus, improve the blood circulation in prostate, inhibit or kill the pathogenic micro-organisms, strengthen or regulate the immune function of the patients, improve local blood circulation, eliminate the accumulation of secretion and relieve the obstruction of the prostatic ducts.

  14. Modern wound care - practical aspects of non-interventional topical treatment of patients with chronic wounds.

    Science.gov (United States)

    Dissemond, Joachim; Augustin, Matthias; Eming, Sabine A; Goerge, Tobias; Horn, Thomas; Karrer, Sigrid; Schumann, Hauke; Stücker, Markus

    2014-07-01

    The treatment of patients with chronic wounds is becoming increasingly complex. It was therefore the aim of the members of the working group for wound healing (AGW) of the German Society of Dermatology (DDG) to report on the currently relevant aspects of non-interventional, topical wound treatment for daily practice. -Beside necessary procedures, such as wound cleansing and débridement, we describe commonly used wound dressings, their indications and practical use. Modern antiseptics, which are currently used in wound therapy, usually contain polyhexanide or octenidine. Physical methods, such as negative-pressure treatment, are also interesting options. It is always important to objectify and adequately treat pain symptoms which often affect these patients. Modern moist wound therapy may promote healing, reduce complications, and improve the quality of life in patients with chronic wounds. Together with the improvement of the underlying causes, modern wound therapy is an important aspect in the overall treatment regime for patients with chronic wounds.

  15. Erythropoietin treatment does not compromise cardiovascular function in chronic renal failure

    DEFF Research Database (Denmark)

    Haedersdal, C; Mehlsen, J; Stenver, Doris Irene;

    1994-01-01

    The anemia in patients with chronic renal failure can be corrected through treatment with recombinant human erythropoietin treatment. This correction is associated with changes in the rheologic variables, which could explain the changes in hemodynamics found by many investigators. The authors hav...

  16. Sofosbuvir and Simeprevir Treatment of a Stem Cell Transplanted Teenager With Chronic Hepatitis C Infection.

    Science.gov (United States)

    Fischler, Björn; Priftakis, Peter; Sundin, Mikael

    2016-06-01

    There have been no previous reports on the use of interferon-free combinations in pediatric patients with chronic hepatitis C infection. An infected adolescent with severe sickle cell disease underwent stem cell transplantation and subsequent treatment with sofosbuvir and simeprevir during ongoing immunosuppression. Despite the emergence of peripheral edema as a side effect, treatment was continued with sustained antiviral response.

  17. Dutch guidance for the treatment of chronic hepatitis C virus infection in a new therapeutic era

    NARCIS (Netherlands)

    Berden, F.A.C.; Kievit, W.; Baak, L.C.; Bakker, C.M.; Beuers, U.; Boucher, C.A.B.; Brouwer, J.T.; Burger, D.M.; Erpecum, K.J. van; Hoek, B. van; Hoepelman, A.I.; Honkoop, P.; Kerbert-Dreteler, M.J.; Knegt, R.J. de; Koek, G.H.; Nieuwkerk, C.M. van; Soest, H. van; Tan, A.C.; Vrolijk, J.M.; Drenth, J.P.H.

    2014-01-01

    BACKGROUND: A new era for the treatment of chronic hepatitis C is about to transpire. With the introduction of the first-generation protease inhibitors the efficacy of hepatitis C treatment improved significantly. Since then, the therapeutic agenda has moved further forward with the recent approval

  18. Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder : A randomized clinical trial

    NARCIS (Netherlands)

    Feder, Adriana; Parides, Michael K.; Murrough, James W.; Perez, Andrew M.; Morgan, Julia E.; Saxena, Shireen; Kirkwood, Katherine; Aan Het Rot, Marije; Lapidus, Kyle A.B.; Wan, Le-Ben; Iosifescu, Dan; Charney, Dennis S.

    2014-01-01

    IMPORTANCE Few pharmacotherapies have demonstrated sufficient efficacy in the treatment of posttraumatic stress disorder (PTSD), a chronic and disabling condition. OBJECTIVE To test the efficacy and safety of a single intravenous subanesthetic dose of ketamine for the treatment of PTSD and associate

  19. [Photophoresis and mesophotophoresis of angioprotectant group preparations for comprehensive treatment of patients with chronic generalized parodontitis].

    Science.gov (United States)

    Prikuls, V F

    2008-01-01

    Examination of 118 patients with chronic generalized parodontitis of medium and heavy severity was performed and treatment was elaborated with the use of laser therapy and angioprotectants' photophoresis and mesophotophoresis. Use of the mentioned physical and physical-pharmacological methods in comprehensive cure let to shorten the course of treatment and increase remission duration.

  20. Treatment of Oppositional Behavior in Children of Parents with Brain Injury and Chronic Pain.

    Science.gov (United States)

    Ducharme, Joseph M.; Davidson, Amy; Rushford, Nancy

    2002-01-01

    This case study evaluated effects of errorless compliance training on cooperation of sons of two fathers with brain injury and chronic pain. Following treatment, children displayed high levels of compliance to parent requests as well as generalization and maintenance of treatment gains. Errorless compliance training is recommended to foster…

  1. Statistical Models of Treatment Effects in Chronic Hepatitis B and C

    NARCIS (Netherlands)

    B.E. Hansen (Bettina)

    2010-01-01

    textabstractThis thesis regards treatment effects in patients with chronic hepatitis B and C, and focuses on the tools that are used to analyse these effects. In this introduction the clinical background of hepatitis B and C along with the current treatment options are described. Clinical questions

  2. Karyotypic findings in chronic myeloid leukemia cases undergoing treatment

    Directory of Open Access Journals (Sweden)

    Anupam Kaur

    2012-01-01

    Full Text Available Background: Chronic myeloid leukemia (CML is a clonal myeloproliferative expansion of primitive hematopoietic progenitor cells. Materials and Methods: In the present study, CML samples were collected from various hospitals in Amritsar, Jalandhar and Ludhiana. Results: Chromosomal alterations seen in peripheral blood lymphocytes of these treated and untreated cases of CML were satellite associations, double minutes, random loss, gain of C group chromosomes and presence of marker chromosome. No aberrations were observed in control samples. Karyotypic abnormalities have also been noted in the Ph-negative cells of some patients in disease remission. Conclusion: This is a novel phenomenon whose prognostic implications require thorough and systematic evaluation.

  3. 糖皮质激素在风湿病治疗中的应用及其并发症的处理%Application of glucocorticoid in the treatment of rheumatic diseases and the prevention and treatment of its complication

    Institute of Scientific and Technical Information of China (English)

    薛愉; 万伟国

    2012-01-01

      Glucocorticoid is the most important and widely used drug in treatment of rheumatic diseases, which has powerful immunosuppressive and anti-inflammatory effects. But when altering the pathological process, it will break the original physiological balance resulting in the occurrence of complication. Therefore, it is very important for the clinical physicians to accurately understand, standardize the application and timely prevent and treat the complication of the glucocorticoid. In this article, we introduce the physiological role, pharmacological mechanism, standardizational use and prevention and treatment of the complication.%  糖皮质激素是风湿病治疗中的最重要药物,具有强力的免疫抑制和抗炎作用,但在改变病理过程的同时也会打破原有的生理平衡,导致并发症的发生。因此,准确认识、规范应用和及时防治糖皮质激素的并发症对临床医师来说十分重要。本文就糖皮质激素的生理作用、药理机制以及规范化应用和并发症防治进行概述。

  4. Local tissue flaps: definitive treatment for chronic blisters after chemical burns.

    Science.gov (United States)

    Maguina, Pirko; Busse, Brittany

    2011-01-01

    Chronic blistering in grafted burn wounds is an infrequently described but severely debilitating complication that can appear after alkali burns and seems to coincide with a delay in initial treatment. Histological studies have concluded that the pathogenesis of chronic subepidermal blister formation in previously grafted burn wounds is related to abnormalities in the basement membrane. Although several reports have described this problem, none have reported adequate treatment for the chronic blistering in previously grafted alkali burns. The authors describe the case of a 30-year-old man in whom caustic soda burns treated with excision and split-thickness skin grafting resulted in chronic subepidermal blistering that failed to improve over the next 2 years. The problem was resolved with full-thickness skin excision and reconstruction with bipedicled fasciocutaneous flaps.

  5. Glucocorticoids in juvenile idiopathic arthritis.

    Science.gov (United States)

    Malattia, Clara; Martini, Alberto

    2014-05-01

    Although the use of corticosteroids in juvenile idiopathic arthritis (JIA) is now much more limited owing to the availability of methotrexate and biological agents, there are clinical scenarios where it is still indicated. For example, corticosteroids may be indicated for intraarticular injections to prevent joint deformities, as a "bridge" drug to relieve symptoms in polyarticular disease while waiting for methotrexate and biologics to exert their full therapeutic effects, and in the treatment of chronic iridocyclitis, macrophage activation syndrome, and systemic JIA, although the advent of interleukin (IL)-1 and IL-6 blockers has greatly reduced the latter indication.

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

    NARCIS (Netherlands)

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

    2010-01-01

    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

  7. Chronic Pain Following Spinal Cord Injury: The Role of Immunogenetics and Time of Injury Pain Treatment

    Science.gov (United States)

    2015-10-01

    central sensitization to nociceptive stimuli culminates in profound debilitating pain that serves no adaptive purpose for the sufferer. It is now...Award Number: W81XWH-11-1-0806 TITLE: Chronic Pain Following Spinal Cord Injury: The Role of Immunogenetics and Time of Injury Pain Treatment...29Sep2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-11-1-0806 Chronic Pain Following Spinal Cord Injury: The Role of Immunogenetics and Time

  8. Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials

    OpenAIRE

    Mary E Lynch; Campbell, Fiona

    2011-01-01

    Effective therapeutic options for patients living with chronic pain are limited. The pain relieving effect of cannabinoids remains unclear. A systematic review of randomized controlled trials (RCTs) examining cannabinoids in the treatment of chronic non-cancer pain was conducted according to the PRISMA statement update on the QUORUM guidelines for reporting systematic reviews that evaluate health care interventions. Cannabinoids studied included smoked cannabis, oromucosal extracts of cannabi...

  9. Blockade of glucocorticoid receptors improves cutaneous wound healing in stressed mice.

    Science.gov (United States)

    de Almeida, Taís Fontoura; de Castro Pires, Taiza; Monte-Alto-Costa, Andréa

    2016-02-01

    Stress is an important condition of modern life. The successful wound healing requires the execution of three major overlapping phases: inflammation, proliferation, and remodeling, and stress can disturb this process. Chronic stress impairs wound healing through the activation of the hypothalamic-pituitary-adrenal axis, and the glucocorticoids (GCs) hormones have been shown to delay wound closure. Therefore, the aim of this study was to investigate the effects of a GC receptor antagonist (RU486) treatment on cutaneous healing in chronically stressed mice. Male mice were submitted to rotational stress, whereas control animals were not subjected to stress. Stressed and control animals were treated with RU486. A full-thickness excisional lesion was generated, and seven days later, lesions were recovered. The RU486 treatment improves wound healing since contraction takes place earlier in RU486-treated in comparison to non-treated mice, and the RU486 treatment also improves the angiogenesis in Stress+RU486 mice when compared to stressed animals. The Stress+RU486 group showed a decrease in inflammatory cell infiltration and in hypoxia-inducible factor-1α and inducible nitric oxide synthase expression; meanwhile, there was an increase in myofibroblasts quantity. In conclusion, blockade of GC receptors with RU486 partially ameliorates stress-impaired wound healing, suggesting that stress inhibits healing through more than one functional pathway.

  10. A case report: Familial glucocorticoid deficiency associated with familial focal segmental glomerulosclerosis

    Directory of Open Access Journals (Sweden)

    Ram Nanik

    2012-12-01

    Full Text Available Abstract Background Familial glucocorticoid deficiency (FGD is a rare autosomal recessive disorder characterized by isolated glucocorticoid deficiency in the presence of normal plasma renin and aldosterone level. Focal segmental glomerulosclerosis (FSGS is a form of glomerular disease associated with proteinuria and nephritic syndrome. This is the first case of familial glucocorticoid deficiency associated with familial focal segmental glomerulosclerosis. Case presentation An eight month old boy presented with increased genital pigmentation. Initial investigation revealed that he was glucocorticoid deficient and was started on hydrocortisone and fludrocortisone with a diagnosis of primary adrenal insufficiency. Later fludrocortisone was withdrawn and he was diagnosed to have isolated glucocorticoid deficiency. He later developed focal segmental glomerulosclerosis for which he underwent renal transplantation at the age of five years. Now at the age of twelve years, this boy is doing well on hydrocortisone treatment. His two siblings and a first degree cousin also had isolated glucocorticoid deficiency. One of the above two siblings died due to renal failure secondary to focal segmental glomerulosclerosis. Conclusion Patients with familial glucocorticoid deficiency should be carefully followed for development of features of nephrotic syndrome.

  11. Neurodevelopment and Chronic Illness: Mechanisms of Disease and Treatment

    Science.gov (United States)

    Armstrong, F. Daniel

    2006-01-01

    Successful treatment of many childhood diseases once considered terminal has resulted in the emergence of long-term effects of the disease or consequences of treatment that were previously unrecognized. Many of these long-term effects involve the central nervous system (CNS) and are developmental in the way that they emerge over time. Because we…

  12. Acupuncture for the treatment or management of chronic pain.

    Science.gov (United States)

    Coeytaux, Remy R; Garland, Eric

    2013-01-01

    Evidence supports the safety and efficacy of acupuncture compared with no treatment, but it is unclear what role the placebo effect plays in acupuncture's efficacy. In determining whether acupuncture is indicated for a given individual or patient population, clinicians should consider acupuncture's effectiveness compared with no acupuncture--as well as the effectiveness, safety, and cost of alternative types of treatment.

  13. Treatment and follow up of children with chronic hepatitis C in Albania

    Directory of Open Access Journals (Sweden)

    Velmishi Virtut

    2012-01-01

    Full Text Available Abstract Background Treatment of Hepatitis C in children has a better outcome than in adults, and for this reason the treatment had different views. However, in pediatric age hepatitis C is seen to have an evolution towards chronicity. Today is a normal option to treat chronic hepatitis C as early as possible according to certain criteria. The aim of this study is to show the results of treatment with interferon and ribavirin and the follow-up of children diagnosed with chronic hepatitis C in our service. Patients and methods This is a prospective study which has included children 3 up to 15 years old (13 boys and 4 girls diagnosed with chronic hepatitis C. All patients underwent a certain protocol, including liver biopsy prior to treatment. Treatment consisted in use for 48 weeks of INF α-2b, 3 MIU/m2 three times a week s/c and ribavirin 15 mg/kg orally divided bid. Two patients were treated with PEGINF α-2b with dose 1.5 mcg/kg once a week s/c and ribavirin 15 mg/kg. After the treatment all patients have stayed under our control for an average period of 24 weeks. Results At the end of the treatment we detected a patient with HCV-RNA positive. End Treatment Viral Response was 94%. Six months later we found three patients who showed relapse of disease. Sustained Viral Response was approximately 83% Conclusion The combination therapy of interferon with Ribavirin in treatment of children with chronic hepatitis C provides a higher SVR when treatment is initiated at the earliest stages of hepatic changes. Side effects of therapy are insignificant in comparison with results obtained

  14. Alendronate prevents glucocorticoid-induced osteoporosis in patients with rheumatic diseases

    OpenAIRE

    Kan, Shun-Li; Yuan, Zhi-Fang; Li, Yan; Ai, Jie; Xu, Hong; Sun, Jing-Cheng; Feng, Shi-Qing

    2016-01-01

    Abstract Glucocorticoid-induced osteoporosis (GIOP) is a serious problem for patients with rheumatic diseases requiring long-term glucocorticoid treatment. Alendronate, a bisphosphonate, has been recommended in the prevention of GIOP. However, the efficacy and safety of alendronate in preventing GIOP remains controversial. We performed a meta-analysis to investigate the efficacy and safety of alendronate in preventing GIOP in patients with rheumatic diseases. We retrieved randomized controlle...

  15. Surgical treatment of chronic pancreatitis. Twenty-two years' experience.

    Science.gov (United States)

    Traverso, L W; Tompkins, R K; Urrea, P T; Longmire, W P

    1979-01-01

    Seventy-four patients underwent operation for chronic pancreatitis during a 22 year period at UCLA Hospital. Follow-up data obtained for 60% of these patients an average of 3.2 years postoperation were analyzed by computer for statistically significant benefit between paired operation combinations and the variables of pain relief, stool habits, alcohol use, readmission for pancreatitis, and narcotic use. The combined group of total and cephalic pancreaticoduodenectomy proved more effective with respect to pain relief and readmission (p less than 0.05) than the group that had pseudocyst drainage. The comparison of groups that underwent resection or ductal drainage showed no statistical differences for the above variables. Regardless of type of operation, if the patient had evidence of pancreatic calcifications and had abstained from alcohol postoperatively, the likelihood of a return to normal activity was more favorable (p less than 0.05). PMID:485605

  16. Treatment of stable chronic obstructive pulmonary disease: the GOLD guidelines.

    Science.gov (United States)

    Lee, Hobart; Kim, Jeffrey; Tagmazyan, Karine

    2013-11-15

    Chronic obstructive pulmonary disease (COPD) is a common problem in primary care. COPD is diagnosed with spirometry only in clinically stable patients with a postbronchodilator forced expiratory volume in one second/forced vital capacity ratio of less than 0.70. All patients with COPD who smoke should be counseled about smoking cessation. Influenza and pneumococcal vaccinations are recommended for all patients with COPD. The Global Initiative for Chronic Obstructive Lung Disease assigns patients with COPD into four groups based on the degree of airflow restriction, symptom score, and number of exacerbations in one year. Pulmonary rehabilitation is recommended for patients in groups B, C, and D. Those in group A should receive a short-acting anticholinergic or short-acting beta2 agonist for mild intermittent symptoms. For patients in group B, long-acting anticholinergics or long-acting beta2 agonists should be added. Patients in group C or D are at high risk of exacerbations and should receive a long-acting anticholinergic or a combination of an inhaled corticosteroid and a long-acting beta2 agonist. For patients whose symptoms are not controlled with one of these regimens, triple therapy with an inhaled corticosteroid, long-acting beta2 agonist, and anticholinergic should be considered. Prophylactic antibiotics and oral corticosteroids are not recommended for prevention of COPD exacerbations. Continuous oxygen therapy improves mortality rates in patients with severe hypoxemia and COPD. Lung volume reduction surgery can improve survival rates in patients with severe, upper lobe-predominant COPD with heterogeneous emphysema distribution.

  17. Obinutuzumab treatment in the elderly patient with chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Seiter K

    2015-06-01

    Full Text Available Karen Seiter, Aleksandra Mamorska-DygaDepartment of Medicine, Division of Hematology/Oncology, New York Medical College, Valhalla, NY, USA Abstract: Chronic lymphocytic leukemia (CLL is the most common leukemia in adults in Western countries. Fludarabine-based regimens demonstrate higher response rates in younger patients but have a significant risk of infection and are thus poorly tolerated by older, frail patients. Anti-CD20 monoclonal antibodies have added to the efficacy of chemotherapy in CLL. Obinutuzumab is a potent Type II anti-CD20 monoclonal antibody with enhanced antibody-dependent cellular toxicity and direct cell death compared with rituximab. In Phase I studies, infusion reactions and neutropenia were the predominant toxicities. Phase II studies demonstrated efficacy both as a single agent and in combination with chemotherapy in patients with CLL. The CLL11 trial was a Phase III randomized trial of chlorambucil alone or with either obinutuzumab or rituximab in elderly, unfit patients. Progression-free survival (the primary end point was 26.7 months for patients receiving obinutuzumab plus chlorambucil versus 16.3 months for those receiving rituximab plus chlorambucil and 11.1 months for those receiving chlorambucil alone (P<0.001. Overall survival was improved for patients receiving obinutuzumab plus chlorambucil versus chlorambucil alone (P=0.002. This trial led to the US Food and Drug Administration (FDA approval of obinutuzumab in this patient population.Keywords: chronic lymphocytic leukemia, obinutuzumab, chlorambucil, elderly

  18. Influence of late treatment on how chronic myeloid leukemia responds to imatinib

    Directory of Open Access Journals (Sweden)

    Ana Carolina Costa Scerni

    2009-01-01

    Full Text Available INTRODUCTION: In Brazil, patients with chronic myeloid leukemia (CML in the chronic phase were not given first-line imatinib treatment until 2008. Therefore, there was a long period of time between diagnosis and the initiation of imatinib therapy for many patients. This study aims to compare the major molecular remission (MMR rates of early versus late imatinib therapy in chronic phase CML patients. METHODS: Between May 2002 and November 2007, 44 patients with chronic phase CML were treated with second-line imatinib therapy at the Hematology Unit of the Ophir Loyola Hospital (Belém, Pará, Brazil. BCR-ABL transcript levels were measured at approximately six-month intervals using quantitative polymerase chain reaction. RESULTS: The early treatment group presented a 60% probability of achieving MMR, while the probability for those patients who received late treatment was 40%. The probability of either not achieving MMR within one year of the initiation of imatinib therapy or losing MMR was higher in patients who received late treatment (79%, compared with patients who received early treatment (21%, odds ratio=5.75, P=0.012. The probability of maintaining MMR at 30 months of treatment was 80% in the early treatment group and 44% in the late treatment group (P=0.0005. CONCLUSIONS: For CML patients in the chronic phase who were treated with second-line imatinib therapy, the probability of achieving and maintaining MMR was higher in patients who received early treatment compared with those patients for whom the time interval between diagnosis and initiation of imatinib therapy was longer than one year.

  19. A peripheral endocannabinoid mechanism contributes to glucocorticoid-mediated metabolic syndrome.

    Science.gov (United States)

    Bowles, Nicole P; Karatsoreos, Ilia N; Li, Xiaosong; Vemuri, V Kiran; Wood, Jodi-Anne; Li, Zhiying; Tamashiro, Kellie L K; Schwartz, Gary J; Makriyannis, Alexandros M; Kunos, George; Hillard, Cecilia J; McEwen, Bruce S; Hill, Matthew N

    2015-01-06

    Glucocorticoids are known to promote the development of metabolic syndrome through the modulation of both feeding pathways and metabolic processes; however, the precise mechanisms of these effects are not well-understood. Recent evidence shows that glucocorticoids possess the ability to increase endocannabinoid signaling, which is known to regulate appetite, energy balance, and metabolic processes through both central and peripheral pathways. The aim of this study was to determine the role of endocannabinoid signaling in glucocorticoid-mediated obesity and metabolic syndrome. Using a mouse model of excess corticosterone exposure, we found that the ability of glucocorticoids to increase adiposity, weight gain, hormonal dysregulation, hepatic steatosis, and dyslipidemia was reduced or reversed in mice lacking the cannabinoid CB1 receptor as well as mice treated with the global CB1 receptor antagonist AM251. Similarly, a neutral, peripherally restricted CB1 receptor antagonist (AM6545) was able to attenuate the metabolic phenotype caused by chronic corticosterone, suggesting a peripheral mechanism for these effects. Biochemical analyses showed that chronic excess glucocorticoid exposure produced a significant increase in hepatic and circulating levels of the endocannabinoid anandamide, whereas no effect was observed in the hypothalamus. To test the role of the liver, specific and exclusive deletion of hepatic CB1 receptor resulted in a rescue of the dyslipidemic effects of glucocorticoid exposure, while not affecting the obesity phenotype or the elevations in insulin and leptin. Together, these data indicate that glucocorticoids recruit peripheral endocannabinoid signaling to promote metabolic dysregulation, with hepatic endocannabinoid signaling being especially important for changes in lipid metabolism.

  20. Glucocorticoid use and abuse in SLE.

    Science.gov (United States)

    Ruiz-Irastorza, Guillermo; Danza, Alvaro; Khamashta, Munther

    2012-07-01

    Glucocorticoids (GCs) are potent anti-inflammatory and immunosuppressive agents. They act by two different mechanisms: the genomic and the non-genomic pathways. The genomic pathway is considered responsible for many adverse effects of GCs, most of them are time and dose dependent. Observational studies support a relationship between GCs and damage in SLE. GCs have been associated with the development of osteoporosis, osteonecrosis, cataracts, hyperglycaemia, coronary heart disease and cognitive impairment, among others. Although no clinical trial has compared high vs low doses of GCs, some studies have shown the efficacy of medium doses in severe forms of SLE. The dose below which treatment can be considered safe has not been defined, but daily doses <7.5 mg of prednisone seem to minimize adverse effects. Combination therapy with HCQ and the judicious use of immunosuppressive drugs help to keep prednisone therapy within those limits.