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21.
《Expert opinion on therapeutic patents》2013,23(6):801-825
Background: The main components of metabolic syndrome (obesity, insulin resistance, hypertension and dyslipidemia) have become prevalent worldwide, and excess glucocorticoid levels have been implicated in patients with these symptoms. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is an enzyme involved in glucocorticoid regulation through catalysis of the conversion of inactive cortisone to its active form cortisol. Numerous rodent studies have demonstrated the potential use of 11β-HSD1 inhibitors as treatment for the components of metabolic syndrome and limited clinical data in humans have shown 11β-HSD1 inhibition to improve glucose levels, insulin sensitivity and lipid profiles. Many organizations have been active in the 11β-HSD1 academic and patent literature, and two previous articles from this journal have reviewed disclosures through August 2007. Objective: To summarize the recent patent literature and progress in defining the utility of small molecule 11β-HSD1 inhibitors. Methods: This review covers the recent 11β-HSD1 patent literature and clinical activity ranging from late 2007 through the end of 2008. Results/conclusion: The exploration of 11β-HSD1 inhibitors continues, as a number of structural classes have been reported by several pharmaceutical companies over the past 16 months. Current clinical trials will ultimately shed light on the feasibility of 11β-HSD1 inhibitors as pharmaceutical agents for the various components of metabolic syndrome. 相似文献
22.
《Current medical research and opinion》2013,29(3):173-181
SummaryBeclomethasone dipropionate has been used by inhalation from a pressurised aerosol by asthmatic patients. In 28 out of 39 patients, it was possible to discontinue oral steroids within 28 days. The length of the study varied from 6 weeks to 28 weeks with an average of 19 weeks. Once the patients had been taken off oral steroids, beclomethasone dipropionate provided the only form of corticosteroid therapy during the period of the study. Clinically, the steroid aerosol provided the expected benefits observed when oral corticosteroids are given to asthmatic patients. In each case there was a rise in plasma Cortisol level which was confirmed by tetracosactrin stimulation tests. This return of adrenal response supports the theory that inhaled beclomethasone dipropionate acts in a similar manner to oral corticosteroids, but does not exhibit the same systemic effect. Airways resistance and lung volumes remained within a constant band throughout the study in spite of complete withdrawal of oral steroids from 28 of the 39 patients. Eleven of the 39 patients had frequent fluctuations in airways resistance, but were, by the end of the study, receiving considerably reduced doses of oral steroids. Only 2 patients completed the study on a higher dose of oral steroids than that on which they entered. 相似文献
23.
《Expert opinion on drug safety》2013,12(4):457-465
ABSTRACTIntroduction: Glucocorticoids represent the standard therapy for reducing inflammation and immune activation in various diseases. However, as with any potent medication, they are not without side effects. Glucocorticoid-associated side effects may involve most major organ systems. Musculoskeletal, gastrointestinal, cardiovascular, endocrine, neuropsychiatric, dermatologic, ocular, and immunologic side effects are all possible.Areas Covered: This article analyzes English-language literature and provides an update on the most recent literature regarding side effects of systemic glucocorticoid treatment.Expert Opinion: The risk/benefit ratio of glucocorticoid therapy can be improved by proper use. Careful monitoring and using appropriate preventive strategies can potentially minimize side effects. 相似文献
24.
Melatonin inhibits neuronal dysfunction‐associated with neuroinflammation by atopic psychological stress in NC/Nga atopic‐like mouse models 下载免费PDF全文
Atopic dermatitis (AD), also known as atopic eczema, is chronic pruritic skin disease. AD can increase psychological stress as well, increasing glucocorticoid release and exacerbating the associated symptoms. Chronic glucocorticoid elevation disturbs neuroendocrine signaling and can induce neuroinflammation, neurotoxicity, and cognitive impairment; however, it is unclear whether AD‐related psychological stress elevates glucocorticoids enough to cause neuronal damage. Therefore, we assessed the effects of AD‐induced stress in a mouse AD model. AD‐related psychological stress increased astroglial and microglial activation, neuroinflammatory cytokine expression, and markers of neuronal loss. Notably, melatonin administration inhibited the development of skin lesions, scratching behavior, and serum IgE levels in the model mice, and additionally caused a significant reduction in corticotropin‐releasing hormone responsiveness, and a significant reduction in neuronal damage. Finally, we produced similar results in a corticosterone‐induced AD‐like skin model. This is the first study to demonstrate that AD‐related psychological stress increases neuroendocrine dysfunction, exacerbates neuroinflammation, and potentially accelerates other neurodegenerative disease states. 相似文献
25.
《The journal of maternal-fetal & neonatal medicine》2013,26(11):2149-2153
Clinical and experimental studies suggest that the growth-restricted fetus at increased risk of impaired cardiovascular function that likely contributes to both increased mortality rate and in survivors, to cardiovascular dysfunction apparent in childhood and later life. Fetal growth restriction is also associated with a high risk of preterm birth. Accordingly, the growth-restricted fetus is more likely than average to receive antenatal glucocorticoids to accelerate lung maturation in preparation for birth. However, glucocorticoids are powerful regulators of vascular tone and antenatal glucocorticoid administration to the intrauterine growth restriction (IUGR) fetus results in systemic cardiovascular changes that are not observed in the healthy normal grown fetus. These responses to glucocorticoids may disturb the IUGR fetus’ ability to appropriately compensate to placental insufficiency. Indeed is it possible that in the setting of severe IUGR exogenous glucocorticoids are detrimental rather than beneficial to the fetus? 相似文献
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Sarah Bertoli Etienne Paubelle Emilie Brard Estelle Saland Xavier Thomas Suzanne Tavitian Marie‐Virginie Larcher Franois Vergez Eric Delabesse Audrey Sarry Franoise Huguet Clment Larrue Claudie Bosc Thomas Farge Jean Emmanuel Sarry Mauricette Michallet Christian Rcher 《European journal of haematology》2019,102(2):131-142
Spontaneous remission (SR) of acute myeloid leukemia (AML) represents a rare phenomenon and is usually of short duration although long‐term remissions are reported. Indeed, mechanisms underlying SR remain unclear, but it is suggested that immunactivation, e.g. caused by infections, plays an important role. Here we report on a patient who suffered from pneumonia and simultaneously experienced very late hematologic AML relapse seventeen years after allogeneic blood stem cell transplantation (allo‐BSCT). Surprisingly in parallel to recovery from pneumonia peripheral blood count which previously showed pancytopenia, had normalized and bone marrow (BM) aspiration revealed spontaneous remission of AML. To the best of our knowledge we here report on the latest AML relapse after allo‐BSCT experiencing SR. 相似文献
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Glucocorticoids and prostate cancer treatment: friend or foe? 总被引:3,自引:0,他引:3
Bruce Montgomery ;Heather H Cheng ;James Drechsler ;Elahe A Mostaghel 《Asian journal of andrology》2014,16(3):354-358
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 defining their contribution to the biology of prostate cancer. 相似文献