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Hypothalamic-Pituitary-Adrenal Suppression and Iatrogenic Cushing's Syndrome as a Complication of Epidural Steroid Injections  [PDF]
Joyce Leary,Arthur Swislocki
Case Reports in Endocrinology , 2013, DOI: 10.1155/2013/617042
Abstract: Epidural steroid injections are well accepted as a treatment for radicular back pain in appropriate candidates. While overall incidence of systemic side effects has not been well established, at least five biochemically proven cases of iatrogenic Cushing's Syndrome have been reported as complications of epidural steroid treatment. We present an additional case of iatrogenic Cushing's Syndrome and adrenal suppression in a middle-aged woman who received three epidural steroid injections over a four-month period. We review this case in the context of previous cases and discuss diagnostic and management issues. 1. Introduction Epidural injections of corticosteroids are an accepted and widely used treatment for radicular low back pain. Nearly 50 million in Medicare dollars went to this treatment in 1999 [1], and from 1994 to 2001, there was a 271% increase in Medicare funded lumbar epidural steroid injections [2]. A typical epidural steroid is triamcinolone in 40?mg or 80?mg doses. Some expert recommendations promote giving up to 3 injections within a year with a minimum of 30 days between injections. Further or more frequent injections are not recommended due to concerns about hypothalamic-pituitary-adrenal suppression [3]. Other practice guidelines provide no recommendations on maximum injection number or dosing interval [4]. The American Society of Interventional Pain Physicians-Interventional Pain Management comments in their 2009 guidelines that there is no “basis for reported assumptions and limitations” on epidural steroid injection doses or frequency and furthermore, that “administration must be based solely on patients’ response, safety profile of the drug, experience of the patient, and pharmacologic and chemical properties such as duration of action and suppression of adrenals [5].” However, they go on to recommend epidural steroid injections be given no more frequently than every 1-2 weeks during the diagnostic phase and thereafter no more frequently than every 2 months. 2. Case The patient is a 53-year-old Caucasian woman of Northern European ancestry referred to Endocrinology by a specialty Pain Clinic for concerns of possible hypercortisolism. She had been seen by the pain specialist for chronic radicular back pain and was given 3 doses of fluoroscopically guided epidural triamcinolone 80?mg via the caudal approach over the course of 4 months. Four weeks elapsed between her first and second doses, 10 weeks between her second and third, her last dose having been given 7 weeks prior to our initial evaluation. She noticed bloating and a buffalo
17 -Ethynyl-androst-5-ene-3 ,7 ,17 -triol (HE3286) Is Neuroprotective and Reduces Motor Impairment and Neuroinflammation in a Murine MPTP Model of Parkinson’s Disease  [PDF]
Ferdinando Nicoletti,Ingrid Philippens,Paolo Fagone,Clarence N. Ahlem,Christopher L. Reading,James M. Frincke,Dominick L. Auci
Parkinson's Disease , 2012, DOI: 10.1155/2012/969418
Abstract: 17α-Ethynyl-androst-5-ene-3β,7β,17β-triol (HE3286) is a synthetic androstenetriol in Phase II clinical development for the treatment of inflammatory diseases. HE3286 was evaluated for blood-brain barrier (BBB) permeability in mice, and efficacy in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) murine model of Parkinson’s disease (PD). We found that HE3286 freely penetrated the BBB. HE3286 treatment significantly improved motor function compared to vehicle in the rotarod test (mean 58.2?sec versus 90.9?sec, ), and reduced inflammatory mediator gene expression in the brain (inducible nitric oxide synthase, 20%, ; tumor necrosis factor α, 40%, , and interleukin-1β, 33%, ) measured by reverse-transcriptase polymerase chain reaction. Brain tissue histopathology and immunohistochemistry showed that HE3286 treatment increased the numbers of tyrosine hydroxylase-positive cells by 17% compared to vehicle ( ), and decreased the numbers of damaged neurons by 38% relative to vehicle ( ). L-3,4-dihydroxyphenylalanine (L-DOPA) efficacy was not enhanced by concurrent administration of HE3286. HE3286 administration prior to MPTP did not enhance efficacy. Our data suggest a potential role for HE3286 in PD treatment, and provides incentive for further investigation. 1. Introduction PD is a neurodegenerative disorder characterized by a progressive degeneration of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNpc) and decreased levels of dopamine in the putamen of the dorsolateral striatum. The loss of dopamine in the striatum manifests clinically as motor disabilities that include bradykinesia, resting tremor, and muscular rigidity. Diagnosis is based on motor symptoms, which become evident only after the loss of more than 50% of the SNpc DAergic neurons and 60–80% of striatal dopamine [1]. Prolonged treatment of PD with L-DOPA usually results in a dyskinesia that can be more disabling than the disease itself; therefore, there is a great need for alternative therapeutic modalities. The acute MPTP mouse model of nigrostriatal degeneration recapitulates the DAergic neuron loss seen in PD and currently represents the most commonly used toxin-induced mouse model of PD [2]. MPTP’s mechanism of toxicity is complex, and exerted through its toxic metabolite, methyl-4-phenylpyridinium (MPP+) ion, which is taken up selectively by DAergic neurons through the dopamine transporter. Inside the cell, MPP+ is a mitochondrial toxin, which induces neuronal death through several mechanisms that include oxidative stress [3], excitotoxicity [4], and
Low-dose steroid pretreatment ameliorates the transient impairment of liver regeneration  [cached]
Toshihito Shibata,Toru Mizuguchi,Yukio Nakamura,Masaki Kawamoto
World Journal of Gastroenterology , 2012, DOI: 10.3748/wjg.v18.i9.905
Abstract: AIM: To determine if liver regeneration (LR) could be disturbed following radiofrequency (RF) ablation and whether modification of LR by steroid administration occurs. METHODS: Sham operation, partial hepatectomy (PH), and partial hepatectomy with radiofrequency ablation (PHA) were performed on adult Fisher 344 rats. We investigated the recovery of liver volume, DNA synthetic activities, serum cytokine/chemokine levels and signal transducers and activators of transcription 3 DNA-binding activities in the nucleus after the operations. Additionally, the effects of steroid (dexamethasone) pretreatment in the PH group (S-PH) and the PHA group (S-PHA) were compared. RESULTS: The LR after PHA was impaired, with high serum cytokine/chemokine induction compared to PH, although the ratio of the residual liver weight to body weight was not significantly different. Steroid pretreatment disturbed LR in the S-PH group. On the other hand, low-dose steroid pretreatment improved LR and suppressed tumor necrosis factor (TNF)-α elevation in the S-PHA group, with recovery of STAT3 DNA-binding activity. On the other hand, low-dose steroid pretreatment improved LR and suppressed TNF-α elevation in the S-PHA group, with recovery of STAT3 DNA-binding activity. CONCLUSION: LR is disturbed after RF ablation, with high serum cytokine/chemokine induction. Low-dose steroid administration can improve LR after RF ablation with TNF-α suppression.
Multifaceted effects of synthetic TLR2 ligand and Legionella pneumophilia on Treg-mediated suppression of T cell activation
Wendy WC van Maren, Stefan Nierkens, Liza W Toonen, Judith M Bolscher, Roger PM Sutmuller, Gosse J Adema
BMC Immunology , 2011, DOI: 10.1186/1471-2172-12-23
Abstract: TLR2 agonists can directly provide a co-stimulatory signal inducing enhanced proliferation and cytokine production of naive CD4+ Teff cells. With respect to cytokine production, DCs appear to be most sensitive to low amounts of TLR agonists. Using wild type and TLR2-deficient cells in Treg suppression assays, we accordingly show that all cells (e.g. Treg, Teff cells and DCs) contributed to overcome Treg-mediated suppression of Teff cell proliferation. Furthermore, while TLR2-stimulated Tregs readily lost their ability to suppress Teff cell proliferation, cytokine production by Teff cells was still suppressed. Similar results were obtained upon stimulation with TLR2 ligand containing bacteria, Legionella pneumophila.These findings indicate that both synthetic and natural TLR2 agonists affect DCs, Teff cells and Treg directly, resulting in multi-modal modulation of Treg-mediated suppression of Teff cells. Moreover, Treg-mediated suppression of Teff cell proliferation is functionally distinct from suppression of cytokine secretion.The immune system is of crucial importance to our health and survival. Faced with pathogenic threats from outside as well as the rise of cancer cells from within, our immune defense must be able to cope with very diverse opponents. Mammals have developed a diverse set of receptors that sense components derived from pathogens and damaged cells. Amongst the best studied receptors are the so called pattern recognition receptors (PRR) like the Toll-like receptor (TLR) family, RIG-I-like receptor (RLR) family and the NOD-like receptor (NLR) family of proteins [1]. In general, engagement of these receptors on immune cells results in their activation, like enhanced antigen presentation, inflammatory cytokine production and the acquisition of immune effector function [2].Pathogen recognition through specific TLRs can be of crucial importance for the induction of protective immunity. For instance, TLR4-deficient mice are more susceptible for infection
Interference Suppression for Ship-Based Passive Synthetic Impulse and Aperture Radar
舰载无源综合脉冲孔径雷达干扰抑制

Zhang Ya-bin,Chen Bai-xiao,Zhang Shou-hong,Shang Hai-yan,
张雅斌
,陈伯孝,张守宏,尚海燕

电子与信息学报 , 2008,
Abstract: Interference statistic characteristics are analyzed in ship-based passive synthetic Impulse and Aperture Radar (SIAR). After estimating covariance matrix at range bin interested using data from some positive and all negative frequency bins with cosine weights, eigen-decomposition is applied to interested data for co-channel interference suppression provided that its power is stronger than target echoes. Meanwhile, improved suppression approach to nonstationary interference from multipath propagation is proposed by forming adaptive STAP in fast-time domain and maintaining slow-time statistical properties of the first order sea clutter output approximately unperturbed by filter fluctuation. Analysis and suppression approach are verified by real data.
ACTUAL TREATS AND THE OPPORTUNITIES OF TOURIST DESTINATIONS DEVELOPMENT IN THE KRASNODAR REGION Современные угрозы и возможности развития туристских дестинаций в краснодарском крае
Kizim A. A.,Saidasheva O. V.
Polythematic Online Scientific Journal of Kuban State Agrarian University , 2012,
Abstract: The article is devoted to the analysis of the main regularities and the modern trends of tourist destinations foundation and development. Actual treats of tourist destinations development in the Krasnodar region are detected. Opportunities and instruments of regional tourist destinations advancement are considered
Molecular Targets for 17α-Ethynyl-5-Androstene-3β,7β,17β-Triol, an Anti-Inflammatory Agent Derived from the Human Metabolome  [PDF]
Christopher L. Reading, James M. Frincke, Steven K. White
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0032147
Abstract: HE3286, 17α-ethynyl-5-androstene-3β, 7β, 17β-triol, is a novel synthetic compound related to the endogenous sterol 5-androstene-3β, 7β, 17β-triol (β-AET), a metabolite of the abundant adrenal steroid dehydroepiandrosterone (DHEA). HE3286 has shown efficacy in clinical studies in impaired glucose tolerance and type 2 diabetes, and in vivo models of types 1 and 2 diabetes, autoimmunity, and inflammation. Proteomic analysis of solid-phase HE3286-bound bead affinity experiments, using extracts from RAW 264.7 mouse macrophage cells, identified 26 binding partners. Network analysis revealed associations of these HE3286 target proteins with nodes in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for type 2 diabetes, insulin, adipokine, and adipocyte signaling. Binding partners included low density lipoprotein receptor-related protein (Lrp1), an endocytic receptor; mitogen activated protein kinases 1 and 3 (Mapk1, Mapk3), protein kinases involved in inflammation signaling pathways; ribosomal protein S6 kinase alpha-3 (Rsp6ka3), an intracellular regulatory protein; sirtuin-2 (Sirt2); and 17β-hydroxysteroid dehydrogenase 1 (Hsd17β4), a sterol metabolizing enzyme.
Synthetic Synthetic  [cached]
Anna Maria Manferdini,Elena Manferdini
DISEGNARECON , 2010,
Abstract: I materiali sono generalmente associati ad una serie di caratteristiche fisiche che determinano le loro possibilità di utilizzo nel campo della produzione industriale. Recentemente stiamo assistendo ad un interesse crescente verso materiali artificiali concepiti come sistemi in cui geometria, texture, lavorabilità e finitura superficiale sono in grado di stimolare nuove sensazioni. Questi materiali possono essere descritti come sintetici, poiché sono il risultato della sovrapposizione combinata di prestazioni e caratteristiche ottenute secondo processi che possono essere naturali oppure progettati artificialmente. L’obiettivo di questo contributo è mostrare come l’utilizzo della micro-scala di elementi naturali quale fonte di ispirazione possa ampliare il repertorio di tipologie di materiali da rivestimento destinati all'architettura. Traditionally materials have been associated with a series of physical properties that can be used as inputs to production and manufacturing. Recently we witnessed an interest in materials considered not only as ‘true matter’, but also as new breeds where geometry, texture, tooling and finish are able to provoke new sensations when they are applied to a substance. These artificial materials can be described as synthetic because they are the outcome of various qualities that are not necessarily true to the original matter, but they are the combination of two or more parts, whether by design or by natural processes. The aim of this paper is to investigate the potential of architectural surfaces to produce effects through the invention of new breeds of artificial matter, using micro-scale details derived from Nature as an inspiration.
Suppression of murine breast cancer metastasis by selective inhibition of CXCR4 by synthetic polypeptide derived from viral macrophage inflammatory protein II
QingLing Yang,YongXing Ding,ChangJie Chen,Jie Tang,Ju Zhang,ZhiFeng Yang
Chinese Science Bulletin , 2010, DOI: 10.1007/s11434-010-3262-9
Abstract: Stromal cell-derived factor-1 and its receptor CXC chemokine receptor-4 (CXCR4) have been implicated in breast cancer metastasis. A significant association between HER2 and CXCR4 expression has been observed in human breast tumor tissues, and overexpression of CXCR4 is essential for HER2-mediated tumor metastasis. Moreover, CXCR4 expression is low in normal breast tissues and high in malignant tumors, suggesting that a blockade of CXCR4 may limit tumor metastasis. The present study investigated the action of a synthetic antagonist 21-mer peptide derived from viral macrophage inflammatory protein II against CXCR4 (NT21MP) in inhibiting metastasis in vitro and in vivo. The results showed that chemotaxis of SKBR3 cells toward SDF-1α was reduced by NT21MP in a dose-dependent manner (P < 0.05). NT21MP inhibited tumor growth at 500 μg/kg and in combination with Herceptin, the anti-HER2 antibody. The in vivo metastatic assay showed that NT21MP significantly inhibited pulmonary metastasis, and the number of metastatic tumor nodes on the surface of the lung was greatly decreased. Compared with the saline-treated control group, PCNA expression was dose-dependently decreased by NT21MP, the percentage of apoptotic cells was increased, and CXCR4 mRNA and protein expression were downregulated. In conclusion, NT21MP inhibits cellular proliferation, promotes apoptosis by downregulating CXCR4 expression, and suppresses the progression of primary and metastatic tumors. CXCR4 may be a useful therapeutic target for breast cancer, and NT21MP may serve as a potential target drug for the treatment of breast cancer metastasis.
Steroid induced glaucoma and cataract  [cached]
Mohan R,Muralidharan A
Indian Journal of Ophthalmology , 1989,
Abstract: Long term use of topical & systemic steroids produce secondary open angle glaucoma similar to chronic simple glaucoma. The increased IOP caused by prolonged steroid therapy is reversible but the damage produced by it is irreversible. In this study, we analysed 25 patients (44 eyes) with steroid induced glaucoma, who reported to us with dimness of vision, haloes and elevated I.O.P. and were using steroids for long duration due to various causes. The behaviour of the I.O.P. due to different steroid preparations, the type of lenticular change, and the management of those cases are discussed in this paper. From our study we conclude that dexamethasone and betamethasone both topical as well as systemic are more potent in producing glaucoma and cataract than medrysone and prednisolone. The condition is reversible without permanent damage when the duration of steroid therapy is short and vice versa.
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