WorldWideScience

Sample records for repeated acth treatment

  1. Causal ACTH-Depot Therapy during Pregnancies following Infertility Treatment

    Directory of Open Access Journals (Sweden)

    Rudolf Klimek

    2012-01-01

    Full Text Available The aim of this paper was to confirm the efficacy of adrenocorticotropin depot (ACTH-depot therapy in pregnancies with threatened miscarriage and preterm delivery through the desired stimulation of the adrenal glands controlled by the rest of organism. The activity of hypothalamic-pituitary-adrenal axis plays a key role in pregnancy. Such naturally stimulated endogenous corticosteroid hormones are free from unwanted side effects of their synthetics analogs. Low level of maternal blood ACTH and insufficient increase of induced by hypothalamic hormones oxytocinases (cystine-β-aminopeptidases were indication to ACTH-depot therapy (0.5 mg/week in our consecutive prospective studies. Contrary to antenatal use of synthetic corticosteroids, there are no temporal limits of this therapy, which has to be more often recommended into clinical prevention of fetal morbidity, treatment of premature delivery, and finally elimination of the newborn's mortality caused by the neuroendocrinological gestoses.

  2. Еctopic ACTH syndrome: clinical picture, diagnosis, treatment

    Directory of Open Access Journals (Sweden)

    N S Kuznetsov

    2012-03-01

    Full Text Available Diagnosis and treatment of ectopic ACTH-syndrome currently is one of the most challenging problems among other forms of endogenous hypercorticism. This syndrome is associated with presence of extrapituitary tumors characterized with different histogenesis and localization, which produce adrenocorticotropic hormone (ACTH, or – rarely – corticotrophin-releasing hormone. In most cases the ectopic synthesis of ACTH is performed in bronchial carcinoid tumors (36–46%, oat cell cancer (18–20%, medullary thyroid cancer (3–7%, pheochromocytoma (9–23%, other sites are infrequent (pancreas, thymus, parotid gland, ovaries, uterus, prostate, colon, stomach, esophagus, etc.. Much of these tumors are aggressive and are characterized with propensity to metastasize and relapse. Currently there are few contradictory data on the comparative evaluation of the effectiveness of methods of topical diagnosis of the source of ectopic ACTH-secretion, and therefore there is an urgent need to develop an optimal and most efficient algorithm for diagnostic procedures to determine the extent of the tumor in patients with ectopic ACTH-syndrome. Indications for surgery, timing and extent of surgical intervention, the effectiveness of the operation, the causes and frequency of relapses are still discussed.The present difficulties of diagnosis, as well as the lack of a unified approach to the treatment of this disease in the complex, often lead to the progression and development of a large number of serious complications functions of up to disability, which in turn does not lead to significant improvement of quality of life. Thus further research is necessary to study of this disease

  3. Transient brain shrinkage in infantile spasms after ACTH treatment. Report of two cases.

    Science.gov (United States)

    Maekawa, K; Ohta, H; Tamai, I

    1980-02-01

    This is the report of two cases of infantile spasms, manifesting transient brain shrinkage in computerized tomography (CT) after ACTH treatment. ACTH was given for 8 weeks to a 8-months-old Japanese girl with infantile spasms. First CT performed at 2 weeks after the final ACTH injection, displayed moderate brain shrinkage. Second CT at 4 months showed marked diminution of the shrinkage. ACTH was also given for 8 weeks to a 14 months old Japanese boy with infantile spasms. First CT, just before ACTH treatment, showed mild cortical atrophy, the second at 7 days after the final ACTH injection revealed marked brain shrinkage and moderate ventricular dilatation, and the third at 2 months, disclosed mild improvement of the shrinkage. ACTH or corticoateroid has widespread effects on the developing nervous system. In animal experiments, ACTH or steroids interfere with brain growth of young rats. CT findings of transient brain shrinkage in a child with infantile spasms might suggest that intensive treatment with ACTH or steroids in infancy interferes with brain growth as seen in the results of animal experiments.

  4. Reactive thymic hyperplasia following treatment of ACTH-producing tumors; Reaktive Thymushyperplasie infolge der Therapie ACTH-produzierender Tumoren

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, S.; Klose, K.J.; Iwinska-Zelder, J. [Abt. Strahlendiagnostik, Medizinisches Zentrum fuer Radiologie, Philipps-Universitaet Marburg (Germany); Frank, M.; Ehlenz, K. [Abt. Gastroenterologie, Zentrum fuer Innere Medizin, Philipps-Universitaet Marburg (Germany); Kisker, O. [Philipps-Universitaet Marburg (Germany). Abt. Allgemeine Chirurgie

    1997-11-01

    Surgical or conservative treatment of ACTH-producing tumors results in acute drop of the previously excessively high cortisol levels. The following associated pathophysiological changes also occur in the organism`s recovery from stress, such as trauma, operation or chemotherapy of tumors. Both cases result in a regeneration of the immune system, which might even be exalted. The corresponding radiographic feature is the `rebound` enlargement of the thymus occuring about six months after remission of hypercortisolism. Histological examination reveals benign thymus hyperplasia. Especially in cases of still unkown primary tumor the apperance of this anterior mediastinal mass can lead to misdiagnosis. We present the cases of two patients with diffuse thymic hyperplasia following surgical and medical correction of hypercortisolism. One patient suffered from classic Cushing`s disease responding to transsphenoidal resection of an ACTH-secreting pituitary microadenoma. Six monsths later CT of the chest incidentally demonstrated an anterior mediastinal mass known as thymic hyperplasia. The second patient presented with an ectopic, still unknown source of ACTH-production. (orig./AJ) [Deutsch] Durch operative oder medikamentoese Therapie von ACTH-produzierenden Tumoren wird der exzessiv erhoehte Kortisolspiegel abrupt korrigiert. Die damit verbundenen pathopysiologischen Veraenderungen entsprechen der Erholungsphase des Organismus nach extremer Stressbelastung durch Trauma, Operation oder Chemotherapie von Tumoren. In beiden Faellen kommt es zu einer - moeglicherweise sogar ueberschiessenden - Regeneration des Immunsystems. In der bildgebenden Diagnostik ist dies als `Rebound` thymushyperplasie zu beobachten. Diese ca. 6 Monate posttherapeutisch auftretende anteriore mediastinale Raumforderung kann besonders in Faellen von noch unbekanntem Primaertumor zu Fehldiagnosen Anlass geben. Anhand der beiden folgenden Kasuistiken wird versucht, den pathophysiologischen und zeitlichen

  5. ACTH antagonists

    Directory of Open Access Journals (Sweden)

    Adrian John Clark

    2016-08-01

    Full Text Available ACTH acts via a highly selective receptor that is a member of the melanocortin receptor subfamily of type 1 G protein-coupled receptors. The ACTH receptor, also known as the melanocortin 2 receptor (MC2R is unusual in that it is absolutely dependent on a small accessory protein, melanocortin receptor accessory protein (MRAP for cell surface expression and function. ACTH is the only known naturally occurring agonist for this receptor. This lack of redundancy and high degree of ligand specificity suggests that antagonism of this receptor could provide a useful therapeutic aid and a potential investigational tool. Clinical situations in which this could be useful include (1 Cushing’s disease and ectopic ACTH syndrome – especially whilst preparing for definitive treatment of a causative tumour, or in refractory cases, or (2 congenital adrenal hyperplasia – as an adjunct to glucocorticoid replacement. A case for antagonism in other clinical situations in which there is ACTH excess can also be made. In this article we will explore the scientific and clinical case for an ACTH antagonist, and will review the evidence for existing and recently described peptides and modified peptides in this role.

  6. Gene array analysis of adrenal glands in broiler chickens following ACTH treatment

    Directory of Open Access Journals (Sweden)

    Guémené Daniel

    2009-09-01

    Full Text Available Abstract Background Difference in adaptability responses to stress has been observed amongst bird species, strains, and individuals. Components of the HPA axis, one of the internal systems involved in homeostasis re-establishment following stress, could play a role in this variability of responses. The aim of the present study was 1 to identify genes involved in the regulation of adrenal activity following ACTH stimulation and 2 to examine adrenal genes differentially expressed in individuals with high and low plasma corticosterone response following ACTH treatment. Results Analysis with 21 K poultry oligo microarrays indicated that ACTH treatment affected the expression of 134 genes. Several transcripts assigned to genes involved in the adrenal ACTH signaling pathway and steroidogenic enzymes were identified as differentially expressed by ACTH treatment. Real-time PCR on 18 selected genes confirmed changes in transcript levels of 11 genes, including MC2R, CREM, Cry, Bmal1, Sqle, Prax1, and StAR. Only 4 genes revealed to be differentially expressed between higher and lower adrenal responders to ACTH treatment. Conclusion The results from the present study reveal putative candidate genes; their role in regulation of adrenal functions and adaptability to stress should be further investigated.

  7. COMPARATIVE EFFECTS OF NITRAZEPAM AND ACTH ON THE TREATMENT OF INFANTILE SPASM

    Directory of Open Access Journals (Sweden)

    MM. Taghdir

    2007-08-01

    Full Text Available ObjectiveInfantile spasms (IS or West syndrome is a convulsive disease characterizedby brief, symmetric axial muscle contractions (neck, trunk, and/or extremities.The therapy universally recognized as most effective in the treatment of IS,is treatment with the adrenocorticotropic hormone (ACTH or oral corticosteroids.This therapy however has important side effects. Many studies have soughtto find alternative therapies with fewer side effects. Nitrazepam, it has beenproven, can be as effective as ACTH in controlling infantile spasms. The aimof this study was to evaluate and compare the efficacy of Nitrazepam andACTH on the treatment of infantile spasms.Materials & MethodsThis randomized controlled clinical trial, enrolled sixty patients with newlydiagnosed and previously untreated IS; diagnosis was made based on thecriteria of The International Classification of Epilepsies of the InternationalLeague Against Epilepsy (ILAE. Prior to treatment, all patients underwentElectro encephalo graphs (EEGs and CT scans. Patients were randomized toreceive 0.5-1 mg/kg Nitrazpam (NZP in three daily doses or 40 IU DepotACTH in a single morning dose. Complete cessation of spasms was consideredto be as optimal response.ResultsOf the sixty patients studied, 24 (40% were girls and 36(60% were boys. Allpatients in the both groups were matched for age and sex.There were nodifferences between the both groups regarding age and sex (non-significant.Following treatments, at the end of the 6-week duration therapy, optimalresponse (Cessation of spasms was obtained in 19 (63% patients of NZPgroup and 9 (30% patients of ACTH group, (P0.05.ConclusionThis study supports the belief that NZP offers an effective and possibly safertherapy than ACTH, for the management of IS and that the therapeuticresponse, if imminent, can be detected within 4-6 weeks of treatment. Cliniciansshould consider using NZP as a first-line therapy for IS.

  8. COMPARATIVE EFFECTS OF NITRAZEPAM AND ACTH ON THE TREATMENT OF INFANTILE SPASM

    Directory of Open Access Journals (Sweden)

    MM. Taghdiri MD

    2009-01-01

    Full Text Available ObjectiveInfantile spasms (IS or West syndrome is a convulsive disease characterized by brief, symmetric axial muscle contractions (neck, trunk, and/or extremities.The therapy universally recognized as most effective in the treatment of IS, is treatment with the adrenocorticotropic hormone (ACTH or oral corticosteroids. This therapy however has important side effects. Many studies have sought to find alternative therapies with fewer side effects. Nitrazepam, it has been proven, can be as effective as ACTH in controlling infantile spasms. The aim of this study was to evaluate and compare the efficacy of Nitrazepam and ACTH on the treatment of infantile spasms. Materials & MethodsThis randomized controlled clinical trial, enrolled sixty patients with newly diagnosed and previously untreated IS; diagnosis was made based on the criteria of The International Classification of Epilepsies of the International League Against Epilepsy (ILAE. Prior to treatment, all patients underwent Electro encephalo graphs (EEGs and CT scans. Patients were randomized to receive 0.5-1 mg/kg Nitrazpam (NZP in three daily doses or 40 IU Depot ACTH in a single morning dose. Complete cessation of spasms was considered to be as optimal response.ResultsOf the sixty patients studied, 24 (40% were girls and 36(60% were boys. All patients in the both groups were matched for age and sex.There were no differences between the both groups regarding age and sex (non-significant. Following treatments, at the end of the 6-week duration therapy, optimal response (Cessation of spasms was obtained in 19 (63% patients of NZP group and 9 (30% patients of ACTH group, (P0.05.ConclusionThis study supports the belief that NZP offers an effective and possibly safer therapy than ACTH, for the management of IS and that the therapeutic response, if imminent, can be detected within 4-6 weeks of treatment. Clinicians should consider using NZP as a first-line therapy for IS

  9. Neuropeptide Y administration reverses tricyclic antidepressant treatment-resistant depression induced by ACTH in mice.

    Science.gov (United States)

    Antunes, Michelle S; Ruff, Jossana Rodrigues; de Oliveira Espinosa, Dieniffer; Piegas, Manuela Bastos; de Brito, Maicon Lenon Otenio; Rocha, Kellen Athaíde; de Gomes, Marcelo Gomes; Goes, André Tiago Rossito; Souza, Leandro Cattelan; Donato, Franciele; Boeira, Silvana Peterini; Jesse, Cristiano R

    2015-07-01

    Depression is one of the most common mental disorders and a primary cause of disability. To better treat patients suffering this illness, elucidation of the underlying psychopathological and neurobiological mechanisms is urgently needed. Based on the above-mentioned evidence, we sought to investigate the effects of neuropeptide Y (NPY) treatment in tricyclic antidepressant treatment-resistant depression induced by adrenocorticotropic hormone (ACTH) administration. Mice were treated with NPY (5.84, 11.7 or 23.4mmol/μl) intracerebroventricularly (i.c.v.) for one or five days. The levels of serum corticosterone, tryptophan (TRP), kynurenine (KYN), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and indoleamine 2,3-dioxygenase (IDO) activity in the hippocampus were analyzed. The behavioral parameters (depressive-like and locomotor activity) were also verified. This study demonstrated that ACTH administration increased serum corticosterone levels, KYN, 5-HIAA levels, IDO activity (hippocampus), immobility in the forced swimming test (FST) and the latency to feed in the novelty suppressed feeding test (NSFT). In addition, ACTH administration decreased the BDNF and NGF levels in the hippocampus of mice. NPY treatment was effective in preventing these hormonal, neurochemical and behavioral alterations. It is suggested that the main target of NPY is the modulation of corticosterone and neuronal plasticity protein levels, which may be closely linked with pharmacological action in a model of tricyclic antidepressant treatment-resistant depression. Thus, this study demonstrated a protective effect of NPY on the alterations induced by ACTH administration in mice, indicating that it could be useful as a therapy for the treatment of tricyclic antidepressant treatment-resistant depression.

  10. The effect of ACTH on suckling rats.

    Science.gov (United States)

    Sato, Y

    1984-01-01

    In the present study, the causes of brain shrinkage induced by synthetic ACTH treatment in epileptic children were investigated using suckling rats. Synthetic ACTH was injected subcutaneously once a day for 5 days into suckling rats aged 15 days. Saline was injected into control subjects in the same way. Rats were sacrificed before the injection, immediately after the repeated injections, and 5 and 14 days from the end of the course of repeated injections. The weight, volume and water content of the brains were measured and the protein, DNA, sodium and potassium contents of the brains were also determined. The mean weight and volume of the brains after 5-day injection of ACTH were slightly smaller compared to those of control rats. No natural increase in brain protein with growth was found from the start of ACTH injections to 14 days after finishing the course of repeated injections. The DNA, sodium and potassium contents of the brains significantly increased immediately after the repeated injections of 5 days. It was suggested that the brain shrinkage of epileptics induced by ACTH treatment might be caused by decreased water content and not cellular degradation.

  11. Residual adrenal function in autoimmune Addison's disease: improvement after tetracosactide (ACTH1-24) treatment.

    Science.gov (United States)

    Gan, Earn H; MacArthur, Katie; Mitchell, Anna L; Hughes, Beverly A; Perros, Petros; Ball, Stephen G; James, R Andrew; Quinton, Richard; Chen, Shu; Furmaniak, Jadwiga; Arlt, Wiebke; Pearce, Simon H S

    2014-01-01

    Despite lifelong steroid hormone replacement, there is excess morbidity and mortality associated with autoimmune Addison's disease. In health, adrenocortical cells undergo continuous self-renewal from a population of subcapsular progenitor cells, under the influence of ACTH, suggesting a therapeutic possibility. We aimed to determine whether tetracosactide (synthetic ACTH1-24) could revive adrenal steroidogenic function in autoimmune Addison's disease. Thirteen patients (aged 16-65 y) with established autoimmune Addison's disease for more than 1 year were recruited at the Newcastle University Clinical Research Facility. The intervention included a 20-week study of regular sc tetracosactide (ACTH1-24) therapy. Serum and urine corticosteroids were measured during medication withdrawal at baseline and every 5 weeks during the study. Serum cortisol levels remained less than 100 nmol/L in 11 of 13 participants throughout the study. However, two women achieved peak serum cortisol concentrations greater than 400 nmol/L after 10 and 29 weeks of tetracosactide therapy, respectively, allowing withdrawal of corticosteroid replacement. Concurrently, urine glucocorticoid and mineralocorticoid metabolite excretion increased from subnormal to above the median of healthy controls. One of these responders remains well with improving peak serum cortisol (672 nmol/L) 28 months after stopping all treatments. The other responder showed a gradual reduction in serum cortisol and aldosterone over time, and steroid therapy was recommenced after a 28-week period without glucocorticoid replacement. This is the first study to demonstrate that established autoimmune Addison's disease is amenable to a regenerative medicine therapy approach.

  12. A Novel Medical Treatment of Cushing's Due to Ectopic ACTH in a Patient With Neurofibromatosis Type 1.

    Science.gov (United States)

    Bano, Gul; Mir, Farheen; Beharry, Nigel; Wilson, Philip; Hodgson, Shirley; Schey, Stephen

    2013-01-01

    A 64-year-old male presented with neurofibromatosis 1 and Cushing's syndrome. Clinically he was over weight, depressed with extensive skin bruising and hypertension. His 24 hours urinary metanephrines, urinary 5HIAA, gut peptides and chromgranin levels were normal. His renal function and renal MRI scan was also normal. His cortisol failed to suppress on overnight dexamethsone suppression test. His low dose dexamethasone suppression with CRH stimulation showed failure of suppression of cortisol to Cushings had resolved on biochemical testing. After a year his plexiform neurofibroma has not increased in size. To our knowledge, this is the first case of NF1 associated with clinical and biochemical features of Cushing's secondary to ectopic ACTH due to MPNST in a plexiform neurofibroma and its resolution on treatment with imatinib.

  13. Imipramine-induced c-Fos expression in the medial prefrontal cortex is decreased in the ACTH-treated rats.

    Science.gov (United States)

    Li, Bingjin; Suemaru, Katsuya; Kitamura, Yoshihisa; Gomita, Yutaka; Araki, Hiroaki; Cui, Ranji

    2013-11-01

    Previous studies have shown that the antidepressive-like effect of tricyclic antidepressants is blocked by repeated treatments with adrenocorticotropic hormone (ACTH). However, little is known about the neuroanatomy underlying the mechanism of the imipramine treatment-resistant depression model. In the present study, first experimental evidence showed no significant difference of the serum imipramine concentrations between the saline and ACTH-treated rats. In further study, imipramine produced significant increases in the c-Fos expression in the medial prefrontal cortex (mPFC), the dentate gyrus of the hippocampus (DGH), and the central nucleus of the amygdala (CeA), in rats repeatedly treated with saline. The imipramine-increased c-Fos immunoreactivity was suppressed in the mPFC of rats repeatedly treated with ACTH. However, there was no significant difference in c-Fos expression in the DGH and CeA between ACTH- and saline-treated rats. These results suggest that the mPFC is maybe involved in effects of the imipramine in the ACTH-treated rats.

  14. ACTH blood test

    Science.gov (United States)

    ... gland not producing enough hormones, such as ACTH ( hypopituitarism ) Tumor of the adrenal gland that produces too ... syndrome due to adrenal tumor Ectopic Cushing syndrome Hypopituitarism Multiple endocrine neoplasia (MEN) I Review Date 10/ ...

  15. Potential of repeated polymer well treatments

    Energy Technology Data Exchange (ETDEWEB)

    Lakatos, I.; Lakatos-Szabo, J. (Hungarian Academy of Sciences, Budapest (Hungary)); Munkacsi, I.; Troemboeczki, S.

    1993-11-01

    This paper analyzes field results obtained by routine application of a polymer/silicate well treatment technique at the Algyo-2 field in Hungary. First, the reservoir is described briefly; then, the basic concept of the method is outlined. Reference is made to the multifunctioning chemical mechanism of gelation and the favorable rheological properties of the treating fluids that jointly result in a highly selective placement and an efficient permeability reduction in the target reservoir space. Application of the method 17 times in 16 producing wells yielded more than 90,000 Mg of incremental oil production. Typical well behaviors also are illustrated. Finally, the potential of repeated treatments is discussed, taking laboratory and field results into account.

  16. ACTH has beneficial effects on stuttering in ADHD and ASD patients with ESES: A retrospective study.

    Science.gov (United States)

    Altunel, Attila; Sever, Ali; Altunel, Emine Özlem

    2017-02-01

    Etiology of stuttering remains unknown and no pharmacologic intervention has been approved for treatment. We aimed to evaluate EEG parameters and the effect of adrenocorticotropic hormone (ACTH) therapy in stuttering. In this retrospective study, 25 patients with attention deficit and hyperactivity (ADHD) or autism spectrum disorder (ASD), and comorbid stuttering were followed and treated with ACTH for electrical status epilepticus in sleep (ESES). Sleep EEGs were recorded at referral and follow-up visits and short courses of ACTH were administered when spike-wave index (SWI) was ⩾15%. The assessment of treatment effectiveness was based on reduction in SWI, and the clinician-reported improvement in stuttering, and ADHD or ASD. Statistical analyses were conducted in order to investigate the relationship between the clinical and EEG parameters. Following treatment with ACTH, a reduction in SWI in all the patients was accompanied by a 72% improvement in ADHD or ASD, and 83.8% improvement in stuttering. Twelve of the 25 patients with stuttering showed complete treatment response. Linear regressions established that SWI at final visit significantly predicted improvement in ADHD or ASD, and in stuttering. If symptoms had recurred, improvement was once again achieved with repeated ACTH therapies. Stuttering always improved prior to, and recurred following ADHD or ASD. The underlying etiology leading to ESES may play a significant role in the pathophysiology of stuttering and connect stuttering to other developmental disorders. ACTH therapy has beneficial effects on stuttering and improves EEG parameters. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  17. ACTH overexpressing pituitary hyperplasia in a patient with ectopic ACTH-syndrome due to carcinoid of the lung

    Directory of Open Access Journals (Sweden)

    Larisa Konstantinovna Dzeranova

    2015-01-01

    Full Text Available Ectopic ACTH-syndrome is the most diagnostically challenging  variant of endogenous hypercortisolism. Particularly difficult differential diagnosis of this syndrome is from Cushing's disease (CD, as currently there is no single test sufficiently accurate to differentiate accurately ectopic ACTH production from the pituitary. The main functional tests are based on the fact that the vast majority of ectopic ACTH production is autonomous and suppresses one from pituitary. But in some cases this is not observed, and then the data obtained all necessary laboratory and instrumental research evidence in favor of central genesis of CD in a patient with ACTH ectopic secretion, which can lead to inappropriate treatment. If you confirm the ectopic ACTH-syndrome, it may take quite a long time of searching for the pathological focus, as there is no sufficiently precise imaging and diagnostic method for determining the localization of ectopic source of ACTH production. Thus, the differential diagnosis of ACTH-dependent hypercortisolism and localization of the ectopic tumor is the cornerstone of early and radical treatment of patients. We present a difficult clinical case of a patient having a pituitary hyperplasia with excessive ACTH expression with primary ectopic ACTH syndrome caused by lung carcinoid.

  18. [Stress hormones liberated by fangotherapy. ACTH and beta-endorphin levels under heat stress].

    Science.gov (United States)

    Giusti, P; Cima, L; Tinello, A; Cozzi, F; Targa, L; Lazzarin, P; Todesco, S

    1990-11-10

    In 6 healthy subjects submitted to fango therapy in the Euganean thermal baths (Italy), the plasma concentrations of beta-endorphin and ACTH increased transitorily but significantly. These results correlate with the release of these peptides by the pituitary in response to thermal stressing. The analgesic and hypothermic action responsible for good toleration of thermal stress induced by fango therapy, can be explained by this increase in plasma beta-endorphin. The repeated brief increases in plasma beta-endorphin during thermal treatment result in progressive improvement in articular and muscular symptomatology. The results of our study on plasma levels of ACTH confirm that the thermal stress associated with fango therapy activates the pituitary gland. Immunomodulatory effects are discussed.

  19. ACTH-Secreting Pheochromocytoma. Case report

    Directory of Open Access Journals (Sweden)

    N S Kuznetsov

    2012-12-01

    Full Text Available Ectopic hormone-secreting pheochromocytomas are rare. Only case reports exist in the literature. Despite the large number of guides on diagnosis and treatment of pheochromocytoma, and Cushing syndrome, the extreme rarity of ectopic ACTH-syndrome caused by pheochromocytoma, and complexity of clinical cause numerous diagnostic errors leading to treatment failure. Therefore, we belive it appropriate to share our experience of this group of patients.

  20. Repeated treatments of drooling with botulinum toxin B in neurology

    DEFF Research Database (Denmark)

    Møller, Eigild; Daugaard, Dorthe; Holm, Ole

    2015-01-01

    OBJECTIVES: To investigate efficacy, saliva flow, and composition in repeated BoNT-B treatments of drooling. MATERIALS AND METHODS: Seventeen neurological patients (median 66 years), referred for treatment of drooling participated in this observational study. Median total doses of 4000 units...

  1. Repeated morphine treatment influences operant and spatial learning differentially

    Institute of Scientific and Technical Information of China (English)

    Mei-Na WANG; Zhi-Fang DONG; Jun CAO; Lin XU

    2006-01-01

    Objective To investigate whether repeated morphine exposure or prolonged withdrawal could influence operant and spatial learning differentially. Methods Animals were chronically treated with morphine or subjected to morphine withdrawal. Then, they were subjected to two kinds of learning: operant conditioning and spatial learning.Results The acquisition of both simple appetitive and cued operant learning was impaired after repeated morphine treatment. Withdrawal for 5 weeks alleviated the impairments. Single morphine exposure disrupted the retrieval of operant memory but had no effect on rats after 5-week withdrawal. Contrarily, neither chronic morphine exposure nor 5-week withdrawal influenced spatial learning task of the Morris water maze. Nevertheless, the retrieval of spatial memory was impaired by repeated morphine exposure but not by 5-week withdrawal. Conclusion These observations suggest that repeated morphine exposure can influence different types of learning at different aspects, implicating that the formation of opiate addiction may usurp memory mechanisms differentially.

  2. Effects of bupropion on the forced swim test and release of dopamine in the nucleus accumbens in ACTH-treated rats.

    Science.gov (United States)

    Kitamura, Yoshihisa; Yagi, Takahiko; Kitagawa, Kouhei; Shinomiya, Kazuaki; Kawasaki, Hiromu; Asanuma, Masato; Gomita, Yutaka

    2010-08-01

    The dopamine reuptake inhibitor bupropion has clinically been proven to improve depression and treatment-resistant depression. We examined its influence on the duration of immobility during the forced swim test in adrenocorticotropic hormone (ACTH)-treated rats and further analyzed the possible role of dopamine receptors in this effect. Additionally, the mechanism by which bupropion acts in this model was explored specifically in relation to the site of action through the use of microinjections into the medial prefrontal cortex and nucleus accumbens. Bupropion significantly decreased the duration of immobility in normal and ACTH-treated rats. This effect was blocked by D2 and D3 receptor antagonists in normal rats. Furthermore, infusions of bupropion into the nucleus accumbens, but not medial prefrontal cortex, decreased the immobility of normal and ACTH-treated rats during the forced swim test. Bupropion treatment plus repeated ACTH treatment significantly increased the extracellular dopamine concentration. These findings suggest the antidepressant-like effect of bupropion to be related to levels of dopamine in the rat nucleus accumbens.

  3. ACTH-producing neuroendocrine tumor of thymus with recurrences. Clinical case

    Directory of Open Access Journals (Sweden)

    E A Dobreva

    2015-06-01

    Full Text Available One of the most difficult in diagnostic and treatment options for endogenous Cushing is the ectopic ACTH syndrome, which causes the development of tumors of different histogenesis localization producing adrenocorticotropic hormone (ACTH, and much less - corticotropin hormone (CRH. ACTH-secreting tumors varied in location, morphological structure and the degree of malignancy. Most of these tumors are characterized by an aggressive course with a propensity to metastasize and relapse. The article presents data of the prevalence, pathogenesis of ectopic ACTH tumors localized in the thymus, analyzis of clinical, morphological features, the methods of diagnosis and treatment. Based on the current literature, the world and our own experience on the diagnosis and treatment of patients with ectopic ACTH syndrome with localization of hormone production in the thymus, we want to highlight the current state of the problem in order to create the most efficient algorithm for diagnostic search and treatment of this difficult group of patients.

  4. The expression of the ACTH receptor

    Directory of Open Access Journals (Sweden)

    L.L.K. Elias

    2000-10-01

    Full Text Available Adrenal glucocorticoid secretion is regulated by adrenocorticotropic hormone (ACTH acting through a specific cell membrane receptor (ACTH-R. The ACTH-R is a member of the G protein superfamily-coupled receptors and belongs to the subfamily of melanocortin receptors. The ACTH-R is mainly expressed in the adrenocortical cells showing a restricted tissue specificity, although ACTH is recognized by the other four melanocortin receptors. The cloning of the ACTH-R was followed by the study of this gene in human diseases such as familial glucocorticoid deficiency (FGD and adrenocortical tumors. FGD is a rare autosomal recessive disease characterized by glucocorticoid deficiency, elevated plasma ACTH levels and preserved renin/aldosterone secretion. This disorder has been ascribed to an impaired adrenal responsiveness to ACTH due to a defective ACTH-R, a defect in intracellular signal transduction or an abnormality in adrenal cortical development. Mutations of the ACTH-R have been described in patients with FGD in segregation with the disease. The functional characterization of these mutations has been prevented by difficulties in expressing human ACTH-R in cells that lack endogenous melanocortin receptor activity. To overcome these difficulties we used Y6 cells, a mutant variant of the Y1 cell line, which possesses a non-expressed ACTH-R gene allowing the functional study without any background activity. Our results demonstrated that the several mutations of the ACTH-R found in FGD result in an impaired cAMP response or loss of sensitivity to ACTH stimulation. An ACTH-binding study showed an impairment of ligand binding with loss of the high affinity site in most of the mutations studied.

  5. Effects of hypophysectomy and ACTH1–10 on responsiveness to electric shock in rats

    NARCIS (Netherlands)

    Gispen, W.H.; Wimersma Greidanus, T.B. van; Wied, D. de

    1967-01-01

    Response behavior of rats to unescapable electric shock was studied in intact and hypophysectomized animals. The threshold for flinch, jerk, run and jump was significantly lowered in hypophysectomized rats as compared to that of intact controls. Treatment with the ACTH analogue ACTH1–10 did not affe

  6. Metabolic effects of chronic ACTH administration, interaction with response to stress.

    Science.gov (United States)

    Armario, A; Campmany, L; Hidalgo, J

    1986-01-01

    The present experiment was undertaken to study the metabolic response to stress of single or chronic ACTH-treated male rats. It was found that chronic ACTH-treated rats showed a slight reduction in food intake and a decrease in body weight gain. This treatment increased basal serum triglyceride and insulin levels. In addition, some differences in response to stress was found in chronic ACTH-treated rats. Thus, these latter animals, unlike the other two groups, showed a decrease in circulating triglyceride and insulin levels in response to short-term stress. Moreover, 24 h after onset of stress a more marked fall in liver weight and glucose levels were found in chronic ACTH-treated rats. It suggests that chronic ACTH treatment might alter the metabolic response to prolonged acute stress what could result in lower resistance to severe stresses.

  7. PTSD among a treatment sample of repeat DUI offenders.

    Science.gov (United States)

    Peller, Allyson J; Najavits, Lisa M; Nelson, Sarah E; LaBrie, Richard A; Shaffer, Howard J

    2010-08-01

    Recent studies indicate that posttraumatic stress disorder (PTSD) is one of the most common psychiatric comorbidities among driving-under-the-influence (DUI) offenders in treatment. Investigation of DUI offenders' PTSD and clinical characteristics could have important implications for prevention and treatment. This prospective study examined the demographic and clinical characteristics of repeat DUI offenders with PTSD symptoms at baseline and 1-year follow-up. Seven hundred twenty-nine DUI offenders admitted to a 2-week inpatient program participated in the study. Participants with PTSD evidenced more severe psychiatric comorbidity and reported a higher DUI recidivism rate at 1-year than those without PTSD. This study suggests a need to address PTSD among DUI offenders, as well as to further develop methodologies for accurately reporting DUI recidivism.

  8. Catheterization during adrenal vein sampling for primary aldosteronism: failure to use (1-24) ACTH may increase apparent failure rate.

    Science.gov (United States)

    Kline, Gregory A; So, Benny; Dias, Valerian C; Harvey, Adrian; Pasieka, Janice L

    2013-07-01

    "Successful" adrenal vein catheterization in primary aldosteronism (PA) is often defined by a ratio of >3:1 of cortisol in the adrenal vein vs the inferior vena cava. Non-use of corticotropin (ACTH) during sampling may increase the apparent failure rate of adrenal vein catheterization due to lower cortisol levels. A retrospective study was performed on all patients with confirmed unilateral PA between June 2005 and August 2011. Adrenal vein sampling (AVS) included simultaneous bilateral baseline samples with repeat sampling 15 minutes after intravenous infusion of 250 μg of Cortrosyn (ACTH-S). Successful catheter placement was judged as adrenal cortisol:IVC cortisol of >3:1, applied to both baseline and ACTH-S samples and lateralization of aldosteronism was judged as normalized aldosterone/cortisol (A/C) ratio >3 times the contralateral A/C ratio. In ACTH-S samples, 94% of right-sided catheterizations were biochemically successful with 100% success on the left. Among baseline samples, only 47% of right- and 44% of left-sided samples met the 3:1 cortisol criteria. However, 95% of apparent "failed" baseline cortisol sets still showed lateralization of A/C ratios that matched the ultimate pathology. Non-ACTH-stimulated samples may be incorrectly judged as failed catheter placement when a 3:1 ratio is used. ACTH-stimulated sampling is the preferred means to confirm catheterization during AVS.

  9. EDTA interference in electrochemiluminescence ACTH assay.

    Science.gov (United States)

    Toprak, Burak; Yalcin, Hulya; Arı, Elif; Colak, Ayfer

    2016-11-01

    Background As plasma is the recommended sample type for Roche adrenocorticotropic hormone (ACTH) assay, we evaluated the effect of EDTA concentration on Cobas ACTH assay. Methods Samples containing twofold and fourfold higher concentrations of EDTA were prepared by adding plasma to empty K2EDTA tubes and by making under-filled EDTA tubes. All measurements were performed with four replicates. Results Increased EDTA concentration resulted in a significant decrease in ACTH concentration. Fifty-per cent-filled EDTA tube showed 19% decrease in ACTH concentration and 25% filled EDTA tube showed 50% decrease in ACTH concentration. Conclusion We recommend that inadequately filled EDTA specimens should be rejected when using Cobas ACTH assay.

  10. Adrenal Cushing syndrome with detectable ACTH from an unexpected source.

    Science.gov (United States)

    Lwin, Thinzar M; Galal, Nehal; Gera, Shweta; Marti, Jennifer L

    2016-11-30

    Mixed corticomedullary adrenal tumours (MCMT) are rare. We describe the second reported case of a male patient presenting with hypertension and Cushing syndrome with MCMT. A man aged 48 years presented with hypertension and signs of Cushing syndrome. 24-hour urine cortisol was elevated, with detectable adrenocorticotropic hormone (ACTH). A high-dose dexamethasone suppression test indicated an adrenal or ectopic Cushing syndrome. Plasma metanephrines were normal. A 3 cm left adrenal mass was identified without potential ectopic sources of ACTH on imaging. After induction of anaesthesia for laparoscopic adrenalectomy, the patient developed resistant hypertension with stress-dose hydrocortisone administration. Surgery was cancelled and repeat testing revealed elevated plasma metanephrines. α-Blockade was administered for a presumed coexisting pheochromocytoma, and the patient underwent adrenalectomy. Pathology revealed an MCMT. This case highlights the importance of a thorough biochemical evaluation in patients with adrenal masses to rule out multiple hormone producing tumours. 2016 BMJ Publishing Group Ltd.

  11. Hormonal secretion and quality of life in Nelson syndrome and Cushing disease after long acting repeatable octreotide: a short series and update.

    Science.gov (United States)

    Arregger, Alejandro L; Cardoso, Estela M L; Sandoval, Olga B; Monardes Tumilasci, Elida G; Sanchez, Rocío; Contreras, Liliana N

    2014-01-01

    Clinical management of persistent adrenocorticotropin hormone (ACTH) excess in Nelson syndrome (NS) and Cushing disease (CD) remains a challenge. Somatostatin and its analogs as octreotide decrease ACTH secretion through somatostatin receptors of pituitary cells. To our knowledge, there are no reports on the effect of long-acting repeatable octreotide (oct-lar) on hormonal secretion and quality of life in patients with NS and CD who failed conventional therapy. Herein, we describe the effects of treatment with oct-lar (20 mg/month intramurally) in 1 woman with NS and 2 women with persistent CD. Oct-lar therapy reduced ACTH secretion and improved the quality of life in NS patient. By contrast, in CD patients, it failed to control ACTH and cortisol secretion, and the quality of life remained unchanged.

  12. Severe Hypoglycemia due to Isolated ACTH Deficiency in Children: A New Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Michael Y. Torchinsky

    2011-01-01

    Full Text Available Isolated ACTH deficiency causes life-threatening severe hypoglycemia. A 7-year-old girl with hypoglycemia due to this rare disorder is described. Our patient had undetectable plasma ACTH repeatedly and cortisol 0 mcg/dl before and after ACTH 1-24 stimulation. There was no evidence of other pituitary hormone deficiency. Glucocorticoid replacement therapy resulted in resolution of all symptoms and normalization of blood glucose. Previously published data on isolated ACTH deficiency in children is summarized. Review of the literature showed that the prevalence of this condition could be underestimated in the neonatal period and in Prader-Willi syndrome. Isolated ACTH deficiency occurs in older children as well as in neonates.

  13. Isolated ACTH deficiency in a patient with empty sella as revealed by severe hyponatremia.

    Science.gov (United States)

    Doroftei, Nicoleta Alina; de Rudder, Catherine; de Visscher, Nathalie; Hanon, Francois

    2016-12-01

    Hyponatremia due to isolated adrenocorticotropic hormone (ACTH) deficiency is difficult to diagnose as it is usually indistinguishable from non-endocrine syndrome of inappropriate antidiuretic hormone secretion (SIADH). We present a case secondary to empty sella. Most patients with empty sella remain asymptomatic throughout life and require no treatment; however, in cases involving the development of isolated ACTH deficiency, corticosteroid treatment should be enforced to avoid fatal consequences.

  14. ACTH adenomas transforming their clinical expression: report of 5 cases.

    Science.gov (United States)

    Zoli, Matteo; Faustini-Fustini, Marco; Mazzatenta, Diego; Marucci, Gianluca; De Carlo, Eugenio; Bacci, Antonella; Pasquini, Ernesto; Lanzino, Giuseppe; Frank, Giorgio

    2015-02-01

    OBJECT Adrenocorticotropic hormone (ACTH) adenomas have been recognized as a more aggressive and invasive subtype of pituitary adenomas. An additional and clinically relevant peculiarity of these tumors is their ability to modify their clinical expression from a silent form to Cushing disease or vice versa. The aim of this study was to review a series of patients with pituitary adenomas and analyze the clinical implications of the transformation of clinical expression in 5 cases that showed this phenomenon. METHODS The authors retrospectively reviewed a series of patients with pituitary adenoma and collected clinical, biohumoral, and neuroradiological data of those who presented with a transformation from silent ACTH adenomas to functioning tumors or vice versa. In all the cases, preoperative assessment consisted of brain MRI, ophthalmological examination, and complete baseline endocrinological investigation. In patients with clinical and/or biochemical findings suspicious for Cushing syndrome, a low-dose dexamethasone suppression test was performed to rule in or out this diagnosis. Endocrinological evaluations were repeated 1 month after surgery, 3 months after surgery, and every 6 months or annually thereafter. Ophthalmological evaluations and brain MRIs were repeated after 3 months and then every 6 or 12 months thereafter. RESULTS Five patients (2 men and 3 women) included in this series had corticotropic tumors that showed transformation from an endocrinologically silent form to manifest Cushing disease and vice versa. The mean age at presentation was 40 years (range 18-51 years). In 3 of these patients, a transformation from silent to functioning ACTH adenoma with manifest Cushing disease occurred. In 1 patient, the authors observed the transition from a functioning to a silent adenoma with spontaneous resolution of hypercortisolism. Another patient's silent adenoma "shifted" to a functioning adenoma and then regressed back to a silent form with spontaneous

  15. ACTH Prevents Deficits in Fear Extinction Associated with Early Life Seizures

    Directory of Open Access Journals (Sweden)

    Andrew T Massey

    2016-05-01

    Full Text Available Early life seizures are often associated with cognitive and psychiatric comorbidities that are detrimental to quality of life. In a rat model of early life seizures (ELS, we explored long-term cognitive outcomes in adult rats. Using ACTH, an endogeneous HPA-axis hormone given to children with severe epilepsy, we sought to prevent cognitive deficits. Through comparisons with dexamethasone, we sought to dissociate the corticosteroid effects of ACTH from other potential mechanisms of action. We found that while rats with a history of ELS were able to acquire a conditioned fear learning paradigm as well as controls, these rats had significant deficits in their ability to extinguish fearful memories. ACTH treatment did not alter any seizure parameters but nevertheless was able to significantly improve this fear extinction, while dexamethasone treatment during the same period did not. This ACTH effect was specific for fear extinction deficits and not for spatial learning deficits in a water maze. Additionally, ACTH did not alter seizure latency or duration suggesting that cognitive and seizure outcomes may be dissociable. Expression levels of melanocortin receptors, which bind ACTH, were found to be significantly lower in animals that had experienced ELS than in control animals, potentially implicating central melanocortin receptor dysregulation in the effects of ELS and suggesting a mechanism of action for ACTH. Taken together, these data suggest that early treatment with ACTH can have significant long-term consequences for cognition in animals with a history of ELS independently of seizure cessation, and may act in part through a CNS melanocortin receptor pathway.

  16. Compressed air massage: repeated treatment causes less muscle oedema than a single treatment

    Directory of Open Access Journals (Sweden)

    M. A. Gregory

    2007-02-01

    Full Text Available Compressed air massage is a new treatment modality that has been shown to cause skeletal muscle capillary dilation for up to 24 hours after a single treatment and significantly hastens healing of diabetic ulcers. This study compares the effect of one treatment of a single muscle group, with repeated treatments of several muscle groups. Methods: Four vervet monkeys underwent one, 15 min, treatment of compressed air massage at 1 Bar, to the tibialis anterior muscle and four animals received similar treatment to the whole lower leg on three consecutive days. The tibialis anterior of the treated and untreated limbs was biopsied immediately after the final treatment. Muscle fibre diameters were measured from 1µm thick toluidine blue stained resin embedded sections using light microscopy and computerized image analysis software. Results: For treatment of the whole lower limb, the mean fibre diameter increased by 6.0% from 47.31±13.4µm(95%CI:46.47-48.16 in control biopsies to 50.14±13.93µm (95%CI:49.26-51.02 in treated muscle (p<0.001.Treatment of a single muscle showed an increase in diameter of 11.3%, from 48.21±12.68µm (95%CI:47.31-49.11 to53.63+14.29µm (95%CI:52.61-54.66 (p<0.001. Treatment of a single muscle caused significantly more oedema thantreatment of the whole limb (p<0.001. Conclusions: Repeated treatment causes skeletal muscle oedema, and this appears to be dose related. Skeletal muscleoedema after three treatments is less than after a single treatment. Further studies on the use of compressed air massage on injured muscle are warranted.

  17. Lipid synthesis and secretion in HepG2 cells is not affected by ACTH

    Directory of Open Access Journals (Sweden)

    Nilsson-Ehle Peter

    2010-05-01

    Full Text Available Abstract Apolipoprotein B (apoB containing lipoproteins, i.e. VLDL, LDL and Lp(a, are consequently lowered by ACTH treatment in humans. This is also seen as reduced plasma apoB by 20-30% and total cholesterol by 30-40%, mostly accounted for by a decrease in LDL-cholesterol. Studies in hepatic cell line (HepG2 cells showed that apoB mRNA expression is reduced in response to ACTH incubation and is followed by a reduced apoB secretion, which may hypothesize that ACTH lowering apoB containing lipoproteins in humans may be mediated by the inhibition of hepatic apoB synthesis. This was recently confirmed in vivo in a human postprandial study, where ACTH reduced transient apoB48 elevation from the small intestine, however, the exogenic lipid turnover seemed unimpaired. In the present study we investigated if lipid synthesis and/or secretion in HepG2 cells were also affected by pharmacological levels of ACTH to accompany the reduced apoB output. HepG2 cells were incubated with radiolabelled precursors ([14C]acetate and [3H]glycerol either before or during ACTH stimuli. Cellular and secreted lipids were extracted with chloroform:methanol and separated by the thin layer chromatography (TLC, and [14C]labelled cholesterol and cholesteryl ester and [3H]labelled triglycerides and phospholipids were quantitated by the liquid scintillation counting. It demonstrated that ACTH administration did not result in any significant change in neither synthesis nor secretion of the studied lipids, this regardless of presence or absence of oleic acid, which is known to stabilize apoB and enhance apoB production. The present study suggests that ACTH lowers plasma lipids in humans mainly mediated by the inhibition of apoB synthesis and did not via the reduced lipid synthesis.

  18. ACTH Modulates PTP-PEST Activity and Promotes Its Interaction With Paxillin.

    Science.gov (United States)

    Gorostizaga, Alejandra Beatriz; Mori Sequeiros Garcia, M Mercedes; Acquier, Andrea B; Lopez-Costa, Juan J; Mendez, Carlos F; Maloberti, Paula M; Paz, Cristina

    2016-09-01

    Adrenocorticotropic hormone (ACTH) treatment has been proven to promote paxillin dephosphorylation and increase soluble protein tyrosine phosphatase (PTP) activity in rat adrenal zona fasciculata (ZF). Also, in-gel PTP assays have shown the activation of a 115-kDa PTP (PTP115) by ACTH. In this context, the current work presents evidence that PTP115 is PTP-PEST, a PTP that recognizes paxillin as substrate. PTP115 was partially purified from rat adrenal ZF and PTP-PEST was detected through Western blot in bioactive samples taken in each purification step. Immunohistochemical and RT-PCR studies revealed PTP-PEST expression in rat ZF and Y1 adrenocortical cells. Moreover, a PTP-PEST siRNA decreased the expression of this phosphatase. PKA phosphorylation of purified PTP115 isolated from non-ACTH-treated rats increased KM and VM . Finally, in-gel PTP assays of immunoprecipitated paxillin from control and ACTH-treated rats suggested a hormone-mediated increase in paxillin-PTP115 interaction, while PTP-PEST and paxillin co-localize in Y1 cells. Taken together, these data demonstrate PTP-PEST expression in adrenal ZF and its regulation by ACTH/PKA and also suggest an ACTH-induced PTP-PEST-paxillin interaction. J. Cell. Biochem. 117: 2170-2181, 2016. © 2016 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc.

  19. Cortisol secretion after adrenocorticotrophin (ACTH and Dexamethasone tests in healthy female and male dogs

    Directory of Open Access Journals (Sweden)

    Castillo Victor

    2009-08-01

    Full Text Available Abstract Background For the conclusive diagnosis of Cushing's Syndrome, a stimulating ACTH test or a low suppressive Dexamethasone test is used. Reports in other species than the dog indicate that plasma cortisol concentration after ACTH administration is affected by gender. We investigated the effect of gender on the cortisol response to ACTH and Dexamethasone tests in dogs. Methods Seven healthy adult Cocker Spaniels (4 females and 3 males were assigned to a two by two factorial design: 4 dogs (2 females and 2 males received IV Dexamethasone 0.01 mg/kg, while the other 3 dogs received an IV saline solution (control group. Two weeks later the treatments were reversed. After one month, ACTH was given IV (250 μg/animal to 4 dogs (2 female and 2 males while the rest was treated with saline solution (control group. Cortisol concentrations were determined by a direct solid-phase radioimmunoassay and cholesterol and triglycerides by commercial kits. Results and Discussion No effect of treatment was observed in metabolite concentrations, but females presented higher cholesterol concentrations. ACTH-treated dogs showed an increase in cortisol levels in the first hour after sampling until 3 hours post injection. Cortisol concentrations in Dexamethasone-treated dogs decreased one hour post injection and remained low for 3 hours, thereafter cortisol concentrations increased. The increase in cortisol levels from one to two hours post ACTH injection was significantly higher in females than males. In Dexamethasone-treated males cortisol levels decreased one hour post injection up to 3 hours; in females the decrease was more pronounced and prolonged, up to 5 hours post injection. Conclusion We have demonstrated that cortisol response to ACTH and Dexamethasone treatment in dogs differs according to sex.

  20. Proliferative signaling initiated in ACTH receptors

    Directory of Open Access Journals (Sweden)

    C.F.P. Lotfi

    2000-10-01

    Full Text Available This article reviews recent results of studies aiming to elucidate modes of integrating signals initiated in ACTH receptors and FGF2 receptors, within the network system of signal transduction found in Y1 adrenocortical cells. These modes of signal integration should be central to the mechanisms underlying the regulation of the G0->G1->S transition in the adrenal cell cycle. FGF2 elicits a strong mitogenic response in G0/G1-arrested Y1 adrenocortical cells, that includes a rapid and transient activation of extracellular signal-regulated kinases-mitogen-activated protein kinases (ERK-MAPK (2 to 10 min, b transcription activation of c-fos, c-jun and c-myc genes (10 to 30 min, c induction of c-Fos and c-Myc proteins by 1 h and cyclin D1 protein by 5 h, and d onset of DNA synthesis stimulation within 8 h. ACTH, itself a weak mitogen, interacts with FGF2 in a complex manner, blocking the FGF2 mitogenic response during the early and middle G1 phase, keeping ERK-MAPK activation and c-Fos and cyclin D1 induction at maximal levels, but post-transcriptionally inhibiting c-Myc expression. c-Fos and c-Jun proteins are mediators in both the strong and the weak mitogenic responses respectively triggered by FGF2 and ACTH. Induction of c-Fos and stimulation of DNA synthesis by ACTH are independent of PKA and are inhibited by the PKC inhibitor GF109203X. In addition, ACTH is a poor activator of ERK-MAPK, but c-Fos induction and DNA synthesis stimulation by ACTH are strongly inhibited by the inhibitor of MEK1 PD98059.

  1. Decrease in adverse reactions after repeated ivermectin treatment in onchocerciasis.

    Science.gov (United States)

    Van der Lelij, A; Rothova, A; Klaassen-Broekema, N; Wilson, W R; Barbe, R F; Stilma, J S

    1990-10-01

    We assessed the side-effects after multiple single-dose treatment with ivermectin (150 micrograms/kg) in onchocerciasis patients form a hyperendemic area in Sierra Leone, in order to investigate whether medical surveillance was always necessary. After initial treatment 87 onchocerciasis patients were examined for adverse reactions. Fourty-four of these 87 patients (51%) received a second dose of ivermectin 5 months later and thirty-five (40%) received a third dose one year later. The side-effects after the second and third doses were significantly diminished, when compared with the initial dose of ivermectin in the treatment of onchocerciasis (chi2 test p less than 0.005, resp. p less than 0.008). Side-effects requiring therapy were observed in 32% of patients after the first dose, in 18% after the second dose and in 11% after the third dose of ivermectin. Severe side-effects (9%) were only seen after the initial ivermectin dose. All the severe adverse reactions appeared within 48 hours. In view of our findings, it seems necessary that the first treatment with ivermectin should take place under strict medical supervision during at least two days. Five months after treatment with a single dose of ivermectin 29 out of 44 patients (66%) still had a positive skin-snip test. Seven months after the second dose 15 of 35 patients (43%) had a positive skin-snip count. Since almost half of the patients had a positive skin-snip test despite two treatments with ivermectin, it could be argued that in hyperendemic areas treatment should consist of at least two doses in the first year.

  2. Reduced nocturnal ACTH-driven cortisol secretion during critical illness

    Science.gov (United States)

    Boonen, Eva; Meersseman, Philippe; Vervenne, Hilke; Meyfroidt, Geert; Guïza, Fabian; Wouters, Pieter J.; Veldhuis, Johannes D.

    2014-01-01

    Recently, during critical illness, cortisol metabolism was found to be reduced. We hypothesize that such reduced cortisol breakdown may suppress pulsatile ACTH and cortisol secretion via feedback inhibition. To test this hypothesis, nocturnal ACTH and cortisol secretory profiles were constructed by deconvolution analysis from plasma concentration time series in 40 matched critically ill patients and eight healthy controls, excluding diseases or drugs that affect the hypothalamic-pituitary-adrenal axis. Blood was sampled every 10 min between 2100 and 0600 to quantify plasma concentrations of ACTH and (free) cortisol. Approximate entropy, an estimation of process irregularity, cross-approximate entropy, a measure of ACTH-cortisol asynchrony, and ACTH-cortisol dose-response relationships were calculated. Total and free plasma cortisol concentrations were higher at all times in patients than in controls (all P cortisol secretion was 54% lower in patients than in controls (P = 0.005), explained by reduced cortisol burst mass (P = 0.03), whereas cortisol pulse frequency (P = 0.35) and nonpulsatile cortisol secretion (P = 0.80) were unaltered. Pulsatile ACTH secretion was 31% lower in patients than in controls (P = 0.03), again explained by a lower ACTH burst mass (P = 0.02), whereas ACTH pulse frequency (P = 0.50) and nonpulsatile ACTH secretion (P = 0.80) were unchanged. ACTH-cortisol dose response estimates were similar in patients and controls. ACTH and cortisol approximate entropy were higher in patients (P ≤ 0.03), as was ACTH-cortisol cross-approximate entropy (P ≤ 0.001). We conclude that hypercortisolism during critical illness coincided with suppressed pulsatile ACTH and cortisol secretion and a normal ACTH-cortisol dose response. Increased irregularity and asynchrony of the ACTH and cortisol time series supported non-ACTH-dependent mechanisms driving hypercortisolism during critical illness. PMID:24569590

  3. Single-Session CT-Guided Percutaneous Microwave Ablation of Bilateral Adrenal Gland Hyperplasia Due to Ectopic ACTH Syndrome.

    Science.gov (United States)

    Sarma, Asha; Shyn, Paul B; Vivian, Mark A; Ng, Ju-Mei; Tuncali, Kemal; Lorch, Jorchen H; Zaheer, Sarah N; Gordon, Michael S; Silverman, Stuart G

    2015-10-01

    Bilateral adrenalectomy is currently the only available treatment for adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (ectopic ACTH syndrome) that is refractory to pharmacologic therapy. We describe two patients with refractory ectopic ACTH syndrome who were treated with CT-guided percutaneous microwave ablation of both hyperplastic adrenal glands in a single session: O ne was not a surgical candidate, and the other had undergone unsuccessful surgery. Following the procedure, both patients achieved substantial decreases in serum cortisol, symptomatic improvement, and decreased anti-hypertensive medication requirements.

  4. Single-Session CT-Guided Percutaneous Microwave Ablation of Bilateral Adrenal Gland Hyperplasia Due to Ectopic ACTH Syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Sarma, Asha, E-mail: ashasarma@gmail.com; Shyn, Paul B., E-mail: pshyn@partners.org [Brigham and Women’s Hospital, Department of Radiology (United States); Vivian, Mark A. [University of Manitoba, Department of Radiology (Canada); Ng, Ju-Mei [Brigham and Women’s Hospital, Department of Anesthesiology (United States); Tuncali, Kemal [Brigham and Women’s Hospital, Department of Radiology (United States); Lorch, Jorchen H. [Dana Farber Cancer Institute, Department of Medicine (United States); Zaheer, Sarah N.; Gordon, Michael S. [Brigham and Women’s Hospital, Department of Endocrinology (United States); Silverman, Stuart G. [Brigham and Women’s Hospital, Department of Radiology (United States)

    2015-10-15

    Bilateral adrenalectomy is currently the only available treatment for adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome (ectopic ACTH syndrome) that is refractory to pharmacologic therapy. We describe two patients with refractory ectopic ACTH syndrome who were treated with CT-guided percutaneous microwave ablation of both hyperplastic adrenal glands in a single session: One was not a surgical candidate, and the other had undergone unsuccessful surgery. Following the procedure, both patients achieved substantial decreases in serum cortisol, symptomatic improvement, and decreased anti-hypertensive medication requirements.

  5. Addison's disease and ACTH-producing pituitary microadenoma

    Directory of Open Access Journals (Sweden)

    S.S. Ortega

    2015-10-01

    Full Text Available A 28-year-old man diagnosed with primary adrenal insufficiency (Addison's disease in 2002. Following diagnosis, replacement therapy with hydrocortisone and fludrocortisone was indicated. Hydrocortisone replacement therapy was unsuccessful, and increased ACTH levels as high as 996 pg/dl were observed on outpatient follow-up. A pituitary MRI revealed a pituitary microadenoma. These findings raised three possibilities: (1 treatment is insufficient; (2 there is no relationship between Addison's disease and pituitary microadenoma; and (3 the microadenoma is similar to Nelson's syndrome. This latter is the most satisfactory explanation of this patient's clinical picture.

  6. Effects of (+)-8-OH-DPAT on the duration of immobility during the forced swim test and hippocampal cell proliferation in ACTH-treated rats.

    Science.gov (United States)

    Miyake, Ayaka; Kitamura, Yoshihisa; Miyazaki, Ikuko; Asanuma, Masato; Sendo, Toshiaki

    2014-07-01

    In the present study, we examined the effect of ACTH on the immobilization of rats in the forced swim test and hippocampal cell proliferation after administration of the 5-HT1A receptor agonist, R-(+)-8-hydroxy-2-di-n-propylamino tetralin ((+)-8-OH-DPAT). Chronic treatment with (+)-8-OH-DPAT (0.01-0.1 mg/kg, s.c.) significantly decreased the duration of immobility in saline- and ACTH-treated rats. Chronic administration of ACTH caused a significant decrease in hippocampal cell proliferation. However, (+)-8-OH-DPAT significantly normalized cell proliferation in ACTH-treated rats. We then investigated the effects of (+)-8-OH-DPAT on the expression of brain-derived neurotrophic factor (BDNF) and cyclin D1 (elements of cyclic adenosine monophosphate response element-binding protein (CREB)-BDNF and Wnt signaling pathways, respectively) in the hippocampus of saline- and ACTH-treated rats. ACTH treatment significantly decreased the expression of cyclin D1, while treatment with (+)-8-OH-DPAT normalized the expression of cyclin D1 in ACTH-treated rats. However, the expression of BDNF did not change in either saline- or ACTH-treated rats. These findings suggest that the antidepressant effects of (+)-8-OH-DPAT in treatment-resistant animals may be attributed to an enhancement of hippocampal cell proliferation, at least in part due to an enhancement of cyclin D1 expression.

  7. Mimecan in pituitary corticotroph cells may regulate ACTH secretion and the HPAA.

    Science.gov (United States)

    Ma, Qin-Yun; Zhang, Xiao-Na; Jiang, He; Wang, Zhi-Quan; Zhang, Hui-Jie; Xue, Li-Qiong; Chen, Ming-Dao; Song, Huai-Dong

    2011-07-20

    Mimecan is a protein of unknown function that is expressed in the pituitary tissues of mouse and human. In this study, we observed the function of mimecan on the proopiomelanocortin (POMC) gene in the pituitary and the hypothalamo-pituitary-adrenal axis (HPAA). Incubating pituitary corticotroph AtT-20 cells with recombinant mimecan protein stimulated adrenocorticotrophic hormone (ACTH) secretion without significantly up-regulating POMC gene expression. In addition, pituitary corticotroph AtT-20 cell corticotropin-releasing hormone receptor 1 (CRHR1) gene expression was induced by mimecan. Interestingly, long-term mimecan overexpression in corticotroph cells increased CRHR1 mRNA levels while slightly decreasing POMC mRNA expression and ACTH secretion. Using mimecan knockout mice, we found that, although the serum ACTH concentration was not significantly different between wild type and mimecan knockout mice under basal conditions, the serum ACTH level was relatively lower in mimecan knockout mice after treatment with corticotropin-releasing hormone (CRH). Meanwhile, we observed that POMC and CRHR1 gene expression decreased in primary cultured knockout mouse pituitary cells compared with wild type cells. Taken together, these data suggest that mimecan expressed in pituitary corticotroph cells mainly regulates ACTH secretion in the pituitary and coordinates the HPAA. Copyright © 2011. Published by Elsevier Ireland Ltd.

  8. Occult secretion of acth and bilateral adrenalectomy: sometimes the messenger has to be shot.

    Science.gov (United States)

    Chicharro, Sandra; Lecube, Albert; Mesa, Jordi

    2008-12-01

    Cushing's syndrome due to ectopic adrenocorticotrophic hormone (ACTH) secretion is infrequent, the most frequent cause being bronchial carcinoid; nevertheless, in a considerable proportion of cases (up to 16%), the origin of ACTH secretion is not found. Treatment of Cushing's syndrome due to ectopic ACTH secretion is surgical resection of the tumor. However, surgical excision is not always feasible, either because the tumor has not been located, or because it is unresectable; in these cases the question is when to carry out a bilateral adrenalectomy. We present a case of ACTH-dependent hypercortisolism, in which the ectopic origin of ACTH secretion was established from the results of complementary tests (suppression tests, petrosal sinus sampling, imaging); nevertheless, none of the imaging tests was able to identify the secreting tumor. Consequently, after a reasonable interval, a bilateral adrenalectomy was performed, with good clinical results. Copyright © 2008 Sociedad Española de Endocrinología y Nutrición. Published by Elsevier Espana. All rights reserved.

  9. Assessing small-volume spinal cord dose for repeat spinal stereotactic body radiotherapy treatments

    Science.gov (United States)

    Ma, Lijun; Kirby, Neil; Korol, Renee; Larson, David A.; Sahgal, Arjun

    2012-12-01

    Spinal cord biologically effective dose (BED) limits are critical to safe spine stereotactic body radiotherapy (SBRT) delivery. In particular, when repeating SBRT to the same site, the problem of adding non-uniform BED distributions within small volumes of spinal cord has yet to be solved. We report a probability-based generalized BED (gBED) model to guide repeat spine SBRT treatment planning. The gBED was formulated by considering the sequential damaging probabilities of repeat spine SBRT treatments. Parameters from the standard linear-quadratic model, such as α/β = 2 Gy for the spinal cord, were applied. We tested the model based on SBRT specific spinal cord tolerance using a simulated and ten clinical repeat SBRT cases. The gBED provides a consistent solution for superimposing non-uniform dose distributions from different fractionation schemes, analogous to the BED for uniform dose distributions. Based on ten clinical cases, the gBED was observed to eliminate discrepancies in the cumulative BED of approximately 5% to 20% within small volumes (e.g. 0.1-2.0 cc) of spinal cord, as compared to a conventional calculation method. When assessing spinal cord tolerance for repeat spinal SBRT treatments, caution should be exercised when applying conventional BED calculations for small volumes of spinal cord irradiated, and the gBED potentially provides more conservative and consistently derived dose surrogates to guide safe treatment planning and treatment outcome modeling.

  10. The role of ACTH and adrenal glucocorticoids in the salt appetite of wild rabbits (Oryctolagus cuniculus (L)).

    Science.gov (United States)

    Blaine, E H; Covelli, M D; Denton, D A; Nelson, J F; Shulkes, A A

    1975-10-01

    The selective appetites of wild rabbits for 500 mEq/1 solutions of NaC1, KC1, MgC1(2), and CaC1(2) were studied in intact and adrenalectomized rabbits during daily treatment with either 4 IU long acting ACTH, 1.0 or 2.5 mg cortisol acetate, or 2.5 mg corticosterone. The animals were individually caged and external sodium balances performed. In intact rabbits, cortisol or corticosterone produced a significant stimulation of NaC1 appetite. The response to concurrent dosage of cortisol and corticosterone was less than half of that obtained with ACTH which produced a comparable alteration of blood glucocorticoid levels but a 10-fold increase in NaC1 intake. CaC1(2) intake was increased in intact rabbits by cortisol treatment but not by corticosterone or ACTH. Adrenalectomized rabbits maintained on daily steroid replacement therapy of 0.1 mg deoxycorticosterone acetate and 0.75 mg cortisone acetate showed a normal pattern of electolyte, food, and water intake. Under these conditions ACTH produced a 4-fold increase in NaC1 intake. Further addition of cortisol and corticosterone to steroid replacement therapy produced an increase in NaC1 intake comparable to their effect on normal rabbits. Thereupon supplementation with ACTH resulted in an increase to a level at least as great as that found in ACTH treated, normal rabbits. The effects of ACTH and glucocorticoids on NaC1 appetite were synergistic. Sodium balance showed that increases in NaC1 intake were not the result of the treatment initially producing a body sodium deficit, which was then corrected by increased intake. The results provide further evidence for the hypothesis that NaC1 appetite may be hormonally regulated, and demonstrate that ACTH is capable of stimulating NaC1 intake by a previously unsuspected non-adrenal pathway.

  11. Contact transcleral ciliary body photodynamic therapy with verteporfin in pigmented rabbits: effect of repeated treatments.

    Science.gov (United States)

    Charisis, Spyridon K; Naoumidi, Irene I; Ginis, Harilaos S; Detorakis, Efstathios T; Tsilimbaris, Miltiadis K

    2010-01-01

    We studied the effect on the intraocular pressure (IOP) and the ciliary body (CB) morphology after four consecutive contact transcleral photodynamic treatments of the ciliary body (CB-PDT) with verteporfin in pigmented rabbits. Twenty-two pigmented rabbits underwent CB-PDT (study group), performed once (six rabbits) or repeated for up to four times (16 rabbits). Six additional rabbits received only laser treatment without photosensitizer administration (control group). CB-PDT was performed in one eye in rabbits of the study group, with the fellow eye serving as internal control. Verteporfin dosage was 1 mg kg(-1) as bolus injection and laser settings were 40 mW (600 microm core optical fiber) for 1.5 min per spot, for 10 spots. In repeated CB-PDT, treatments were performed in 4-day intervals. Daily IOP measurements were recorded. Histological studies were performed at selected time points. An IOP reduction, more sustained following repeated treatments, was detected in all treated eyes but not in fellow eyes or in the control group. On the average, the IOP was restored to pretreatment levels 4 days after the last treatment. No serious adverse events were observed and the CB architecture was intact at the end of the experiment. Repeated CB-PDT is safe and results in a short-term reduction of IOP. Induced CB alterations are reversible.

  12. Adrenocorticotrophic hormone (ACTH) stimulation of sheep fetal adrenal cortex can occur without increased expression of ACTH receptor (ACTH-R) mRNA

    DEFF Research Database (Denmark)

    Carter, A M; Petersen, Y M; Towstoless, M

    2002-01-01

    In the present study, it was hypothesized that the adrenocorticotrophin hormone receptor (ACTH-R) would be up-regulated in the adrenal gland of the sheep fetus following infusion of physiological amounts of ACTH, as shown for adrenal cortical cells in culture. In chronically catheterized sheep, a...

  13. Repeated ketamine treatment induces sex-specific behavioral and neurochemical effects in mice.

    Science.gov (United States)

    Thelen, Connor; Sens, Jonathon; Mauch, Joseph; Pandit, Radhika; Pitychoutis, Pothitos M

    2016-10-01

    One of the most striking discoveries in the treatment of major depression was the finding that infusion of a single sub-anesthetic dose of ketamine induces rapid and sustained antidepressant effects in treatment-resistant depressed patients. However, ketamine's antidepressant-like actions are transient and can only be sustained by repeated drug treatment. Despite the fact that women experience major depression at roughly twice the rate of men, research regarding the neurobiological antidepressant-relevant effects of ketamine has focused almost exclusively on the male sex. Importantly, knowledge regarding the sex-differentiated effects, the frequency and the dose on which repeated ketamine administration stops being beneficial, is limited. In the current study, we investigated the behavioral, neurochemical and synaptic molecular effects of repeated ketamine treatment (10mg/kg; 21days) in male and female C57BL/6J mice. We report that ketamine induced beneficial antidepressant-like effects in male mice, but induced both anxiety-like (i.e., decreased time spent in the center of the open field arena) and depressive-like effects (i.e., enhanced immobility duration in the forced swim test; FST) in their female counterparts. Moreover, repeated ketamine treatment induced sustained sex-differentiated neurochemical and molecular effects, as it enhanced hippocampal synapsin protein levels and serotonin turnover in males, but attenuated glutamate and aspartate levels in female mice. Taken together, our findings indicate that repeated ketamine treatment induces opposite behavioral effects in male and female mice, and thus, present data have far-reaching implications for the sex-oriented use of ketamine in both experimental and clinical research settings.

  14. Safety and Efficacy of Repeated-Dose Intravenous Ketamine for Treatment-Resistant Depression

    NARCIS (Netherlands)

    aan het Rot, Marije; Collins, Katherine A.; Murrough, James W.; Perez, Andrew M.; Reich, David L.; Charney, Dennis S.; Mathew, Sanjay J.

    2010-01-01

    Background: A single subanesthetic (intravenous) IV dose of ketamine might have rapid but transient antidepressant effects in patients with treatment-resistant depression (TRD). Here we tested the tolerability, safety, and efficacy of repeated-dose open-label IV ketamine (six infusions over 12 days)

  15. Impact of ACTH administration on the oviductal sperm reservoir in sows: the local endocrine environment and distribution of spermatozoa.

    Science.gov (United States)

    Brandt, Y; Lang, A; Madej, A; Rodriguez-Martinez, H; Einarsson, S

    2006-03-01

    The objective of the study was to investigate if short-term stress in sows (simulated by injections of synthetic adrenocorticotrophic hormone (ACTH)) during standing oestrus had a negative effect on the local environment in the utero-tubal junction (UTJ) and isthmus and the distribution of spermatozoa in these segments. Fourteen sows were monitored for ovulation using ultrasonography in two consecutive oestruses. The sows were fitted with jugular catheters and, from onset of the second oestrus, blood samples were collected every second hour. In the 2nd oestrus, seven sows were given ACTH every second hour, from the onset of standing oestrus until the sow ovulated (ACTH-group), whereas the other seven sows remained as controls (C-group) and were given NaCl solution. The sows were artificially inseminated 16-18 h before expected ovulation. Six hours after ovulation the sows were anaesthetised, and blood samples were repeatedly taken from veins draining the uterus and the UTJ-isthmus, respectively. This oviduct was thereafter removed and divided in four adjacent sections consisting of: (i) the UTJ, (ii) the first, and (iii) the second isthmus segment prior to (iv), the ampullary-isthmic junction (AIJ) and the ampulla. The three first-mentioned segments were flushed to retrieve spermatozoa, whereas the last one was flushed to collect oocytes/ova. The number of spermatozoa attached to the zona pellucida was counted. The concentrations of cortisol in jugular blood of the ACTH-group sows during the time of ACTH-injections were significantly higher than of the C-group sows (pAIJ. In conclusion, simulated stress induced by injections of ACTH during standing oestrus results in elevated concentrations of progesterone before ovulation and may interfere with the rise of progesterone after ovulation. However, ACTH-injections appeared to augment transport of spermatozoa through the female genital tract of pigs.

  16. Changes in pathological pattern and treatment regimens based on repeat renal biopsy in lupus nephritis

    Institute of Scientific and Technical Information of China (English)

    WANG Guo-bao; XU Zheng-jin; LIU Hong-fa; ZHOU Qiu-gen; ZHOU Zhan-mei; JIA Nan

    2012-01-01

    Background Relapses occur frequently in patients with lupus nephritis.Renal biopsy is the gold standard for assessing renal activity and hence guiding the treatment.Whether repeat renal biopsy is helpful during flares of lupus nephritis remains inconclusive.In the present study,we retrospectively reviewed the patients with lupus nephritis who had more than one renal biopsy with the hope to find the clinical value of repeat biopsy.Methods Patients who had a diagnosis of lupus nephritis and two or more renal biopsies were selected from the database of the patient pathology registration at this renal division.Renal biopsy was evaluated according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification of lupus nephritis.The pathological patterns and treatment regimens were analyzed after a repeat biopsy.Results We identified 44 systemic lupus erythematosus patients with serial renal biopsies.In total,there were 94 renal biopsies.Overall,the pathological transition occurred in 64% instances according to the ISN/RPS class.When the transition was analyzed according to proliferative,membranous or mix lesions,it showed different profile:35% in patients with proliferative lesion,23.5% patients with mix lesions,100% in patients with pure membranous lesion.The pathological transition could not be predicted by any clinical characteristics.After the repeat renal biopsy,34% of patients had a change in their treatment regimens.Conclusions The pathological conversion was very prevalent in patients with lupus nephritis.However,the transitions became less prevalent when they were analyzed according to pure membranous,proliferative,and mix lesion.Repeat biopsy might be helpful to avoid unnecessary increased immunosuppression therapy.

  17. Intracranial aneurysms that repeatedly reopen over time after coiling: imaging characteristics and treatment outcome

    Energy Technology Data Exchange (ETDEWEB)

    Rooij, Willem J. van; Sprengers, Marieke E.; Sluzewski, Menno [St Elisabeth Ziekenhuis, Department of Radiology, Tilburg (Netherlands); Beute, Guus N. [St Elisabeth Ziekenhuis, Department of Neurosurgery, Tilburg (Netherlands)

    2007-04-15

    We report imaging and clinical characteristics of patients with aneurysms that repeatedly reopened over time and were coiled three times or more during a follow-up period of 2-11 years. At angiographic follow-up of 624 of 827 aneurysms coiled between 1995 and 2005, 74 aneurysms (8.9%) reopened and were additionally coiled. During an extended follow-up, 12 aneurysms (1.5%) in 12 patients repeatedly reopened and were repeatedly coiled. Initial aneurysm sizes ranged from 15 to 30 mm. Four aneurysms contained intraluminal thrombus. Eight aneurysms were associated with subarachnoid hemorrhage and two with a mass effect, and two were incidentally discovered. The locations of aneurysms were basilar artery (eight), carotid artery (two), anterior communicating artery (one) and middle cerebral artery (one). Altogether, 49 coil treatments were performed in the 12 aneurysms, ranging from three to six coil treatments per aneurysm. Of the 49 coil treatments, 20 (41%) were performed with a supporting device. There were no procedural complications (0%, 97.5% CI 0-5.7%). The mean clinical follow-up period was 70.6 months (median 60, range 25-135 months). All 12 patients are neurologically doing well (GOS 5). Reopening was by compaction in nine aneurysms and by migration of coils into intraluminal thrombus in three aneurysms. In two aneurysms, late regrowth became apparent at 76 and 95 months after the previous coiling. Aneurysms that reopen over time and need to be coiled for a second time should be imaged at regular intervals to detect repeated reopening or regrowth. The treatment strategy of regular follow-up and additional treatments when necessary is effective and safe. (orig.)

  18. Inmate responses to prison-based drug treatment: a repeated measures analysis.

    Science.gov (United States)

    Welsh, Wayne N

    2010-06-01

    Using a sample of 347 prison inmates and general linear modeling (GLM) repeated measures analyses, this paper examined during-treatment responses (e.g., changes in psychological and social functioning) to prison-based TC drug treatment. These effects have rarely been examined in previous studies, and never with a fully multivariate model accounting for within-subjects effects (changes over time), between-subjects effects (e.g., levels of risk and motivation), and within/between-subjects interactions (timexriskxmotivation). The results provide evidence of positive inmate change in response to prison TC treatment, but the patterns of results varied depending upon: (a) specific indicators of psychological and social functioning, motivation, and treatment process; (b) the time periods examined (1, 6, and 12 months during treatment); and (c) baseline levels of risk and motivation. Significant interactions between time and type of inmate suggest important new directions for research, theory, and practice in offender-based substance abuse treatment.

  19. [Changes in plasma cortisol and ACTH caused by diazepam, bromazepam, triazolam, and alprazolam in oral premedication].

    Science.gov (United States)

    Rodríguez-Huertas, F; Carrasco, M S; García-Baquero, A; Coq, F D; Freire, J

    1992-01-01

    Benzodiazepines relieve anxiety and modify the endocrine response to surgical-anesthetic stress. The aim of this study was to evaluate the effects of four benzodiazepines on preoperative secretion of cortisol and ACTH. We studied 60 patients programmed for abdominal surgery. Patients were randomly allocated into six groups of treatment: control group (placebo), diazepam 10 mg, triazolam 0.5 mg, alprazolam 0.5 mg, bromazepam 6 mg, and bromazepam 12 mg. Blood samples for cortisol and ACTH measurements were obtained at five different stages of the anesthetic-surgical procedure: baseline, preanesthesia, anesthesia, surgery, and postoperative phase. Diazepam and bromazepam (6 and 12 mg) lessened the increase in plasmatic cortisol induced by preanesthesia and anesthesia in control patients. Triazolam attenuated the cortisol response only during preanesthesia. Administration of 12 mg of bromazepam decreased ACTH levels during preanesthesia and anesthesia with respect to the control group. Benzodiazepines failed to modify cortisol and ACTH levels during surgery and during the immediate postoperative period. The most marked attenuation of adrenocortical response was achieved with 12 mg of bromazepam and the less marked lessening was induced by 0.5 mg of alprazolam.

  20. Hydrogen production by anaerobic microbial communities exposed to repeated heat treatments.

    Science.gov (United States)

    Duangmanee, T; Padmasiri, S I; Simmons, J J; Raskin, L; Sung, S

    2007-09-01

    Biological hydrogen production by anaerobic mixed communities was studied in laboratory-scale bioreactors using sucrose as the substrate. A bioreactor in which a fraction of the return sludge was exposed to repeated heat treatments performed better than a control bioreactor without repeated heat treatment of return sludge and produced a yield of 2.15 moles of hydrogen per mole of sucrose, with 50% hydrogen in the biogas. Terminal restriction fragment length polymorphism analysis showed that two different Clostridium groups (comprised of one or more species) were dominant during hydrogen production. The relative abundance of two other non-Clostridium groups increased during periods of decreased hydrogen production. The first group consisted of Bifidobacterium thermophilum, and the second group included one or more of Bacillus, Melissococcus, Spirochaeta, and Spiroplasma spp.

  1. Comparisons of synthetic 1-18 ACTH (Organon 2001) and 1-39 ACTH of animal origin in human subjects.

    Science.gov (United States)

    Danowski, T S; Fisher, E R; Robinson, S M

    The studies in human subjects herein reported provide data on the relative effects of 1-18 ACTH (Organon 2001) and commercial 1-39 ACTH of animal origin on plasma cortisol, serum non-esterified fatty acids, and certain urinary steroids.

  2. A patient with recurrent hypercortisolism after removal of an ACTH-secreting pituitary adenoma due to an adrenal macronodule.

    Science.gov (United States)

    Timmers, H J L M; van Ginneken, E M; Wesseling, P; Sweep, C G J; Hermus, A R M M

    2006-11-01

    A 41-yr-old female was referred for signs and symptoms of Cushing's syndrome. Cortisol was not suppressed by 1 mg dexamethasone (0.41 micromol/l). Midnight cortisol and ACTH were 0.44 micromol/l and 18 pmol/l, respectively. Urinary cortisol excretion was 250 nmol/24 h (normal between 30 and 150 nmol/24 h). A magnetic resonance imaging (MRI) revealed a pituitary lesion of 7 mm. ACTH and cortisol levels were unaltered by administration of human CRH and high-dose dexamethasone. Inferior sinus petrosus sampling showed CRH-stimulated ACTH levels of 128.4 (left sinus) vs a peripheral level of 19.2 pmol/l, indicating Cushing's disease. After 4 months of pre-treatment with metyrapone and dexamethasone, endoscopic transsphenoidal resection of an ACTH-positive pituitary adenoma was performed. ACTH levels decreased to 2.6 pmol/l and fasting cortisol was 0.35 micromol/l. Despite clinical regression of Cushing's syndrome and normalization of urinary cortisol, cortisol was not suppressed by 1 mg dexamethasone (0.30 micromol/l). Ten months post-operatively, signs and symptoms of Cushing's syndrome reoccurred. A high dose dexamethasone test according to Liddle resulted in undetectable ACTH, but no suppression of cortisol levels, pointing towards adrenal-dependent Cushing's syndrome. Computed tomography (CT)-scanning showed a left-sided adrenal macronodule. Laparoscopic left adrenalectomy revealed a cortical macronodule (3.5 cm) surrounded by micronodular hyperplasia. Fasting cortisol had decreased to 0.02 micromol/l. Glucocorticoid suppletion was started and tapered over 12 months. Symptoms and signs of hypercortisolism gradually disappeared. This case illustrates, that longstanding ACTH stimulation by a pituitary adenoma can induce unilateral macronodular adrenal hyperplasia with autonomous cortisol production.

  3. Multiple treatment comparisons in a series of anti-malarial trials with an ordinal primary outcome and repeated treatment evaluations

    Directory of Open Access Journals (Sweden)

    Youdom Solange

    2012-05-01

    Full Text Available Abstract Background Artemisinin-based combination therapies (ACT are widely used in African countries, including Cameroon. Between 2005 and 2007, five randomized studies comparing different treatment arms among artesunate-amodiaquine and other ACT were conducted in Cameroonian children aged two to 60 months who had uncomplicated Plasmodium falciparum malaria. In these studies, the categorical criterion proposed by the World Health Organization (WHO to assess the relative effectiveness of anti-malarial drugs was repeatedly evaluated on Days 14, 21 and 28 after treatment initiation. The aim of the present study was to compare the effects of different treatments on this repeated ordinal outcome, hence using the fully available information. Methods The quantitative synthesis was based on individual patient data. Due to the incomplete block design concerning treatment arms between different trials, a mixed treatment comparison (MTC meta-analysis approach was adopted. The repeated ordinal outcome was modelled through a latent variable, as a proportional odds mixed model with trial, period and treatment arms as covariates. The model was further complexified to account for the variance heterogeneity, and the individual log-residual variance was modelled as a linear mixed model, as well. The effects of individual covariates at inclusion, such as parasitaemia, fever, gender and weight, were also tested. Model parameters were estimated using a Bayesian approach via the WinBUGS software. After selecting the best model using Deviance Information Criterion (DIC, mixed treatment comparisons were based on the estimated treatment effects. Results Modeling the residual variance improved the model ability to adjust the data. The results showed that, compared to artesunate-amodiaquine (ASAQ, dihydroartemisinin-piperaquine (DHPP was significantly more efficacious. Artesunate-chlorproguanil-dapsone (ASCD was less efficacious than artesunate

  4. Treatment of bacterial brain abscess by repeated aspiration. Follow up by serial computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Masaaki; Fukushima, Takeo; Hirakawa, Katsuyuki; Kimura, Hideo; Tomonaga, Masamichi [Fukuoka Univ. (Japan). School of Medicine

    2000-02-01

    Bacterial brain abscess often requires repeated aspiration before the abscess finally resolves. However, there are no guidelines for treatment by aspiration; for example, when should the abscess be tapped again, or when can an abscess be treated by antibiotics alone without further aspiration. Eleven patients with bacterial brain abscess treated by aspiration were evaluated to establish treatment guidelines for brain abscess, in particular the abscess size on serial computed tomography (CT) after aspiration. CT was performed about 24 hours after aspiration to evaluate the size of the abscess, and almost weekly during follow up. The diameter of the brain abscess before and after the initial and last aspirations were reviewed. In eight of the 11 patients, abscesses were aspirated repeatedly: two to three times in most patients. The diameter of the abscesses was 2.5-4.5 cm (mean 3.5 cm) before the last aspiration, and 1.4-3.4 cm (mean 2.3 cm) after the last aspiration, or when continuous drainage was discontinued. Perifocal edema was moderately decreased within 3 weeks after the last aspiration by medical treatment alone, with a concomitant decrease in the volume of the abscess. There were no deaths, and most patients had a favorable outcome. These results suggest that after the diameter of the abscess becomes less than 2 to 3 cm and does not increase anymore on serial CT, medical treatment alone can be anticipated to give satisfactory results without further aspiration. (author)

  5. The ACTH test in the diagnosis of hirsutism

    Directory of Open Access Journals (Sweden)

    Marco Fábio Prata Lima

    Full Text Available The ACTH test has been used to confirm the diagnosis of adrenal insufficiency and the classic and the non-classic adrenal hyperplasia due to the 3-HSD, 21 OH e 110H deficiencies. This article reviews the historical aspects of the use of ACTH in the diagnosis of hirsutism and points out its mains indications. In spite of new biological molecular advances in the diagnosis of adrenal enzymatic deficiencies, the use of the ACTH test can help the physician to predict both genothipus and fenothipus in populations with hyperandrogenic manifestations due to non-classical or late-onset congenital adrenal hyperplasia.

  6. Use of adrenal arterial embolization in severe ACTH-dependent Cushing's syndrome.

    OpenAIRE

    Blunt, S B; Pirmohamed, M.; Chatterjee, V K; Burrin, J. M.; Allison, D J; Joplin, G. F.

    1989-01-01

    The management of a patient with severe Cushing's syndrome due to ectopic ACTH produced by a medullary carcinoma of the thyroid is described. Initial treatment with maximal adrenolytic medical therapy and two attempts at bilateral adrenal venous infarction had failed to control the disease, and she was at that time unfit for surgery. Subsequent use of bilateral adrenal arterial embolization enabled medical therapy to produce sufficient control of the Cushing's syndrome to allow bilateral adre...

  7. ACTH stimulation test in the captive cheetah (Acinonyx jubatus

    Directory of Open Access Journals (Sweden)

    L.S. Koster

    2007-06-01

    Full Text Available Serum cortisol response was assessed in 8 captive cheetahs, of varying ages, after the intravenous administration of 500 µg of tetracosactide (Synacthen Depot(R, Novartis, Kempton Park while maintained under general anaesthesia. In addition, 8 cheetahs were anaesthetised and given an equal volume of saline in order to establish baseline cortisol concentrations at similar stages of anaesthesia. A significant difference in the median cortisol concentration measured over time was found following ACTH administration in the ACTH group (P < 0.001. There was no difference between the median cortisol concentrations in the ACTH group at time-points 120, 150 and 180 min after ACTH stimulation (P = 0.867. Thus it appears appropriate to collect serum 120 to 180 min after tetracosactide administration to assess maximal stimulation of the adrenal in the cheetah. No statistically significant rise was seen in the anaesthetised control group following the injection of saline (P = 0.238.

  8. ACTH-secreting bronchial carcinoid: a diagnostic and therapeutic challenge.

    LENUS (Irish Health Repository)

    McDermott, J H

    2008-09-01

    We describe a case of Cushing\\'s syndrome due to ectopic ACTH secretion, where the only potential source on conventional imaging was a tiny benign-appearing lung nodule, which failed to take up radiolabelled octreotide.

  9. Direct actions of ACTH on ovarian function of pseudopregnant rabbits

    OpenAIRE

    Guelfi, Gabriella; Zerani, Massimo; Brecchia, Gabriele; Parillo, Francesco; Dall'Aglio, Cecilia; Maranesi, Margherita; Boiti, Cristiano

    2011-01-01

    Abstract The present study sought to assess whether the receptors for adrenocorticotropic hormone (ACTH), MC2R, and for glucocorticoid (GR) are expressed in corpora lutea (CL) of pseudopregnant rabbits and whether ACTH and cortisol exert any direct action on luteal function. By immunohistochemistry, positive reaction for MC2R and GR was detectable within luteal cells of CL. The MC2R mRNA levels were five-fold less abundant in day 9 than in day 4 CL (P , Italy.--> ...

  10. Botulinum toxin type A in the treatment of bilateral primary axillary hyperhidrosis: efficacy and duration with repeated treatments.

    Science.gov (United States)

    Lowe, Phillipa L; Cerdan-Sanz, Suzanne; Lowe, Nicholas J

    2003-05-01

    Botulinum toxin type A (BTX-A) has been shown to be effective for the temporary reduction of local hyperhidrosis. To investigate the duration of efficacy of BTX-A with repeat treatments for axillary hyperhidrosis. Patients who completed a prior randomized, controlled, parallel-group study comparing BTX-A with vehicle for bilateral primary axillary hyperhidrosis were eligible for this 18-month, open-label, noncomparative, follow-up study. Patients had to request further treatment, fulfill the preceding study inclusion/exclusion criteria, and have spontaneous sweat production that was more than 50% of the baseline value of the previous study. Patients received up to four treatments of intradermal BTX-A (2 mL, 50 U). All of the 12 patients who were enrolled completed the study. Two of the 12 patients (17%) were previously treated with placebo. In the 18 months of study and follow-up, five patients (42%) required a total of two active injections. Three patients (25%) required a total of three active injections, and four patients (33%) required a total of four active injections. The response rate was 83% (10 of 12) at 4 weeks after the first treatment. The mean percentage change from baseline in overall sweat production was approximately 80% at Week 4. The mean time between the first and second treatment in this study was just over 29 weeks, with a range of 17.8 to 57.5 weeks. BTX-A is an effective repeat treatment for axillary hyperhidrosis giving variable but clinically helpful remission. No clinically relevant changes in vital signs or safety parameters were noted.

  11. Clinical, biological and genetic analysis of 8 cases of congenital isolated adrenocorticotrophic hormone (ACTH deficiency.

    Directory of Open Access Journals (Sweden)

    Luu-Ly Pham

    Full Text Available BACKGROUND: Congenital isolated adrenocorticotrophic hormone (ACTH deficiency may be rare, but it could be an underestimated cause of neonatal death. Our objective was to shorten the time between first symptoms and diagnosis. METHODS: This single-centre retrospective case-cohort study was carried out on eight consecutive patients. RESULTS: Two had the neonatal form and 6 the late onset form. Six were admitted to an intensive care unit at least once for seizures with hypoglycemia, major hypothermia, fever, and/or collapsus. The 2 neonatal cases presented with hypoglycemia and in a state of "apparent death" at birth or hypothermia (29°C at 6 days. All 6 late onset cases had also been admitted to an emergency department 1-3 times, but had left hospital incorrectly diagnosed. Their first symptoms were noted at 3-12.3 years, and they were diagnosed at 3.3-14.4 years. All had hypoglycemia, and 4 had had seizures. The presenting symptoms were vomiting and/or abdominal pain, asthenia, irritability, difficulty with physical activities, and anorexia. The school performance of 4 deteriorated. Two underwent psychotherapy and treatment for depression, which was stopped when Hydrocortisone® replacement therapy began. The plasma concentrations in spontaneous hypoglycemia were: ACTH<5 to 17.1 pg/mL, with concomitant cortisol <3.5 to 37 ng/mL. The plasma dehydroepiandrosterone sulfate (DHAS concentrations were low in the 7 evaluated. The coding sequence of TPIT was normal in all. CONCLUSION: Several unexplained symptoms in a child, mainly gastro-intestinal symptoms and seizures due to hypoglycemia, may indicate ACTH deficiency. A low or normal basal plasma ACTH despite concomitant low cortisol at 8 a.m. and/or in spontaneous hypoglycemia, associated with low DHAS, in a patient not given corticosteroids is highly suggestive of ACTH deficiency. The isolated character of ACTH deficiency must be confirmed by determining the other hypothalamic-pituitary functions

  12. ACTH Action on Messenger RNA Stability Mechanisms

    Science.gov (United States)

    Desroches-Castan, Agnès; Feige, Jean-Jacques; Cherradi, Nadia

    2017-01-01

    The regulation of mRNA stability has emerged as a critical control step in dynamic gene expression. This process occurs in response to modifications of the cellular environment, including hormonal variations, and regulates the expression of subsets of proteins whose levels need to be rapidly adjusted. Modulation of messenger RNA stability is usually mediated by stabilizing or destabilizing RNA-binding proteins (RNA-BP) that bind to the 3′-untranslated region regulatory motifs, such as AU-rich elements (AREs). Destabilizing ARE-binding proteins enhance the decay of their target transcripts by recruiting the mRNA decay machineries. Failure of such mechanisms, in particular misexpression of RNA-BP, has been linked to several human diseases. In the adrenal cortex, the expression and activity of mRNA stability regulatory proteins are still understudied. However, ACTH- or cAMP-elicited changes in the expression/phosphorylation status of the major mRNA-destabilizing protein TIS11b/BRF1 or in the subcellular localization of the stabilizing protein Human antigen R have been reported. They suggest that this level of regulation of gene expression is also important in endocrinology.

  13. alpha(7) Nicotinic acetylcholine receptor activation prevents behavioral and molecular changes induced by repeated phencyclidine treatment

    DEFF Research Database (Denmark)

    Thomsen, Morten Skøtt; Christensen, Ditte Z; Hansen, Henrik H;

    2009-01-01

    , and administration of the NMDA-antagonist phencyclidine (PCP) in rodents is a well validated model of such cognitive deficits. Here we show that repeated PCP treatment (10 mg/kg/day for 10 days) decreased the expression of parvalbumin and synaptophysin mRNA in the mouse PFC, which corresponds to changes seen...... in patients with schizophrenia. In addition, PCP increased the basal mRNA expression in the PFC of the activity-regulated cytoskeleton-associated protein (Arc), a molecule involved in synaptic plasticity. These molecular changes produced by PCP were accompanied by a behavioral impairment as determined...... in a modified Y-maze test. Polymorphisms in the alpha(7) nicotinic acetylcholine receptor (nAChR) gene have been linked to schizophrenia. Here we demonstrate that acute administration of the selective alpha(7) nAChR partial agonist SSR180711 dose-dependently reversed the behavioral impairment induced by PCP...

  14. Repeated dexamphetamine treatment alters the dopaminergic system and increases the phMRI response to methylphenidate

    Science.gov (United States)

    Schrantee, Anouk; Tremoleda, Jordi L.; Wylezinska-Arridge, Marzena; Bouet, Valentine; Hesseling, Peter; Meerhoff, Gideon F.; de Bruin, Kora M.; Koeleman, Jan; Freret, Thomas; Boulouard, Michel; Desfosses, Emilie; Galineau, Laurent; Gozzi, Alessandro; Dauphin, François; Gsell, Willy; Booij, Jan; Lucassen, Paul J.; Reneman, Liesbeth

    2017-01-01

    Dexamphetamine (AMPH) is a psychostimulant drug that is used both recreationally and as medication for attention deficit hyperactivity disorder. Preclinical studies have demonstrated that repeated exposure to AMPH can induce damage to nerve terminals of dopamine (DA) neurons. We here assessed the underlying neurobiological changes in the DA system following repeated AMPH exposure and pre-treated rats with AMPH or saline (4 times 5 mg/kg s.c., 2 hours apart), followed by a 1-week washout period. We then used pharmacological MRI (phMRI) with a methylphenidate (MPH) challenge, as a sensitive and non-invasive in-vivo measure of DAergic function. We subsequently validated the DA-ergic changes post-mortem, using a.o. high-performance liquid chromatography (HPLC) and autoradiography. In the AMPH pre-treated group, we observed a significantly larger BOLD response to the MPH challenge, particularly in DA-ergic brain areas and their downstream projections. Subsequent autoradiography studies showed that AMPH pre-treatment significantly reduced DA transporter (DAT) density in the caudate-putamen (CPu) and nucleus accumbens, whereas HPLC analysis revealed increases in the DA metabolite homovanillic acid in the CPu. Our results suggest that AMPH pre-treatment alters DAergic responsivity, a change that can be detected with phMRI in rats. These phMRI changes likely reflect increased DA release together with reduced DAT binding. The ability to assess subtle synaptic changes using phMRI is promising for both preclinical studies of drug discovery, and for clinical studies where phMRI can be a useful tool to non-invasively investigate DA abnormalities, e.g. in neuropsychiatric disorders. PMID:28241065

  15. The peripheral cytoplasm of adrenocortical cells: zone-specific responses to ACTH.

    Science.gov (United States)

    Loesser, K E; Cain, L D; Malamed, S

    1994-05-01

    Differences in the cytoskeletal protein actin in cells from the zona glomerulosa and zona fasciculata would be of considerable interest because there is persuasive evidence that rat corticosteroids are secreted by mechanisms that are somewhat zone-specific. We have previously shown evidence that actin may be involved in steroid secretion, possibly in connection with changes in adrenocortical microvilli. However, the cells upon which the data were based were not separated according to zone of origin. Immunogold electron microscopy and morphometric procedures were used to determine whether ACTH-induced changes in the peripheral cytoplasm of isolated adrenocortical cells occur in both zona fasciculata and zona glomerulosa cells. Actin immunoreactivity was more concentrated in the cytoplasm adjacent to the plasma membrane (including the cytoplasm within the microvilli) than it was in the internal cytoplasm in cells from both zones (4-6 times more concentrated in zona glomerulosa cells and 3-6 times more concentrated in zona fasciculata cells). However, the mean aggregate microvillar surface length (microvillar index) of untreated zona fasciculata cells (previously reported (Loesser and Malamed, 1987)) was 23% greater than that of untreated zona glomerulosa cells. Although ACTH (at a maximal steroidogenic concentration) had no effect on the peripheral cytoplasmic actin concentration of zona glomerulosa cells, there was a 24% increase in the aggregate microvillar length. In contrast, in zona fasciculata cells, ACTH treatment was accompanied by an increase in peripheral cytoplasmic actin concentration of 58-64% and an increase in aggregate microvillar surface length of 40% (previously reported (Loesser and Malamed, 1987)), almost twice that for zona glomerulosa cells. The results suggest that ACTH-induced hormone release from zona fasciculata cells is mediated by increases in peripheral cytoplasmic actin and aggregate microvillar length; in zona glomerulosa cells such

  16. Structure-activity studies with ACTH/α-MSH fragments on corticosteroid secretion of isolated zona glomerulosa and fasciculata cells

    NARCIS (Netherlands)

    Szalay, Katalin Sz.; Wied, D. De; Stark, E.; Folly, G.

    1985-01-01

    The steroidogenic action of ACTH/α-MSH fragments was studied on isolated zona glomerulosa and zona fasciculata cells dispersed by collagenase. ACTH-(4–7), ACTH-(6–10), ACTH-(4–10) and ACTH-(11–13) stimulated corticosterone production of the zona fasciculata and aldosterone production of the zona glo

  17. Adrenocorticotropin (ACTH) and corticosterone secretion by perifused pituitary and adrenal glands from rodents exposed to 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD).

    Science.gov (United States)

    Pitt, J A; Buckalew, A R; House, D E; Abbott, B D

    2000-10-26

    Although in utero maternal stress has been shown to have lasting effects on rodent offspring, fetal effects of chemically-induced alterations of the maternal hypothalamic-pituitary-adrenal axis (HPA) have not been well studied. This study examined the effects of in vivo 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure on pituitary-adrenal function in the male rat, pregnant female rat and pregnant female mouse. The secretion of adrenocorticotropin (ACTH) and corticosterone (CORT) in pituitary and adrenal glands, respectively, was assessed in ex vivo perifusion cultures. Male and pregnant female (gestation day 8) Sprague-Dawley rats were gavaged once with 10 microgram/kg TCDD, pregnant female mice once with 24 microgram/kg TCDD, and euthanized 10 days later. Hemi-pituitary (rat) or whole anterior pituitaries (mice) and right adrenal glands from the same animal were quartered, perifused under baseline and stimulated conditions. In both males and pregnant females, TCDD did not affect corticotropin releasing hormone (CRH)-stimulated ACTH secretion. Neither total pituitary ACTH nor plasma ACTH was altered in either sex or species by TCDD treatment. ACTH-stimulated CORT secretion was not affected by TCDD in either sex or species, and adrenal tissue and plasma CORT levels were unchanged in males and pregnant females by TCDD. However, the plasma ACTH:CORT ratio was decreased about 46% in male rats treated with TCDD. Plasma CORT levels were 23-fold higher and plasma ACTH levels were 1.5-fold higher in pregnant females than in male rats. In male versus female rats, adrenal CORT and anterior pituitary ACTH tissue levels were about 7.5- and 1.75-fold higher and ACTH, respectively. Female mouse adrenal tissue CORT was about 4-fold greater than female rat. The reduced plasma ACTH:CORT ratio in the male rat suggests that TCDD disturbs HPA function. Exposure of male rat to a 5-fold higher dose in earlier studies clearly demonstrated effects of TCDD on male rat HPA. The present

  18. Cardiometabolic treatment decisions in patients with type 2 diabetes : the role of repeated measurements and medication burden

    NARCIS (Netherlands)

    Voorham, J.; Haaijer-Ruskamp, F. M.; Wolffenbuttel, B. H. R.; Stolk, R. P.; Denig, P.

    2010-01-01

    Purpose Clinical guidelines for cardiometabolic risk management indicate a simple threshold-based strategy for treatment, but physicians and their patients may be reluctant to modify drug treatment after a single elevated measurement. We determined how repeated measurements of blood pressure, choles

  19. Cardiometabolic treatment decisions in patients with type 2 diabetes : the role of repeated measurements and medication burden

    NARCIS (Netherlands)

    Voorham, J.; Haaijer-Ruskamp, F. M.; Wolffenbuttel, B. H. R.; Stolk, R. P.; Denig, P.

    2010-01-01

    Purpose Clinical guidelines for cardiometabolic risk management indicate a simple threshold-based strategy for treatment, but physicians and their patients may be reluctant to modify drug treatment after a single elevated measurement. We determined how repeated measurements of blood pressure,

  20. Glucagon-like peptide-2 but not imipramine exhibits antidepressant-like effects in ACTH-treated mice.

    Science.gov (United States)

    Iwai, Takashi; Ohnuki, Tomoko; Sasaki-Hamada, Sachie; Saitoh, Akiyoshi; Sugiyama, Azusa; Oka, Jun-Ichiro

    2013-04-15

    We investigated the effectiveness of glucagon-like peptide-2 (GLP-2) against refractory depression in adrenocorticotropic hormone (ACTH)-treated mice as a model of tricyclic antidepressant (TCA)-resistant depression. Chronic ACTH treatment (0.45 mg/kg, s.c., 14 days) weakened the antidepressant-like effects of imipramine (20 mg/kg, i.p., 6 days) in the forced-swim test (FST). Conversely, GLP-2 (3 μg/mice, i.c.v., 6 days) induced antidepressant-like effects in the ACTH-treated mice in the FST. ACTH-treatment increased basal serum corticosterone levels, with an additional increase induced by the FST. Imipramine or GLP-2 had no effect on the basal corticosterone level, but GLP-2 attenuated the additional increase caused by the FST. Moreover, GLP-2 increased 5-HT levels, but not 5-HIAA. These results suggest that GLP-2 induced antidepressant-like effects under imipramine-resistant conditions through increase in 5-HT levels.

  1. Differential diagnosis of ACTH-dependent hypercortisolism: imaging versus laboratory.

    Science.gov (United States)

    Andrioli, Massimiliano; Pecori Giraldi, Francesca; De Martin, Martina; Cattaneo, Agnese; Carzaniga, Chiara; Cavagnini, Francesco

    2009-01-01

    Differential diagnosis of ACTH-dependent Cushing's syndrome often presents major difficulties. Diagnostic troubles are increased by suboptimal specificity of endocrine tests, the rarity of ectopic ACTH secretion and the frequent incidental discovery of pituitary adenomas. A 43-year-old female reported with mild signs and symptoms of hypercortisolism, and initial hormonal tests and results of pituitary imaging (7-mm adenoma) were suggestive for Cushing's disease. However, inadequate response to corticotrophin-releasing hormone and failure to suppress after 8 mg dexamethasone pointed towards an ectopic source. Total body CT scan visualized only a small, non-specific nodule in the right posterior costophrenic excavation. Inferior petrosal sinus sampling revealed an absent center:periphery ACTH gradient but octreoscan and (18)F-FDG-PET-CT failed to detect abnormal tracer accumulation. We weighed results of the laboratory with those of imaging and decided to remove the lung nodule. Pathology identified a typical, ACTH-staining carcinoid and the diagnosis was confirmed by postsurgical hypoadrenalism. In conclusion, imaging may prove unsatisfactory or even misleading for the etiologial diagnosis of ACTH-dependent Cushing's syndrome and should therefore be interpreted only in context with results of hormonal dynamic testing.

  2. Anticonvulsant effects of acute treatment with cyane-carvone at repeated oral doses in epilepsy models.

    Science.gov (United States)

    Marques, Thiago Henrique Costa; Marques, Maria Leonildes Boavista Gomes Castelo Branco; Medeiros, Jand-Venes Rolim; Lima, Tamires Cardoso; de Sousa, Damião Pergentino; de Freitas, Rivelilson Mendes

    2014-09-01

    Epilepsy affects about 40 million people worldwide. Many drugs block seizures, but have little effect in preventing or curing this disease. So the search for new drugs for epilepsy treatment using animal models prior to testing in humans is important. Increasingly pharmaceutical industries invest in the Re​search & Drug Development area to seek safe and effective new therapeutic alternatives to the currently available epilepsy treatment. In this perspective, natural compounds have been investigated in epilepsy models, particularly the monoterpenes obtained from medicinal plants. In our study we investigated the effects of cyane-carvone (CC), a synthetic substance prepared from natural a monoterpene, carvone, against pilocarpine- (PILO), pentylenetetrazole- (PTZ) and picrotoxine (PTX)-induced seizures in mice after acute treatment with repeated oral doses (CC 25, 50 and 75 mg/kg) for 14 days. CC in all doses tested showed increase in latency to first seizure, decrease in percentages of seizuring animals as well as reduction percentages of dead animals (pepilepsy models. In addition, our data suggest that CC could act in an allosteric site of GABAA, which would be different from the site in which BDZ acts, since flumazenil was not able to reverse any of CC effects on the modulation of seizure parameters related with epilepsy models investigated. New studies should be conducted to investigate CC effects in other neurotransmitter systems. Nevertheless, our study reinforces the hypothesis that CC could be used, after further research, as a new pharmaceutical formulation and a promising alternative for epilepsy treatment, since it showed anticonvulsant effects. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Quantitative aspects of spermatogenesis in rats and dogs after repeated hexachlorophene treatment.

    Science.gov (United States)

    James, R W; Heywood, R; Crook, D

    1980-05-01

    Hexachlorophene was administered orally, at subneurotoxic doses, to rats (5 mg/kg/day) and dogs (3 mg/kg/day) for 9 weeks: some of the rats and dogs were observed for a further 13 weeks. The serum concentrations of pituitary gonadotrophin and testosterone were unaffected in either species. No changes were induced in the testicular dimensions or semen characteristics of dogs and no macroscopic post mortem abnormalities, organ weight differences or lesions detectable by conventional light microscopy were found in their testes, pituitaries or secondary sex organs. A transient reduction in the number of germ cells counted in cross-sections of seminiferous tubules was seen in rats after 4 weeks treatment. After 9 weeks treatment, reduced spermatogonial counts were recorded in canine seminiferous tubules; in other respects spermatogenesis was proceeding normally. No delayed effects were apparent in eith species. It is concluded that repeated administration of hexachlorophene at subneurotoxic levels did not induce significant impairment of spermatogenesis in rats or dogs.

  4. EXPERIENCE WITH CORTISONE AND ACTH IN A PRIVATE CLINIC

    Science.gov (United States)

    Krupp, Marcus A.; Saier, Milton; Keddie, Frances; Tanner, Ralph; Snell, A. M.

    1951-01-01

    Cortisone and ACTH are valuable agents for treating a large variety of diseases. In appropriate situations they may save life. It may be possible to prevent loss of vision in eye disease or permanent damage to important viscera in generalized disease. With ready access to these agents through the pharmacist, it is important to know that cortisone and ACTH can be used in office practice provided patients are selected carefully and followed frequently and closely. Strict observation of criteria for selection of patients limited the size of the series of patients reported upon, but by the same token the incidence of complications from therapy was exceptionally small. Every physician who elects to employ these potent hormones must become familiar with their physiological effects and with the various methods of exhibiting them. Some of these effects are noted in this paper, but the experiences reviewed here provide an incomplete picture of the wide application of cortisone and ACTH. PMID:14848715

  5. Imaging in covert ectopic ACTH secretion: a CT pictorial review

    Energy Technology Data Exchange (ETDEWEB)

    Sookur, Paul A.; Sahdev, Anju; Rockall, Andrea G.; Reznek, Rodney H. [St Bartholomew' s Hospital, Department of Academic Radiology, Dominion House, London (United Kingdom); Isidori, Andrea M. [Sapienza University of Rome, Department of Medical Pathophysiology, Rome (Italy); Monson, John P.; Grossman, Ashley B. [St Bartholomew' s Hospital, Department of Endocrinology, London (United Kingdom)

    2009-05-15

    The syndrome of ectopic adrenocorticotrophin secretion (EAS) is rare and is due to excess adrenocorticotrophin (ACTH) production from a nonpituitary tumour. These tumours can be covert, where the tumours are not readily apparent, and very small making them challenging to image. It is clinically and biochemically difficult to distinguish between covert EAS and Cushing's disease. The first-line investigation in locating the source of ACTH production is computed tomography (CT). The aim of this pictorial review is to illustrate the likely covert sites and related imaging findings. We review the CT appearances of tumours resulting in covert EAS and the associated literature. The most common tumours were bronchial carcinoid tumours, which appear as small, well-defined, round or ovoid pulmonary lesions. Rarer causes included thymic carcinoids, gastrointestinal carcinoids and pancreatic neuroendocrine tumours. Awareness of the imaging characteristics will aid identification of the source of ACTH production and allow potentially curative surgical resection. (orig.)

  6. Brain shrinkage and subdural effusion associated with ACTH administration.

    Science.gov (United States)

    Satoh, J; Takeshige, H; Hara, H; Fukuyama, Y

    1982-01-01

    Sequential computed tomographic (CT) studies of 11 patients (aged five months to seven years) with intractable epilepsy treated with synthetic ACTH-Z showed brain shrinkage in all cases. Brain shrinkage started to appear on daily ACTH injections for seven days, reached the maximum within four weeks of administration (14 injections every day and then 7 injections every other day), and almost returned to the original status in seven out of nine cases which were followed up for one to three months after the therapy. The subjects aged less than two years showed more remarkable brain shrinkage than did those aged more than five years. Furthermore, two other cases were complicated by subdural effusion after ACTH therapy. It is the authors' assumption that both of these phenomena are caused by the high concentration of corticosteroid through a change of the water and electrolyte contents in the brain.

  7. Regulation of decoction shugan bushen on testosterone and ACTH in ratswith hepatic fibrosis

    Institute of Scientific and Technical Information of China (English)

    Zhong Pang Fan; Jian Cheng Wu; Xing Zhu; Qian Hong Wan; Ting Zan Li

    2000-01-01

    AIM To observe the regulating effect of decoction shugan bushen (SGBS) on testosterone (Te) andadrenocortiotropin (ACTH).METHODS Fifty wistar male rats divided into four groups randomly, that is, normal group, hepaticfibrosis group, and two Chinese herb medicine treatment groups. The model of toxic hepatic fibrosis wasinduced by 0.5% dimethylnitrosamine (DMN). The decoction SGBS is composed of such herbs as bupleurumRoot. Dodder Seed, curcuma rood indianmulberry etc. According to the different doses of the drugs, ratsare divided into two groups in the treatment groups. The Chinese herb medicine treatment begins in a weekafter the second celiac injection of DMN, lastiong 8 weeks. The rats of normal group and hepatic fibrosisgroup are fed with distilled water once a day. After 11 weeks of Chinese herb medicine treatment, the Teand ACTH were tested insera of rats, and the livers were dissected for the pathology examination.RESULTS The results of pathology examination in rat livers of each group show that the hepatocytes of thenormal group have normal array, no degeneration and fibrosis. Those in the pathology group have obviousdegenerative necrosis and hepatic fibrosis, and in some cases show the evidence of cirrosis. The results intreatment groups are essentially similar to those of normal group. Variance analysis of least significantdifference (LSD) method is employed to compare the hormone level between groups. The serum levels of Teand ACTH in the normal group are 75.30±45.25 ng/dl and 141.02±68.70 ng/L. The levels in hepaticfibrosis group are obviously lower than those of normal group, as 19.77±16.92 ng/dl and 92.85±27.24ng/L, respectivite and with statistically different (P 0.05).Two different doses make no obvious difference between the treatment groups (P>0.05).CONCLUSION SGBS can correct the hormone disturbance and shows the effect of anti-hepatic fibrosis.

  8. Live-Birth Rate Associated With Repeat In Vitro Fertilization Treatment Cycles.

    Science.gov (United States)

    Smith, Andrew D A C; Tilling, Kate; Nelson, Scott M; Lawlor, Debbie A

    The likelihood of achieving a live birth with repeat in vitro fertilization (IVF) is unclear, yet treatment is commonly limited to 3 or 4 embryo transfers. To determine the live-birth rate per initiated ovarian stimulation IVF cycle and with repeated cycles. Prospective study of 156,947 UK women who received 257,398 IVF ovarian stimulation cycles between 2003 and 2010 and were followed up until June 2012. In vitro fertilization, with a cycle defined as an episode of ovarian stimulation and all subsequent separate fresh and frozen embryo transfers. Live-birth rate per IVF cycle and the cumulative live-birth rates across all cycles in all women and by age and treatment type. Optimal, prognosis-adjusted, and conservative cumulative live-birth rates were estimated, reflecting 0%, 30%, and 100%, respectively, of women who discontinued due to poor prognosis and having a live-birth rate of 0 had they continued. Among the 156,947 women, the median age at start of treatment was 35 years (interquartile range, 32-38; range, 18-55), and the median duration of infertility for all 257,398 cycles was 4 years (interquartile range, 2-6; range, live-birth rate for the first cycle was 29.5% (95% CI, 29.3%-29.7%). This remained above 20% up to and including the fourth cycle. The cumulative prognosis-adjusted live-birth rate across all cycles continued to increase up to the ninth cycle, with 65.3% (95% CI, 64.8%-65.8%) of women achieving a live birth by the sixth cycle. In women younger than 40 years using their own oocytes, the live-birth rate for the first cycle was 32.3% (95% CI, 32.0%-32.5%) and remained above 20% up to and including the fourth cycle. Six cycles achieved a cumulative prognosis-adjusted live-birth rate of 68.4% (95% CI, 67.8%-68.9%). For women aged 40 to 42 years, the live-birth rate for the first cycle was 12.3% (95% CI, 11.8%-12.8%), with 6 cycles achieving a cumulative prognosis-adjusted live-birth rate of 31.5% (95% CI, 29.7%-33.3%). For women older than 42

  9. Successful long-term control of Cushing’s disease after partial resection of gigantic ACTH-secreting pituitary adenoma

    Directory of Open Access Journals (Sweden)

    Vatroslav Čerina

    2016-03-01

    Full Text Available Only 4-9% of patients with Cushing’s disease (CD harbor pituitary macroadenomas. Clinical and biochemical features of macrocorticotropinomas are poorly understood. Some evidence exist that these tumors presents clinical features more similar to a non-functioning adenomas, being though defined silent corticotropinomas, rather than to ACTH-secreting adenomas. In this paper, we report a case of a 60-year old woman with a history of obesity, arterial hypertension and diabetes mellitus who presented with overt central hypothyroidism. Magnetic resonance imaging disclosed giant pituitary adenoma measuring 50 mm. Endocrinological evaluation confirmed CD: ACTH 50.3 pmol/L, urinary free-cortisol of 739 nmol/24h and cortisol of 639 nmol/L after 1 mg dexamethasone suppression test. Tumor mass was reduced by 50% using purely endoscopic transsphenoidal approach. Thirty-eight months after the partial resection, the patient had well controlled CD: ACTH 20.2 pmol/L, urinary free-cortisol of 238 nmol/24h, cortisol of 105 nmol/L after 1 mg dexamethasone suppression test. To the best of our knowledge, this is the largest ACTH-secreting adenoma ever reported. Our case suggests that tumor size does not necessarily correlate with aggressiveness of CD in patients with macrocorticotropinomas and that long-term control of CD may be achieved albeit incomplete surgical removal. Further studies are needed in order to determine the best treatment option for patients with macrocorticotropinomas.

  10. Effects of pramipexole on the duration of immobility during the forced swim test in normal and ACTH-treated rats.

    Science.gov (United States)

    Kitagawa, Kouhei; Kitamura, Yoshihisa; Miyazaki, Toshiaki; Miyaoka, Junya; Kawasaki, Hiromu; Asanuma, Masato; Sendo, Toshiaki; Gomita, Yutaka

    2009-07-01

    The dopamine D2/D3 receptor agonist pramipexole has clinically been proven to improve depression or treatment-resistant depression. However, the involvement of the dopamine receptor system on the effect of pramipexole on depression remains unclear. We examined the influence of pramipexole on the duration of immobility during the forced swim test in normal and adrenocorticotropic hormone (ACTH)-treated rats and further analyzed the possible role of dopamine receptors in this effect. Additionally, the mechanism by which pramipexole acts in this model was explored specifically in relation to the site of action through the use of microinjections into the intramedial prefrontal cortex and nucleus accumbens. Pramipexole (0.3-1 mg/kg) significantly decreased the duration of immobility in normal and ACTH-treated rats. This effect was blocked by L-741,626, a D2 receptor antagonist, and nafadotride, a D3 receptor antagonist, in normal rats. Furthermore, infusions of pramipexole into the intranucleus accumbens, but not the medial prefrontal cortex, decreased the immobility of normal and ACTH-treated rats during the forced swim test. Taken together, the results of these experiments suggested that pramipexole, administered into the intranucleus accumbens rather than the medial prefrontal cortex, exerted an antidepressant-like effect on ACTH-treated rats via the dopaminergic system. The immobility-decreasing effect of pramipexole may be mediated by dopamine D2 and D3 receptors.

  11. ACTH stimulation test in the captive cheetah (Acinonyx jubatus).

    Science.gov (United States)

    Köster, L S; Schoeman, J P; Meltzer, D G A

    2007-09-01

    Serum cortisol response was assessed in 8 captive cheetahs, of varying ages, after the intravenous administration of 500 microg of tetracosactide (Synacthen Depot, Novartis, Kempton Park) while maintained under general anaesthesia. In addition, 8 cheetahs were anaesthetised and given an equal volume of saline in order to establish baseline cortisol concentrations at similar stages of anaesthesia. A significant difference in the median cortisol concentration measured over time was found following ACTH administration in the ACTH group (P cheetah. No statistically significant rise was seen in the anaesthetised control group following the injection of saline (P = 0.238).

  12. Aroma improvement by repeated freeze-thaw treatment during Tuber melanosporum fermentation

    Science.gov (United States)

    Xiao, Deng-Rong; Liu, Rui-Sang; He, Long; Li, Hong-Mei; Tang, Ya-Ling; Liang, Xin-Hua; Chen, Tao; Tang, Ya-Jie

    2015-01-01

    The aroma attributes of sulfurous, mushroom and earthy are the most important characteristics of the aroma of Tuber melanosporum. However, these three aroma attributes are absent in the T. melanosporum fermentation system. To improve the quality of the aroma, repeated freeze-thaw treatment (RFTT) was adopted to affect the interplay of volatile organic compounds (VOCs). Using RFTT, not only was the score on the hedonic scale of the aroma increased from the “liked slightly” to the “liked moderately” grade, but the aroma attributes of sulfurous, mushroom and earthy could also be smelled in the T. melanosporum fermentation system for the first time. A total of 29 VOCs were identified, and 9 compounds were identified as the key discriminative volatiles affected by RFTT. Amino acid analysis revealed that methionine, valine, serine, phenylalanine, isoleucine and threonine were the key substrates associated with the biosynthesis of the 9 key discriminative VOCs. This study noted that amino acid metabolism played an important role in the regulation of the aroma of the T. melanosporum fermentation system. PMID:26607288

  13. Aroma improvement by repeated freeze-thaw treatment during Tuber melanosporum fermentation.

    Science.gov (United States)

    Xiao, Deng-Rong; Liu, Rui-Sang; He, Long; Li, Hong-Mei; Tang, Ya-Ling; Liang, Xin-Hua; Chen, Tao; Tang, Ya-Jie

    2015-11-26

    The aroma attributes of sulfurous, mushroom and earthy are the most important characteristics of the aroma of Tuber melanosporum. However, these three aroma attributes are absent in the T. melanosporum fermentation system. To improve the quality of the aroma, repeated freeze-thaw treatment (RFTT) was adopted to affect the interplay of volatile organic compounds (VOCs). Using RFTT, not only was the score on the hedonic scale of the aroma increased from the "liked slightly" to the "liked moderately" grade, but the aroma attributes of sulfurous, mushroom and earthy could also be smelled in the T. melanosporum fermentation system for the first time. A total of 29 VOCs were identified, and 9 compounds were identified as the key discriminative volatiles affected by RFTT. Amino acid analysis revealed that methionine, valine, serine, phenylalanine, isoleucine and threonine were the key substrates associated with the biosynthesis of the 9 key discriminative VOCs. This study noted that amino acid metabolism played an important role in the regulation of the aroma of the T. melanosporum fermentation system.

  14. Acute withdrawal from repeated cocaine treatment enhances latent inhibition of a conditioned fear response.

    Science.gov (United States)

    Murphy, C A; Heidbreder, C; Feldon, J

    2001-02-01

    Psychostimulant-induced locomotor sensitization and disrupted latent inhibition (LI) of a classically conditioned association are two paradigms that have been widely studied as animal behavioural models of psychosis. In this study we assessed the effects of withdrawal from the repeated intermittent administration of cocaine on LI of a conditioned fear response. Animals which were either preexposed (PE) to a tone conditioned stimulus (CS) or naive to the tone (i.e. non-preexposed: NPE) subsequently experienced 10 pairings of the tone CS with footshock. Afterwards, both groups received five daily injections of cocaine (20 mg/kg, i.p.) or saline. After 3 days of withdrawal from drug treatment, animals were tested for conditioned freezing to the context of the footshock chamber, and 1 day later, for conditioned freezing to the tone CS. Cocaine-sensitized animals exhibited markedly enhanced LI compared to saline-treated animals, due to the fact that NPE-cocaine animals spent more time freezing during the tone CS than NPE-saline animals, whereas PE-cocaine animals showed a tendency toward reduced freezing compared to the saline groups. While these results suggest the presence of increased anxiety in cocaine-withdrawn NPE animals, the absence of this effect in cocaine-withdrawn PE rats indicates that cocaine withdrawal also influences the retrieval of previously learned information.

  15. Live-birth rate associated with repeat in vitro fertilisation treatment cycles

    Science.gov (United States)

    Smith, Andrew D.A.C.; Tilling, Kate

    2016-01-01

    Importance The likelihood of achieving a live-birth with repeat in-vitro fertilisation (IVF) is unclear, yet treatment is commonly limited to three or four embryo transfers. Objective To determine the live-birth rate per initiated IVF cycle and with repeated cycles. Design, Setting and Participants Prospective study of 156,947 UK women who received 257,398 IVF ovarian stimulation cycles between 2003 and 2010 and were followed until June 2012. Main exposure IVF, with a cycle defined as an episode of ovarian stimulation and all subsequent separate fresh and frozen embryo transfers. Main Outcome(s) Live-birth rate per IVF cycle and the cumulative live-birth rates across all cycles in all women and by age and treatment type. Optimal, prognosis-adjusted and conservative cumulative live-birth rates were estimated, reflecting 0%, 30% and 100% of women discontinuing due to poor prognosis and having a live-birth rate of zero had they continued. Results In all women the live-birth rate for the first cycle was 29.5% (95%CI: 29.3, 29.7). This remained above 20% up to and including the fourth cycle. The cumulative prognosis-adjusted live-birth rate across all cycles continued to increase up to the ninth, with 65.3% (64.8, 65.8) of women achieving a live-birth by the sixth cycle. In women younger than 40 using their own oocytes, the live-birth rate for the first cycle was 32.3% (32.0, 32.5), and remained above 20% up to and including the fourth cycle. Six cycles achieved a cumulative prognosis-adjusted live-birth rate of 68.4% (67.8, 68.9). For women aged 40-42, the live-birth rate for the first cycle was 12.3% (95%CI: 11.8, 12.8), with six cycles achieving a cumulative prognosis-adjusted live-birth rate of 31.5% (29.7, 33.3). For women older than 42 years all rates within each cycle were less than 4%. No age differential was observed among women using donor oocytes. Rates were lower in those with untreated male factor infertility compared to those with any other cause, but

  16. [Safety of repeat median sternotomy in the palliative treatment of patients with univentricular heart].

    Science.gov (United States)

    Díliz-Nava, Héctor; Meléndez-Sagaón, Isis; Tamaríz-Cruz, Orlando; García-Benitez, Luis; Araujo-Martínez, Aric; Palacios-Macedo, Alexis

    2017-01-13

    Establish the morbidity and mortality of patients with univentricular hearts who underwent repeat median sternotomy at the Instituto Nacional de Pediatría METHOD: We retrospectively review the clinical charts of all patient who underwent repeat median sternotomy from 2001 to 2016. Sixty-five patients underwent 76 surgeries through repeat median sternotomy. Fifty-nine patients had a first repeat median sternotomy with a mean age of 36months (range 4-176months) and a mean weight of 12.2kg (range 3.2-21.5kg). Forty patients had a Glenn procedure and 19 patients had a Fontan procedure. There were 17 patients with second repeat median sternotomy, mean age of 89months (range 48-156months) and mean weight of 22.7kg (14.4-41kg). In all 17 patients a Fontan procedure was done. Section of the right coronary artery with electrocardiographic changes and a right atrium tear that caused hypotension, occurred during first repeat sternotomy. An aortic tear occurred during a second repeat sternotomy with massive bleeding and consequent death. This represents a 3.9% of reentry injury. We conclude that repeat median sternotomy is a safe procedure. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

  17. Efficacy and Safety of Repeated Courses of rTMS Treatment in Patients with Chronic Subjective Tinnitus

    Science.gov (United States)

    Lehner, Astrid; Schecklmann, Martin; Poeppl, Timm B.; Kreuzer, Peter M.; Peytard, Juliette; Frank, Elmar; Langguth, Berthold

    2015-01-01

    Background. Repetitive transcranial magnetic stimulation (rTMS) has shown promising effects in the treatment of chronic subjective tinnitus. However, little is known about maintenance treatment in order to achieve long-lasting improvements. Objective. This study addresses the questions whether the repeated application of rTMS treatment can contribute to the maintenance or enhancement of treatment effects and if so in which cases repetitive treatment courses are beneficial. Methods. 55 patients with chronic tinnitus were treated with two rTMS treatment courses with ten treatment sessions each. The mean intertreatment interval was 20.65 ± 18.56 months. Tinnitus severity was assessed before and after each treatment course. Results. Both treatments were well tolerated and caused significant improvement of tinnitus severity. The main predictor for the outcome of the second treatment was the development of tinnitus distress in the phase between both treatment courses: the more patients worsened in this interval, the more they improved during the second treatment course. Conclusion. Repeated application of rTMS seems to be useful in tinnitus management and should preferentially be offered to patients who experience a worsening of their tinnitus during the intertreatment interval, irrespective of their response to the first treatment course. PMID:26583152

  18. Efficacy and Safety of Repeated Courses of rTMS Treatment in Patients with Chronic Subjective Tinnitus

    Directory of Open Access Journals (Sweden)

    Astrid Lehner

    2015-01-01

    Full Text Available Background. Repetitive transcranial magnetic stimulation (rTMS has shown promising effects in the treatment of chronic subjective tinnitus. However, little is known about maintenance treatment in order to achieve long-lasting improvements. Objective. This study addresses the questions whether the repeated application of rTMS treatment can contribute to the maintenance or enhancement of treatment effects and if so in which cases repetitive treatment courses are beneficial. Methods. 55 patients with chronic tinnitus were treated with two rTMS treatment courses with ten treatment sessions each. The mean intertreatment interval was 20.65 ± 18.56 months. Tinnitus severity was assessed before and after each treatment course. Results. Both treatments were well tolerated and caused significant improvement of tinnitus severity. The main predictor for the outcome of the second treatment was the development of tinnitus distress in the phase between both treatment courses: the more patients worsened in this interval, the more they improved during the second treatment course. Conclusion. Repeated application of rTMS seems to be useful in tinnitus management and should preferentially be offered to patients who experience a worsening of their tinnitus during the intertreatment interval, irrespective of their response to the first treatment course.

  19. The Effect of Repeated Ketamine Infusion Over Facial Emotion Recognition in Treatment-Resistant Depression: A Preliminary Report.

    Science.gov (United States)

    Shiroma, Paulo R; Albott, C Sophia; Johns, Brian; Thuras, Paul; Wels, Joseph; Lim, Kelvin O

    2015-01-01

    In contrast to improvement in emotion recognition bias by traditional antidepressants, the authors report preliminary findings that changes in facial emotion recognition are not associated with response of depressive symptoms after repeated ketamine infusions or relapse during follow-up in treatment-resistant depression.

  20. Effects of imipramine and bupropion on the duration of immobility of ACTH-treated rats in the forced swim test: involvement of the expression of 5-HT2A receptor mRNA.

    Science.gov (United States)

    Kitamura, Yoshihisa; Fujitani, Yoshika; Kitagawa, Kouhei; Miyazaki, Toshiaki; Sagara, Hidenori; Kawasaki, Hiromu; Shibata, Kazuhiko; Sendo, Toshiaki; Gomita, Yutaka

    2008-02-01

    We examined the effect of chronic administration of imipramine and bupropion, monoamine reuptake inhibitors, on the duration of immobility in the forced swim test and serotonin (5-HT)(2A) receptor function in the form of 5-HT(2A) receptor mRNA levels in rats chronically treated with adrenocorticotropic hormone (ACTH). The immobility-decreasing effect of bupropion without imipramine did not influence the chronic ACTH treatment. The effect on the expression of 5-HT(2A) receptor mRNA of chronic ACTH treatment was decreased by bupropion, but not imipramine. These results suggest that bupropion has the effect of reducing immobility time in the forced swim test in the tricyclic antidepressant-resistant depressive model induced by chronic ACTH treatment in rats, and that decreased 5-HT(2A) receptor mRNA levels may be involved in this phenomenon.

  1. Molecular transduction mechanisms in ACTH-induced grooming

    NARCIS (Netherlands)

    Gispen, W.H.; Colbern, D.; Spruijt, B.M.

    1988-01-01

    Intraventricular administration of ACTH1-24 induces excessive grooming in the rat. Ethogram analysis shows that the peptide does not alter grooming behavior seen in a novel box, but that it prolongs the duration of the grooming bout. Extensive structure-activity studies have been performed which sug

  2. Short- and long-term effects of ACTH on the adrenal zona glomerulosa of the rat. A coupled stereological and enzymological study.

    Science.gov (United States)

    Mazzocchi, G; Malendowicz, L K; Rebuffat, P; Robba, C; Gottardo, G; Nussdorfer, G G

    1986-01-01

    Short-term ACTH treatment provoked a decrease in volume of the lipid-droplet compartment in rat zona glomerulosa cells, and a rise in plasma and intracellular concentrations of corticosterone and aldosterone. It enhanced activities of 3 beta-hydroxysteroid dehydrogenase (3 beta HSD), 11 beta-hydroxylase (11 beta OH) and 18-hydroxylase (18OH). Long-term ACTH administration produced a hypertrophy of the zona glomerulosa and its parenchymal cells, a result of the increase in volume of the smooth endoplasmic reticulum and the mitochondrial compartment. The surface area per cell of mitochondrial inner membranes increased; the tubular cristae were transformed into a homogeneous population of vesicles. The plasma and intracellular concentrations of corticosterone further increased, whereas those of aldosterone fell below basal levels (the "aldosterone-escape" phenomenon). The activities of 3 beta HSD and 11 beta OH were enhanced, that of 180H decreased. Therefore, ACTH stimulates zona glomerulosa growth and transforms parenchymal elements into zona fasciculata cell-types. Cyanoketone nullified acute ACTH effects on plasma and intracellular concentrations of corticosterone and aldosterone, but did not affect the activities of 11 beta OH and 18OH. Chronic ACTH treatment produced similar results, although 18OH activity was not suppressed. The mechanism underlying the "aldosterone-escape" phenomenon may thus involve a rise in the intracellular concentration of corticosterone, caused by the enhanced synthesis and activation of 3 beta HSD and 11 beta OH.

  3. Effect of Repeated Anthelminthic Treatment on Malaria in School Children in Kenya: A Randomized, Open-Label, Equivalence Trial.

    Science.gov (United States)

    Kepha, Stella; Nuwaha, Fred; Nikolay, Birgit; Gichuki, Paul; Mwandawiro, Charles S; Mwinzi, Pauline N; Odiere, Maurice R; Edwards, Tansy; Allen, Elizabeth; Brooker, Simon J

    2016-01-15

    School children living in the tropics are often concurrently infected with plasmodium and helminth parasites. It has been hypothesized that immune responses evoked by helminths may modify malaria-specific immune responses and increase the risk of malaria. We performed a randomized, open-label, equivalence trial among 2436 school children in western Kenya. Eligible children were randomized to receive either 4 repeated doses or a single dose of albendazole and were followed up during 13 months to assess the incidence of clinical malaria. Secondary outcomes were Plasmodium prevalence and density, assessed by repeat cross-sectional surveys over 15 months. Analysis was conducted on an intention-to-treat basis with a prespecified equivalence range of 20%. During 13 months of follow-up, the incidence rate of malaria was 0.27 episodes/person-year in the repeated treatment group and 0.26 episodes/person-year in the annual treatment group (incidence difference, 0.01; 95% confidence interval, -.03 to .06). The prevalence and density of malaria parasitemia did not differ by treatment group at any of the cross-sectional surveys. Our findings suggest that repeated deworming does not alter risks of clinical malaria or malaria parasitemia among school children and that school-based deworming in Africa may have no adverse consequences for malaria. NCT01658774. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.

  4. Selective serotonin re-uptake inhibitors potentiate gene blunting induced by repeated methylphenidate treatment: Zif268 versus Homer1a.

    Science.gov (United States)

    Van Waes, Vincent; Vandrevala, Malcolm; Beverley, Joel; Steiner, Heinz

    2014-11-01

    There is a growing use of psychostimulants, such as methylphenidate (Ritalin; dopamine re-uptake inhibitor), for medical treatments and as cognitive enhancers in the healthy. Methylphenidate is known to produce some addiction-related gene regulation. Recent findings in animal models show that selective serotonin re-uptake inhibitors (SSRIs), including fluoxetine, can potentiate acute induction of gene expression by methylphenidate, thus indicating an acute facilitatory role for serotonin in dopamine-induced gene regulation. We investigated whether repeated exposure to fluoxetine, in conjunction with methylphenidate, in adolescent rats facilitated a gene regulation effect well established for repeated exposure to illicit psychostimulants such as cocaine-blunting (repression) of gene inducibility. We measured, by in situ hybridization histochemistry, the effects of a 5-day repeated treatment with methylphenidate (5 mg/kg), fluoxetine (5 mg/kg) or a combination on the inducibility (by cocaine) of neuroplasticity-related genes (Zif268, Homer1a) in the striatum. Repeated methylphenidate treatment alone produced minimal gene blunting, while fluoxetine alone had no effect. In contrast, fluoxetine added to methylphenidate robustly potentiated methylphenidate-induced blunting for both genes. This potentiation was widespread throughout the striatum, but was most robust in the lateral, sensorimotor striatum, thus mimicking cocaine effects. For illicit psychostimulants, blunting of gene expression is considered part of the molecular basis of addiction. Our results thus suggest that SSRIs, such as fluoxetine, may increase the addiction liability of methylphenidate.

  5. 60 YEARS OF POMC: Adrenal and extra-adrenal functions of ACTH.

    Science.gov (United States)

    Gallo-Payet, Nicole

    2016-05-01

    The pituitary adrenocorticotropic hormone (ACTH) plays a pivotal role in homeostasis and stress response and is thus the major component of the hypothalamo-pituitary-adrenal axis. After a brief summary of ACTH production from proopiomelanocortin (POMC) and on ACTH receptor properties, the first part of the review covers the role of ACTH in steroidogenesis and steroid secretion. We highlight the mechanisms explaining the differential acute vs chronic effects of ACTH on aldosterone and glucocorticoid secretion. The second part summarizes the effects of ACTH on adrenal growth, addressing its role as either a mitogenic or a differentiating factor. We then review the mechanisms involved in steroid secretion, from the classical Cyclic adenosine monophosphate second messenger system to various signaling cascades. We also consider how the interaction between the extracellular matrix and the cytoskeleton may trigger activation of signaling platforms potentially stimulating or repressing the steroidogenic potency of ACTH. Finally, we consider the extra-adrenal actions of ACTH, in particular its role in differentiation in a variety of cell types, in addition to its known lipolytic effects on adipocytes. In each section, we endeavor to correlate basic mechanisms of ACTH function with the pathological consequences of ACTH signaling deficiency and of overproduction of ACTH.

  6. Molecular interpretation of ACTH-β-endorphin coaggregation: relevance to secretory granule biogenesis.

    Directory of Open Access Journals (Sweden)

    Srivastav Ranganathan

    Full Text Available Peptide/protein hormones could be stored as non-toxic amyloid-like structures in pituitary secretory granules. ACTH and β-endorphin are two of the important peptide hormones that get co-stored in the pituitary secretory granules. Here, we study molecular interactions between ACTH and β-endorphin and their colocalization in the form of amyloid aggregates. Although ACTH is known to be a part of ACTH-β-endorphin aggregate, ACTH alone cannot aggregate into amyloid under various plausible conditions. Using all atom molecular dynamics simulation we investigate the early molecular interaction events in the ACTH-β-endorphin system, β-endorphin-only system and ACTH-only system. We find that β-endorphin and ACTH formed an interacting unit, whereas negligible interactions were observed between ACTH molecules in ACTH-only system. Our data suggest that ACTH is not only involved in interaction with β-endorphin but also enhances the stability of mixed oligomers of the entire system.

  7. Repeatability and Reproducibility of Quantitative Corneal Shape Analysis after Orthokeratology Treatment Using Image-Pro Plus Software

    Science.gov (United States)

    Mei, Ying; Tang, Zhiping

    2016-01-01

    Purpose. To evaluate the repeatability and reproducibility of quantitative analysis of the morphological corneal changes after orthokeratology treatment using “Image-Pro Plus 6.0” software (IPP). Methods. Three sets of measurements were obtained: two sets by examiner 1 with 5 days apart and one set by examiner 2 on the same day. Parameters of the eccentric distance, eccentric angle, area, and roundness of the corneal treatment zone were measured using IPP. The intraclass correlation coefficient (ICC) and repetitive coefficient (COR) were used to calculate the repeatability and reproducibility of these three sets of measurements. Results. ICC analysis suggested “excellent” reliability of more than 0.885 for all variables, and COR values were less than 10% for all variables within the same examiner. ICC analysis suggested “excellent” reliability for all variables of more than 0.90, and COR values were less than 10% for all variables between different examiners. All extreme values of the eccentric distance and area of the treatment zone pointed to the same material number in three sets of measurements. Conclusions. IPP could be used to acquire the exact data of the characteristic morphological corneal changes after orthokeratology treatment with good repeatability and reproducibility. This trial is registered with trial registration number: ChiCTR-IPR-14005505.

  8. Repeatability and Reproducibility of Quantitative Corneal Shape Analysis after Orthokeratology Treatment Using Image-Pro Plus Software

    Directory of Open Access Journals (Sweden)

    Ying Mei

    2016-01-01

    Full Text Available Purpose. To evaluate the repeatability and reproducibility of quantitative analysis of the morphological corneal changes after orthokeratology treatment using “Image-Pro Plus 6.0” software (IPP. Methods. Three sets of measurements were obtained: two sets by examiner 1 with 5 days apart and one set by examiner 2 on the same day. Parameters of the eccentric distance, eccentric angle, area, and roundness of the corneal treatment zone were measured using IPP. The intraclass correlation coefficient (ICC and repetitive coefficient (COR were used to calculate the repeatability and reproducibility of these three sets of measurements. Results. ICC analysis suggested “excellent” reliability of more than 0.885 for all variables, and COR values were less than 10% for all variables within the same examiner. ICC analysis suggested “excellent” reliability for all variables of more than 0.90, and COR values were less than 10% for all variables between different examiners. All extreme values of the eccentric distance and area of the treatment zone pointed to the same material number in three sets of measurements. Conclusions. IPP could be used to acquire the exact data of the characteristic morphological corneal changes after orthokeratology treatment with good repeatability and reproducibility. This trial is registered with trial registration number: ChiCTR-IPR-14005505.

  9. Attention deficit associated with early life interictal spikes in a rat model is improved with ACTH.

    Directory of Open Access Journals (Sweden)

    Amanda E Hernan

    Full Text Available Children with epilepsy often present with pervasive cognitive and behavioral comorbidities including working memory impairments, attention deficit hyperactivity disorder (ADHD and autism spectrum disorder. These non-seizure characteristics are severely detrimental to overall quality of life. Some of these children, particularly those with epilepsies classified as Landau-Kleffner Syndrome or continuous spike and wave during sleep, have infrequent seizure activity but frequent focal epileptiform activity. This frequent epileptiform activity is thought to be detrimental to cognitive development; however, it is also possible that these IIS events initiate pathophysiological pathways in the developing brain that may be independently associated with cognitive deficits. These hypotheses are difficult to address due to the previous lack of an appropriate animal model. To this end, we have recently developed a rat model to test the role of frequent focal epileptiform activity in the prefrontal cortex. Using microinjections of a GABA(A antagonist (bicuculline methiodine delivered multiple times per day from postnatal day (p 21 to p25, we showed that rat pups experiencing frequent, focal, recurrent epileptiform activity in the form of interictal spikes during neurodevelopment have significant long-term deficits in attention and sociability that persist into adulthood. To determine if treatment with ACTH, a drug widely used to treat early-life seizures, altered outcome we administered ACTH once per day subcutaneously during the time of the induced interictal spike activity. We show a modest amelioration of the attention deficit seen in animals with a history of early life interictal spikes with ACTH, in the absence of alteration of interictal spike activity. These results suggest that pharmacological intervention that is not targeted to the interictal spike activity is worthy of future study as it may be beneficial for preventing or ameliorating adverse

  10. Nucleus accumbens deep-brain stimulation efficacy in ACTH-pretreated rats: alterations in mitochondrial function relate to antidepressant-like effects

    Science.gov (United States)

    Kim, Y; McGee, S; Czeczor, J K; Walker, A J; Kale, R P; Kouzani, A Z; Walder, K; Berk, M; Tye, S J

    2016-01-01

    Mitochondrial dysfunction has a critical role in the pathophysiology of mood disorders and treatment response. To investigate this, we established an animal model exhibiting a state of antidepressant treatment resistance in male Wistar rats using 21 days of adrenocorticotropic hormone (ACTH) administration (100 μg per day). First, the effect of ACTH treatment on the efficacy of imipramine (10 mg kg−1) was investigated alongside its effect on the prefrontal cortex (PFC) mitochondrial function. Second, we examined the mood-regulatory actions of chronic (7 day) high-frequency nucleus accumbens (NAc) deep-brain stimulation (DBS; 130 Hz, 100 μA, 90 μS) and concomitant PFC mitochondrial function. Antidepressant-like responses were assessed in the open field test (OFT) and forced swim test (FST) for both conditions. ACTH pretreatment prevented imipramine-mediated improvement in mobility during the FST (P0.05). Analyses of PFC mitochondrial function revealed that ACTH-treated animals had decreased capacity for adenosine triphosphate production compared with controls. In contrast, ACTH animals following NAc DBS demonstrated greater mitochondrial function relative to controls. Interestingly, a proportion (30%) of the ACTH-treated animals exhibited heightened locomotor activity in the OFT and exaggerated escape behaviors during the FST, together with general hyperactivity in their home-cage settings. More importantly, the induction of this mania-like phenotype was accompanied by overcompensative increased mitochondrial respiration. Manifestation of a DBS-induced mania-like phenotype in imipramine-resistant animals highlights the potential use of this model in elucidating mechanisms of mood dysregulation. PMID:27327257

  11. Polymicrobial Gardnerella biofilm resists repeated intravaginal antiseptic treatment in a subset of women with bacterial vaginosis: a preliminary report.

    Science.gov (United States)

    Swidsinski, Alexander; Loening-Baucke, Vera; Swidsinski, Sonja; Verstraelen, Hans

    2015-03-01

    Bacterial vaginosis is a recalcitrant polymicrobial biofilm infection that often resists standard antibiotic treatment. We therefore considered repeated treatment with octenidine, a local antiseptic that has previously been shown to be highly effective in several biofilm-associated infections. Twenty-four patients with recurrent BV were treated with a 7-day course of octenidine (octenidine dihydrochloride spray application with the commercial product Octenisept). In case of treatment failure or relapse within 6 months, patients were re-treated with a 28-day course of octenidine. In case of recurrence within 6 months after the second treatment course, patients were treated again with a 28-day course followed by weekly applications for 2 months. Treatment effect was evaluated by assessment of the presence of the biofilm on voided vaginal epithelial cells through fluorescence in situ hybridisation. The initial cure rate following a 7-day course of octenidine was as high as 87.5%. The 6-month relapse rate was, however, as high as 66.6%. Repeated treatment for 28 days led to an overall cure rate of 75.0%; however, it was also associated with emergence of complete resistance to octenidine in a subset of women. The overall cure rate after three treatment courses with 1-year follow-up was 62.5 %, with 37.5 % of the patients showing complete resistance to octenidine. Our preliminary results showed that octenidine dihydrochloride was initially highly effective, but the efficacy of repeated and prolonged treatment dropped quickly as challenge with the antiseptic rapidly led to bacterial resistance in a considerable subset of women.

  12. Hormone (ACTH, T3) content of immunophenotyped lymphocyte subpopulations.

    Science.gov (United States)

    Pállinger, Éva; Kiss, Gergely Attila; Csaba, György

    2016-12-01

    Cells of the immune system synthesize, store, and secrete polypeptide and amino acid type hormones, which also influence their functions, having receptors for different hormones. In the present experiment immunophenotyped immune cells isolated from bone marrow, thymus, and peritoneal fluid of mice were used for demonstrating the adrenocorticotropic hormone (ACTH) and triiodothyronine (T3) hormone production of differentiating immune cells. Both hormones were found in each cell type, and in each maturation state, which means that all cells are participating in the hormonal function of the immune system. The lineage-independent presence of ACTH and T3 in differentiating hematopoietic cells denotes that their expression ubiquitous during lymphocyte development. Higher ACTH and T3 content of B cells shows that these cells are the most hormonally active and suggests that the hormones may have an autocrine regulatory role in B cell development. Developing T cells showed heterogeneous hormone production which was associated with their maturation state. Differences in the hormone contents of immune cells isolated from different organs indicate that their hormone production is defined by their differentiation or maturation state, however, possibly also by the local microenvironment.

  13. Aged PROP1 deficient dwarf mice maintain ACTH production.

    Directory of Open Access Journals (Sweden)

    Igor O Nasonkin

    Full Text Available Humans with PROP1 mutations have multiple pituitary hormone deficiencies (MPHD that typically advance from growth insufficiency diagnosed in infancy to include more severe growth hormone (GH deficiency and progressive reduction in other anterior pituitary hormones, eventually including adrenocorticotropic hormone (ACTH deficiency and hypocortisolism. Congenital deficiencies of GH, prolactin, and thyroid stimulating hormone have been reported in the Prop1(null (Prop1(-/- and the Ames dwarf (Prop1(df/df mouse models, but corticotroph and pituitary adrenal axis function have not been thoroughly investigated. Here we report that the C57BL6 background sensitizes mutants to a wasting phenotype that causes approximately one third to die precipitously between weaning and adulthood, while remaining homozygotes live with no signs of illness. The wasting phenotype is associated with severe hypoglycemia. Circulating ACTH and corticosterone levels are elevated in juvenile and aged Prop1 mutants, indicating activation of the pituitary-adrenal axis. Despite this, young adult Prop1 deficient mice are capable of responding to restraint stress with further elevation of ACTH and corticosterone. Low blood glucose, an expected side effect of GH deficiency, is likely responsible for the elevated corticosterone level. These studies suggest that the mouse model differs from the human patients who display progressive hormone loss and hypocortisolism.

  14. Repeated treatment with (-)-sulpiride plus a low dose of SCH 23390 displays wider neuroleptic activity without inducing dopaminergic supersensitivity.

    Science.gov (United States)

    Dall'Olio, R; Gandolfi, O; Roncada, P; Vaccheri, A; Montanaro, N

    1990-01-01

    Combined treatment with (-)-sulpiride plus a low dose of the D1 receptor antagonist SCH 23390, unlike (-)-sulpiride given alone, blocked rat striatal dopaminergic transmission. Five days after the withdrawal of 21-day repeated administration of the combined treatment, no increase in apomorphine-induced stereotyped behaviour was observed. The results suggest that the combination of a D2 blocker and a low dose of a D1 blocker produces a wider spectrum of neuroleptic activity without an overt risk of inducing dopaminergic behavioural supersensitivity.

  15. ACTH-like peptides increase pain sensitivity and antagonize opiate analgesia

    Science.gov (United States)

    Heybach, J. P.; Vernikos, J.

    1981-01-01

    The role of the pituitary and of ACTH in pain sensitivity was investigated in the rat. Pain sensitivity was assessed by measuring paw-lick and jump latencies in response to being placed on a grid at 55 C. Hypophysectomy reduced pain sensitivity, and this effect was reversed by the intracerebroventricular (ICV) injection of the opiate antagonist naloxone. Similarly, the analgesia produced by a dose of morphine was antagonized by the administration of ACTH or alpha-MSH. The peripheral injection of ACTH or alpha-MSH in normal rats did not increase pain sensitivity. However, ACTH administered ICV increased pain sensivity within 10 min. The results indicate that the pituitary is the source of an endogenous opiate antagonist and hyperalgesic factor and that this factor is ACTH or an ACTH-like peptide. This activity resides in the N-terminal portion of the ACTH molecule since ACTH sub 4-10 is not active in this respect, nor does this activity require a free N-terminal serine since alpha-MSH appears to be almost as potent as the ACTH sub 1-24 peptide. It is concluded that ACTH-like peptides of pituitary origin act as endogenous hyperalgesic and opiate antagonistic factors.

  16. [Anxiogenic and anxiolytic effects of lithium chloride under preventive and therapeutic treatments of male mice with repeated experience of aggression].

    Science.gov (United States)

    Smagin, D A; Kudryavtseva, N N

    2014-01-01

    Repeated experience of aggression in daily agonistic interactions is accompanied by development of changes in behaviors and psychoemotional states indicating the development of the psychopathology of aggressive behavior, which are difficult to correct by drugs used for decrease of aggression in the clinics. In this paper the influence of lithium chloride on the behavior of aggressive males in different tests assessing anxiety, communication and exploratory activity (elevated plus maze test, social interaction test, partition test), as well as aggressiveness (agonistic interaction test) were studied. Lithium chloride (Sigma-Aldrich Co, 100 mg/kg/day, i.p.) was administered preventively to male in ranging from the 7th day of agonistic interactions, as well as therapeutically to males with 21 days of aggression experience during the period without agonistic interactions. Also the effects of chronic lithium chloride treatment on behaviors of animals without agonistic interactions (intact mice) were studied. Period of drug and saline (as the controls) treatment--14 days. It has been shown that preventive lithium chloride treatment of male mice with repeated experience of aggression induced pronounced anxiogenic effect, under therapeutic treatment--nxiolytic effects. Anxiolytic effect was also observed in intact males. There is no effect of lithium chloride on aggression. Differences in the effects of lithium chloride under preveitive and therapeutic treatments, as well as the causes of individual sensitivity to the drug in male mice in one group were discussed.

  17. Early detection of response in small cell bronchogenic carcinoma by changes in serum concentrations of creatine kinase, neuron specific enolase, calcitonin, ACTH, serotonin and gastrin releasing peptide

    DEFF Research Database (Denmark)

    Bork, E; Hansen, M; Urdal, P

    1988-01-01

    Creatine kinase (CK-BB), neuron specific enolase (NSE), ACTH, calcitonin, serotonin and gastrin releasing peptide (GRP) were measured in serum or plasma before and immediately after initiation of treatment in patients with small cell lung cancer (SCC). Pretherapeutic elevated concentrations of CK...

  18. Clinical features of congenital adrenal insufficiency including growth patterns and significance of ACTH stimulation test.

    Science.gov (United States)

    Koh, Ji Won; Kim, Gu Hwan; Yoo, Han Wook; Yu, Jeesuk

    2013-11-01

    Congenital adrenal insufficiency is caused by specific genetic mutations. Early suspicion and definite diagnosis are crucial because the disease can precipitate a life-threatening hypovolemic shock without prompt treatment. This study was designed to understand the clinical manifestations including growth patterns and to find the usefulness of ACTH stimulation test. Sixteen patients with confirmed genotyping were subdivided into three groups according to the genetic study results: congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH, n=11), congenital lipoid adrenal hyperplasia (n=3) and X-linked adrenal hypoplasia congenita (n=2). Bone age advancement was prominent in patients with CAH especially after 60 months of chronologic age (n=6, 67%). They were diagnosed in older ages in group with bone age advancement (Pcongenital adrenal insufficiency. ACTH stimulation test played an important role to support the diagnosis and serum 17-hydroxyprogesterone levels were significantly elevated in all of the CAH patients. The test will be important for monitoring growth and puberty during follow up of patients with congenital adrenal insufficiency.

  19. Repeat transsphenoidal surgery for the treatment of remaining or recurring pituitary tumors in acromegaly.

    Science.gov (United States)

    Yamada, Shozo; Fukuhara, Noriaki; Oyama, Kenichi; Takeshita, Akira; Takeuchi, Yasuharu

    2010-10-01

    Acromegaly is a disorder characterized by hypersecretion of growth hormone caused by a growth hormone-secreting pituitary adenoma. To evaluate the long-term efficacy and safety of repeat transsphenoidal surgery for persistent or recurrent acromegaly. We retrospectively reviewed records for 53 acromegalic patients who underwent repeat transsphenoidal surgery for persistent or progressive acromegaly at Toranomon Hospital between 1987 and 2006. Multivariate logistic regression was performed to evaluate preoperative factors influencing the surgical outcome. Thirty-one patients (58.5%) met the criteria for cure on long-term follow-up endocrine findings. Furthermore, 17 patients were well controlled with normal insulin-like growth factor I levels without (2 patients) or with medication (15 patients), whereas insulin-like growth factor I levels were still above normal in 5 patients after postoperative adjuvant therapy. Only 1 patient was undergoing additional hormonal replacement after surgery, although transient cerebrospinal fluid leak, transient abducens nerve palsy, severe nasal bleeding, and pituitary abscess occurred in each patient, respectively. Multivariate analysis clarified that a favorable surgical outcome was achieved in patients without cavernous sinus invasion (hazard ratio 12.56), tumor segmentation (hazard ratio 5.82), or in those older than 40 years old (hazard ratio 3.21). Repeat surgery can be performed safely with an approximately 60% long-term cure rate in this series. Reoperation should therefore be considered for persistent or recurrent disease in acromegalic patients in whom adjuvant therapy is not effective enough or cannot be accepted. The careful study of initial or preoperative magnetic resonance imaging and the use of micro-Doppler, endoscope, and eye movement monitoring device during surgery can help increase cure rate with a lower complication rate.

  20. Repeatability of dose painting by numbers treatment planning in prostate cancer radiotherapy based on multiparametric magnetic resonance imaging

    Science.gov (United States)

    van Schie, Marcel A.; Steenbergen, Peter; Viet Dinh, Cuong; Ghobadi, Ghazaleh; van Houdt, Petra J.; Pos, Floris J.; Heijmink, Stijn W. T. J. P.; van der Poel, Henk G.; Renisch, Steffen; Vik, Torbjørn; van der Heide, Uulke A.

    2017-07-01

    Dose painting by numbers (DPBN) refers to a voxel-wise prescription of radiation dose modelled from functional image characteristics, in contrast to dose painting by contours which requires delineations to define the target for dose escalation. The direct relation between functional imaging characteristics and DPBN implies that random variations in images may propagate into the dose distribution. The stability of MR-only prostate cancer treatment planning based on DPBN with respect to these variations is as yet unknown. We conducted a test-retest study to investigate the stability of DPBN for prostate cancer in a semi-automated MR-only treatment planning workflow. Twelve patients received a multiparametric MRI on two separate days prior to prostatectomy. The tumor probability (TP) within the prostate was derived from image features with a logistic regression model. Dose mapping functions were applied to acquire a DPBN prescription map that served to generate an intensity modulated radiation therapy (IMRT) treatment plan. Dose calculations were done on a pseudo-CT derived from the MRI. The TP and DPBN map and the IMRT dose distribution were compared between both MRI sessions, using the intraclass correlation coefficient (ICC) to quantify repeatability of the planning pipeline. The quality of each treatment plan was measured with a quality factor (QF). Median ICC values for the TP and DPBN map and the IMRT dose distribution were 0.82, 0.82 and 0.88, respectively, for linear dose mapping and 0.82, 0.84 and 0.94 for square root dose mapping. A median QF of 3.4% was found among all treatment plans. We demonstrated the stability of DPBN radiotherapy treatment planning in prostate cancer, with excellent overall repeatability and acceptable treatment plan quality. Using validated tumor probability modelling and simple dose mapping techniques it was shown that despite day-to-day variations in imaging data still consistent treatment plans were obtained.

  1. Effect of repeated pulsed electric field treatment on the quality of hot-boned beef loins and topsides.

    Science.gov (United States)

    Bekhit, Alaa El-Din A; Suwandy, Via; Carne, Alan; van de Ven, Remy; Hopkins, David L

    2016-01-01

    The effects of repeated (1×, 2×, 3×) pulsed electric field (PEF) treatment (10 kV, 90 Hz, 20 μs) on the quality of beef loins and topsides were evaluated, including the tenderness, purge loss, cooking loss, myofibrillar protein profile and post-mortem proteolysis. Both muscle types were obtained from each of 12 steers and were processed within 6h. After PEF treatment samples of both muscle types were subjected to 3, 7, 14 and 21 days ageing. The 1× and 2× PEF treatments had no effect on the tenderisation of hot-boned beef Musculus longissimus lumborum muscle for all ageing treatment times, while the 3× treatment reduced the tenderness. The opposite effect was observed in hot-boned beef Musculus semimembranosus muscles where the 3× treatment produced meat with lowest shear force at 3 days post-treatment time, but this beneficial effect disappeared with longer ageing times. An increase in proteolysis of troponin T was seen to the largest extent with 1× PEF treatment and decreased with every extra application of treatment.

  2. Transitory FGF treatment results in the long-lasting suppression of the proliferative response to repeated FGF stimulation.

    Science.gov (United States)

    Poole, Ashleigh; Knowland, Nicholas; Cooper, Emily; Cole, Rebecca; Wang, Hongchuan; Booth, Lucas; Kacer, Doreen; Tarantini, Francesca; Friesel, Robert; Prudovsky, Igor

    2014-05-01

    FGF applied as a single growth factor to quiescent mouse fibroblasts induces a round of DNA replication, however continuous stimulation results in arrest in the G1 phase of the next cell cycle. We hypothesized that FGF stimulation induces the establishment of cell memory, which prevents the proliferative response to repeated or continuous FGF application. When a 2-5 days quiescence period was introduced between primary and repeated FGF treatments, fibroblasts failed to efficiently replicate in response to secondary FGF application. The establishment of "FGF memory" during the first FGF stimulation did not require DNA synthesis, but was dependent on the activity of FGF receptors, MEK, p38 MAPK and NFκB signaling, and protein synthesis. While secondary stimulation resulted in strongly decreased replication rate, we did not observe any attenuation of morphological changes, Erk1/2 phosphorylation and cyclin D1 induction. However, secondary FGF stimulation failed to induce the expression of cyclin A, which is critical for the progression from G1 to S phase. Treatment of cells with a broad range histone deacetylase inhibitor during the primary FGF stimulation rescued the proliferative response to the secondary FGF treatment suggesting that the establishment of "FGF memory" may be based on epigenetic changes. We suggest that "FGF memory" can prevent the hyperplastic response to cell damage and inflammation, which are associated with an enhanced FGF production and secretion. "FGF memory" may present a natural obstacle to the efficient application of recombinant FGFs for the treatment of ulcers, ischemias, and wounds.

  3. A rare case of Cushing syndrome by cyclic ectopic-ACTH.

    Science.gov (United States)

    Farage, Mariana; Costa, Mario Alberto da Dantas Loures; Godoy-Matos, Amélio Fernando

    2012-07-01

    ACTH-dependent Cushing syndrome (CS) due to ectopic ACTH production is most times difficult to manage. The identification of the source of ACTH may take many years. Surgery or chemotherapy for the primary tumor is not always possible. Control of Cushing symptoms is many times achieved using medication, or bilateral adrenalectomy in refractory cases. This case presents a Brazilian male who showed severe hypertension, mood changes, muscle weakness, darkening of skin, and increased abdominal fat. An investigation for Cushing syndrome was carried out and, after a four-year follow-up, a carotid glomus tumor (chemodectoma) was confirmed, a rare ectopic ACTH-producing tumor. Besides, the patient presented cyclic Cushing syndrome that was exacerbated by diverticulitis episodes. This case presents interesting pitfalls on diagnosis and management of ACTH-dependent CS. This is the only report of a chemodectoma that produced ACTH in the literature.

  4. Corticotropin (ACTH) regulates alternative RNA splicing in Y1 mouse adrenocortical tumor cells.

    Science.gov (United States)

    Schimmer, Bernard P; Cordova, Martha

    2015-06-15

    The stimulatory effect of ACTH on gene expression is well documented and is thought to be a major mechanism by which ACTH maintains the functional and structural integrity of the gland. Previously, we showed that ACTH regulates the accumulation of over 1200 transcripts in Y1 adrenal cells, including a cluster with functions in alternative splicing of RNA. On this basis, we postulated that some of the effects of ACTH on the transcription landscape of Y1 cells are mediated by alternative splicing. In this study, we demonstrate that ACTH regulates the alternative splicing of four transcripts - Gnas, Cd151, Dab2 and Tia1. Inasmuch as alternative splicing potentially affects transcripts from more than two-thirds of the mouse genome, we suggest that these findings are representative of a genome-wide effect of ACTH that impacts on the mRNA and protein composition of the adrenal cortex.

  5. Pre- and postnatally administered ACTH, Organon 2766 and CRF facilitate or inhibit active avoidance task performance in young adult mice.

    Science.gov (United States)

    Honour, L C; White, M H

    1988-01-01

    This study investigated the effect of learning/memory-related neuropeptides on behavioral task performance in later life. A 1 mg/kg dosage of adrenocorticotropic hormone 4-9, Organon 2766, ACTH/MSH 4-10, ACTH 1-24, CRF, or diluent was subcutaneously injected into either pregnant females or into newborn pups during specific neural developmental windows. Each of the progeny was trained in an active-avoidance task and tested for acquisition on postpartum days 35-37. The mice were then tested for memory task performance and reacquisition on days 42-44 postpartum using the identical experimental paradigm as that used in the training sessions. Prenatal treatment with these memory-related neuropeptides resulted in significant facilitation of learning/memory task performance in male and female mice treated with Organon 2766 (p less than 0.001), and a significant inhibition of learning/memory task performance in males and females treated with ACTH 1-24 (p less than 0.01). Additional sex-specific performance facilitations and inhibitions resulted from the pre- or postnatal administration of the various neuropeptides used in this study. These results suggest that neuropeptides, when available in increased amounts during specific neural developmental windows, can significantly improve or suppress related behavioral performance capability in later life.

  6. Primary empty sella, hyperprolactinemia, and isolated ACTH deficiency after postpartum hemorrhage.

    Science.gov (United States)

    Stacpoole, P W; Kandell, T W; Fisher, W R

    1983-05-01

    In a 20-year-old woman, a complicated full-term delivery was followed by a 14-month history of galactorrhea, amenorrhea, and symptoms of hypocortisolism. Evaluation revealed the presence of an empty sella, hyperprolactinemia, and an isolated pituitary deficiency of ACTH, resulting in secondary adrenal insufficiency. The defect in ACTH secretion was apparently due to intrinsic pituitary rather than hypothalamic disease, because administration of lysine vasopressin did not stimulate ACTH release. An empty sella with hyperprolactinemia has been described before. However, to the authors' knowledge, isolated ACTH deficiency as a complication of postpartum hypopituitarism (atypical Sheehan's syndrome) in association with an empty sella and hyperprolactinemia has not previously been reported.

  7. Omeprazole versus ranitidine in the medical treatment of acute upper gastrointestinal bleeding: assessment by early repeat endoscopy.

    Science.gov (United States)

    Fasseas, P; Leybishkis, B; Rocca, G

    2001-12-01

    The purpose of this study was to assess the effects of acid suppression in patients with upper gastrointestinal bleeding using early repeat endoscopy. Ninety-two patients with the diagnosis of acute upper gastrointestinal bleeding (endoscopically verified), entered a single-blind, randomised study comparing two treatment groups: omeprazole (40 mg orally daily) to ranitidine (50 mg intravenously four times daily). The lesions considered were gastric ulcers, duodenal ulcers and erosive gastritis. All patients were candidates for medical treatment. The parameters assessed included: 1) stabilisation of the lesion by repeat endoscopy at 7.0 +/- 3.0 days, 2) bleeding recurrence, 3) duration of stay in the intermediate medical care unit. For erosive gastritis only parameters 2 and 3 were considered. The study was limited to the hospitalisation period. Endoscopic stabilisation rate at 7.0 +/- 3.0 days for duodenal lesions was higher in the omeprazole group (71% vs 37%, p=0.03), but there was no significant difference for gastric lesions (50% vs 54%, NS). The overall bleeding recurrence rate (0% vs 17%, p=0.013) and the duration of stay (3.9 vs 6.4 days, p<0.01) were significantly lower in the omeprazole group. Our study suggests that omeprazole is more effective than ranitidine in the pharmacological treatment of acute upper gastrointestinal bleeding.

  8. Effects of repeat fenbendazole treatment in dairy calves with giardiosis on cyst excretion, clinical signs and production.

    Science.gov (United States)

    O'Handley, R M; Cockwill, C; Jelinski, M; McAllister, T A; Olson, M E

    2000-04-28

    In this 90-day study, 60 male Holstein dairy calves were experimentally infected with Giardia duodenalis. Calves were randomly blocked by weight into treatment (N=30) and placebo (N=30) groups. Beginning on study Day 0, calves in the treatment group were administered an oral dose of 5mg/kg of fenbendazole once daily for three consecutive days. Calves in the placebo group received a daily oral treatment of 5 ml of saline for 3 days. These treatments were repeated on Days 30 and 60 of the study. Fecal samples were collected from calves once per week and examined for the presence of Giardia cysts. Calves were monitored daily for clinical signs of intestinal disease and all episodes of diarrhea recorded. Calves were weighed once per week and total feed intake, on a dry matter basis, was calculated daily. Following each treatment, the number of calves shedding Giardia cysts in the fenbendazole group was reduced (pfenbendazole group had fewer cysts (pfenbendazole had fewer total days with diarrhea (pfenbendazole is an effective treatment for giardiosis, resulting in a clinical benefit and reducing the number of infective cysts shed by calves. However, this treatment regime had no impact on production parameters and reinfection occurred rapidly in these calves.

  9. Aberrant expression of glucagon receptors in adrenal glands of a patient with Cushing's syndrome and ACTH-independent macronodular adrenal hyperplasia

    Directory of Open Access Journals (Sweden)

    Valeria de Miguel

    2010-06-01

    Full Text Available Adrenocorticotropin (ACTH independent bilateral macronodular adrenal hyperplasia (AIMAH is a rare cause of Cushing´s syndrome, characterized by bilateral adrenal lesions and excess cortisol production despite ACTH suppression. Cortisol synthesis is produced in response to abnormal activation of G-protein- coupled receptors, such as gastric inhibitory peptide, vasopressin, beta adrenergic agonists, LH/hCG and serotonin receptors. The aim of this study was to analyze the expression of glucagon receptors in adrenal glands from an AIMAH patient. A patient with ACTH-independent Cushing´s syndrome and bilateral macronodular adrenal hyperplasia was screened for altered activation of adrenal receptors by physiological (mixed meal and pharmacological (gonadotrophin releasing hormone, ACTH and glucagon tests. The results showed abnormally high levels of serum cortisol after stimulation with glucagon. Hypercortisolism was successfully managed with ketoconazole treatment. Interestingly, a 4-month treatment with a somatostatin analogue (octreotide was also able to reduce cortisol secretion. Finally, Cushing's syndrome was cured after bilateral adrenalectomy. Abnormal mRNA expression for glucagon receptor in the patient´s adrenal glands was observed by Real-Time PCR procedure. These results strongly suggest that the mechanism of AIMAH causing Cushing´s syndrome in this case involves the illicit activation of adrenal glucagon receptors. This is the first case reported of AIMAH associated with ectopic glucagon receptors.

  10. Motion sickness susceptibility related to ACTH, ADH and TSH

    Science.gov (United States)

    Kohl, R. L.; Leach, C.; Homick, J. L.; Larochelle, F. T.

    1983-01-01

    The hypothesis that endogenous levels of certain hormones might be indicative of an individual's susceptibility to stressful motion is tested in a comparison of subjects classified as less prone to motion sickness with those of higher susceptibility. The levels of ACTH and vasopressin measured before exposure to stressful motion were twice as high in the less-suceptible group. No significant differences were noted in the levels of angiotensin, aldosterone, or TSH. The differences between the two groups were greater for a given hormone than for any of the changes induced by exposure to stressful motion.

  11. Comparative Genomic Hybridization Selection of Blastocysts for Repeated Implantation Failure Treatment: A Pilot Study

    Science.gov (United States)

    Greco, Ermanno; Bono, Sara; Ruberti, Alessandra; Lobascio, Anna Maria; Greco, Pierfrancesco; Biricik, Anil; Spizzichino, Letizia; Greco, Alessia; Tesarik, Jan; Minasi, Maria Giulia; Fiorentino, Francesco

    2014-01-01

    The aim of this study is to determine if the use of preimplantation genetic screening (PGS) by array comparative genomic hybridization (array CGH) and transfer of a single euploid blastocyst in patients with repeated implantation failure (RIF) can improve clinical results. Three patient groups are compared: 43 couples with RIF for whom embryos were selected by array CGH (group RIF-PGS), 33 couples with the same history for whom array CGH was not performed (group RIF NO PGS), and 45 good prognosis infertile couples with array CGH selected embryos (group NO RIF PGS). A single euploid blastocyst was transferred in groups RIF-PGS and NO RIF PGS. Array CGH was not performed in group RIF NO PGS in which 1-2 blastocysts were transferred. One monoembryonic sac with heartbeat was found in 28 patients of group RIF PGS and 31 patients of group NO RIF PGS showing similar clinical pregnancy and implantation rates (68.3% and 70.5%, resp.). In contrast, an embryonic sac with heartbeat was only detected in 7 (21.2%) patients of group RIF NO PGS. In conclusion, PGS by array CGH with single euploid blastocyst transfer appears to be a successful strategy for patients with multiple failed IVF attempts. PMID:24779011

  12. Neurotrophic ACTH4-9 analogue therapy normalizes electroencephalographic alterations in chronic experimental allergic encephalomyelitis.

    Science.gov (United States)

    Duckers, H J; van Dokkum, R P; Verhaagen, J; van Luijtelaar, E L; Coenen, A M; Lopes da Silva, F H; Gispen, W H

    1998-12-01

    Chronic experimental allergic encephalomyelitis (CEAE) is an established experimental model for multiple sclerosis (MS). The demyelinating lesions in the white matter of the central nervous system observed in CEAE and in MS are accompanied by various neurophysiological alterations. Among the best defined electrophysiological abnormalities are the changes in event-related potentials, in particular evoked potentials involving the spinal cord, i.e. motor and sensory evoked potentials. Less familiar are the changes observed in the electroencephalogram of CEAE-affected animals, which are also encountered in the human equivalent, MS. In the present experiment we evaluated the therapeutic value of a neurotrophic peptide treatment [H-Met(O2)-Glu-His-Phe-D-Lys-Phe-OH, an ACTH4-9 analogue] and its effect on the delayed flash visual evoked potentials (VEP) and power spectra of the electroencephalogram, during a 17-week follow-up of CEAE. CEAE animals treated with the neurotrophic peptide were protected against the development of neurological symptoms during the course of the demyelinating syndrome. VEPs of animals suffering from CEAE showed a delay of the latencies of the late components which was significantly counteracted by peptide treatment. The peak-to-peak amplitude of the VEP afterdischarge recorded from CEAE animals was significantly increased during the course of CEAE and correlated closely with the progression of the myelinopathy. Furthermore, CEAE animals showed an increase of electroencephalogram (EEG) beta activity of up to 500% as compared with the age-matched control group. This increase in beta power mainly consisted of a prevailing 20-21 Hz peak, a frequency that normally is not dominant in control EEG recordings of the rat during passive wakefulness. All these electrophysiological phenomena were absent in ACTH4-9 analogue-treated animals. The present findings underscore the potential importance of a neurotrophic peptide treatment in the pharmacotherapy of

  13. Repeated superovulation using a simplified FSH/eCG treatment for in vivo embryo production in sheep.

    Science.gov (United States)

    Forcada, F; Ait Amer-Meziane, M; Abecia, J A; Maurel, M C; Cebrián-Pérez, J A; Muiño-Blanco, T; Asenjo, B; Vázquez, M I; Casao, A

    2011-03-01

    This study investigated the efficacy of a simplified repeated superovulation treatment (eCG plus FSH in a single dose, rather than the usual protocol of six decreasing doses of FSH) in the in vivo embryo production in Ojalada donor ewes during the breeding season. In vitro viability after vitrification and warming of embryos recovered from both treatments was also assessed. In addition, the study examined the effects of the concentration of anti-eCG antibodies before each eCG/FSH treatment on in vivo embryo production. Thirty-eight females at the end of their reproductive lives were given the decreasing (n = 19) or simplified (n = 19) superovulatory treatment up to three times at intervals of ≥ 50 d. The onset of estrus was 5 h earlier (P < 0.05) among ewes that received the eCG/FSH protocol (25.2 ± 0.80 h) than it was among those that received the decreasing superovulatory treatment (30.1 ± 1.0 h), but the two treatments did not differ significantly in ovulation rates or the number and viability of embryos recovered. Both of the superovulatory protocols were significantly (P < 0.05 to P < 0.01) less effective after the first application. After three superovulatory treatments, the average number of viable embryos per ewe was 14.1 ± 2.3 and 13.7 ± 2.5 in the decreasing and simplified protocols, respectively. High anti-eCG antibody concentrations just before the superovulatory treatment with eCG/FSH were associated with a significant decrease (P < 0.05) in the rates of fertilization, viability, and freezability, especially in the second and third recoveries. Repeated superovulatory treatments with eCG/FSH can provide an efficient means of producing high quality embryos in the ewes of endangered breeds at the end of their reproductive lives, although further studies are needed to characterize the response associated with high concentrations of anti-eCG antibodies. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Are There Linguistic Markers of Suicidal Writing That Can Predict the Course of Treatment? A Repeated Measures Longitudinal Analysis.

    Science.gov (United States)

    Brancu, Mira; Jobes, David; Wagner, Barry M; Greene, Jeffrey A; Fratto, Timothy A

    2016-07-02

    The purpose of this pilot study was to predict resolution of suicidal ideation and risk over the course of therapy among suicidal outpatients (N = 144) using a novel method for analyzing Self- verses Relationally oriented qualitative written responses to the Suicide Status Form (SSF). A content analysis software program was used to extract word counts and a repeated measures longitudinal design was implemented to assess improvement over time. Patients with primarily Relationally focused word counts were more likely to have a quicker suicide risk resolution than those with more Self-focused word counts (6-7 sessions versus 17-18 sessions). Implications of these data are discussed, including the potential for enhancing treatment outcomes using this method with individuals entering treatment.

  15. Utility of repeated praziquantel dosing in the treatment of schistosomiasis in high-risk communities in Africa: a systematic review.

    Directory of Open Access Journals (Sweden)

    Charles H King

    2011-09-01

    Full Text Available Controversy persists about the optimal approach to drug-based control of schistosomiasis in high-risk communities. In a systematic review of published studies, we examined evidence for incremental benefits from repeated praziquantel dosing, given 2 to 8 weeks after an initial dose, in Schistosoma-endemic areas of Africa.We performed systematic searches of electronic databases PubMed and EMBASE for relevant data using search terms 'schistosomiasis', 'dosing' and 'praziquantel' and hand searches of personal collections and bibliographies of recovered articles. In 10 reports meeting study criteria, improvements in parasitological treatment outcomes after two doses of praziquantel were greater for S. mansoni infection than for S. haematobium infection. Observed cure rates (positive to negative conversion in egg detection assays were, for S. mansoni, 69-91% cure after two doses vs. 42-79% after one dose and, for S. haematobium, 46-99% cure after two doses vs. 37-93% after a single dose. Treatment benefits in terms of reduction in intensity (mean egg count were also different for the two species-for S. mansoni, the 2-dose regimen yielded an weighted average 89% reduction in standardized egg counts compared to a 83% reduction after one dose; for S. haematobium, two doses gave a 93% reduction compared to a 94% reduction with a single dose. Cost-effectiveness analysis was performed based on Markov life path modeling.Although schedules for repeated treatment with praziquantel require greater inputs in terms of direct costs and community participation, there are incremental benefits to this approach at an estimated cost of $153 (S. mansoni-$211 (S. haematobium per additional lifetime QALY gained by double treatment in school-based programs. More rapid reduction of infection-related disease may improve program adherence, and if, as an externality of the program, transmission can be reduced through more effective coverage, significant additional benefits are

  16. Cerebral blood flow and brain shrinkage seen on CT during ACTH therapy.

    Science.gov (United States)

    Futagi, Y; Abe, J; Kawahigashi, K

    1986-01-01

    By means of the Doppler ultrasound method, the cerebral blood flow (CBF) was assessed in 21 children with epilepsy undergoing treatment with adrenocorticotrophic hormone (ACTH). The maximum reduction in the internal carotid velocity, as an index of CBF during therapy, was about 35 percent compared with the values before therapy. Furthermore, sequential computed tomography (CT) examinations of the same subjects were performed to evaluate the change in the area of the intracranial brain parenchyma during therapy. The maximum reduction in the parenchymal area during therapy was about 10 percent. This corresponds to a 20 percent reduction in CBF according to Poiseuille's law, however, the remaining reduction in CBF demonstrated by velocity measurement cannot be explained only by that mechanical vascular factor. From these findings, it is concluded that in order to elucidate the mechanism of the CBF reduction, physiological factors such as changes in metabolism during therapy should also be evaluated in addition to the mechanical and physical causes.

  17. An ectopic ACTH-producing small cell lung carcinoma associated with enhanced corticosteroid biosynthesis in the peritumoral areas of adrenal metastasis.

    Science.gov (United States)

    Satoh, Hironori; Saito, Ryoko; Hisata, Shu; Shiihara, Jun; Taniuchi, Shinji; Nakamura, Yasuhiro; Nukiwa, Toshihiro; Ebina, Masahito; Sasano, Hironobu

    2012-06-01

    A 60-year-old Japanese male presented with swelling of bilateral cervical lymph nodes was subsequently diagnosed as the late stage of primary small cell lung carcinoma (SCLC). He was then treated with cisplatin and irinotecan as first-line chemotherapy, but hypokalemia with muscle weakness of the bilateral legs became gradually noticeable following two months of effective chemotherapy. A computed tomography (CT) scan revealed enlargement of bilateral adrenal glands and abdominal and mediastinal lymph nodes, though primary lung tumor remained the same in size. An ectopic ACTH-producing syndrome (EAS) was subsequently revealed by the following endocrinological studies. Hypokalemia was clinically improved by the treatment with metyrapone and the second-line chemotherapy with amrubicin for SCLC was started, but the patient died 12 days after the second-line chemotherapy. Post-mortem examination revealed ACTH immunoreactivity in tumor cells of all the metastatic lesions. Non-neoplastic adrenal cortex demonstrated hyperplasia associated with lipid depletion and marked expression of steroidogenic enzymes, especially in cortical cells around tumor infiltration, suggestive of paracrine ACTH stimulation of cortisol production. This is the first report evaluating expression of steroidogenic enzymes in adrenal cortex especially adjacent to the adrenal metastasis in the patients with EAS due to SCLC. These findings suggest that ACTH producing adrenal metastasis can induce EAS more frequently and severely, and that the symptoms and examination of EAS should be monitored carefully in the patients with adrenal metastasis of SCLC.

  18. Repeated potentiation of the metabotropic glutamate receptor 5 and the alpha 7 nicotinic acetylcholine receptor modulates behavioural and GABAergic deficits induced by early postnatal phencyclidine (PCP) treatment

    DEFF Research Database (Denmark)

    Kjaerby, Celia; Bundgaard, Christoffer; Fejgin, Kim;

    2013-01-01

    treatment, pyramidal neurons displayed a reduced mIPSC frequency and up-regulation of extrasynaptic THIP-induced current. ADX47273 treatment restored this up-regulation of THIP-induced current. Reduced receptor function seems to be the underlying cause of the reported changes, since repeated treatment...

  19. Community treatment orders in the UK 5 years on: a repeat national survey of psychiatrists

    Science.gov (United States)

    DeRidder, Ritz; Molodynski, Andrew; Manning, Catherine; McCusker, Pearse; Rugkåsa, Jorun

    2016-01-01

    Aims and method Community treatment orders (CTOs) are increasingly embedded into UK practice and their use continues to rise. However, they remain highly controversial. We surveyed psychiatrists to establish their experiences and current opinions of using CTOs and to compare findings with our previous survey conducted in 2010. Results The opinions of psychiatrists in the UK have not changed since 2010 in spite of recent evidence questioning the effectiveness of CTOs. Clinical factors (the need for engagement and treatment adherence, and the achievement of adherence and improved insight) remain the most important considerations in initiating and discharging a CTO. Clinical implications Given the accumulating evidence from research and clinical practice that CTOs do not improve outcomes, it is concerning that psychiatrists' opinions have not altered in response, particularly given the implications for patient care. PMID:27280030

  20. The effects of ACTH- and vasopressin-analogues on CO2-induced retrograde amnesia in rats

    NARCIS (Netherlands)

    Rigter, H.; Riezen, H. van; Wied, D. de

    1974-01-01

    Amnesia for a one-trial step-through passive avoidance response was induced in rats by application of CO2 until respiratory arrest occurred. The ACTH-analogue ACTH4–10 alleviated the amnesia when administered 1 hr prior to the retrieval test but not when given 1 hr prior to the acquisition trial. Th

  1. Effect of angiotensin II, catecholamines and glucocorticoid on corticotropin releasing factor (CRF-induced ACTH release in pituitary cell cultures.

    Directory of Open Access Journals (Sweden)

    Murakami,Kazuharu

    1984-08-01

    Full Text Available The effects of angiotensin II, catecholamines and glucocorticoid on CRF-induced ACTH release were examined using rat anterior pituitary cells in monolayer culture. Synthetic ovine CRF induced a significant ACTH release in this system. Angiotensin II produced an additive effect on CRF-induced ACTH release. The ACTH releasing activity of CRF was potentiated by epinephrine and norepinephrine. Dopamine itself at 0.03-30 ng/ml did not show any significant effect on ACTH release, but it inhibited CRF-induced ACTH release. Corticosterone at 10(-7 and 10(-6M inhibited CRF-induced ACTH release. These results indicate that angiotensin II, catecholamines and glucocorticoid modulate ACTH release at the pituitary level.

  2. Effects of repeated quetiapine treatment on conditioned avoidance responding in rats.

    Science.gov (United States)

    Gao, Jun; Feng, Min; Swalve, Natashia; Davis, Collin; Sui, Nan; Li, Ming

    2015-12-15

    The present study characterized the behavioral mechanisms of avoidance-disruptive effect of quetiapine in the conditioned avoidance response test under two behavioral testing (2 warning signals vs. 1 warning signal) and two drug administration conditions (subcutaneous vs. intravenous). In Experiments 1 and 2, well-trained adult male Sprague-Dawley rats were tested under the subcutaneous (s.c.) quetiapine treatment (5.0, 15.0, 25.0, 50.0mg/kg) for 7 days in a novel procedure consisting of two conditioned stimuli (CS) (white noise serving as CS1 and pure tone as CS2). Only the highest dose (50.0mg/kg) produced a persistent suppression of the avoidance response without impairing the escape response. The magnitude of suppression of the CS1 avoidance was similar to that of CS2 avoidance. No significant group difference was found in the quetiapine (15.0mg/kg, s.c.) challenge test, indicating a lack of a long-term quetiapine effect. In Experiment 3, well-trained rats were tested under the intravenous (i.v.) quetiapine treatment (3.0, 9.0, 15.0mg/kg) for 5 days and challenged with quetiapine (6.0mg/kg, i.v. followed by 9.0mg/kg, s.c.). Only the white noise was used as the CS. Similar to what was being observed in Experiments 1 and 2, intravenously administered quetiapine dose-dependently suppressed avoidance responding during the drug test days, but did not alter drug sensitivity in the challenge days. Thus, quetiapine does not appear to show a preferential inhibition of the avoidance response to a less salient stimulus; and prior quetiapine treatment (s.c. and i.v.) does not cause a sensitization or tolerance to quetiapine.

  3. Repeated Treatments with Chitosan in Combination with Antibiotics Completely Eradicate Uropathogenic Escherichia coli From Infected Mouse Urinary Bladders.

    Science.gov (United States)

    Erman, Andreja; Hergouth, Veronika Križan; Blango, Matthew G; Kos, Mojca Kerec; Mulvey, Matthew A; Veranic, Peter

    2017-08-01

    Uropathogenic Escherichia coli (UPEC), the primary causative agents of urinary tract infections, colonize and invade the epithelial cells of the bladder urothelium. Infection of immature urothelial cells can result in the formation of persistent intracellular reservoirs that are refractory to antibiotic treatments. Previously, we defined a novel therapeutic strategy that used the bladder cell exfoliant chitosan to deplete UPEC reservoirs. However, although a single treatment of chitosan followed by ciprofloxacin administration had a marked effect on reducing UPEC titers within the bladder, this treatment failed to prevent relapsing bacteriuria. We show here that repeated use of chitosan in conjunction with the antibiotic ciprofloxacin completely eradicates UPEC from the urinary tract and prevents the development of relapsing bouts of bacteriuria. In addition, microscopy revealed rapid restoration of bladder integrity following chitosan treatment, indicating that chitosan can be used to effectively combat recalcitrant bladder infections without causing lasting harm to the urothelium. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  4. Hypothermic and antipyretic effects of ACTH (1-24) and alpha-melanotropin in guinea-pigs

    Science.gov (United States)

    Kandasamy, S. B.; Williams, B. A.

    1984-01-01

    Intracerebroventricular administration of adrenocorticotropin (ACTH 1-24) and alpha-melanotropin (alpha-MSH), peptides which occur naturally in brain induced dose-related hypothermia in guinea-pigs at room temperature (21 C) and also produced greater hypothermia at low (10 C) ambient temperature. However, when the experiments were repeated in a warm (30 C) environment, no effect on body temperature was observed. These results indicate that the peptides did not reduce the central set-point of temperature control. The hypothermia induced by ACTH and alpha-MSH was not mediated via histamine H1- or H2-receptors and serotonin since the H1-receptor antagonist, mepyramine, the H2-receptor antagonist, cimetidine, and the serotonin antagonist, methysergide, had no antagonistic effects. The peptides were antipyretic since they reduced pyrogen-induced-fever and hyperthermia due to prostaglandin E2, norepinephrine and dibutyryl cAMP, at a dose which did not affect normal body temperature. The powerful central effects of these peptides on normal body temperature, fever and hyperthermia, together with their presence of the brain regions important to temperature control, suggest that they participate in thermoregulation.

  5. In vitro kinetics of amiodarone and its major metabolite in two human liver cell models after acute and repeated treatments.

    Science.gov (United States)

    Pomponio, Giuliana; Savary, Camille C; Parmentier, Céline; Bois, Frederic; Guillouzo, André; Romanelli, Luca; Richert, Lysiane; Di Consiglio, Emma; Testai, Emanuela

    2015-12-25

    The limited value of in vitro toxicity data for the in vivo extrapolation has been often attributed to the lack of kinetic data. Here the in vitro kinetics of amiodarone (AMI) and its mono-N-desethyl (MDEA) metabolite was determined and modelled in primary human hepatocytes (PHH) and HepaRG cells, after single and repeated administration of clinically relevant concentrations. AMI bioavailability was influenced by adsorption to the plastic and the presence of protein in the medium (e.g. 10% serum protein reduced the uptake by half in HepaRG cells). The cell uptake was quick (within 3h), AMI metabolism was efficient and a dynamic equilibrium was reached in about a week after multiple dosing. In HepaRG cells the metabolic clearance was higher than in PHH and increased over time, as well as CYP3A4. The interindividual variability in MDEA production in PHHs was not proportional to the differences in CYP3A4 activities, suggesting the involvement of other CYPs and/or AMI-related CYP inhibition. After repeated treatment AMI showed a slight potential for bioaccumulation, whereas much higher intracellular MDEA levels accumulated over time, especially in the HepaRG cells, associated with occurrence of phospholipidosis. The knowledge of in vitro biokinetics is important to transform an actual in vitro concentration-effect into an in vivo dose-effect relationship by using appropriate modelling, thus improving the in vitro-to-in vivo extrapolation.

  6. Cysteine Metabolism and Oxidative Processes in the Rat Liver and Kidney after Acute and Repeated Cocaine Treatment.

    Directory of Open Access Journals (Sweden)

    Danuta Kowalczyk-Pachel

    Full Text Available The role of cocaine in modulating the metabolism of sulfur-containing compounds in the peripheral tissues is poorly understood. In the present study we addressed the question about the effects of acute and repeated (5 days cocaine (10 mg/kg i.p. administration on the total cysteine (Cys metabolism and on the oxidative processes in the rat liver and kidney. The whole pool of sulfane sulfur, its bound fraction and hydrogen sulfide (H2S were considered as markers of anaerobic Cys metabolism while the sulfate as a measure of its aerobic metabolism. The total-, non-protein- and protein- SH group levels were assayed as indicators of the redox status of thiols. Additionally, the activities of enzymes involved in H2S formation (cystathionine γ-lyase, CSE; 3-mercaptopyruvate sulfurtransferase, 3-MST and GSH metabolism (γ-glutamyl transpeptidase, γ-GT; glutathione S-transferase, GST were determined. Finally, we assayed the concentrations of reactive oxygen species (ROS and malondialdehyde (MDA as markers of oxidative stress and lipid peroxidation, respectively. In the liver, acute cocaine treatment, did not change concentrations of the whole pool of sulfane sulfur, its bound fraction, H2S or sulfate but markedly decreased levels of non-protein SH groups (NPSH, ROS and GST activity while γ-GT was unaffected. In the kidney, acute cocaine significantly increased concentration of the whole pool of sulfane sulfur, reduced the content of its bound fraction but H2S, sulfate and NPSH levels were unchanged while ROS and activities of GST and γ-GT were reduced. Acute cocaine enhanced activity of the CSE and 3-MST in the liver and kidney, respectively. Repeatedly administered cocaine enhanced the whole pool of sulfane sulfur and reduced H2S level simultaneously increasing sulfate content both in the liver and kidney. After repeated cocaine, a significant decrease in ROS was still observed in the liver while in the kidney, despite unchanged ROS content, a marked

  7. Cysteine Metabolism and Oxidative Processes in the Rat Liver and Kidney after Acute and Repeated Cocaine Treatment.

    Science.gov (United States)

    Kowalczyk-Pachel, Danuta; Iciek, Małgorzata; Wydra, Karolina; Nowak, Ewa; Górny, Magdalena; Filip, Małgorzata; Włodek, Lidia; Lorenc-Koci, Elżbieta

    2016-01-01

    The role of cocaine in modulating the metabolism of sulfur-containing compounds in the peripheral tissues is poorly understood. In the present study we addressed the question about the effects of acute and repeated (5 days) cocaine (10 mg/kg i.p.) administration on the total cysteine (Cys) metabolism and on the oxidative processes in the rat liver and kidney. The whole pool of sulfane sulfur, its bound fraction and hydrogen sulfide (H2S) were considered as markers of anaerobic Cys metabolism while the sulfate as a measure of its aerobic metabolism. The total-, non-protein- and protein- SH group levels were assayed as indicators of the redox status of thiols. Additionally, the activities of enzymes involved in H2S formation (cystathionine γ-lyase, CSE; 3-mercaptopyruvate sulfurtransferase, 3-MST) and GSH metabolism (γ-glutamyl transpeptidase, γ-GT; glutathione S-transferase, GST) were determined. Finally, we assayed the concentrations of reactive oxygen species (ROS) and malondialdehyde (MDA) as markers of oxidative stress and lipid peroxidation, respectively. In the liver, acute cocaine treatment, did not change concentrations of the whole pool of sulfane sulfur, its bound fraction, H2S or sulfate but markedly decreased levels of non-protein SH groups (NPSH), ROS and GST activity while γ-GT was unaffected. In the kidney, acute cocaine significantly increased concentration of the whole pool of sulfane sulfur, reduced the content of its bound fraction but H2S, sulfate and NPSH levels were unchanged while ROS and activities of GST and γ-GT were reduced. Acute cocaine enhanced activity of the CSE and 3-MST in the liver and kidney, respectively. Repeatedly administered cocaine enhanced the whole pool of sulfane sulfur and reduced H2S level simultaneously increasing sulfate content both in the liver and kidney. After repeated cocaine, a significant decrease in ROS was still observed in the liver while in the kidney, despite unchanged ROS content, a marked increase

  8. Treatment and functional result of desmoplastic fibroma with repeated recurrences in the forearm: A case report

    Science.gov (United States)

    RUI, JING; GUAN, WENJIE; GU, YUDONG; LAO, JIE

    2016-01-01

    Desmoplastic fibroma, alternatively known as aggressive fibromatosis or desmoid tumors, occurs in the form of benign locally aggressive tumors that possess a high rate of recurrence. The forearm bones are rarely involved. The current study presents a case of desmoplastic fibroma in the distal forearm of a 23-year-old man. The tumor was widely resected, and the bone defect was reconstructed using an autologous vascularized fibular graft during the resection procedure. The patient experienced recurrence three times and underwent four resections during the subsequent 3 years following the initial resection. After 10 years of follow-up, the patient's functional recovery remains positive. Despite the implication that surgical resection may be involved in the development of aggressive fibromatosis, surgical wide local excision and functional reconstruction were recommended for the treatment of the present patient. PMID:26893769

  9. Repeated Insulin-like Growth Factor 1 (IGF1 treatment in a patient with Rett Syndrome: a single case study

    Directory of Open Access Journals (Sweden)

    Giorgio ePini

    2014-06-01

    Full Text Available Rett syndrome (RTT is a devastating neurodevelopmental disorder that has no cure. Patients show regression of acquired skills, motor and speech impairment, cardio-respiratory distress, microcephaly and stereotyped hand movements. The majority of RTT patients display mutations in the gene that codes for the Methyl-CpG binding protein 2 (MeCP2, which is involved in the development of the central nervous system, especially synaptic and circuit maturation. Thus, agents that promote brain development and synaptic function are good candidates for ameliorating the symptoms of RTT. In particular, Insulin-like growth Factor 1 (IGF1 and its active peptide (1-3IGF1 cross the Blood Brain Barrier, and therefore are ideal treatments for RTT Indeed, both (1-3IGF1 and IGF1 treatment significantly ameliorates RTT symptoms in a mouse model of the disease In a previous study we established that IGF1 is safe and well tolerated on Rett patients. In this open label clinical case study, we assess the safety and tolerability of IGF1 administration in two cycles of the treatment. Before and after each cycle we monitored the clinical and blood parameters, autonomic function and social and cognitive abilities, and we found that IGF1 was well tolerated each time and did not induce any side effect, nor it interfered with the other treatments that the patient was undergoing. We noticed a moderate improvement in the cognitive, social and autonomic abilities of the patient after each cycle but the benefits were not retained between the two cycles, consistent with the preclinical observation that treatments for RTT should be administered through life. We find that repeated IGF1 treatment is safe and well tolerated in Rett patients but observed effects are not retained between cycles. These results have applications to other pathologies considering that IGF1 has been shown to be effective in other disorders of the autism spectrum.

  10. Repeated insulin-like growth factor 1 treatment in a patient with rett syndrome: a single case study.

    Science.gov (United States)

    Pini, Giorgio; Scusa, M Flora; Benincasa, Alberto; Bottiglioni, Ilaria; Congiu, Laura; Vadhatpour, Cyrus; Romanelli, Anna Maria; Gemo, Ilaria; Puccetti, Chetti; McNamara, Rachel; O'Leary, Seán; Corvin, Aiden; Gill, Michael; Tropea, Daniela

    2014-01-01

    Rett syndrome (RTT) is a devastating neurodevelopmental disorder that has no cure. Patients show regression of acquired skills, motor, and speech impairment, cardio-respiratory distress, microcephaly, and stereotyped hand movements. The majority of RTT patients display mutations in the gene that codes for the Methyl-CpG binding protein 2 (MeCP2), which is involved in the development of the central nervous system, especially synaptic and circuit maturation. Thus, agents that promote brain development and synaptic function are good candidates for ameliorating the symptoms of RTT. In particular, insulin-like growth factor 1 (IGF1) and its active peptide (1-3) IGF1 cross the Blood Brain Barrier, and therefore are ideal treatments for RTT Indeed, both (1-3) IGF1 and IGF1 treatment significantly ameliorates RTT symptoms in a mouse model of the disease In a previous study, we established that IGF1 is safe and well tolerated on Rett patients. In this open label clinical case study, we assess the safety and tolerability of IGF1 administration in two cycles of the treatment. Before and after each cycle, we monitored the clinical and blood parameters, autonomic function, and social and cognitive abilities, and we found that IGF1 was well tolerated each time and did not induce any side effect, nor it interfered with the other treatments that the patient was undergoing. We noticed a moderate improvement in the cognitive, social, and autonomic abilities of the patient after each cycle but the benefits were not retained between the two cycles, consistent with the pre-clinical observation that treatments for RTT should be administered through life. We find that repeated IGF1 treatment is safe and well tolerated in Rett patients but observed effects are not retained between cycles. These results have applications to other pathologies considering that IGF1 has been shown to be effective in other disorders of the autism spectrum.

  11. The inhibitory effect of ACTH 1–10 on extinction of a conditioned avoidance response: Its independence of thyroid function

    NARCIS (Netherlands)

    Wied, D. de; Pirie, Gail

    1968-01-01

    The effect of the ACTH analogue ACTH 1–10 was studied on the rate of extinction of a pole jumping avoidance response in thyroidectomized rats with or without replacement therapy with 1-thyroxin. ACTH 1–10 appeared to delay the rate of extinction of the CAR in thyroidectomized rats in a similar way a

  12. Optimising glucocorticoid replacement therapy in severely adrenocorticotropin (ACTH) deficient hypopituitary male patients.

    LENUS (Irish Health Repository)

    Behan, Lucy-Ann

    2011-04-18

    Context:  The optimal replacement regimen of hydrocortisone in adults with severe ACTH deficiency remains unknown. Management strategies vary from treatment with 15mg to 30mg or higher in daily divided doses, reflecting the paucity of prospective data on the adequacy of different glucocorticoid regimens. Objective:  Primarily to define the hydrocortisone regimen which results in a 24hour cortisol profile that most closely resembles that of healthy controls and secondarily to assess the impact on quality of life (QoL). Design:  10 male hypopituitary patients with severe ACTH deficiency (basal cortisol <100nM and peak response to stimulation <400nM) were enrolled in a prospective, randomised, crossover study of 3 hydrocortisone dose regimens. Following 6 weeks of each regimen patients underwent 24hour serum cortisol sampling and QoL assessment with the Short Form 36 and the Nottingham Health Profile questionnaires. Free cortisol was calculated using Coolen\\'s equation. All results were compared to those of healthy, matched controls. Results:  CBG was significantly lower across all dose regimens compared to controls (p<0.05). The lower dose regimen C(10mg mane\\/5mg tarde) produced a 24hour free cortisol profile which most closely resembled that of controls. Both regimen A(20mg mane\\/10mg tarde) and B(10mg mane\\/10mg tarde) produced supraphysiological post-absorption peaks. There was no significant difference in QoL in patients between the three regimens, however energy level was significantly lower across all dose regimens compared to controls (p<0.001). Conclusions:  The lower dose of HC(10mg\\/5mg) produces a more physiological cortisol profile, without compromising quality of life, compared to higher doses still used in clinical practice. This may have important implications in these patients, known to have excess cardiovascular mortality.

  13. Is it important to repeat the positioning maneuver after the treatment for benign paroxysmal positional vertigo?

    Directory of Open Access Journals (Sweden)

    Alexandra Kolontai de Sousa Oliveira

    2015-04-01

    Full Text Available INTRODUCTION: Benign paroxysmal positional vertigo (BPPV is the most common cause of peripheral vestibular dysfunction.OBJECTIVE: To assess whether the performance of the Dix-Hallpike maneuver after the Epley positioning maneuver has prognostic value in the evolution of unilateral ductolithiasis of posterior semicircular canal.METHODS: A prospective cohort study in monitored patients at otoneurology ambulatory with a diagnosis of BPPV; they were submitted to the therapeutic maneuver and then to a retest in order to evaluate the treatment effectiveness; all cases were reassessed one week later and the retest prognostic value was evaluated.RESULTS: A sample of 64 patients which 47 belonging to negative retest group and 17 belonging to positive retest. Performed the maneuver in all patients, the retest presented 51.85% sensitivity, 91.89% specificity, 82.35% positive predictive value and 72.34% negative predictive value.CONCLUSION: The study shows that doing the retest after repositioning maneuver of particles in BPPV is effectual, since it has high specificity.

  14. Repeated BCG treatment of mouse bladder selectively stimulates small GTPases and HLA antigens and inhibits single-spanning uroplakins

    Directory of Open Access Journals (Sweden)

    O'Donnell Michael A

    2007-11-01

    Full Text Available Abstract Background Despite being a mainstay for treating superficial bladder carcinoma and a promising agent for interstitial cystitis, the precise mechanism of Bacillus Calmette-Guerin (BCG remains poorly understood. It is particularly unclear whether BCG is capable of altering gene expression beyond its well-recognized pro-inflammatory effects and how this relates to its therapeutic efficacy. The objective of this study was to determine differentially expressed genes in the mouse bladder following repeated intravesical BCG therapy. Methods Mice were transurethrally instilled with BCG or pyrogen-free on days 1, 7, 14, and 21. Seven days after the last instillation, urothelia along with the submucosa was removed and amplified ds-DNA was prepared from control- and BCG-treated bladder mucosa and used to generate suppression subtractive hybridization (SSH. Plasmids from control- and BCG-specific differentially expressed clones and confirmed by Virtual Northern were then purified and the inserts were sequenced and annotated. Finally, chromatin immune precipitation combined with real-time polymerase chain reaction assay (ChIP/Q-PCR was used to validate SSH-selected transcripts. Results Repeated intravesical BCG treatment induced an up regulation of genes associated with antigen presentation (B2M, HLA-A, HLA-DQA1, HLA-DQB2, HLA-E, HLA-G, IGHG, and IGH and representatives of two IFNγ-induced small GTPase families: the GBPs (GBP1, GBP2, and GBP5 and the p47GTPases (IIGTP1, IIGTP2, and TGTP. Genes expressed in saline-treated bladders but down-regulated by BCG included: the single-spanning uroplakins (UPK3a and UPK2, SPRR2G, GSTM5, and RSP 19. Conclusion Here we introduced a hypothesis-generator approach to determine key genes involved in the urothelium/sumbmucosa responses to BCG therapy. Urinary bladder responds to repeated BCG treatment by up-regulating not only antigen presentation-related genes, but also GBP and p47 small GTPases, both potentially

  15. Repeated cisplatin treatment can lead to a multiresistant tumor cell population with stem cell features and sensitivity to 3-bromopyruvate.

    Science.gov (United States)

    Wintzell, My; Löfstedt, Lina; Johansson, Joel; Pedersen, Anne B; Fuxe, Jonas; Shoshan, Maria

    2012-12-01

    Cisplatin is used in treatment of several types of cancer, including epithelial ovarian carcinoma (EOC). In order to mimic clinical treatment and to investigate longterm effects of cisplatin in surviving cancer cells, two EOC cell lines were repeatedly treated with low doses. In the SKOV-3 cell line originating from malignant ascites, but not in A2780 cells from a primary tumor, this led to emergence of a stable population (SKOV-3-R) which in the absence of cisplatin showed increased motility, epithelial-mesenchymal transition (EMT) and expression of cancer stem cell markers CD117, CD44 and ALDH1. Accordingly, the cells formed self-renewing spheres in serum-free stem cell medium. Despite upregulation of mitochondrial mass and cytochrome c, and no upregulation of Bcl-2/Bcl-xL, SKOV-3-R were multiresistant to antineoplastic drugs. Cancer stem cells, or tumor-initiating cells (TICs) are highly chemoresistant and are believed to cause relapse into disseminated and resistant EOC. Our second aim was therefore to target resistance in these TIC-like cells. Resistance could be correlated with upregulation of hexokinase-II and VDAC, which are known to form a survival-promoting mitochondrial complex. The cells were thus sensitive to 3-bromopyruvate, which dissociates hexokinase-II from this complex, and were particularly sensitive to combination treatment with cisplatin at doses down to 0.1 x IC 50. 3-bromopyruvate might thus be of use in targeting the especially aggressive TIC populations.

  16. Impact monitoring of the national scale up of zinc treatment for childhood diarrhea in Bangladesh: repeat ecologic surveys.

    Directory of Open Access Journals (Sweden)

    Charles P Larson

    2009-11-01

    Full Text Available BACKGROUND: Zinc treatment of childhood diarrhea has the potential to save 400,000 under-five lives per year in lesser developed countries. In 2004 the World Health Organization (WHO/UNICEF revised their clinical management of childhood diarrhea guidelines to include zinc. The aim of this study was to monitor the impact of the first national campaign to scale up zinc treatment of childhood diarrhea in Bangladesh. METHODS/FINDINGS: Between September 2006 to October 2008 seven repeated ecologic surveys were carried out in four representative population strata: mega-city urban slum and urban nonslum, municipal, and rural. Households of approximately 3,200 children with an active or recent case of diarrhea were enrolled in each survey round. Caretaker awareness of zinc as a treatment for childhood diarrhea by 10 mo following the mass media launch was attained in 90%, 74%, 66%, and 50% of urban nonslum, municipal, urban slum, and rural populations, respectively. By 23 mo into the campaign, approximately 25% of urban nonslum, 20% of municipal and urban slum, and 10% of rural under-five children were receiving zinc for the treatment of diarrhea. The scale-up campaign had no adverse effect on the use of oral rehydration salt (ORS. CONCLUSIONS: Long-term monitoring of scale-up programs identifies important gaps in coverage and provides the information necessary to document that intended outcomes are being attained and unintended consequences avoided. The scale-up of zinc treatment of childhood diarrhea rapidly attained widespread awareness, but actual use has lagged behind. Disparities in zinc coverage favoring higher income, urban households were identified, but these were gradually diminished over the two years of follow-up monitoring. The scale up campaign has not had any adverse effect on the use of ORS. Please see later in the article for the Editors' Summary.

  17. Immunohistochemical detection of ACTH and MSH cells in the hypophysis of the hermaphroditic teleost, Diplodus sargus.

    Science.gov (United States)

    Ferrandino, I; Pica, A; Grimaldi, M C

    2000-01-01

    Hypophyseal ACTH and MSH cells were immunohistochemically characterised in the teleost fish, Diplodus sargus, using anti-ACTH (1-24) and anti alpha-MSH polyclonal antisera. ACTH cells were found both in the pars distalis and in the pars intermedia. In the former region, they appeared small, round-shaped and clustered; in the latter, they were either small or large and elongated. Moreover, a few ACTH-immunoreactive cells resembling microglia were present in the neurohypophysis. Conversely, MSH cells were found only in the pars intermedia, and were similar to the larger ACTH cells of the same region. In the pars intermedia, co-localisation of ACTH and MSH immunoreactivity in the same cell was revealed by double immunostaining, though the two hormones were also observed in distinct cell types. The distribution of ACTH cells appeared quite uniform, without any marked difference between the specimens tested. Conversely, MSH cell amount varied according to the stage of the sexual cycle of this teleost fish, which is characterised by protandrous hermaphroditism. In fact, a lower amount of MSH cells were observed in females, whereas no significant difference was found between immature and male specimens.

  18. Immunohistochemical detection of acth and msh cells in the hypophysis of the hermaphroditic teleost, Diplodus sargus

    Directory of Open Access Journals (Sweden)

    M Consiglio Grimaldi

    2009-12-01

    Full Text Available Hypophyseal ACTH and MSH cells were immunohistochemically characterised in the teleost fish, Diplodus sargus, using anti-ACTH (1-24 and anti a-MSH polyclonal antisera. ACTH cells were found both in the pars distalis and in the pars intermedia. In the former region, they appeared small, round-shaped and clustered; in the latter, they were either small or large and elongated. Moreover, a few ACTH-immunoreactive cells resembling microglia were present in the neurohypophysis. Conversely, MSH cells were found only in the pars intermedia, and were similar to the larger ACTH cells of the same region. In the pars intermedia, co-localisation of ACTH and MSH immunoreactivity in the same cell was revealed by double immunostaining, though the two hormones were also observed in distinct cell types. The distribution of ACTH cells appeared quite uniform, without any marked difference between the specimens tested. Conversely, MSH cell amount varied according to the stage of the sexual cycle of this teleost fish, which is characterised by protandrous hermaphroditism. In fact, a lower amount of MSH cells were observed in females, whereas no significant difference was found between immature and male specimens.

  19. Repeated quick hot-and-chilling treatments for the inactivation of Escherichia coli O157:H7 in mung bean and radish seeds.

    Science.gov (United States)

    Bari, Md Latiful; Sugiyama, Jun; Kawamoto, Shinnichi

    2009-01-01

    The majority of the seed sprout-related outbreaks have been associated with Escherichia coli O157:H7. Therefore, it is necessary to find an effective method to inactivate these organisms on the seeds prior to sprouting. This study was conducted to assess the effectiveness of repeated quick hot-and-chilling treatments with various chemicals to inactivate E. coli O157:H7 populations inoculated onto mung bean and radish seeds intended for sprout production and to determine the effect of these treatments on seed germination. The treatment time was 20 sec for quick hot and 20 sec for quick chilling in one repeat. Likewise up to five repeats were done throughout the experiments. The chemicals used for this study were electrolyzed acidic (EO) water, phytic acid (0.05%), oxalic acid (3%), surfcera(R), and alpha-torino water(R), and distilled water was used as control. The quick hot treatment was done with 75 degrees C, 70 degrees C, and 60 degrees C, and the chilling temperature was 0 degrees C. The treated seeds were then assessed for the efficacy of this treatment in reducing populations of the pathogens and the effects of repeated quick hot-and-chilling treatments on germination yield. It was found that repeating treatment at 75 degrees C for two or three repeats with phytic acid and oxalic acid could reduce 4.38-log colony-forming unit (CFU)/g of E. coli O157:H7 in mung bean seeds. EO water and distilled water were found equally effective at 75 degrees C for four or five repeats to inactivate E. coli O157:H7 in mung bean seeds. However, alpha-torino water(R) and surfcera(R) were not found effective in comparison to other sanitizers used in this experiment. Irrespective of sanitizer used, the germination yield of the mung bean seed was not affected significantly. On the other hand, distilled water, EO water, and alpha-torino water(R) at 75 degrees C for five repeats were found effective in reducing 5.80-log CFU/g of E. coli O157:H7 in radish seeds; however, the

  20. Effect of repeated sauna treatment on exercise tolerance and endothelial function in patients with chronic heart failure.

    Science.gov (United States)

    Ohori, Takashi; Nozawa, Takashi; Ihori, Hiroyuki; Shida, Takuya; Sobajima, Mitsuo; Matsuki, Akira; Yasumura, Satoshi; Inoue, Hiroshi

    2012-01-01

    Repeated sauna treatment, known as Waon therapy, has been shown to improve cardiac function as well as exercise tolerance in patients with chronic heart failure. However, the underlying mechanisms of this therapy regarding these improvements remain to be elucidated. Forty-one patients with chronic heart failure (mean age 68.3 ± 13.5 years old) underwent Waon therapy 5 times a week for 3 weeks. Before and after treatment, a number of assessments were performed in all subjects: 6-minute walk test, echocardiography, determination of neurohumoral factors and number of circulating CD34(+) cells, and a flow-mediated dilation (FMD) test of endothelial function. Cardiopulmonary exercise testing was also performed in 20 patients. Waon therapy increased the left ventricular ejection fraction (from 30.4 ± 12.6% to 32.5% ± 12.8%, p = 0.023) and reduced plasma levels of norepinephrine (from 400 ± 258 to 300 ± 187 pg/ml, p = 0.015) and brain natriuretic peptide (from 550 ± 510 to 416 ± 431 pg/ml, p = 0.035). Waon therapy increased the 6-minute walk distance (from 337 ± 120 to 379 ± 126 m, p sauna therapy in patients with chronic heart failure improves exercise tolerance in association with improvement in endothelial function.

  1. Effect of adrenalectomy or long term cortisol or adrenocorticotropin (ACTH)-releasing factor infusion on the concentration and molecular weight distribution of ACTH in fetal sheep plasma.

    Science.gov (United States)

    Ozolins, I Z; Antolovich, G C; Browne, C A; Perry, R A; Robinson, P M; Silver, M; McMillen, I C

    1991-10-01

    It is unclear whether the maturation of corticotrophs from the fetal to the adult type in the fetal sheep pituitary in late gestation is associated with changes in the sensitivity of the fetal pituitary to corticotrophic secretagogues and in the form of ACTH-containing peptides (IR-ACTH) secreted into the circulation. The maturation of the pituitary corticotroph population is known to be accelerated by intrafetal cortisol infusion and delayed by bilateral fetal adrenalectomy. We have therefore investigated the mol wt profile of IR-ACTH present in fetal sheep plasma from 110 days gestation until term (147 +/- 3 days) and determined whether intrafetal cortisol infusion between 105-117 days (2.5 mg cortisol/day), or bilateral fetal adrenalectomy can alter the mol wt profile of IR-ACTH in fetal sheep plasma. We have also investigated whether prior exposure to cortisol alters the subsequent responsiveness of the fetal pituitary to a long term infusion of ovine (o) CRF (10 micrograms oCRF/day). In the control group, the proportion of IR-ACTH which eluted in the low-mol wt (LMW) range (i.e. less than 12K) was significantly higher between 121-125 days (43.9 +/- 4.2%) than between 126-139 days (26.8 +/- 9.3%) but not different to that after 140 days gestation (29.9 +/- 5.5%). Between 110-117 days, cortisol infusion had no effect on the proportion of IR-ACTH in the LMW range (43.9 +/- 5.7%, saline infused; 44.1 +/- 2.4%, cortisol infused). Between 121-125 days, the proportion of IR-ACTH in the LMW range in the CRF-infused groups (with or without prior exposure to cortisol) was significantly lower (27.4 +/- 2.1%) than in the saline-infused control group. In contrast, after fetal adrenalectomy, the proportion of IR-ACTH in the LMW range between 126-139 days was significantly higher (48.0 +/- 6.7%) than in intact control animals (23.8 +/- 3.5%). We conclude that the change in the mol wt profile of IR-ACTH in fetal plasma after 125 days may be a consequence of changes in the

  2. Hexanucleotide Repeat Expansion in C9ORF72 Is Not Detected in the Treatment-Resistant Schizophrenia Patients of Chinese Han.

    Science.gov (United States)

    Xu, Xijia; Xie, Shiping; Shi, Xiaomeng; Lv, Jie; Tang, Xiaowei; Wang, Xiaolan; Lu, Shuiping; Wang, Mingzhong; Zhang, Xiaobing; Sun, Jing; Yao, Hui

    2015-01-01

    Hexanucleotide (GGGGCC) repeat expansion in C9ORF72 (HRE) causes frontotemporal lobar degeneration, frontotemporal dementia-amyotrophic lateral sclerosis, and amyotrophic lateral sclerosis. HRE was also seen in the genomes of patients suffering from several other degenerative diseases. However, whether it is present in the treatment-resistant schizophrenia patients remains unknown. Genotyping 386 patients suffering from treatment-resistant schizophrenia using the method of Repeat-Primed PCR, we reported here that no HRE was detected in the patients of Chinese Han.

  3. Budd-Chiari syndrome and heparin-induced thrombocytopenia in polycythemia vera: Successful treatment with repeated TIPS and interferon alpha

    Directory of Open Access Journals (Sweden)

    Akoum Riad

    2009-01-01

    Full Text Available Polycythemia vera (PV is a common cause of Budd-Chiari syndrome (BCS and portal vein thrombosis (PVT. The postpartum period is a precipitating cofactor. An additional heparin-induced thrombocytopenia/thrombosis (HIT/T leads to a life-threatening condition in which transjugular intrahepatic portosystemic shunting (TIPS seems to be the only life-saving procedure. We describe the case of a subacute BCS and PVT in the late postpartum period. The diagnosis was established using CT scan, MRI, and Doppler ultrasonography of abdominal vessels and the laboratory findings were compatible with PV. After a successful creation of TIPS, a HIT/T worsened the hemorrhagic and thrombotic picture. TIPS procedure was successfully repeated and heparin was replaced with Fondaparinux and then vitamin K antagonist. The treatment with interferon alpha-2A, started after the normalization of liver functions, resulted in a complete remission within 6 months. The JAK2 V617F mutation clone remained undetectable after 2 years′ follow-up.

  4. Aging of the rat adrenocortical cell: response to ACTH and cyclic AMP in vitro.

    Science.gov (United States)

    Malamed, S; Carsia, R V

    1983-03-01

    To study intrinsic age-related changes in adrenocortical steroid production, cells isolated from rats of different ages (3 to 24 months) were used. Acute (2 hour) corticosterone production in response to stimulation by adrenocorticotrophic hormone (ACTH) and adenosine 3':5'-cyclic monophosphate (cAMP) was measured by radioimmunoassay. With age, adrenocortical cells lose much of their ability to produce corticosterone in the absence or presence of ACTH or cAMP. The loss is progressive from 6 to 24 months of age. Analysis of the data suggests that from 6 to 12 months, an intracellular steroidogenic lesion develops; in addition there may be a loss in ACTH receptors on the plasma membrane. After 12 months these defects increase and are accompanied by a decrease in receptor sensitivity to ACTH.

  5. Direct activating effects of adrenocorticotropic hormone (ACTH) on brown adipose tissue are attenuated by corticosterone.

    Science.gov (United States)

    van den Beukel, Johanna C; Grefhorst, Aldo; Quarta, Carmelo; Steenbergen, Jacobie; Mastroberardino, Pier G; Lombès, Marc; Delhanty, Patric J; Mazza, Roberta; Pagotto, Uberto; van der Lely, Aart Jan; Themmen, Axel P N

    2014-11-01

    Brown adipose tissue (BAT) and brown-like cells in white adipose tissue (WAT) can dissipate energy through thermogenesis, a process mediated by uncoupling protein 1 (UCP1). We investigated whether stress hormones ACTH and corticosterone contribute to BAT activation and browning of WAT. ACTH and corticosterone were studied in male mice exposed to 4 or 23°C for 24 h. Direct effects were studied in T37i mouse brown adipocytes and primary cultured murine BAT and inguinal WAT (iWAT) cells. In vivo effects were studied using (18)F-deoxyglucose positron emission tomography. Cold exposure doubled serum ACTH concentrations (P=0.03) and fecal corticosterone excretion (P=0.008). In T37i cells, ACTH dose-dependently increased Ucp1 mRNA (EC50=1.8 nM) but also induced Ucp1 protein content 88% (P=0.02), glycerol release 32% (P=0.03) and uncoupled respiration 40% (P=0.003). In cultured BAT and iWAT, ACTH elevated Ucp1 mRNA by 3-fold (P=0.03) and 3.7-fold (P=0.01), respectively. In T37i cells, corticosterone prevented induction of Ucp1 mRNA and Ucp1 protein by both ACTH and norepinephrine in a glucocorticoid receptor (GR)-dependent fashion. ACTH and GR antagonist RU486 independently doubled BAT (18)F-deoxyglucose uptake (P=0.0003 and P=0.004, respectively) in vivo. Our results show that ACTH activates BAT and browning of WAT while corticosterone counteracts this. © FASEB.

  6. Adrenocortical response to low-dose ACTH test in female patients with rheumatoid arthritis.

    Science.gov (United States)

    Radikova, Zofia; Rovensky, Jozef; Vlcek, Miroslav; Penesova, Adela; Kerlik, Jana; Vigas, Milan; Imrich, Richard

    2008-12-01

    Alterations in adrenal steroid production have been suggested in females with rheumatoid arthritis (RA). The aim of the present study was to assess adrenocortical function in RA females. We examined 11 female RA patients (RA: age 30 +/- 2 years, BMI 21.0 +/- 0.7 kg/m(2)) and 10 matched healthy controls (C: age 31 +/- 1 years, BMI 21.6 +/- 0.6 kg/m(2)). Low-dose adrenocorticotropic hormone (ACTH) test (i.v. bolus of 1 microg synthetic ACTH) was performed at 10.00 h with blood sampling every 15 min for 90 min. Cortisol, 17-OH-progesterone (17OHP), androstenedione (ASD), and dehydroepiandrosterone (DHEA) were assayed in plasma. Baseline cortisol levels were higher in RA patients (RA: 385 +/- 38 versus C: 229 +/- 28 nmol/L, P= 0.007). In both study groups, ACTH administration increased all the four steroids measured (P < 0.001). Cortisol response to ACTH administration was diminished in RA patients when compared to controls (Delta(max): 284 +/- 24 in RA versus 424 +/- 31 nmol/L in C, P= 0.002). ACTH-induced maximal rise in plasma DHEA was significantly lower in RA patients when compared to controls (Delta(max): 2.59 +/- 0.68 in RA versus 5.57 +/- 1.25 ng/mL in C, P= 0.015). No significant between-groups differences were found in responses of ASD or 17OHP. The molar ratio of ASD:cortisol was significantly lower (P < 0.05) in RA patients at base line, but did not differ during ACTH test. After ACTH bolus, the cortisol:17OHP ratio decreased significantly in the RA group (P < 0.001), whereas there was no change in the control group. The present results show decreased secretion of cortisol and DHEA in RA patients in response to ACTH, suggesting a subtle HPA hypofunction at the adrenocortical level.

  7. Cushing's syndrome in infancy due to ectopic ACTH secretion by a sacro-coccygeal teratoma.

    Science.gov (United States)

    Rydzewska, Marta; Krawczuk-Rybak, Maryna; Zajkowska, Adrianna; Jurczuk, Natalia; Polnik, Dariusz; Szalecki, Mieczysław; Moszczyńska, Elżbieta; Savage, Martin O; Bossowski, Artur

    2017-04-01

    Adenocorticotropic hormone (ACTH)-dependent Cushing's syndrome in infancy is extremely rare. We describe the case of a sacro-coccygeal ectopic ACTH-secreting immature teratoma in an infant who also presented the triad of defects characteristic of Currarino syndrome. A girl was born with a large immature teratoma in the sacro-coccygeal region associated with anal atresia. At the age of 7 days, the concentration of α-fetoprotein (AFP) was above the age-specific normal range. Two non-radical surgical excisions of the tumour were performed. At the age of 7 months, she developed polyphagia, acne, hirsutism, hypertension and hypokalemia with elevated ACTH and absence of serum cortisol circadian rhythm. Immunostaining of tumour tissue showed ACTH-immunoreactive cells. Due to unsuccessful therapy with ketoconazole and resistance to antihypertensive medications [blood pressure (BP) 210/160 mmHg], metyrapone was administered, which controlled her ACTH and cortisol levels in the normal range. Following further removal of tumour bulk after three operations during the first year of life, there was a decrease of BP to normal values. A rare case of ectopic ACTH syndrome causing Cushing's syndrome in infancy in the context of Currarino syndrome is reported. Radical surgery has resulted in excision of the tumour and current control of Cushing's syndrome.

  8. Decrease of N-acetylaspartate after ACTH therapy in patients with infantile spasms.

    Science.gov (United States)

    Maeda, H; Furune, S; Nomura, K; Kitou, O; Ando, Y; Negoro, T; Watanabe, K

    1997-10-01

    Apparent brain atrophy has been frequently observed at CT and MRI after ACTH therapy in patients with infantile spasms. There are several hypotheses to explain ACTH-induced brain shrinkage: 1) a catabolic effect of ACTH on brain tissue, 2) a mineralocorticoid effect resulting in a loss of water and 3) an increase in cerebrospinal fluid (CSF) pressure compressing the brain. An average of 0.21 +/- 0.03 mg/kg of ACTH was administered to nine patients over a period of 14 to 17 days. Water content and concentrations of N-acetylaspartate (NAA), creatine and phosphocreatine (Cr + PCr), and choline (Cho) were measured before, immediately after, and several months after the ACTH therapy by using in-vivo 1H magnetic resonance spectroscopy (MRS). Only NAA concentration exhibited a significant change during the study (6.6 +/- 1.5 mmol/kg, 5.4 +/- 1.1, and 7.0 +/- 1.5, p = 0.017). There was no significant change in Cr + PCr, in Cho, or in water content. These data suggest catabolic effects of ACTH on brain tissue, such as cell loss, decrease in NAA synthesis in mitochondria, and leakage of NAA from cell membrane.

  9. Lower birth weight and attenuated adrenocortical response to ACTH in offspring from sows that orally received cortisol during gestation.

    Science.gov (United States)

    Kranendonk, Godelieve; Hopster, Hans; Fillerup, Maaike; Ekkel, E Dinand; Mulder, Eduard J H; Wiegant, Victor M; Taverne, Marcel A M

    2006-03-01

    Prenatal stress is known to affect several offspring characteristics, but its effects depend among other factors on the period of gestation in which it is applied. In the present study, oral administration of hydrocortisone-acetate (HCA) was used to elevate cortisol concentrations in pregnant sows to levels also observed after psychological stress. HCA was administered during three different periods of gestation (115 days in pigs): period 1: 21-50 (P1, n = 10), period 2: 51-80 (P2, n = 10) and period 3: 81-110 (P3, n = 10) days after insemination. Control sows (n = 11) received vehicle from 21-110 days after insemination. When P1-, P2- and P3-sows did not receive HCA, they also received vehicle. During gestation, weekly saliva samples were taken from the sows to determine salivary cortisol concentrations. Treatment effects on sow, litter and piglet characteristics were determined. In addition, two female piglets per litter were subjected to an ACTH-challenge test at 6 weeks of age to determine the adrenocortical response to ACTH. Pigs were slaughtered at 6 months of age and slaughter weight, back fat thickness and percentage of lean meat were analysed. During the period of treatment with HCA, salivary cortisol concentrations were increased in P1-, P2- and P3-sows compared to control sows (P 0.30), but pooled HCA-litters had a higher percentage of live born piglets (P Gestation length did not differ among treatment groups (P = 0.21), but did affect treatment effects on birth weight. Overall, HCA-piglets weighed less at birth, and remained lighter until weaning (P < 0.05). The salivary cortisol concentrations after i.m. injection of ACTH (2.5 IU/kg) were lower in P1- and P3-piglets compared to control piglets. At slaughter, HCA-treatment indirectly decreased lean meat percentage and increased back fat thickness. In conclusion, elevated peripheral cortisol concentrations in pregnant sows affect both litter characteristics and piglet physiology, the latter depending on

  10. Negative correlation between tumour size and cortisol/ACTH ratios in patients with Cushing's disease harbouring microadenomas or macroadenomas.

    Science.gov (United States)

    Machado, M C; Alcantara, A E E; Pereira, A C L; Cescato, V A S; Castro Musolino, N R; de Mendonça, B B; Bronstein, M D; Fragoso, M C B V

    2016-12-01

    Pituitary macroadenomas (MACs) represent 10-30 % of Cushing's disease (CD) cases. The aim of this study was to report the clinical, laboratorial and imaging features and postsurgical outcomes of microadenoma (MIC) and MAC patients. Retrospective study with 317 CD patients (median 32 years old, range 9-71 years) admitted between 1990 and 2014, 74 (23.3 %) of whom had MAC. Hirsutism, plethora facial, muscular weakness and muscular atrophy were more frequent in the MIC patients. Nephrolithiasis, osteopenia, hyperprolactinaemia and galactorrhoea were more prevalent in MAC patients. The morning serum cortisol (Fs), nocturnal salivary cortisol (NSC), nocturnal Fs (Fs 2400 h), low- and high-dose dexamethasone suppression test results and CRH and desmopressin test results were similar between the subgroups. MIC patients showed higher urinary cortisol at 24 h (UC), and MAC patients presented higher ACTH levels but lower Fs/ACTH, Fs 2400 h/ACTH, NSC/ACTH and UC/ACTH ratios. There were negative correlations of tumour size with Fs/ACTH, Fs 2400 h/ACTH, NSC/ACTH and UC/ACTH ratios. Overall, the postsurgical remission and recurrence rates were similar between MIC and MAC. However, patients in remission (MIC + MAC) showed smaller tumour diameters and a lower prevalence of invasion and extension on MRI. Despite exhibiting higher plasma ACTH levels, CD patients with MAC presented lower cortisol/ACTH ratios than did patients with MIC, with a negative correlation between tumour size and cortisol/ACTH ratios. The overall postsurgical remission and recurrence rates were similar between MIC and MAC patients, with those with larger and/or invasive tumours showing a lower remission rate.

  11. Multidrug-Resistant Tuberculosis and Its Association with Adrenal Insufficiency: Assessment with the Low-Dose ACTH Stimulation Test

    Directory of Open Access Journals (Sweden)

    René Rodríguez-Gutiérrez

    2016-01-01

    Full Text Available Background. Multidrug-resistant tuberculosis (MDR-TB is a major public health care concern that affects the life of millions of people around the world. The association of tuberculosis and adrenal insufficiency is well known; however, it is thought to be less prevalent every time. A spike in TB incidence and a lack of evidence of this association in patients with MDR-TB call for reassessment of an illness (adrenal dysfunction that if not diagnosed could seriously jeopardize patients’ health. Objective. To determine the prevalence of adrenocortical insufficiency in patients with MDR-TB using the low-dose (1 μg ACTH stimulation test at baseline and at 6–12 months of follow-up after antituberculosis treatment and culture conversion. Methods. A total of 48 men or women, aged ≥18 years (HIV-negative patients diagnosed with pulmonary MDR-TB were included in this prospective observational study. Blood samples for serum cortisol were taken at baseline and 30 and 60 minutes after 1 μg ACTH stimulation at our tertiary level university hospital before and after antituberculosis treatment. Results. Forty-seven percent of subjects had primary MDR-TB; 43.8% had type 2 diabetes; none were HIV-positive. We found at enrollment 2 cases (4.2% of adrenal insufficiency taking 500 nmol/L as the standard cutoff point value and 4 cases (8.3% alternatively, using 550 nmol/L. After antituberculosis intensive phase drug-treatment and a negative mycobacterial culture (10.2±3.6 months adrenocortical function was restored in all cases. Conclusions. In patients with MDR-TB, using the low-dose ACTH stimulation test, a low prevalence of mild adrenal insufficiency was observed. After antituberculosis treatment adrenal function was restored in all cases. Given the increasing and worrying epidemic of MDR-TB these findings have important clinical implications that may help clinicians and patients make better decisions when deciding to test for adrenocortical

  12. Multidrug-Resistant Tuberculosis and Its Association with Adrenal Insufficiency: Assessment with the Low-Dose ACTH Stimulation Test

    Science.gov (United States)

    Rodríguez-Gutiérrez, René; Rendon, Adrian; Barrera-Sánchez, Maximiliano; Carlos-Reyna, Kevin Erick Gabriel; Álvarez-Villalobos, Neri Alejandro; González-Saldivar, Gloria; González-González, José Gerardo

    2016-01-01

    Background. Multidrug-resistant tuberculosis (MDR-TB) is a major public health care concern that affects the life of millions of people around the world. The association of tuberculosis and adrenal insufficiency is well known; however, it is thought to be less prevalent every time. A spike in TB incidence and a lack of evidence of this association in patients with MDR-TB call for reassessment of an illness (adrenal dysfunction) that if not diagnosed could seriously jeopardize patients' health. Objective. To determine the prevalence of adrenocortical insufficiency in patients with MDR-TB using the low-dose (1 μg) ACTH stimulation test at baseline and at 6–12 months of follow-up after antituberculosis treatment and culture conversion. Methods. A total of 48 men or women, aged ≥18 years (HIV-negative patients diagnosed with pulmonary MDR-TB) were included in this prospective observational study. Blood samples for serum cortisol were taken at baseline and 30 and 60 minutes after 1 μg ACTH stimulation at our tertiary level university hospital before and after antituberculosis treatment. Results. Forty-seven percent of subjects had primary MDR-TB; 43.8% had type 2 diabetes; none were HIV-positive. We found at enrollment 2 cases (4.2%) of adrenal insufficiency taking 500 nmol/L as the standard cutoff point value and 4 cases (8.3%) alternatively, using 550 nmol/L. After antituberculosis intensive phase drug-treatment and a negative mycobacterial culture (10.2 ± 3.6 months) adrenocortical function was restored in all cases. Conclusions. In patients with MDR-TB, using the low-dose ACTH stimulation test, a low prevalence of mild adrenal insufficiency was observed. After antituberculosis treatment adrenal function was restored in all cases. Given the increasing and worrying epidemic of MDR-TB these findings have important clinical implications that may help clinicians and patients make better decisions when deciding to test for adrenocortical dysfunction or

  13. The Effect of Age and Initial Central Retinal Thickness on Earlier Need of Repeat Ozurdex Treatment for Macular Edema Due to Retinal Vein Occlusion: A Retrospective Case Series.

    Science.gov (United States)

    Lin, Chun-Ju; Chen, Huan-Sheng; Su, Cheng-Wen; Tien, Peng-Tai; Lin, Jane-Ming; Chen, Wen-Lu; Kuo, Chung-Yuan; Lai, Chun-Ting; Tsai, Yi-Yu

    2017-09-26

    To evaluate the effects of dexamethasone intravitreal implant (Ozurdex) and identify risk factors for repeated treatment in patients with macula edema due to branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO). Patients followed up for at least 6 months were enrolled from 2013 to 2016. Dexamethasone intravitreal implant was given as the baseline treatment. For evaluation of dexamethasone intravitreal implant effects and complications, the demographics, medical history, best-corrected visual acuity (BCVA), intraocular pressure, and central retinal thickness (CRT) were recorded. Multivariate Cox proportional hazard model and logistic regression were used to identify factors for repeated treatment. Twenty-three BRVO and 11 CRVO patients were enrolled. There were 15 males and 19 females. Fifteen (44.12%) patients needed only one dexamethasone intravitreal implant. The peak CRT and BCVA significantly improved. Comparing single-injection with multiple-injection group, age and initial CRT more than 400 μm were significantly higher in the multiple-injection group. From multivariate logistic regression and Cox proportional hazards analysis, patients with age older than 55 years and initial CRT more than 400 μm had higher risk for multiple injections. Patients receiving as-needed schedule of dexamethasone intravitreal implant had significant peak CRT and BCVA improvement. Age older than 55 years and initial CRT more than 400 μm were significant risk factors associated with repeated dexamethasone intravitreal implant treatment.

  14. Mediation of ACTH and prolactin responses to 5-HTP by 5-HT2 receptors.

    Science.gov (United States)

    Gartside, S E; Cowen, P J

    1990-04-10

    Serotonin has a facilitatory role in the role of prolactin and adrenocorticotropin (ACTH) secretion. The serotonin precursor 5-hydroxy-L-tryptophan (5-HTP) dose dependently (30-100 mg/kg i.p.) increased plasma prolactin and ACTH in the male rat. Prolactin and ACTH responses to 5-HTP (100 mg/kg) were attenuated by pretreatment with the non-selective 5-HT receptor antagonist, metergoline (0.5 mg/kg), and by the selective 5-HT2 receptor antagonists, ritanserin (0.4 mg/kg), ketanserin (2.5 mg/kg), ICI (5.0 mg/kg) and spiperone (1.0 mg/kg). The 5-HT1 receptor antagonists, propranolol (40 mg/kg) and pindolol (4.0 mg/kg), failed to antagonize the prolactin and ACTH responses to 5-HTP (100 mg/kg), as did the selective 5-HT3 receptor antagonist, BRL 43694 (1.0 mg/kg). The results suggest that the prolactin and ACTH responses to 5-HTP in the male rat are mediated by 5-HT2 receptors.

  15. IS THERE A ROLE OF ACTH IN INCREASED CHOROIDAL THICKNESS IN CUSHING SYNDROME?

    Science.gov (United States)

    Karaca, Cagatay; Karaca, Zuleyha; Kahraman, Nisa; Sirakaya, Ender; Oner, Ayse; Mirza, Galip Ertugrul

    2017-03-01

    To evaluate choroidal thickness (CT) in patients with Cushing syndrome (CS) with enhanced depth imaging optical coherence tomography. Twenty-eight patients with CS and 38 healthy volunteers were enrolled in this observational cross-sectional study. Patients with newly diagnosed CS who have been admitted to Erciyes University Department of Endocrinology in 3 years time interval were compared with age- and sex-matched healthy volunteers. Choroidal thickness was measured at the fovea and 2 points nasal and 2 points temporal to the fovea with 500-μm intervals each. Choroidal thickness measurements were higher in patients with CS than in the control group at all examination points; however, the difference was found to be significant at the center of the fovea (367.8 ± 94.4 μm vs. 329 ± 90.5 μm) and 1,000 μm temporal to the fovea. Choroidal thickness measurements were significantly higher in adrenocorticotrophic hormone (ACTH)-dependent CS group than in the control group at all measurement points (CT at fovea 388.2 ± 92.4 μm vs. 329.1 ± 90.5 μm). All CT measurements were found to be correlated with ACTH levels. Cushing syndrome is associated with increased CT. The ACTH-dependent CS may increase CT more than ACTH-independent CS. This effect may be directly related to ACTH itself or increased plasma cortisol levels or both.

  16. Response of plasma cortisol and progesterone after ACTH challenge in ovariectomized lactating dairy cows.

    Science.gov (United States)

    Yoshida, Chikako; Nakao, Toshihiko

    2005-02-01

    Shortened and weakened estrous expressions could be one of the causes of poor heat detection rate. Non-specific acute stresses are assumed to depress expression of estrus by an increase of plasma progesterone which may originate from the adrenal cortex. The objective of the present study was to examine whether the adrenal cortex can secrete significant amounts of progesterone in response to exogenous adrenocorticotropic hormone (ACTH) in lactating cows. Four cows had estrus synchronized and were ovariectomized in the luteal phase. The cows were given 25 IU ACTH through an indwelling catheter 5 h after catheterization. Blood samples were collected at an interval of 30 min. In 3 of the 4 cows, plasma progesterone concentrations increased significantly 0.5-1.5 h after the first ACTH challenge with a mean peak value of 4.2 +/- 0.4 (S.D.) ng/ml. A similar response was also observed after the second ACTH challenge. Peak plasma progesterone concentrations in the 3 cows after first ACTH challenge were comparable with the progesterone values in the luteal phase of each cow. The results suggest that lactating cows have the capability to secrete a significant amount of progesterone from the adrenal cortex.

  17. A case of ACTH-independent bilateral macronodular adrenal hyperplasia and severe congestive heart failure.

    Science.gov (United States)

    Suri, D; Alonso, M; Weiss, R E

    2006-11-01

    Cortisol secretion in ACTH independent bilateral macronodular adrenal hyperplasia (AIMAH) can be regulated by aberrant adrenal receptors. We describe a patient with Cushing's syndrome (CS) due to AIMAH and concomitant Class IV congestive heart failure (CHF). Clinical testing for the presence of aberrant receptors revealed a pronounced serum cortisol (257%) and aldosterone response (212%) to the administration of ACTH and a partial serum cortisol (35%) and aldosterone (106%) response to upright posture. This suggested the possible presence of aberrant hormone receptors for ACTH [melanocortin 2 receptor (MC2-R)], vasopressin, catecholamines or angiotensin II (AT-II) on the patient's adrenal glands. Adrenal tissue from the patient demonstrated an eight-fold increased expression of MC2-R compared to normal adrenal tissue. This increased expression was consistent with the increase in cortisol and aldosterone seen in response to exogenous ACTH. We propose that the severe CHF resulted in activation of the renin-angiotensin system, with an increased production of AT-II. The elevated circulating levels of AT-II may have led to increased expression of MC2-R on the patient's adrenal glands and increased responsiveness to ACTH. This unusual case of CS may elucidate a heretofore unknown mechanism for the development of AIMAH.

  18. Effect of Repeated Stress Treatments During the Follicular Phase and Early Pregnancy on Reproductive Performance of Gilts

    NARCIS (Netherlands)

    Soede, N.M.; Roelofs, J.B.; Verheijen, R.J.E.; Schouten, W.G.P.; Hazeleger, W.; Kemp, B.

    2007-01-01

    In pig husbandry, stress is being considered an important cause of impaired reproductive performance. Therefore, an experiment was performed to quantify effects of repeated stressors during the follicular phase and/or during early pregnancy on reproductive performance of gilts. Eighty-one cyclic

  19. Risk Factors of Repeated Infectious Disease Incidence among Substance Dependent Girls and Boys Court-Referred to Treatment

    Science.gov (United States)

    Pagano, Maria E.; Maietti, Candice M.; Levine, Alan D.

    2015-01-01

    A small portion of Americans account for a disproportionate amount of the incidences of sexually transmitted infection observed over a short period of time. Studies with adults have begun to characterize this population, yet there is very little data on adolescent sexually transmitted infection repeaters (STIR). This study explores characteristics…

  20. Treatment of neuroblastoma in congenital central hypoventilation syndrome with a PHOX2B polyalanine repeat expansion mutation: New twist on a neurocristopathy syndrome.

    Science.gov (United States)

    Armstrong, Amy E; Weese-Mayer, Debra E; Mian, Amir; Maris, John M; Batra, Vandana; Gosiengfiao, Yasmin; Reichek, Jennifer; Madonna, Mary Beth; Bush, Jonathan W; Shore, Richard M; Walterhouse, David O

    2015-11-01

    Neuroblastoma in patients with congenital central hypoventilation syndrome (CCHS) as part of a neurocristopathy syndrome is a rare finding and has only been associated with paired-like homeobox 2b (PHOX2B) non-polyalanine-repeat-expansion mutations. To the best of our knowledge, we report the first case of a child with CCHS and Hirschsprung disease who had a PHOX2B polyalanine-repeat-expansion mutation (PARM) (genotype 20/33) and developed high-risk neuroblastoma. We further describe his treatment including chemotherapy and therapeutic I(131) -metaiodobenzylguanidine. This case highlights the need to consider neuroblastoma in patients with CCHS and the longest PHOX2B PARMs and to individualize treatment based on co-morbidities.

  1. Lycopene and beta-carotene induce growth inhibition and proapoptotic effects on ACTH-secreting pituitary adenoma cells.

    Directory of Open Access Journals (Sweden)

    Natália F Haddad

    Full Text Available Pituitary adenomas comprise approximately 10-15% of intracranial tumors and result in morbidity associated with altered hormonal patterns, therapy and compression of adjacent sella turcica structures. The use of functional foods containing carotenoids contributes to reduce the risk of chronic diseases such as cancer and vascular disorders. In this study, we evaluated the influence of different concentrations of beta-carotene and lycopene on cell viability, colony formation, cell cycle, apoptosis, hormone secretion, intercellular communication and expression of connexin 43, Skp2 and p27(kip1 in ACTH-secreting pituitary adenoma cells, the AtT20 cells, incubated for 48 and 96 h with these carotenoids. We observed a decrease in cell viability caused by the lycopene and beta-carotene treatments; in these conditions, the clonogenic ability of the cells was also significantly decreased. Cell cycle analysis revealed that beta-carotene induced an increase of the cells in S and G2/M phases; furthermore, lycopene increased the proportion of these cells in G0/G1 while decreasing the S and G2/M phases. Also, carotenoids induced apoptosis after 96 h. Lycopene and beta-carotene decreased the secretion of ACTH in AtT20 cells in a dose-dependent manner. Carotenoids blocked the gap junction intercellular communication. In addition, the treatments increased the expression of phosphorylated connexin43. Finally, we also demonstrate decreased expression of S-phase kinase-associated protein 2 (Skp2 and increased expression of p27(kip1 in carotenoid-treated cells. These results show that lycopene and beta-carotene were able to negatively modulate events related to the malignant phenotype of AtT-20 cells, through a mechanism that could involve changes in the expression of connexin 43, Skp2 and p27(kip1; and suggest that these compounds might provide a novel pharmacological approach to the treatment of Cushing's disease.

  2. In-vitro cervical mucus-sperm penetration tests and outcome of infertility treatments in couples with repeatedly negative post-coital tests.

    Science.gov (United States)

    Farhi, J; Valentine, A; Bahadur, G; Shenfield, F; Steele, S J; Jacobs, H S

    1995-01-01

    The results of in-vitro cervical mucus-sperm penetration tests and cross-hostility tests in 178 couples with repeatedly negative post-coital tests were recorded. Using a protocol of three cycles with intra-uterine inseminations (IUI) followed by three cycles with ovulation induction + IUI, the association between the cause of infertility, results of the in-vitro tests and the outcome of infertility treatment was investigated. We found that repeatedly negative post-coital tests are a good indicator of a cervical mucus-sperm penetration problem. The cross-hostility test clearly differentiates the abnormal factor in this interaction, and a good performance of the donors' spermatozoa in the cervical mucus correlates with increased pregnancy rate. In male factor infertility, failure of the husbands' spermatozoa to penetrate cervical mucus was not indicative of a deficient fertilization potential in vivo. In these patients a serious attempt should therefore be made to reverse the infertility by treatment with IUI or ovulation induction + IUI before attempting assisted reproduction. Women with polycystic ovaries and repeatedly negative post-coital tests should be investigated for sperm receptivity of the cervical mucus. Low receptivity of the cervical mucus may imply that endometrial receptivity and oocyte quality are also low. Ovulation induction and not IUI alone should therefore be used as the preferred mode of treatment to improve pregnancy rate.

  3. Beta-endorphin and ACTH in plasma during attacks of common and classic migraine

    DEFF Research Database (Denmark)

    Bach, F W; Jensen, K; Blegvad, N;

    1985-01-01

    Plasma levels of beta-endorphin and ACTH were measured during and outside migraine attacks in 17 patients with common migraine and 11 patients with classic migraine. Specific radioimmunoassays for beta-endorphin and ACTH were used. The beta-endorphin assay did not cross-react with beta......-lipotropin. In common migraine, median plasma beta-endorphin was 3.3 pmol/l (95% confidence limits: 2.5-4.0 pmol/l) during attacks and 2.9 (2.4-3.2) pmol/l in the headache-free period. In classic migraine, plasma beta-endorphin was 3.2 (1.4-4.3) pmol/l during attacks and 2.4 (1.1-3.6) pmol/l outside attacks. ACTH...

  4. Vasopressin and angiotensin II in reflex regulation of ACTH, glucocorticoids, and renin: effect of water deprivation

    Science.gov (United States)

    Brooks, V. L.; Keil, L. C.

    1992-01-01

    Angiotensin II (ANG II) and vasopressin participate in baroreflex regulation of adrenocorticotropic hormone (ACTH), glucocorticoid, and renin secretion. The purpose of this study was to determine whether this participation is enhanced in water-deprived dogs, with chronically elevated plasma ANG II and vasopressin levels, compared with water-replete dogs. The baroreflex was assessed by infusing increasing doses of nitroprusside (0.3, 0.6, 1.5, and 3.0 micrograms.kg-1.min-1) in both groups of animals. To quantitate the participation of ANG II and vasopressin, the dogs were untreated or pretreated with the competitive ANG II antagonist saralasin, a V1-vasopressin antagonist, or combined V1/V2-vasopressin antagonist, either alone or in combination. The findings were as follows. 1) Larger reflex increases in ANG II, vasopressin, and glucocorticoids, but not ACTH, were produced in water-deprived dogs compared with water-replete dogs. 2) ANG II blockade blunted the glucocorticoid and ACTH responses to hypotension in water-deprived dogs, but not water-replete dogs. In contrast, vasopressin blockade reduced the ACTH response only in water-replete dogs. 3) Vasopressin or combined vasopressin and ANG II blockade reduced the plasma level of glucocorticoids related either to the fall in arterial pressure or to the increase in plasma ACTH concentration in water-replete dogs, and this effect was enhanced in water-deprived dogs. 4) In both water-deprived and water-replete animals, saralasin and/or a V1-antagonist increased the renin response to hypotension, but a combined V1/V2-antagonist did not. These results reemphasize the importance of endogenous ANG II and vasopressin in the regulation of ACTH, glucocorticoid, and renin secretion.(ABSTRACT TRUNCATED AT 250 WORDS).

  5. Using microarrays to identify positional candidate genes for QTL: the case study of ACTH response in pigs

    DEFF Research Database (Denmark)

    Jouffe, Vincent; Rowe, Suzanne; Liaubet, Laurence

    2009-01-01

    of 237 differentially expressed cDNA clones in adrenal tissue from two pig breeds, before and after treatment with adrenocorticotropic hormone (ACTH) Microarray studies can supplement QTL studies by suggesting potential candidate genes in the QTL regions, which by themselves are too large to provide......Background: Microarray studies can supplement QTL studies by suggesting potential candidate. Microarray studies can supplement QTL studies by suggesting potential candidate genes in the QTL regions, which by themselves are too large to provide a limited selection of candidate genes. Here we provide...... a case study where we explore ways to integrate QTL data and microarray data for the pig, which has only a partial genome sequence. We outline various procedures to localize differentially expressed genes on the pig genome and link this with information on published QTL. The starting point is a set...

  6. Efficacy and safety of fixed-dose artesunate-amodiaquine vs. artemether-lumefantrine for repeated treatment of uncomplicated malaria in Ugandan children.

    Directory of Open Access Journals (Sweden)

    Adoke Yeka

    Full Text Available The safety and efficacy of the two most widely used fixed-dose artemisinin-based combination therapies (ACT, artesunate-amodiaquine (ASAQ and artemether-lumefantrine (AL are well established for single episodes of uncomplicated Plasmodium falciparum malaria, but the effects of repeated, long-term use are not well documented. We conducted a 2-year randomized, open-label, longitudinal, phase IV clinical trial comparing the efficacy and safety of fixed-dose ASAQ and AL for repeated treatment of uncomplicated malaria in children under 5 years at Nagongera Health Centre, Uganda. Participants were randomized to ASAQ or AL and all subsequent malaria episodes were treated with the same regimen. 413 children were enrolled and experienced a total of 6027 malaria episodes (mean 15; range, 1-26. For the first malaria episode, the PCR-corrected-cure rate for ASAQ (97.5% was non-inferior to that for AL (97.0%; 95% CI [-0.028; 0.037]. PCR-corrected cure rates for subsequent malaria episodes that had over 100 cases (episodes 2-18, ranged from 88.1% to 98.9% per episode, with no clear difference between the treatment arms. Parasites were completely cleared by day 3 for all malaria episodes and gametocyte carriage was less than 1% by day 21. Fever clearance was faster in the ASAQ group for the first episode. Treatment compliance for subsequent episodes (only first dose administration observed was close to 100%. Adverse events though common were similar between treatment arms and mostly related to the disease. Serious adverse events were uncommon, comparable between treatment arms and resolved spontaneously. Anemia and neutropenia occurred in <0.5% of cases per episode, abnormal liver function tests occurred in 0.3% to 1.4% of cases. Both regimens were safe and effective for repeated treatment of malaria.Current Controlled Trials NCT00699920.

  7. Level of cortisol and reactivity of adrenal cortex to exogenous ACTH at neonatal period in calves

    Energy Technology Data Exchange (ETDEWEB)

    Friedrich, M. [Akademia Rolnicza, Szczecin (Poland)

    1992-12-31

    The studies were carried out on calves from 1st to 21st day of life. Cortisol level and reactivity of adrenal cortex to exogenous ACTH were analysed. The highest level of cortisol in blood was observed in first days of life in the calves. Then the level became considerably decreased. In the experimental group two subgroups differing in cortisol level were distinguished. High or low level occurred on the first day and the difference kept over two weeks of their life. Adrenal cortex just on the day of birth showed full functional maturity of molecular receptors binding ACTH. (author). 15 refs.

  8. Loss of sensitivity to ACTH of adrenocortical cells isolated from maturing domestic fowl.

    Science.gov (United States)

    Carsia, R V; Scanes, C G; Malamed, S

    1985-07-01

    Maturation of domestic fowl corticosteroidogenesis was evaluated using purified adrenocortical cells. Basal corticosterone production decreased steadily from 2 days to 26 weeks after hatching. However, maximally stimulated corticosterone production was not changed. In contrast, the half-maximal steroidogenic concentrations (ED50 values or effective doses for 50% maximal effect) of ACTH analogs increased approximately 40 times by 26 weeks, but the ED50 values of 8-bromo-cyclic AMP and pregnenolone were not changed. This suggests that adrenocortical cell sensitivity to ACTH decreases with maturation of the domestic fowl.

  9. [1H-NMR studies of the ACTH-like immunoregulatory peptides].

    Science.gov (United States)

    Khristoforov, V S; Kutyshenko, V P; Abramov, V M; Zav'ialov, V P

    1997-01-01

    A comparative study of the conformational and dynamics properties of the ACTH-like linear peptides, sequences of which correspond to amino acid residues 11-20 of the heavy chain of human immunoglobulin G1 Eu, residues 78-85 of human pro-interleukin-1 alpha and site 10-18 of human ACTH, was performed in aqueous solution and dimethylsulfoxide by 1H-NMR spectroscopy at 400 MHz. The peptides were shown to possess an unordered unfolded flexible conformation in aqueous solution. The revealed structural and dynamic features of the peptides are discussed together with biological activity of this class of compounds.

  10. Deployment Repeatability

    Science.gov (United States)

    2016-04-01

    controlled to great precision, but in a Cubesat , there may be no attitude determination at all. Such a Cubesat might treat sun angle and tumbling rates as...could be sensitive to small differences in motor controller timing. In these cases, the analyst might choose to model the entire deployment path, with...knowledge of the material damage model or motor controller timing precision. On the other hand, if many repeated and environmentally representative

  11. Biological wastewater treatment by a bioreactor with repeated coupling of aerobes and anaerobes aiming at on-site reduction of excess sludge.

    Science.gov (United States)

    Yu, Anfeng; Feng, Quan; Liu, Zehua; Zhou, Yunan; Xing, Xin-Hui

    2006-01-01

    Activated sludge has been widely used in wastewater treatment throughout the world. However, the biggest disadvantage of this method is the by-production of excess sludge in a large amount, resulting in difficulties in operation and high costs for wastewater treatment. Technological innovations for wastewater treatment capable of reducing excess sludge have thus become research topics of interest in recent years. In our present research, we developed a new biological wastewater treatment process by repeated coupling of aerobes and anaerobes (rCAA) to reduce the excess sludge during the treatment of wastewater. During 460-day continuous running, COD (300-700 mg/L) and TOC (100-350 mg/L) were effectively removed, of which the removal rate was above 80 and 90%, respectively. SS in the effluent was 13 mg/L on average in the rCAA bioreactor without a settling tank. The on-site reduction of the excess sludge in the rCAA might be contributed by several mechanisms. The degradation of the grown aerobes after moving into the anaerobic regions was considered to be one of the most important factors. Besides, the repeatedly coupling of aerobes and anaerobes could also result in a complex microbial community with more metazoans and decoupling of the microbial anabolism and catabolism.

  12. Repeated maternal dexamethasone treatments in late gestation increases 11beta-hydroxysteroid dehydrogenase type 1 expression in the hippocampus of the newborn rat.

    Science.gov (United States)

    Wan, Shunlun; Hao, Rusong; Sun, Kang

    This study was designed to investigate the effect of repeated maternal injections of dexamethasone in late gestation on the expression of newborn hippocampal 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), the enzyme amplifying glucocorticoids' action by converting biologically inactive 11-ketone metabolites into active glucocorticoids. Daily dexamethasone treatments (0.10 mg/kg body weight) in the last week of gestation were carried out in the pregnant rat. The expression of 11beta-HSD1 in the newborn hippocampal tissue was analyzed with Western blot and real-time polymerase chain reaction (PCR). The effect of corticosterone on the expression of 11beta-HSD1 was studied in cultured hippocampal neurons derived from newborn offspring received prenatal dexamethasone treatments. Both body and brain weights of the offspring were reduced significantly by repeated dexamethasone treatments in the last week of gestation. Western blot and real-time PCR analysis showed that both 11beta-HSD1 protein and mRNA expressions were increased significantly in the hippocampus of the newborn offspring on the first and seventh days after birth. Corticosterone could induce 11beta-HSD1 expression in cultured hippocampal neurons prepared from newborns received prenatal dexamethasone treatments, which was blocked by glucocorticoid receptor antagonist RU38486. The above findings suggest that repeated prenatal dexamethasone treatments at the end of gestation increase 11beta-HSD1 expression in the hippocampal tissue of the offspring, which may trigger a positive feedback pathway for the generation of biologically active glucocorticoids in the hippocampal tissue of the newborns.

  13. Soil microarthropods are only weakly impacted after 13 years of repeated drought treatment in wet and dry heathland soils

    DEFF Research Database (Denmark)

    Holmstrup, Martin; Sørensen, Jesper G.; Schmidt, Inger Kappel

    2013-01-01

    Studies of biological responses in the terrestrial environment to rapid changes in climate have mostly been concerned with aboveground biota, whereas less is known of belowground organisms. The present study focuses on mites and springtails of heathland ecosystems and how the microarthropod...... and frequency of drought had only weak persistent effects on springtail species composition, but practically no effect on major mite groups (Oribatida, Prostigmata or Mesostigmata) suggesting that ecosystem functions of microarthropods may only be transiently impacted by repeated spring or summer drought....

  14. The involvement of noradrenergic transmission in the morphine-induced locomotor hyperactivity in mice withdrawn from repeated morphine treatment

    OpenAIRE

    Airio, Juha; Ahtee, Liisa

    1999-01-01

    Our previous studies suggest that in addition to the cerebral dopaminergic systems the noradrenergic ones have a crucial role in the morphine-induced behavioural sensitization in mice. Therefore the effects of α2-adrenoceptor antagonist, idazoxan (1 and 3 mg kg−1, i.p.) on morphine-induced locomotor hyperactivity as well as on morphine-induced changes in cerebral noradrenaline (NA) and striatal dopamine (DA) metabolism were studied in mice withdrawn for 3 days from 5 day repeated morphine tre...

  15. Effects of 7-day repeated treatment with the 5-HT2A inverse agonist/antagonist pimavanserin on methamphetamine vs. food choice in male rhesus monkeys.

    Science.gov (United States)

    Banks, Matthew L

    2016-08-01

    Preclinical drug vs. food choice is an emerging group of drug self-administration procedures that have shown predictive validity to clinical drug addiction. Emerging data suggest that serotonin (5-HT)2A receptors modulate mesolimbic dopamine function, such that 5-HT2A antagonists blunt the abuse-related neurochemical effects of monoamine transporter substrates, such as amphetamine or methamphetamine. Whether subchronic 5-HT2A antagonist treatment attenuates methamphetamine reinforcement in any preclinical drug self-administration procedure is unknown. The study aim was therefore to determine 7-day treatment effects with the 5-HT2A inverse agonist/antagonist pimavanserin on methamphetamine vs. food choice in monkeys. Behavior was maintained under a concurrent schedule of food delivery (1g pellets, fixed-ratio 100 schedule) and intravenous methamphetamine injections (0-0.32 mg/kg/injection, fixed-ratio 10 schedule) in male rhesus monkeys (n=3). Methamphetamine choice dose-effect functions were determined daily before and during 7-day repeated pimavanserin (1.0-10mg/kg/day, intramuscular) treatment periods. Under control conditions, increasing methamphetamine doses resulted in a corresponding increase in methamphetamine vs. food choice. Repeated pimavanserin administration failed to attenuate methamphetamine choice and produce a reciprocal increase in food choice in any monkey up to doses (3.2-10mg/kg) that suppressed rates of operant responding primarily during components where behavior was maintained by food pellets. Repeated 5-HT2A receptor inverse agonist/antagonist treatment did not attenuate methamphetamine reinforcement under a concurrent schedule of intravenous methamphetamine and food presentation in nonhuman primates. Overall, these results do not support the therapeutic potential of 5-HT2A inverse agonists/antagonists as candidate medications for methamphetamine addiction. Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights

  16. Corticotropin (ACTH)-reactive immunoglobulins in adolescents in relation to antisocial behavior and stress-induced cortisol response. The TRAILS study.

    Science.gov (United States)

    Schaefer, Johanna M; Fetissov, Serguei O; Legrand, Romain; Claeyssens, Sophie; Hoekstra, Pieter J; Verhulst, Frank C; Van Oort, Floor V A

    2013-12-01

    Elevated levels of corticotropin (ACTH)-reactive immunoglobulins (ACTH IgG) were found in males with conduct disorder, suggesting their involvement in the biology of antisocial behavior. We first aimed to confirm these findings in a large general population sample of adolescents. Secondly, we studied the association between ACTH IgG levels and hypothalamic-pituitary-adrenal (HPA) axis response to stress. Free and total ACTH IgG levels were measured in sera of 1230 adolescents (15-18 years). HPA axis activity was determined by measuring salivary cortisol before, during, and after a social stress test. Antisocial behavior was assessed using the Antisocial Behavior Questionnaire. ACTH peptide and IgG affinity kinetics for ACTH were assayed in a subsample of 90 adolescents selected for high or low ACTH IgG levels. In boys, higher total ACTH IgG levels were associated with higher antisocial behavior scores (β=1.05, p=0.04), especially at high levels of free ACTH IgG. In girls, antisocial behavior was associated with low free ACTH IgG levels (β=-0.20, p=0.04). Stress-induced cortisol release was associated with free ACTH IgG in boys (βareaunderthecurve=-0.67, pantisocial behavior and HPA axis response to stress in adolescents. The mechanisms behind these associations, including different ACTH binding properties of IgG in subjects with antisocial behavior, deserve further attention.

  17. Cerebellin and des-cerebellin exert ACTH-like effects on corticosterone secretion and the intracellular signaling pathway gene expression in cultured rat adrenocortical cells--DNA microarray and QPCR studies.

    Science.gov (United States)

    Rucinski, Marcin; Ziolkowska, Agnieszka; Szyszka, Marta; Malendowicz, Ludwik K

    2009-04-01

    Precerebellins (Cbln) belong to the C1q/TNF superfamily of secreted proteins which have diverse functions. They are abundantly expressed in the cerebellum, however, three of them are also expressed in the rat adrenal gland. All members of the Cbln family form homomeric and heteromeric complexes with each other in vitro and it was suggested that such complexes play a crucial role in normal development of the cerebellum. The aim of our study was to investigate whether Cbln1-derived peptides, cerebellin (CER) and des-Ser1-cerebellin (desCER) are involved in regulating biological functions of rat adrenocortical cells. In the primary culture of rat adrenocortical cells, 24 h exposure to CER or desCER notably stimulated corticosterone output and inhibited proliferative activity and similar effects were evoked by ACTH. To study gene transcript regulation by CER, desCER and ACTH, we applied Oligo GEArray DNA Microarray: Rat Signal Transduction Pathway Finder. In relation to the control culture, 13 of the 113 transcripts present on the array were differentially expressed. These transcripts were either up- or down-regulated by ACTH and/or CER or desCER treatment. Validation of DNA Microarray data by QPCR revealed that only 5 of 13 genes studied were differentially expressed. Of those genes, Fos and Icam1 were up-regulated and Egr1 was down-regulated by ACTH, CER and desCER. The remaining two genes, Fasn (insulin signaling pathway) and Hspb1 (HSP27) (stress signaling pathway), were regulated only by CER and desCER, but not by ACTH. Thus, both CER and desCER have effects similar to and different from corticotrophin on the intracellular signaling pathway gene expression in cultured rat adrenocortical cells.

  18. Influence of a prenatal stressor on ACTH-induced cortisol secretion in yearling Brahman heifers

    Science.gov (United States)

    The objective of this study was to test whether prenatal stress affects postnatal adrenocortical responsiveness to exogenous adrenocorticotropin-releasing hormone (ACTH) in calves of Brahman cows transported for 2-hour periods at 60, 80, 100, 120, and 140 days of gestation. Prenatally stressed yearl...

  19. Short-term effects of ACTH on protein synthesis in adrenal cortex cells of young rats.

    Science.gov (United States)

    Magalhães, M C; Magalhães, M M; Cimbra, A

    1975-11-19

    Two units of ACTH were administered intraperitoneally to young 20 gm-rats which received an intravenous injection of L-leucine-3H thirteen min later. ACTH-injected rats, and control rats which received the isotope alone, were killed at 2-, 10-, 30- and 60-min intervals. Electron microscope autoradiographs in control animals showed strong amino-acid uptake at pulse time (2-min) in the cytoplasm of adrenal zona fasciculata cells. Label was shared between the endoplasmic reticulum (ER) and mitochondria, and a lower but still considerable uptake was seen in nucleoli. At first chase time interval (10-min) cytoplasmic labelling declined, while nuclear and nucleolar labelling increased, both changing little thereafter, and there was a 10-30 min Golgi peak. ACTH administration provoked an overall increase in amino-acid incorporation into cytoplasm, nucleus and nucleolus at pulse time, with no changes in the distribution of the reactions among organelles. Intensification of labelling was most evident over nucleoli, the grain density of which was four-times as high as in controls. The short-term increase in ER and mitochondrial protein synthesis observed after ACTH injections was considered to be consistent with the hypothesis that most newly-formed proteins in these cells may be involved in the regulation of steroidogenesis. The marked increase in nucleolar labelling suggested the presence of proteins involved in RNA synthesis.

  20. Progression of an Invasive ACTH Pituitary Macroadenoma with Cushing’s Disease to Pituitary Carcinoma

    Directory of Open Access Journals (Sweden)

    Clarissa Groberio Borba

    2015-01-01

    Full Text Available Pituitary carcinomas are very rare tumors that in most cases produce prolactin and adrenocorticotropic hormone (ACTH. It is a challenge to diagnosis of a pituitary carcinoma before disclosed symptomatic metastasis. We report the case of a female patient with Cushing’s disease who underwent three transsphenoidal surgeries, with pathological findings of common ACTH pituitary adenoma including Ki-67 expression <3%. She achieved hypocortisolism after the 3rd surgery although ACTH levels remained slightly elevated. The patient returned some time later with fast worsening of hypercortisolism. Magnetic resonance imaging showed clivus invasion, which led to a fourth surgery and radiation. This time, immunohistochemistry revealed strong Ki-67 (10% to 15% and p53 expression. Liver and lumbar spine metastases were found on workup. The patient died after few months due to lung infection. Pituitary carcinomas are rare, and the transformation of an ACTH-secreting pituitary adenoma into a carcinoma is exceptional. The difficulty of defining markers for the diagnosis of carcinoma, before metastasis diagnosis, in order to change the management of the disease, is a challenge.

  1. Beta-endorphin and ACTH in plasma during attacks of common and classic migraine

    DEFF Research Database (Denmark)

    Bach, F W; Jensen, K; Blegvad, N

    1985-01-01

    Plasma levels of beta-endorphin and ACTH were measured during and outside migraine attacks in 17 patients with common migraine and 11 patients with classic migraine. Specific radioimmunoassays for beta-endorphin and ACTH were used. The beta-endorphin assay did not cross-react with beta......-lipotropin. In common migraine, median plasma beta-endorphin was 3.3 pmol/l (95% confidence limits: 2.5-4.0 pmol/l) during attacks and 2.9 (2.4-3.2) pmol/l in the headache-free period. In classic migraine, plasma beta-endorphin was 3.2 (1.4-4.3) pmol/l during attacks and 2.4 (1.1-3.6) pmol/l outside attacks. ACTH...... plasma levels were 15 (10.5-20) pmol/l during and 15.7 (13.4-17) pmol/l outside attacks in common migraine. In classic migraine, plasma ACTH was 16 (7-36) pmol/l and 12.3 (8-28) pmol/l respectively. No significant differences were found between attacks and headache-free periods in common or classic...

  2. A case of West syndrome well controlled by very short and low-dose ACTH therapy.

    Science.gov (United States)

    Kimura, M; Miyamoto, S; Sejima, H; Yamaguchi, S

    1999-02-01

    The case of a 5-month-old boy with tuberous sclerosis and West syndrome is reported. Tonic spasms were noted from the age of 4 months. High-dose pyridoxal phosphate could not control the seizures completely. Very short and low-dose adrenocorticotropic hormone (ACTH) therapy (i.e. 0.011 mg/kg per dose, 12 times in 20 days) controlled the seizures, while pyridoxal phosphate was on. Early tapering of ACTH was successfully done while abnormal electroencephalogram (EEG) findings remained. Although side effects such as hypertension and brain shrinkage were transiently observed, both the cognitive and seizure prognoses were excellent at the age of 3 years and 2 months. The good response to a small dosage of ACTH might be due to some responsiveness of the high-dose pyridoxal phosphate and the underlying cause of tuberous sclerosis with normal development before onset. The present case illustrates that the duration and dosage of ACTH therapy in West syndrome should be modified according to the individual's requirements.

  3. Acute effects of ACTH on dissociated adrenocortical cells: quantitative changes in mitochondria and lipid droplets.

    Science.gov (United States)

    Zoller, L C; Malamed, S

    1975-08-01

    To study the role of certain organelles in steroidogenesis, dissociated rat adrenocortical cells were incubated for two hours with ACTH at a concentration that induces a high level of steroid production. Sections of ACTH treated and untreated cells were photographed in the electron microscope, and morphometric analysis was undertaken to assess possible ACTH-induced changes in total cell volume, volume density and numerical denisty of lipid droplets and mitochondria. There was no change in total cell volume. Lipid droplet volume density and numerical density decreased. Mitochondrial volume density did not change, but numerical density increased. The decrease in lipid droplet volume density indicates a rapid depletion of cholesterol for steroid production. This depletion is almost entirely due to the disappearance of lipid droplets, rather than to an overall diminution in their size, as shown by the decrease in lipid droplet numerical density. The mitochondrial data suggest that the adrenocortical cell has an adedquate mitochondrial apparatus to respond to acute ACTH stimulation with increased steroid output without an increase inmitochondrial volume.

  4. Seasonal effects on plasma cortisol concentrations in the Bedouin buck: circadian studies and response to ACTH.

    Science.gov (United States)

    Chergui, N; Mormede, P; Foury, A; Khammar, F; Amirat, Z

    2017-03-01

    Our work aims at the exploration of cortisol secretion in the Bedouin goat, native to the Algerian Sahara desert, to understand the mechanisms of adaptation to extreme hot climates. In the present study, diurnal and seasonal variations of cortisol concentrations were measured in basal conditions, as well as the response to ACTH stimulation tests across seasons in bucks. The plasma concentrations of cortisol showed no diurnal cycle but a large variation across seasons. The highest levels occurred in summer and winter when the environmental conditions are at their extreme levels. The rectal temperature showed nychthemeral and seasonal variations, and BW was also different across seasons with highest values in summer and lowest in winter. The results obtained after administration of two doses (2 or 10 μg/kg BW) of synthetic ACTH to three different age groups (kids, adults and elderly animals) showed a strong increase in plasma cortisol concentrations under all conditions with maximum levels achieved between 15 and 120 min. The analysis of the area under the cortisol curve showed no significant difference between the responses to the two doses of ACTH and between age groups, but showed seasonal variations with the lowest response in autumn than in other seasons. We conclude that season significantly affects secretion of cortisol in both basal state and under ACTH stimulation. However, the variation of adrenal reactivity to ACTH is not sufficient to explain seasonal differences, and in particular the summer peak in basal circulating cortisol concentrations. Further research should focus on the respective contribution of environmental factors (such as day length, temperature, humidity) and the mechanisms involved in cortisol regulation.

  5. Repeated 100 Hz TENS for the Treatment of Chronic Inflammatory Hyperalgesia and Suppression of Spinal Release of Substance P in Monoarthritic Rats

    Directory of Open Access Journals (Sweden)

    Hong-Xiang Liu

    2007-01-01

    Full Text Available Transcutaneous electrical nerve stimulation (TENS has been shown to be an effective measure for pain relief. The aim of the present study was to determine the optimal intensity and interval of repeated 100 Hz TENS for the treatment of chronic inflammatory hyperalgesia in a monoarthritic pain model of the rat, and to assess the changes of the spinal substance P (SP release in response to TENS treatment. A reliable, reproducible chronic monoarthritic pain model was produced by intra-articular injection of complete Freund's adjuvant (CFA at single ankle joint. The efficacy of 100 Hz TENS treatments with different frequencies and intensities was compared. In the acute period (within 3 weeks of monoarthritis, twice-a-week schedule of TENS reduced the swelling of the inflamed ankle significantly. In the stable period (4–9 weeks, however, once-a-week schedule produced a significantly better therapeutic effect on both inflammation and arthritic hyperalgesia than that of twice- or five-times-a-week schedule. Using three levels of intensity of TENS, we found that the weaker (1-1-2 mA stimulation produced significantly better therapeutic effects. Repeated TENS produced a reduction of SP content in spinal perfusate in parallel with the progressive reduction of the arthritic pain scores. Our results suggest that (i consecutive TENS treatments produced cumulative effect for chronic hyperalgesia, (ii for chronic inflammatory hyperalgesia, a weaker intensity and more sparsely arranged treatment schedule may produce better therapeutic effect and (iii a decrease in SP release may serve as one of the possible neurochemical mechanisms underlying the therapeutic effects of multiple TENS treatments on chronic inflammatory hyperalgesia.

  6. Effects of repeated high-dose methamphetamine and ceftriaxone post-treatments on tissue content of dopamine and serotonin as well as glutamate and glutamine.

    Science.gov (United States)

    Althobaiti, Yusuf S; Almalki, Atiah H; Das, Sujan C; Alshehri, Fahad S; Sari, Youssef

    2016-11-10

    Repeated exposure to high doses of methamphetamine (METH) is known to alter several neurotransmitters in certain brain regions. Little is known about the effects of ceftriaxone (CEF), a β-lactam antibiotic, known to upregulate glutamate transporter subtype 1, post-treatment on METH-induced depletion of dopamine and serotonin (5-HT) tissue content in brain reward regions. Moreover, the effects of METH and CEF post-treatment on glutamate and glutamine tissue content are not well understood. In this study, Wistar rats were used to investigate the effects of METH and CEF post-treatment on tissue content of dopamine/5-HT and glutamate/glutamine in the nucleus accumbens (NAc) and prefrontal cortex (PFC). Rats received either saline or METH (10mg/kg, i.p. every 2h×4) followed by either saline or CEF (200mg/kg, i.p, every day×3) post-treatment. METH induced a significant depletion of dopamine and 5-HT in the NAc and PFC. Importantly, dopamine tissue content was completely restored in the NAc following CEF post-treatment. Additionally, METH caused a significant decrease in glutamate and glutamine tissue content in PFC, and this effect was attenuated by CEF post-treatment. These findings demonstrate for the first time the attenuating effects of CEF post-treatment on METH induced alterations in the tissue contents of dopamine, glutamate, and glutamine. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Acylated ghrelin as provocative test for the diagnosis of ACTH deficiency in patients with hypothalamus-pituitary disease.

    Science.gov (United States)

    Gasco, Valentina; Berton, Alessandro; Caprino, Mirko Parasiliti; Karamouzis, Ioannis; Maccario, Mauro; Ghigo, Ezio; Grottoli, Silvia

    2015-11-01

    The insulin tolerance test (ITT) is the gold standard to evaluate adrenocorticotropic hormone (ACTH) insufficiency. However, alternative tests have been proposed such as metyrapone, glucagon, and ACTH stimulation test. We determined the diagnostic reliability of testing with ghrelin, the natural GH secretagogue that is a potent stimulus exploring the integrity of hypothalamic-pituitary-adrenal axis. We studied the ACTH and cortisol response to acylated ghrelin in 49 patients with history of pituitary disease. The best cortisol and ACTH cut offs to ghrelin test, defined as those with the best sensitivity (SE) and specificity (SP), were identified using the ROC analysis. We also compared accuracy of ghrelin test with that of a simple and cheap test like basal cortisol and ACTH levels. The best cortisol and ACTH cut offs to ghrelin test were ≤11.6 µg/dl (SE 86.4%, SP 77.8%) and ≤32.5 pg/ml (SE 72.7%, SP 51.9%), respectively; the best basal cortisol and ACTH cut offs were ≤10.7 µg/dl (SE 90.9%, SP 70.4%) and ≤25.0 pg/ml (SE 85%, SP 37%), respectively. The diagnostic accuracy was 81.6, 60.9, 79.6, and 57.4%, respectively. A comparison between ROC AUC showed a great diagnostic power for cortisol, both stimulated and basal, versus ACTH, both stimulated and basal, but no difference between stimulated and basal cortisol evaluation. Our data show that testing with acylated ghrelin is not a useful diagnostic tool for the diagnosis of central hypocortisolism; particularly ghrelin test adds no more information that basal cortisol evaluation in the diagnosis of ACTH deficiency in patients with hypothalamus-pituitary disease.

  8. ACTH-secreting pancreatic neoplasms associated with Cushing syndrome: clinicopathologic study of 11 cases and review of the literature.

    Science.gov (United States)

    Maragliano, Roberta; Vanoli, Alessandro; Albarello, Luca; Milione, Massimo; Basturk, Olca; Klimstra, David S; Wachtel, Antonio; Uccella, Silvia; Vicari, Emanuela; Milesi, Marina; Davì, Maria Vittoria; Scarpa, Aldo; Sessa, Fausto; Capella, Carlo; La Rosa, Stefano

    2015-03-01

    Adrenocorticotropic hormone (ACTH)-secreting pancreatic neuroendocrine tumors (PanNETs), although rare, are responsible for about 15% of ectopic Cushing syndrome (CS). They represent a challenging entity because their preoperatory diagnosis is frequently difficult, and clear-cut morphologic criteria useful to differentiate them from other types of PanNETs have not been defined. Ectopic ACTH secretion associated with CS can also be rarely due to pancreatic acinar cell carcinoma (ACC) and pancreatoblastoma, rare tumor types with morphologic features sometimes overlapping those of PanNETs and, for this reason, representing a diagnostic challenge for pathologists. We herein describe the clinicopathologic and immunohistochemical features of 10 PanNETs and 1 ACC secreting ACTH and associated with CS together with an extensive review of the literature to give the reader a comprehensive overview on ACTH-producing pancreatic neoplasms. ACTH-secreting PanNETs are aggressive neoplasms with an immunohistochemical profile that partially overlaps that of pituitary corticotroph adenomas. They are generally large and well-differentiated neoplasms without distinctive histologic features but with signs of aggressiveness including vascular and perineural invasion. They are more frequent in female individuals with a mean age of 42 years. At 5 and 10 years after diagnosis, 35% and 16.2% of patients, respectively, were alive. ACTH-secreting ACCs and pancreatoblastomas are very aggressive pediatric tumors with a poor prognosis. Using an appropriate immunohistochemical panel including ACTH, β-endorphin, trypsin, and BCL10 it is possible to recognize ACTH-secreting PanNETs and to distinguish them from the very aggressive ACTH-secreting ACCs.

  9. Prevalence of apical periodontitis relative to endodontic treatment in an adult Dutch population: a repeated cross-sectional study

    NARCIS (Netherlands)

    Peters, L.B.; Lindeboom, J.A.; Elst, M.E.; Wesselink, P.R.

    2011-01-01

    We aimed to compare an Amsterdam subpopulation's current prevalence of root canal fillings and associated periapical radiolucencies with a similar patient sample from 1988. An Amsterdam subpopulation was evaluated for missing teeth, restorations, quality of endodontic treatment, and periapical

  10. Aberrant expression of glucagon receptors in adrenal glands of a patient with Cushing's syndrome and ACTH-independent macronodular adrenal hyperplasia Expresion aberrante de receptores de glucagón en tejido adrenal de un paciente con síndrome de Cushing e hiperplasia adrenal macronodular indedependiente de ACTH

    Directory of Open Access Journals (Sweden)

    Valeria de Miguel

    2010-06-01

    Full Text Available Adrenocorticotropin (ACTH independent bilateral macronodular adrenal hyperplasia (AIMAH is a rare cause of Cushing´s syndrome, characterized by bilateral adrenal lesions and excess cortisol production despite ACTH suppression. Cortisol synthesis is produced in response to abnormal activation of G-protein- coupled receptors, such as gastric inhibitory peptide, vasopressin, beta adrenergic agonists, LH/hCG and serotonin receptors. The aim of this study was to analyze the expression of glucagon receptors in adrenal glands from an AIMAH patient. A patient with ACTH-independent Cushing´s syndrome and bilateral macronodular adrenal hyperplasia was screened for altered activation of adrenal receptors by physiological (mixed meal and pharmacological (gonadotrophin releasing hormone, ACTH and glucagon tests. The results showed abnormally high levels of serum cortisol after stimulation with glucagon. Hypercortisolism was successfully managed with ketoconazole treatment. Interestingly, a 4-month treatment with a somatostatin analogue (octreotide was also able to reduce cortisol secretion. Finally, Cushing's syndrome was cured after bilateral adrenalectomy. Abnormal mRNA expression for glucagon receptor in the patient´s adrenal glands was observed by Real-Time PCR procedure. These results strongly suggest that the mechanism of AIMAH causing Cushing´s syndrome in this case involves the illicit activation of adrenal glucagon receptors. This is the first case reported of AIMAH associated with ectopic glucagon receptors.La hiperplasia adrenal macronodular bilateral independiente de ACTH (HAMIA es una causa infrecuente de Síndrome de Cushing, caracterizada por lesiones adrenales bilaterales, hipercortisolismo y ACTH plasmática suprimida. La síntesis de cortisol estaría regulada a través de ligandos de receptores asociados a proteína G que se expresan en forma aberrante en la corteza de las glándulas adrenales. El objetivo de este trabajo es analizar

  11. Are repeated assisted reproductive technology treatments and an unsuccessful outcome risk factors for unipolar depression in infertile women?

    DEFF Research Database (Denmark)

    Sejbaek, Camilla S; Pinborg, Anja; Hageman, Ida

    2015-01-01

    INTRODUCTION: Previous studies have shown conflicting results whether unsuccessful medically assisted reproduction is a risk factor for depression among women. This study therefore investigated if women with no live birth after assisted reproductive technology (ART) treatment had a higher risk...... of unipolar depression compared with women with a live birth after ART treatment. MATERIAL AND METHODS: The Danish National ART-Couple (DANAC) Cohort is a national register-based cohort study that consists of women who received ART treatment from 1 January 1994 to 30 September 2009, in Denmark (n = 41 050......). Information on unipolar depression was obtained from the Danish Psychiatric Central Research Register. The analyses were conducted in Cox regression analysis. RESULTS: During the 308 494 person-years of follow up, 552 women were diagnosed with unipolar depression. A Cox proportional hazards model showed...

  12. The cortisol response to ACTH in pigs, heritability and influence of corticosteroid-binding globulin.

    Science.gov (United States)

    Larzul, C; Terenina, E; Foury, A; Billon, Y; Louveau, I; Merlot, E; Mormede, P

    2015-12-01

    In the search for biological basis of robustness, this study aimed (i) at the determination of the heritability of the cortisol response to ACTH in juvenile pigs, using restricted maximum likelihood methodology applied to a multiple trait animal model, and (ii) at the study of the relationships between basal and stimulated cortisol levels with corticosteroid-binding globulin (CBG), IGF-I and haptoglobin, all important players in glucose metabolism and production traits. At 6 weeks of age, 298 intact male and female piglets from 30 litters (30 dams and 30 boars) were injected with 250 µg ACTH(1-24) (Synacthen). Blood was taken before ACTH injection to measure basal levels of cortisol, glucose, CBG, IGF-I and haptoglobin, and 60 min later to measure stimulated cortisol levels and glucose. Cortisol increased 2.8-fold after ACTH injection, with a high correlation between basal and stimulated levels (phenotypic correlation, r p=0.539; genetic correlation, r g=0.938). Post-ACTH cortisol levels were highly heritable (h 2=0.684) and could therefore be used for genetic selection of animals with a more reactive hypothalamic-pituitary-adrenocortical axis. CBG binding capacity correlated with cortisol levels measured in basal conditions in males only. No correlation was found between CBG binding capacity and post-ACTH cortisol levels. Basal IGF-I concentration was positively correlated with BW at birth and weaning, and showed a high correlation with CBG binding capacity with a strong sexual dimorphism, the correlation being much higher in males than in females. Basal haptoglobin concentrations were negatively correlated with CBG binding capacity and IGF-I concentrations. Complex relationships were also found between circulating glucose levels and these different variables that have been shown to be related to glucose resistance in humans. These data are therefore valuable for the genetic selection of animals to explore the consequences on production and robustness traits, but

  13. Interactions of histaminergic and serotonergic neurons in the hypothalamic regulation of prolactin and ACTH secretion.

    Science.gov (United States)

    Jørgensen, H; Knigge, U; Kjaer, A; Warberg, J

    1996-11-01

    Serotonergic and histaminergic neuronal systems are both involved in mediation of the stress-induced release of the pituitary hormones prolactin (PRL) and ACTH. We investigated the possibility of an interaction between serotonin (5-HT) and histamine (HA) in regulation of PRL and ACTH secretion in conscious male rats. Animals were pretreated systemically with antagonists to 5-HT1, 5-HT2 or 5-HT3 receptors prior to intracerebroventricular (icv) administration of HA. The 5-HT1 + 2 receptor antagonist methysergide prevented and the 5-HT2 receptor antagonist LY 53857 attenuated the HA-induced PRL release while the 5-HT3 receptor antagonist ondansetron had no effect on this response. None of the three 5-HT receptor antagonists affected the ACTH response to HA. Specific blockade of HA synthesis by alpha-fluoromethylhistidine or blockade of postsynaptic HA receptors by icv infusion of the H1 receptor antagonist mepyramine or the H2 receptor antagonist cimetidine inhibited the PRL response to 5-HT or to the 5-HT precursor 5-hydroxytryptophan (5- HTP) given in combination with the 5-HT reuptake inhibitor fluoxetine (Flx). Blockade of the histaminergic system had no effect on the ACTH response to serotonergic stimulation. The H3 receptors are inhibitory HA receptors. Systemic pretreatment with the H3 receptor agonist R(alpha)methylhistamine, or the H3 receptor antagonist thioperamide had no effect on the hormone response to activation of the serotonergic system by 5-HTP plus Flx. We conclude that the serotonergic and histaminergic neuronal systems interact in their stimulation of PRL secretion, but not in their stimulation of ACTH secretion. This interaction involves serotonergic 5-HT1 and 5-HT2 receptors and histaminergic H1 and H2 receptors. Furthermore, the previously observed inhibitory effect of the H3 receptor agonist R(alpha)methylhistamine on stress-induced PRL and ACTH release seems not to be exerted by activation of presynaptic H3 receptors located on serotonergic

  14. Alterations in brain-derived neurotrophic factor in the mouse hippocampus following acute but not repeated benzodiazepine treatment.

    Directory of Open Access Journals (Sweden)

    Stephanie C Licata

    Full Text Available Benzodiazepines (BZs are safe drugs for treating anxiety, sleep, and seizure disorders, but their use also results in unwanted effects including memory impairment, abuse, and dependence. The present study aimed to reveal the molecular mechanisms that may contribute to the effects of BZs in the hippocampus (HIP, an area involved in drug-related plasticity, by investigating the regulation of immediate early genes following BZ administration. Previous studies have demonstrated that both brain derived neurotrophic factor (BDNF and c-Fos contribute to memory- and abuse-related processes that occur within the HIP, and their expression is altered in response to BZ exposure. In the current study, mice received acute or repeated administration of BZs and HIP tissue was analyzed for alterations in BDNF and c-Fos expression. Although no significant changes in BDNF or c-Fos were observed in response to twice-daily intraperitoneal (i.p. injections of diazepam (10 mg/kg + 5 mg/kg or zolpidem (ZP; 2.5 mg/kg + 2.5 mg/kg, acute i.p. administration of both triazolam (0.03 mg/kg and ZP (1.0 mg/kg decreased BDNF protein levels within the HIP relative to vehicle, without any effect on c-Fos. ZP specifically reduced exon IV-containing BDNF transcripts with a concomitant increase in the association of methyl-CpG binding protein 2 (MeCP2 with BDNF promoter IV, suggesting that MeCP2 activity at this promoter may represent a ZP-specific mechanism for reducing BDNF expression. ZP also increased the association of phosphorylated cAMP response element binding protein (pCREB with BDNF promoter I. Future work should examine the interaction between ZP and DNA as the cause for altered gene expression in the HIP, given that BZs can enter the nucleus and intercalate into DNA directly.

  15. Rapid and Longer-Term Antidepressant Effects of Repeated Ketamine Infusions in Treatment-Resistant Major Depression

    NARCIS (Netherlands)

    Murrough, James W.; Perez, Andrew M.; Pillemer, Sarah; Stern, Jessica; Parides, Michael K.; aan het Rot, Marije; Collins, Katherine A.; Mathew, Sanjay J.; Charney, Dennis S.; Iosifescu, Dan V.

    2013-01-01

    Background: Ketamine is reported to have rapid antidepressant effects; however, there is limited understanding of the time-course of ketamine effects beyond a single infusion. A previous report including 10 participants with treatment-resistant major depression (TRD) found that six ketamine

  16. Rapid and Longer-Term Antidepressant Effects of Repeated Ketamine Infusions in Treatment-Resistant Major Depression

    NARCIS (Netherlands)

    Murrough, James W.; Perez, Andrew M.; Pillemer, Sarah; Stern, Jessica; Parides, Michael K.; aan het Rot, Marije; Collins, Katherine A.; Mathew, Sanjay J.; Charney, Dennis S.; Iosifescu, Dan V.

    2013-01-01

    Background: Ketamine is reported to have rapid antidepressant effects; however, there is limited understanding of the time-course of ketamine effects beyond a single infusion. A previous report including 10 participants with treatment-resistant major depression (TRD) found that six ketamine infusion

  17. Nutrient and toxic element soil concentrations during repeated mineral and compost fertilization treatments in a Mediterranean agricultural soil.

    Science.gov (United States)

    Baldantoni, Daniela; Morra, Luigi; Saviello, Giovanni; Alfani, Anna

    2016-12-01

    Agricultural soils of semi-arid Mediterranean areas are often subjected to depletion of their chemical, physical, and biological properties. In this context, organic fertilization, in addition to providing nutrients for a longer time in respect to mineral fertilization, improves many other characteristics related to soil fertility. Moreover, the combined use of organic and mineral fertilizers may promote a more sustainable crop production. However, a concern on the long-term use of organic fertilizers arises in relation to the possible accumulation of toxic elements in soil and their transfer to human beings. For this reason, a long-term study on nutrient and toxic element total concentrations and availabilities during fertilization treatments was carried out. In particular, mineral NPK fertilized soils, soils amended with biowaste compost, soils amended with biowaste compost plus mineral nitrogen, and unfertilized soils were analyzed for 11 chemical elements. The results highlighted that temporal variations in total and bioavailable concentrations of both nutrients and toxic elements, occurring also in unfertilized soils, are wider than those related to fertilization treatments. Anyway, soil amendments with biowaste compost, alone or in combination with mineral fertilizers, reduce Cu bioavailability but improve K, Fe, Mn, and Zn availabilities, excluding at the same time a long-term accumulation in soil. Total and bioavailable toxic element concentrations (apart from available Cd) do not vary in relation to fertilization treatments.

  18. Variation in target and rectum dose due to prostate deformation: an assessment by repeated MR imaging and treatment planning

    Energy Technology Data Exchange (ETDEWEB)

    Kerkhof, E M; Put, R W van der; Raaymakers, B W; Heide, U A van der; Vulpen, M van; Lagendijk, J J W [Department of Radiotherapy, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht (Netherlands)], E-mail: E.Kerkhof@umcutrecht.nl

    2008-10-21

    In daily clinical practice, implanted fiducial markers are used to correct for prostate motion, but not for prostate deformation. The aim of this study is to investigate the variation in target and rectum dose due to the deformation of the prostate gland (without seminal vesicles). Therefore, we performed five to six MRI scans of eight healthy volunteers that exhibited large variation in rectal volume and thus prostate deformation. Prostate motion was corrected by a mask-based rigid registration which uses the delineation as well as the internal structures of the prostate gland. Per MRI scan, one IMRT plan with a PTV margin of 4 mm was created, resulting in 41 IMRT plans. The dose distribution of the IMRT plan based on the MRI scan with the minimum rectal volume was applied to the other rigidly registered MRI scans to evaluate the impact of prostate deformation. In conclusion, pre-treatment planning on the minimum rectal volume can cause a fraction dose increase (up to 15%) to the rectum due to prostate deformation. The impact on the total dose increase to the rectum depends on the intrapatient rectum variation during treatment, but is negligible with the currently used PTV margins in a fractionated treatment.

  19. Variation in target and rectum dose due to prostate deformation: an assessment by repeated MR imaging and treatment planning

    Science.gov (United States)

    Kerkhof, E. M.; van der Put, R. W.; Raaymakers, B. W.; van der Heide, U. A.; van Vulpen, M.; Lagendijk, J. J. W.

    2008-10-01

    In daily clinical practice, implanted fiducial markers are used to correct for prostate motion, but not for prostate deformation. The aim of this study is to investigate the variation in target and rectum dose due to the deformation of the prostate gland (without seminal vesicles). Therefore, we performed five to six MRI scans of eight healthy volunteers that exhibited large variation in rectal volume and thus prostate deformation. Prostate motion was corrected by a mask-based rigid registration which uses the delineation as well as the internal structures of the prostate gland. Per MRI scan, one IMRT plan with a PTV margin of 4 mm was created, resulting in 41 IMRT plans. The dose distribution of the IMRT plan based on the MRI scan with the minimum rectal volume was applied to the other rigidly registered MRI scans to evaluate the impact of prostate deformation. In conclusion, pre-treatment planning on the minimum rectal volume can cause a fraction dose increase (up to 15%) to the rectum due to prostate deformation. The impact on the total dose increase to the rectum depends on the intrapatient rectum variation during treatment, but is negligible with the currently used PTV margins in a fractionated treatment.

  20. Variation in target and rectum dose due to prostate deformation: an assessment by repeated MR imaging and treatment planning.

    Science.gov (United States)

    Kerkhof, E M; van der Put, R W; Raaymakers, B W; van der Heide, U A; van Vulpen, M; Lagendijk, J J W

    2008-10-21

    In daily clinical practice, implanted fiducial markers are used to correct for prostate motion, but not for prostate deformation. The aim of this study is to investigate the variation in target and rectum dose due to the deformation of the prostate gland (without seminal vesicles). Therefore, we performed five to six MRI scans of eight healthy volunteers that exhibited large variation in rectal volume and thus prostate deformation. Prostate motion was corrected by a mask-based rigid registration which uses the delineation as well as the internal structures of the prostate gland. Per MRI scan, one IMRT plan with a PTV margin of 4 mm was created, resulting in 41 IMRT plans. The dose distribution of the IMRT plan based on the MRI scan with the minimum rectal volume was applied to the other rigidly registered MRI scans to evaluate the impact of prostate deformation. In conclusion, pre-treatment planning on the minimum rectal volume can cause a fraction dose increase (up to 15%) to the rectum due to prostate deformation. The impact on the total dose increase to the rectum depends on the intrapatient rectum variation during treatment, but is negligible with the currently used PTV margins in a fractionated treatment.

  1. Small-cell Lung Cancer in a Young Adult Nonsmoking Patient with Ectopic Adrenocorticotropin (ACTH) Production.

    Science.gov (United States)

    Aoki, Masahiko; Fujisaka, Yasuhito; Tokioka, Satoshi; Hirai, Ai; Henmi, Yujiro; Inoue, Yosuke; Narabayashi, Ken; Yamano, Takeshi; Tamura, Yosuke; Egashira, Yutaro; Higuchi, Kazuhide

    2016-01-01

    Cushing's syndrome due to young small-cell lung cancer (SCLC) is recognized as being extremely rare. We herein present the case of a 35-year-old nonsmoking man who presented with thirst and polyuria. Laboratory examinations showed hyperglycemia, hypokalemia and liver enzyme elevation. Imaging examinations revealed the presence of multiple liver tumors and lymph node swelling. The levels of serum neuroendocrine tumor markers were elevated. The patient was diagnosed with SCLC based on the pathological examination of a biopsy specimen from the right supraclavicular lymph node. The physical findings, including proximal myopathy, truncal obesity and pigmentation suggested high levels of glucocorticoids. An immunohistochemical examination of the tumor showed that it was positive for adrenocorticotropin (ACTH). An endocrinological investigation allowed for the definitive diagnosis of SCLC with ectopic ACTH production.

  2. Comparative effect of ACTH and related peptides on proliferation and growth of rat adrenal gland

    Directory of Open Access Journals (Sweden)

    Claudimara Ferini Pacicco Lotfi

    2016-05-01

    Full Text Available Pro-opiomelanocortin (POMC is a polypeptide precursor known to yield biologically active peptides related to a range of functions. These active peptides include the adrenocorticotropic hormone (ACTH, which is essential for maintenance of adrenal growth and steroidogenesis, and the alpha-melanocyte stimulation hormone, which plays a key role in energy homeostasis. However, the role of the highly conserved N-terminal region of POMC peptide fragments has begun to be unraveled only recently. Here we review the cascade of events involved in regulation of proliferation and growth of murine adrenal cortex triggered by ACTH and other POMC-derived peptides. Key findings regarding signaling pathways and modulation of genes and proteins required for the regulation of adrenal growth are summarized. We have outlined the known mechanisms as well as future challenges for research on the regulation of adrenal proliferation and growth triggered by these peptides.

  3. Severe hypokalemia, metabolic alkalosis and hypertension in a 54 year old male with ectopic ACTH syndrome: a case report

    OpenAIRE

    Martínez-Valles, Miguel Angel; Palafox-Cazarez, Asael; Paredes-Avina, Jose Antonio

    2009-01-01

    Ectopic ACTH syndrome is a rare cause of Cushing’s syndrome accounting for about 15% of all cases. Small cell lung cancer and bronchial carcinoids account for about half of the cases. Malignant neoplasm has rapid and more aggressive metabolic effects. We report a 54-year-old male patient with phenotypic features of Cushing’s syndrome with severe hypokalemia, metabolic alkalosis, hypertension and altered mental status as manifestations of an ACTH-secreting small cell carcinoma from the lung. E...

  4. Role of ACTH in the Interactive/Paracrine Regulation of Adrenal Steroid Secretion in Physiological and Pathophysiological Conditions.

    OpenAIRE

    Herve Lefebvre; Michael Thomas; Duparc, Céline; Jerome Bertherat; Estelle Louiset

    2016-01-01

    International audience; In the normal human adrenal gland, steroid secretion is regulated by a complex network of autocrine/paracrine interactions involving bioactive signals released by endothelial cells, nerve terminals, chromaffin cells, immunocompetent cells, and adrenocortical cells themselves. ACTH can be locally produced by medullary chromaffin cells and is, therefore, a major mediator of the corticomedullary functional interplay. Plasma ACTH also triggers the release of angiogenic and...

  5. Prognostic value of repeated {sup 123}I-metaiodobenzylguanidine imaging in patients with dilated cardiomyopathy with congestive heart failure before and after optimized treatments. Comparison with neurohumoral factors

    Energy Technology Data Exchange (ETDEWEB)

    Matsui, Toshiki; Tsutamoto, Takayoshi; Maeda, Keiko; Kusukawa, Junya; Kinoshita, Masahiko [Shiga Univ. of Medical Science, Otsu (Japan)

    2002-06-01

    The present study was undertaken to assess whether repeated measurement of cardiac {sup 123}I-metaiodobenzylguanidine (MIBG) imaging parameters before and after optimized treatments is useful for predicting the prognosis of patients with congestive heart failure (CHF) resulting from dilated cardiomyopathy (DCM). The subjects were 85 consecutive patients with DCM who had a left ventricular ejection fraction (LVEF) of less than 45%. The MIBG and the concentrations of neurohumoral factors were measured at baseline and after 6 months of optimized treatments. Cox proportional hazards analysis was performed to assess the various parameters before and after treatment. Twenty-three patients had a cardiac event (12 died; 11 hospitalized) during a mean follow-up period of 2 years. Although there was no difference between the baseline heart to mediastinum (H/M) ratio measured by MIBG between survivors and nonsurvivors, the H/M ratio was significantly decreased in nonsurvivors after 6 months. Multivariate analysis revealed that a high plasma concentration of brain natriuretic peptide level after 6 months (p=0.0049) and absolute changes in the H/M ratio (p=0.0046) were independent predictors of mortality. Comparison of the H/M ratio on MIBG imaging before and after optimized additional treatment provided useful information for predicting mortality and was independent of clinical and neurohumoral factors previously shown to be associated with poor prognosis in patients with DCM. (author)

  6. 胚胎反复植入失败的母体因素及应对策略%Mothers’ Factors and Treatment of Repeated Implantation Failure

    Institute of Scientific and Technical Information of China (English)

    张伟伟; 张云山

    2014-01-01

    胚胎反复植入失败(repeated implantation failure, RIF)是在经过多次IVF-ET后,移植的胚胎没有着床。胚胎植入失败与母体或胚胎因素有关,其中母体因素包括宫腔病理学、血栓形成倾向和免疫因素等。近年来许多方法用于改善和治疗引起RIF的母体因素,如宫腔内灌注β-hCG、阴道用西地那非和静脉输注英脱利匹特注射液等。临床医生应积极探寻导致RIF的病因,并采取积极有效的措施改善RIF患者的妊娠结局。%[ABSTRACT]Repeated implantation failure (RIF) is determined when transferred embryos fail to implant after several IVF treatment attempts. Implantation failure is related to either maternal factors or embryonic causes. Maternal factors include uterine anatomic abnormalities, thrombophilia and immunological factors. In recent years, many methods are used to improve and treat the maternal factors, such as intrauterine administration of hCG, vaginal sildenafil and administer intralipid solution. Clinicans should explore the reasons for RIF and take effective measures to improve the outcome of these patients.

  7. Effects of the 5-HT(1A) Receptor Agonist Tandospirone on ACTH-Induced Sleep Disturbance in Rats.

    Science.gov (United States)

    Tsutsui, Ryuki; Shinomiya, Kazuaki; Sendo, Toshiaki; Kitamura, Yoshihisa; Kamei, Chiaki

    2015-01-01

    The aim of this study was to compare the effect of the serotonin (5-HT)1A receptor agonist tandospirone versus that of the benzodiazepine hypnotic flunitrazepam in a rat model of long-term adrenocorticotropic hormone (ACTH)-induced sleep disturbance. Rats implanted with electrodes for recording electroencephalogram and electromyogram were injected with ACTH once daily at a dose of 100 µg/rat. Administration of ACTH for 10 d caused a significant increase in sleep latency, decrease in non-rapid eye movement (non-REM) sleep time, and increase in wake time. Tandospirone caused a significant decrease in sleep latency and increase in non-REM sleep time in rats treated with ACTH. The effect of tandospirone on sleep patterns was antagonized by the 5-HT1A receptor antagonist WAY-100635. In contrast, flunitrazepam had no significant effect on sleep parameters in ACTH-treated rats. These results clearly indicate that long-term administration of ACTH causes sleep disturbance, and stimulating the 5-HT1A receptor by tandospirone may be efficacious for improving sleep in cases in which benzodiazepine hypnotics are ineffective.

  8. Role of ACTH in the interactive/paracrine regulation of adrenal steroid secretion in physiological and pathophysiological conditions

    Directory of Open Access Journals (Sweden)

    Herve Lefebvre

    2016-07-01

    Full Text Available In the normal human adrenal gland, steroid secretion is regulated by a complex network of autocrine/paracrine interactions involving bioactive signals released by endothelial cells, nerve terminals, chromaffin cells, immunocompetent cells and adrenocortical cells themselves. ACTH can be locally produced by medullary chromaffin cells and is therefore a major mediator of the corticomedullary functional interplay. Plasma ACTH also triggers the release of angiogenic and vasoactive agents from adrenocortical cells and adrenal mast cells, and thus indirectly regulates steroid production through modulation of the adrenal blood flow. Adrenocortical neoplasms associated with steroid hypersecretion exhibit molecular and cellular defects which tend to reinforce the influence of paracrine regulatory loops on corticosteroidogenesis. Especially, ACTH has been found to be abnormally synthesized in bilateral macronodular adrenal hyperplasia responsible for hypercortisolism. In these tissues, ACTH is detected in a subpopulation of adrenocortical cells which express gonadal markers. This observation suggests that ectopic production of ACTH may result from impaired embryogenesis leading to abnormal maturation of the adrenogonadal primordium. Globally, the current literature indicates that ACTH is a major player in the autocrine/paracrine processes occurring in the adrenal gland in both physiological and pathological conditions.

  9. Role of ACTH in the Interactive/Paracrine Regulation of Adrenal Steroid Secretion in Physiological and Pathophysiological Conditions.

    Science.gov (United States)

    Lefebvre, Hervé; Thomas, Michaël; Duparc, Céline; Bertherat, Jérôme; Louiset, Estelle

    2016-01-01

    In the normal human adrenal gland, steroid secretion is regulated by a complex network of autocrine/paracrine interactions involving bioactive signals released by endothelial cells, nerve terminals, chromaffin cells, immunocompetent cells, and adrenocortical cells themselves. ACTH can be locally produced by medullary chromaffin cells and is, therefore, a major mediator of the corticomedullary functional interplay. Plasma ACTH also triggers the release of angiogenic and vasoactive agents from adrenocortical cells and adrenal mast cells and, thus, indirectly regulates steroid production through modulation of the adrenal blood flow. Adrenocortical neoplasms associated with steroid hypersecretion exhibit molecular and cellular defects that tend to reinforce the influence of paracrine regulatory loops on corticosteroidogenesis. Especially, ACTH has been found to be abnormally synthesized in bilateral macronodular adrenal hyperplasia responsible for hypercortisolism. In these tissues, ACTH is detected in a subpopulation of adrenocortical cells that express gonadal markers. This observation suggests that ectopic production of ACTH may result from impaired embryogenesis leading to abnormal maturation of the adrenogonadal primordium. Globally, the current literature indicates that ACTH is a major player in the autocrine/paracrine processes occurring in the adrenal gland in both physiological and pathological conditions.

  10. Repeated treatments with ingenol mebutate for prophylaxis of UV-induced squamous cell carcinoma in hairless mice

    DEFF Research Database (Denmark)

    Erlendsson, Andrés M; Thaysen-Petersen, Daniel; Bay, Christiane

    2016-01-01

    of a corticosteroid would reduce IngMeb-induced local skin responses (LSRs) without affecting tumor postponement. METHODS: Hairless mice (n=150; 6 groups á 25 mice) were irradiated with solar simulated ultraviolet radiation (UVR) until SCC developed. During UV-irradiation and before tumor development, five single......, 1-, 2-, 3-, 4-, 5-, 6-, and 7days after each IngMeb treatment. RESULTS: IngMeb significantly delayed tumor development compared to UVR alone (UVR day 168 vs. UVR+IngMeb day 189; p=0.025). LSR included erythema, flaking, crusting, bleeding, vesiculation, and ulceration. The composite LSR-scores were...... of moderate intensity in non-UV irradiated skin (max LSR IngMeb Tx 1-5: 1.5-2.5) and more pronounced in photodamaged skin (max LSR Tx 5; IngMeb 1.5 vs. UVR+IngMeb 1.8; p

  11. Activation of the dopamine receptor type-2 (DRD2) promoter by 9-cis retinoic acid in a cellular model of Cushing's disease mediates the inhibition of cell proliferation and ACTH secretion without a complete corticotroph-to-melanotroph transdifferentiation.

    Science.gov (United States)

    Occhi, Gianluca; Regazzo, Daniela; Albiger, Nora Maria; Ceccato, Filippo; Ferasin, Sergio; Scanarini, Massimo; Denaro, Luca; Cosma, Chiara; Plebani, Mario; Cassarino, Maria Francesca; Mantovani, Giovanna; Stalla, Günter K; Pecori Giraldi, Francesca; Paez-Pareda, Marcelo; Scaroni, Carla

    2014-09-01

    Cushing's disease (CD) is a rare condition in which hypercortisolemia is secondary to excessive ACTH release from a pituitary corticotroph adenoma. CD is associated with significant morbidity and mortality, and a safe therapy that effectively targets the pituitary tumor is still lacking. Retinoic acid (RA) and dopamine agonists (DAs) have recently been considered as monotherapy in CD patients, and satisfactory results have been reported, albeit in a limited number of patients. Given the permissive role of RA on the dopamine receptor type-2 (DRD2), the aim of the present study was to see whether a combination of 9-cis RA and the DA bromocriptine (Br) might represent a possible treatment for CD. Here we show that 9-cis RA induces a functional DRD2 in the pituitary corticotroph cell line AtT20, and increases cell sensitivity to Br via a mechanism only partially related to corticotroph-to-melanotroph transdifferentiation. In addition, 9-cis RA and Br act synergistically to modulate cell viability, with favorable implications for clinical use. In nearly 45% of corticotropinoma-derived primary cultures, the combined administration of 9-cis RA and Br lowered the steady-state level of the ACTH precursor proopiomelanocortin (POMC) more efficiently than either of the drugs alone. In conclusion, the effects of a combination of 9-cis RA and Br on ACTH synthesis/secretion and cell viability in AtT20, and on POMC transcriptional activity in human corticotropinomas might represent a suitable starting point for assessing the potential of this treatment regimen for ACTH-secreting pituitary adenomas. This study thus has potentially important implications for novel therapeutic approaches to CD.

  12. 促肾上腺皮质激素依赖性库欣综合征的诊断与治疗策略%The strategy for diagnosis and management of ACTH-dependent Cushing's syndrome

    Institute of Scientific and Technical Information of China (English)

    陆召麟

    2010-01-01

    Majority of the patients (about 80% ) with Cushing's syndrome are ACTH-dependent,which including pituitary-dependent Cushing's syndrome and ectopic ACTH syndrome. The diagnosis and treatment of this disease is rather complicated and difficult. A lot of progresses in this field have been made within the recent decades, though there are still many problems. Here introduces and evaluates the methods which are used widely for diagnosis, differential diagnosis and treatment. The strategy of the choice making are discussed. Brief introduction for guideline on the diagnosis of Cushing's syndrome and for the consensus of ACTH-dependent Cushing's syndrome which was published in 2008 is also be made.%促肾上腺皮质激素(ACTH)依赖性库欣综合征占库欣综合征病例总数的80%,主要包括垂体性库欣综合征和异位ACTH综合征.ACTH依赖性库欣综合征的诊断和治疗比较复杂,也比较困难.近年来,本病的诊断和治疗有很大的进步,但还存在不少问题.现对目前广泛应用于ACTH依赖性库欣综合征的各种诊断、鉴别诊断及治疗方法进行介绍和评价,并讨论治疗方法的选择以及治疗效果的评估.还对国际内分泌学会于2008年发表的关于库欣综合征的诊断指南及欧洲神经内分泌学会和垂体学会关于ACTH依赖性库欣综合征治疗的共识作简要介绍.

  13. Diverse action of repeated corticosterone treatment on synaptic transmission, neuronal plasticity, and morphology in superficial and deep layers of the rat motor cortex.

    Science.gov (United States)

    Kula, Joanna; Gugula, Anna; Blasiak, Anna; Bobula, Bartosz; Danielewicz, Joanna; Kania, Alan; Tylko, Grzegorz; Hess, Grzegorz

    2017-07-27

    One of the adverse effects of prolonged stress in rats is impaired performance of skilled reaching and walking tasks. The mechanisms that lead to these abnormalities are incompletely understood. Therefore, we compared the effects of twice daily repeated corticosterone injections for 7 days on miniature excitatory postsynaptic currents (mEPSCs), as well as on synaptic plasticity and morphology of layers II/III and V pyramidal neurons of the primary motor cortex (M1) of male Wistar rats. Corticosterone treatment resulted in increased frequency, but not amplitude, of mEPSCs in layer II/III neurons accompanied by increased complexity of the apical part of their dendritic tree, with no changes in the density of dendritic spines. The frequency and amplitude of mEPSCs as well as the parameters characterizing the complexity of the dendritic tree were not changed in layer V cells; however, their dendritic spine density was increased. While corticosterone treatment resulted in an increase in the amplitude of field potentials evoked in intralaminar connections within layer II/III, it did not influence field responses in layer V intralaminar connections, as well as the extent of chemically induced layer V long-term potentiation (chemLTP) by the application of tetraethylammonium (TEA, 25 mM). However, chemLTP induction in layer II/III was impaired in slices prepared from corticosterone-treated animals. These data indicate that repeated 7-day administration of exogenous corticosterone induces structural and functional plasticity in the M1, which occurs mainly in layer II/III pyramidal neurons. These findings shed light on potential sites of action and mechanisms underlying stress-induced impairment of motor functions.

  14. Tratamento das formas severas de miastenia pelo ACTH por via intravenosa

    Directory of Open Access Journals (Sweden)

    José Lamartine de Assis

    1960-12-01

    Full Text Available O autor inicia o trabalho referindo as bases bioquímicas, fisiopatológicas e anátomo-patológicas do tratamento da miastenia pelo ACTH. Na miastenia grave há diminuição da síntese da acetilcolina no organismo, atuando o ACTH no sentido de aumentar esta síntese seja diretamente, por ativação da colinacetilase, seja indiretamente, mediante a redução da massa dos tecidos linfóides, em particular do timo, responsáveis pela elaboração de substâncias que diminuem a síntese da acetilcolina. O autor empregou o ACTH "Armour" e a Cortrofina "Organon", nas doses de 2,5 a 25 mg, sempre pela via intravenosa, diluídos em 250 a 1.000 ml de soluto glicosado a 5%, administrado gota a gôta, na velocidade média de 20 gôtas por minuto, durante 8 horas. Como medicação associada foi administrada a Prostigmina a todos os pacientes, substituída, depois, em alguns casos, pelo Mestinon ou pela Mytelaze. Como adjuvantes foram empregados o cloreto de potássio (2 a 8 g por dia e o sulfato de efedrina (25 mg 3 vêzes ao dia. Os pacientes foram mantidos em regime hiperprotéico e acloretado, sendo tomados todos os cuidados inerentes ao uso do ACTH. Foram estudados 10 pacientes portadores de miastenia com sintomatologia acentuada (8 casos e média (2 casos. Todos os doentes vinham sendo tratados com drogas anticolinesterásicas em doses adequadas (Prostigmina, Mestinon, Mytelaze e a sua sintomatologia respondia cada vez menos a esta terapêutica. Em alguns casos haviam sido tentados outros tratamentos (timectomia, denervação do seio carotídeo, irradiação da região tímica sem resultado. É de notar que as remissões espontâneas neste grupo de enfermos foram excepcionais e de curta duração. A evolução foi acompanhada do ponto de vista clínico, com a sintomatologia classificada como muito acentuada, acentuada, média e leve. Em todos os casos houve remissão completa ou quase completa da sintomatologia após dosagens variáveis de ACTH; no

  15. The Recombinant ACTH (4-10) -GDNF Fusion Protein and Study ofIts Biological Activity%重组ACTH(4-10)与GDNF融合蛋白及其生物活性研究

    Institute of Scientific and Technical Information of China (English)

    陈哲宇; 张勇; 何成; 路长林; 吴祥甫

    2001-01-01

    通过PCR方法构建了促肾上腺皮质激素4-10(ACTH(4-10))与胶质细胞源性神经营养因子(GDNF)的 融合基因,并将它重组克隆到表达载体pET-28a(+)中,构建表达质粒pET-ACTH(4-10)-GDNF,转化大肠 杆菌BL21(DE3),经IPTG诱导可高效表达ACTH(4-10)-GDNF融合蛋白.用Ni2+-NTA树脂一步法纯化目 的蛋白,纯度达85%以上.纯化和复性的ACTH(4-10)-GDNF融合蛋白能显著促进脊髓神经元存活,作用强 于ACTH(4-10)及GDNF蛋白.%The chimeric gene of ACTH (4-10) with GDNF was constructed by PCR amplification. The fused gene was inserted into the expression vector pET-28a ( + ) and expressed in E. coli . with a level of 30% of the total bacterial proteins. The expressed product was purified by Ni2+ -NTA resin, up to 85% purity. The results of activity assays showed that the chimeric protein could significantly promote the survival of spinal cord neurons and had a higher neurotrophic activity than ACTH (4-10) and GDNF respectively.

  16. Case report: ACTH-secreting pituitary carcinoma metastatic to the liver in a patient with a history of atypical pituitary adenoma and Cushing's disease.

    Science.gov (United States)

    Joehlin-Price, Amy S; Hardesty, Douglas A; Arnold, Christina A; Kirschner, Lawrence S; Prevedello, Daniel M; Lehman, Norman L

    2017-04-18

    Pituitary carcinoma is a rare entity requiring the presence of metastasis to confirm its malignant potential. We report a case of pituitary carcinoma and discuss the diagnosis and management of this lesion in relation to the existing literature. The patient is a 51-year-old woman with Cushing's disease and intact adrenal glands who was diagnosed with metastatic pituitary carcinoma to the liver, 29 months after initial resection of an ACTH-secreting primary atypical pituitary adenoma (APA). Prior to detection of this metastasis the patient underwent repeat resection and radiotherapy for residual cavernous sinus disease. The metastatic lesion was detected by interval surveillance of serum ACTH and 24-hour urine cortisol, which despite stable pituitary MRI, were significantly elevated. These abnormalities prompted a PET scan that demonstrated hypermetabolic liver parenchyma, which was suspicious for metastasis on abdominal MRI. An ultrasound-guided liver biopsy demonstrated nests of moderately-differentiated cells with intermediate-sized, monotonous nuclei, distinct nucleoli, and abundant basophilic cytoplasm, confirmed by immunohistochemistry to represent metastatic pituitary carcinoma. The liver lesion was subsequently successfully removed by wedge resection. One year later, the patient's residual cavernous sinus disease grew markedly, and she was placed on dual-agent chemotherapy consisting of oral temozolomide and capecitabine, with stabilization of her intracranial disease to present, although liver metastases recurred. Pituitary carcinoma is a rare entity impossible to recognize as a primary tumor because its diagnosis by definition requires the presence of metastasis. Maintaining awareness of the entity and its precursor lesion APA is essential for its accurate pathologic diagnosis and appropriate management.

  17. Comparison of salivary and calculated free cortisol levels during low and standard dose of ACTH stimulation tests in healthy volunteers.

    Science.gov (United States)

    Elbuken, Gulsah; Tanriverdi, Fatih; Karaca, Zuleyha; Kula, Mustafa; Gokahmetoglu, Selma; Unluhizarci, Kursad; Kelestimur, Fahrettin

    2015-03-01

    Salivary cortisol (SC) has been increasingly used as a surrogate biomarker of free cortisol (FC) for the assessment of hypothalamo-pituitary-adrenal (HPA) axis, but there are not enough data regarding its use during ACTH stimulation tests. Therefore, we aimed to determine the responses of SC, calculated free cortisol (cFC) and free cortisol index (FCI) to ACTH stimulation tests in healthy adults. Forty-four healthy volunteers (24 men and 20 women) were included in the study. Low-dose (1 µg) and standard-dose (250 µg) ACTH stimulation tests were performed on two consecutive days. Basal and stimulated total cortisol (TC) and cortisol-binding globulin (CBG) levels and SC levels were measured during both doses of ACTH stimulation tests. cFC (by Coolens' equation) and FCI levels were calculated from simultaneously measured TC and CBG levels. The minimum SC, cFC, FCI levels after low-dose ACTH stimulation test were 0.21, 0.33, 16.06 µg/dL, and after standard-dose ACTH were 0.85, 0.46, 26.11 µg/dL, respectively, in healthy individuals who all had TC responses higher than 20 µg/dL. Peak CBG levels after both doses of ACTH stimulation tests were found to be higher in women than in men. So, by its effect, peak cFC and FCI levels were found to be lower in female than in male group. Neither TC nor SC levels were affected by gender. cFC and FCI levels depend on CBG levels and they are affected by gender. Cut-off levels for SC, cFC, FCI levels after both low- and standard-dose ACTH stimulation are presented. Studies including patients with adrenal insufficiency would be helpful to see the diagnostic value of these suggested cut-off levels.

  18. The results of surgical treatment of 14 patients underwent repeated tricuspid valve operations%三尖瓣再次手术14例

    Institute of Scientific and Technical Information of China (English)

    周明阳; 张健群; 孟旭; 李温斌; 孔晴宇

    2008-01-01

    目的 总结三尖瓣再次手术的治疗效果及经验.方法 2002年至2006年,收治14例三尖瓣再次手术病人,其中三尖瓣成形术后再次出现关闭不全12例,三尖瓣置换术后人工瓣膜功能障碍2例.结果 再次实施三尖瓣成形术5例,三尖瓣置换术9例.死亡2例,余者治愈出院.10例随访2~40个月,1例心功能Ⅲ级,余者均为Ⅰ~Ⅱ级.结论 再次三尖瓣手术治疗效果确切,手术死亡与手术方式的选择以及围术期心、肾功能衰竭有关.%Objective To evaluate the results and surgical treatment of the repeated tricuspid valve operations. Methods The hospital records was reviewed for 14 patients who underwent repeated tricuspid valve operations between 2003 and 2006, including 12 patients with tricuspid regurgitation received first tricuspid valve repair and 2 patients, with prosthetic valve dysfunction. Results Reoperations of tricuspid valve included 5 tricuspid valve repair and 9 tricuspid valve replacement. There were two postoperative deaths. Post-operative heart function (NYHA) was improved significantly, 1 case in Ⅲ and 9 in Ⅰ-Ⅱ. Ten survivors were followed up for 2 - 40 months. Conclusion Tricuspid valve reoperations may be performed with acceptable operative mortality. Perioperative death was associated with surgical methods and heart or renal function failure.

  19. Diagnostic accuracy of increased urinary cortisol/cortisone ratio to differentiate ACTH-dependent Cushing's syndrome.

    Science.gov (United States)

    Ceccato, Filippo; Trementino, Laura; Barbot, Mattia; Antonelli, Giorgia; Plebani, Mario; Denaro, Luca; Regazzo, Daniela; Rea, Federico; Frigo, Anna Chiara; Concettoni, Carolina; Boscaro, Marco; Arnaldi, Giorgio; Scaroni, Carla

    2017-06-07

    Differential diagnosis between Cushing's Disease (CD) and Ectopic ACTH Syndrome (EAS) may be a pitfall for endocrinologists. The increasing use in clinical practice of chromatography and mass spectrometry improves the measurement of urinary free cortisol (UFF) and cortisone (UFE). We have recently observed that cortisol to cortisone ratio (FEr) was higher in a small series of EAS; in this study we collected a larger number of ACTH-dependent Cushing's Syndrome (CS) to study the role of FEr to characterize the source of corticotropin secretion. High-pressure liquid chromatography with UV detection (HPLC-UV, n=35) or liquid chromatography-tandem mass spectrometry (LC-MS/MS, n=72) were used to measure UFF, UFE and FEr in 83 patients with CD and 24 with EAS. UFF, UFE and FEr levels were higher in EAS than in CD (UFF: 6671 vs 549 nmol/24 hours; UFE: 2069 vs 464 nmol/24 hours; FEr: 4.13 vs 0.97; all P1.15 (the best ROC-based threshold) was able to distinguish CD from EAS with 75% sensitivity (SE) and 75% specificity (SP), AUC 0.811; results were similar between HPLC-UV (SE 73%, SP 79%, AUC 0.708) and LC-MS/MS (SE 77%, SP 73%, AUC 0.834; P=.727). The diagnostic accuracy of FEr was similar to that of CRH test or high-dose dexamethasone suppression test (respectively P=.171 and P=.683), also combined. Finally, FEr was able to increase the number of correct diagnosis in patients with discordant dynamic tests. Urinary FEr >1.15 was able to suggest EAS, with a diagnostic accuracy similar to that of other dynamic tests proposed to study ACTH-dependent CS. © 2017 John Wiley & Sons Ltd.

  20. Predicting the onset of Addison's disease: ACTH, renin, cortisol and 21-hydroxylase autoantibodies

    Science.gov (United States)

    Baker, Peter R.; Nanduri, Priyaanka; Gottlieb, Peter A.; Yu, Liping; Klingensmith, Georgeanna J.; Eisenbarth, George S.; Barker, Jennifer M.

    2016-01-01

    Summary Context Autoantibodies to 21-hydroxylase (21OH-AA) precede onset of autoimmune Addison's disease (AD). Progression to AD can take months to years, and early detection of metabolic decompensation may prevent morbidity and mortality. Objective To define optimal methods of predicting progression to overt AD (defined by subnormal peak cortisol response to Cosyntropin) in 21OH-AA+ individuals. Design, Setting and Participants Individuals were screened for 21OH-AA at the Barbara Davis Center from 1993 to 2011. Subjects positive for 21OH-AA (n = 87) were tested, and the majority prospectively followed for the development of Addison's disease, including seven diagnosed with AD upon 21OH-AA discovery (discovered), seven who progressed to AD (progressors) and 73 nonprogressors. Main Outcome Measured Plasma renin activity (PRA), ACTH, baseline cortisol, peak cortisol and 21OH-AA were measured at various time points relative to diagnosis of AD or last AD-free follow-up. Results Compared with nonprogressors, in the time period 2 months–2 years prior to the onset of AD, progressors were significantly more likely to have elevated ACTH (11–22 pm, P < 1E-4), with no significant differences in mean PRA (P = 0·07) or baseline cortisol (P = 0·08), and significant but less distinct differences seen with 21OH-AA levels (P < 1E-4) and poststimulation cortisol levels (P = 6E-3). Conclusion Moderately elevated ACTH is a more useful early indicator of impending AD than 21OH-AA, PRA or peak cortisol, in the 2 months–2 years preceding the onset of AD. PMID:22066755

  1. ACTH-Independent Cushing’s Syndrome with Bilateral Micronodular Adrenal Hyperplasia and Ectopic Adrenocortical Adenoma

    Science.gov (United States)

    Louiset, Estelle; Gobet, Françoise; Libé, Rossella; Horvath, Anelia; Renouf, Sylvie; Cariou, Juliette; Rothenbuhler, Anya; Bertherat, Jérôme; Clauser, Eric; Grise, Philippe; Stratakis, Constantine A.; Kuhn, Jean-Marc; Lefebvre, Hervé

    2010-01-01

    Context: Bilateral micronodular adrenal hyperplasia and ectopic adrenocortical adenoma are two rare causes of ACTH-independent Cushing’s syndrome. Objective: The aim of the study was to evaluate a 35-yr-old woman with ACTH-independent hypercortisolism associated with both micronodular adrenal hyperplasia and ectopic pararenal adrenocortical adenoma. Design and Setting: In vivo and in vitro studies were performed in a University Hospital Department and academic research laboratories. Intervention: Mutations of the PRKAR1A, PDE8B, and PDE11A genes were searched for in leukocytes and adrenocortical tissues. The ability of adrenal and adenoma tissues to synthesize cortisol was investigated by immunohistochemistry, quantitative PCR, and/or cell culture studies. Main Outcome Measure: Detection of 17α-hydroxylase and 21-hydroxylase immunoreactivities, quantification of CYP11B1 mRNA in adrenal and adenoma tissues, and measurement of cortisol levels in supernatants by radioimmunological assays were the main outcomes. Results: Histological examination of the adrenals revealed nonpigmented micronodular cortical hyperplasia associated with relative atrophy of internodular cortex. No genomic and/or somatic adrenal mutations of the PRKAR1A, PDE8B, and PDE11A genes were detected. 17α-Hydroxylase and 21-hydroxylase immunoreactivities as well as CYP11B1 mRNA were detected in adrenal and adenoma tissues. ACTH and dexamethasone activated cortisol secretion from adenoma cells. The stimulatory action of dexamethasone was mediated by a nongenomic effect involving the protein kinase A pathway. Conclusion: This case suggests that unknown molecular defects can favor both micronodular adrenal hyperplasia and ectopic adrenocortical adenoma associated with Cushing’s syndrome. PMID:19915020

  2. Infundibular neurons of the human hypothalamus simultaneously reactive with antisera against endorphins, ACTH, MSH and beta-LPH.

    Science.gov (United States)

    Bugnon, C; Bloch, B; Lenys, D; Fellmann, D

    1979-06-27

    In man, discrete neurons of the infundibular (arcuate) nucleus contain compounds that can be stained with anti-endorphin (alpha and beta), anti-ACTH, anti-MSH (alpha and beta) and anti-beta-LPH immune sera (I.S.). In the fetus, certain neurons stain with anti-beta-endorphin or anti((17--39)ACTH starting from the 11th week of fetal life. At the ultrastructural level, these neurons contain elementary granules that are immunoreactive with anti-beta-endorphin. In the adult, neurons immunoreactive with anti-beta-endorphin are found in the infundibular nucleus. Their axonal fibers terminate around blood vessels in the neurovascular zone and in the pituitary stalk, or establish contacts with non-immunoreactive perikarya of the infundibular nucleus. These neurons can be stained with anti(17--39)ACTH and anti-beta-endorphin I.S. The most reactive are also stained moderately with anti-alpha-MSH, anti-beta-MSH, anti-beta-LPH, anti-alpha-endorphin, or anti(1--24)ACTH I.S. These results indicate that, in man, compound(s) identical with or immunologically related to endorphins, beta-LPH, ACTH and MSH are secreted by certain hypothalamic neurons. These agents probably originate from a common precursor molecula similar to the so-called pro-opiocortin.

  3. Research progress in ectopic ACTH syndrome%异位ACTH综合征研究进展

    Institute of Scientific and Technical Information of China (English)

    宁光

    2006-01-01

    @@ 异位ACTH综合征(EAS)是Cushing综合征的一种特殊类型,是由于垂体以外的肿瘤组织分泌过量有生物活性的促肾上腺皮质激素(ACTH),刺激肾上腺皮质增生,产生过量皮质类固醇引起的临床综合征,占Cushing综合征患者总数的5%~10%.

  4. A Case of Primary Hyperparathyroidism Combined with Cushing Syndrome due to Ectopic ACTH Secretion

    Directory of Open Access Journals (Sweden)

    N.T. Rikhsiieva

    2015-03-01

    Full Text Available A rare case of primary hyperparathyroidism (PHPT combined with Cushing syndrome due to ectopic ACTH secretion in 37-year-old women is described. The patient gradually underwent surgeries after compensation of general condition: bilateral parathyroidectomy, in 4 months — removal of carcinoid tumor of the lung. In case of Cushing syndrome or PHPT, the authors recommended to carry out careful examination of patients to exclude MEN-1 and MEN-2 syndromes. In addition, it is necessary to exclude the presence of familial forms of the disease, i.e., it is necessary to carry out a survey of first-degree relatives.

  5. Repeat-until-success quantum repeaters

    Science.gov (United States)

    Bruschi, David Edward; Barlow, Thomas M.; Razavi, Mohsen; Beige, Almut

    2014-09-01

    We propose a repeat-until-success protocol to improve the performance of probabilistic quantum repeaters. Conventionally, these rely on passive static linear-optics elements and photodetectors to perform Bell-state measurements (BSMs) with a maximum success rate of 50%. This is a strong impediment for entanglement swapping between distant quantum memories. Every time a BSM fails, entanglement needs to be redistributed between the corresponding memories in the repeater link. The key ingredients of our scheme are repeatable BSMs. Under ideal conditions, these turn probabilistic quantum repeaters into deterministic ones. Under realistic conditions, our protocol too might fail. However, using additional threshold detectors now allows us to improve the entanglement generation rate by almost orders of magnitude, at a nominal distance of 1000 km, compared to schemes that rely on conventional BSMs. This improvement is sufficient to make the performance of our scheme comparable to the expected performance of some deterministic quantum repeaters.

  6. Anxiolytic effects of repeated treatment with an essential oil from Lippia alba and (R-(--carvone in the elevated T-maze

    Directory of Open Access Journals (Sweden)

    V.Y. Hatano

    2012-03-01

    Full Text Available Lippia alba (Mill. N.E. Brown (Verbenaceae is widely used in different regions of Central and South America as a tranquilizer. The plant’s anxiolytic properties, however, merit investigation. The present study evaluated the effects of repeated daily (14 days intraperitoneal (ip treatment with an essential oil (EO from a chemotype of L. alba (LA, chemotype II, 12.5 and 25 mg/kg; N = 6-8 and (R-(--carvone (25 mg/kg; N = 8-12, the main constituent of this chemotype, on male Wistar rats (weighing 250 g at the beginning of the experiments submitted to the elevated T-maze (ETM. The ETM allows the measurement of two defensive responses: inhibitory avoidance and one-way escape. In terms of psychopathology, these responses have been related to generalized anxiety and panic disorder, respectively. Treatment with the EO impaired ETM avoidance latencies, without altering escape, in a way similar to the reference drug diazepam (P < 0.05 (avoidance 2: control = 84.6 ± 35.2; EO 12.5 mg/kg = 11.8 ± 3.8; EO 25 mg/kg = 14.6 ± 2.7; diazepam = 7 ± 2.1. (R-(--carvone also significantly altered this same response (P < 0.05; avoidance 1: control = 91.9 ± 31.5; carvone = 11.6 ± 1.8; diazepam = 8.1 ± 3.3. These results were not due to motor changes since no significant effects were detected in an open field. These observations suggest that LA exerts anxiolytic-like effects on a specific subset of defensive behaviors that have been implicated in generalized anxiety disorder, and suggest that carvone is one of the constituents of LA responsible for its action as a tranquilizer.

  7. Anxiolytic effects of repeated treatment with an essential oil from Lippia alba and (R)-(-)-carvone in the elevated T-maze

    Energy Technology Data Exchange (ETDEWEB)

    Hatano, V.Y.; Torricelli, A.S. [Departamento de Biociências, Universidade Federal de São Paulo, Santos, SP (Brazil); Giassi, A.C.C. [Cellular and Molecular Medicine, University of Ottawa, Ottawa (Canada); Coslope, L.A. [Parque Nacional da Chapada Diamantina, Chapada Diamantina, BA (Brazil); Viana, M.B. [Departamento de Biociências, Universidade Federal de São Paulo, Santos, SP (Brazil)

    2012-02-27

    Lippia alba (Mill.) N.E. Brown (Verbenaceae) is widely used in different regions of Central and South America as a tranquilizer. The plant's anxiolytic properties, however, merit investigation. The present study evaluated the effects of repeated daily (14 days) intraperitoneal (ip) treatment with an essential oil (EO) from a chemotype of L. alba (LA, chemotype II, 12.5 and 25 mg/kg; N = 6-8) and (R)-(-)-carvone (25 mg/kg; N = 8-12), the main constituent of this chemotype, on male Wistar rats (weighing 250 g at the beginning of the experiments) submitted to the elevated T-maze (ETM). The ETM allows the measurement of two defensive responses: inhibitory avoidance and one-way escape. In terms of psychopathology, these responses have been related to generalized anxiety and panic disorder, respectively. Treatment with the EO impaired ETM avoidance latencies, without altering escape, in a way similar to the reference drug diazepam (P < 0.05) (avoidance 2: control = 84.6 ± 35.2; EO 12.5 mg/kg = 11.8 ± 3.8; EO 25 mg/kg = 14.6 ± 2.7; diazepam = 7 ± 2.1). (R)-(-)-carvone also significantly altered this same response (P < 0.05; avoidance 1: control = 91.9 ± 31.5; carvone = 11.6 ± 1.8; diazepam = 8.1 ± 3.3). These results were not due to motor changes since no significant effects were detected in an open field. These observations suggest that LA exerts anxiolytic-like effects on a specific subset of defensive behaviors that have been implicated in generalized anxiety disorder, and suggest that carvone is one of the constituents of LA responsible for its action as a tranquilizer.

  8. Anxiolytic effects of repeated treatment with an essential oil from Lippia alba and (R)-(-)-carvone in the elevated T-maze.

    Science.gov (United States)

    Hatano, V Y; Torricelli, A S; Giassi, A C C; Coslope, L A; Viana, M B

    2012-03-01

    Lippia alba (Mill.) N.E. Brown (Verbenaceae) is widely used in different regions of Central and South America as a tranquilizer. The plant's anxiolytic properties, however, merit investigation. The present study evaluated the effects of repeated daily (14 days) intraperitoneal (ip) treatment with an essential oil (EO) from a chemotype of L. alba (LA, chemotype II, 12.5 and 25 mg/kg; N = 6-8) and (R)-(-)-carvone (25 mg/kg; N = 8-12), the main constituent of this chemotype, on male Wistar rats (weighing 250 g at the beginning of the experiments) submitted to the elevated T-maze (ETM). The ETM allows the measurement of two defensive responses: inhibitory avoidance and one-way escape. In terms of psychopathology, these responses have been related to generalized anxiety and panic disorder, respectively. Treatment with the EO impaired ETM avoidance latencies, without altering escape, in a way similar to the reference drug diazepam (P < 0.05) (avoidance 2: control = 84.6 ± 35.2; EO 12.5 mg/kg = 11.8 ± 3.8; EO 25 mg/kg = 14.6 ± 2.7; diazepam = 7 ± 2.1). (R)-(-)-carvone also significantly altered this same response (P < 0.05; avoidance 1: control = 91.9 ± 31.5; carvone = 11.6 ± 1.8; diazepam = 8.1 ± 3.3). These results were not due to motor changes since no significant effects were detected in an open field. These observations suggest that LA exerts anxiolytic-like effects on a specific subset of defensive behaviors that have been implicated in generalized anxiety disorder, and suggest that carvone is one of the constituents of LA responsible for its action as a tranquilizer.

  9. [Surgery treatment of ectopic adrenocorticotrophic hormone syndrome].

    Science.gov (United States)

    Fan, H; Li, H Z; Xu, W F; Ji, Z G; Zhang, Y S

    2017-08-18

    To investigation the diagnosis and treatment of ectopic adrenocorticotrophic hormone (ACTH) syndrome. The clinical characters of 57 cases of ecotopic ACTH syndrome from Jan. 1996 to Dec. 2016 were collected and analyzed. The 57 cases included 32 males and 25 females. The age ranged from 11 to 68 years (average 32 years). ACTH levels significantly increased from 16.5 to 365.6 pmol/L, with average 77.6 pmol/L (normal range ectopic ACTH syndrome cases (44%) were group A, without identified source of ectopic hormone, were treated with bilateral or unilateral adrenalectomy due to the severity of the disease and difficulty of operation. Group B was composed of 16 cases (28%) diagnosed as ectopic ACTH syndrome by finding ectopic ACTH tumors and surgical resection. Group C included 16 cases (28%) with nonsurgical therapy. Different treatment results and prognosis were analyzed. In the study, 40 cases of the 57 had been followed up for 6 months to 10 years. In group A, of the 25 cases with bilateral or unilateral adrenalectomy, 4 died of diabetes and severe pulmonary infection, 18 survived, and 3 were lost to the follow-up, and the survival rate was 81% (18/22). In group B, of the 16 cases with radical tumor resection, 5 died of tumor recurrence 0.5-6.0 years after operation, 3 survived, and 8 were lost to the follow-up, and the survival rate was 37.5% (3/8). In group C, of the 16 non-operation patients, 4 with radiotherapy and chemotherapy died of metastases, diabetes or pulmonary infection, 6 with chemotherapy died of pulmonary infection within 1 year and the others were lost to the follow-up, and the survival rate was 0. Ectopic ACTH syndrome is difficult to treat. Adrenalectomy is effective for the management of ectopic ACTH syndrome, especially for those patients with severe Cushing's syndrome, but the primary tumor can not be located.

  10. Sensitivity and Specificity of Multiple Kato-Katz Thick Smears and a Circulating Cathodic Antigen Test for Schistosoma mansoni Diagnosis Pre- and Post-repeated-Praziquantel Treatment

    Science.gov (United States)

    Lamberton, Poppy H. L.; Kabatereine, Narcis B.; Oguttu, David W.; Fenwick, Alan; Webster, Joanne P.

    2014-01-01

    Background Two Kato-Katz thick smears (Kato-Katzs) from a single stool are currently recommended for diagnosing Schistosoma mansoni infections to map areas for intervention. This ‘gold standard’ has low sensitivity at low infection intensities. The urine point-of-care circulating cathodic antigen test (POC-CCA) is potentially more sensitive but how accurately they detect S. mansoni after repeated praziquantel treatments, their suitability for measuring drug efficacy and their correlation with egg counts remain to be fully understood. We compared the accuracies of one to six Kato-Katzs and one POC-CCA for the diagnosis of S. mansoni in primary-school children who have received zero to ten praziquantel treatments. We determined the impact each diagnostic approach may have on monitoring and evaluation (M&E) and drug-efficacy findings. Method/Principle Findings In a high S. mansoni endemic area of Uganda, three days of consecutive stool samples were collected from primary school-aged children (six - 12 years) at five time-points in year one: baseline, one-week-post-, four-weeks-post-, six-months-post-, and six-months-one-week-post-praziquantel and three time-points in years two and three: pre-, one-week-post- and four-weeks-post-praziquantel-treatment/retreatment (n = 1065). Two Kato-Katzs were performed on each stool. In parallel, one urine sample was collected and a single POC-CCA evaluated per child at each time-point in year one (n = 367). At baseline, diagnosis by two Kato-Katzs (sensitivity = 98.6%) or one POC-CCA (sensitivity = 91.7%, specificity = 75.0%) accurately predicted S. mansoni infections. However, one year later, a minimum of three Kato-Katzs, and two years later, five Kato-Katzs were required for accurate diagnosis (sensitivity >90%) and drug-efficacy evaluation. The POC-CCA was as sensitive as six Kato-Katzs four-weeks-post and six-months-post-treatment, if trace readings were classified as positive. Conclusions

  11. Sensitivity and specificity of multiple Kato-Katz thick smears and a circulating cathodic antigen test for Schistosoma mansoni diagnosis pre- and post-repeated-praziquantel treatment.

    Directory of Open Access Journals (Sweden)

    Poppy H L Lamberton

    2014-09-01

    Full Text Available Two Kato-Katz thick smears (Kato-Katzs from a single stool are currently recommended for diagnosing Schistosoma mansoni infections to map areas for intervention. This 'gold standard' has low sensitivity at low infection intensities. The urine point-of-care circulating cathodic antigen test (POC-CCA is potentially more sensitive but how accurately they detect S. mansoni after repeated praziquantel treatments, their suitability for measuring drug efficacy and their correlation with egg counts remain to be fully understood. We compared the accuracies of one to six Kato-Katzs and one POC-CCA for the diagnosis of S. mansoni in primary-school children who have received zero to ten praziquantel treatments. We determined the impact each diagnostic approach may have on monitoring and evaluation (M&E and drug-efficacy findings.In a high S. mansoni endemic area of Uganda, three days of consecutive stool samples were collected from primary school-aged children (six - 12 years at five time-points in year one: baseline, one-week-post-, four-weeks-post-, six-months-post-, and six-months-one-week-post-praziquantel and three time-points in years two and three: pre-, one-week-post- and four-weeks-post-praziquantel-treatment/retreatment (n = 1065. Two Kato-Katzs were performed on each stool. In parallel, one urine sample was collected and a single POC-CCA evaluated per child at each time-point in year one (n = 367. At baseline, diagnosis by two Kato-Katzs (sensitivity = 98.6% or one POC-CCA (sensitivity = 91.7%, specificity = 75.0% accurately predicted S. mansoni infections. However, one year later, a minimum of three Kato-Katzs, and two years later, five Kato-Katzs were required for accurate diagnosis (sensitivity >90% and drug-efficacy evaluation. The POC-CCA was as sensitive as six Kato-Katzs four-weeks-post and six-months-post-treatment, if trace readings were classified as positive.Six Kato-Katzs (two/stool from three stools and/or one POC-CCA are required

  12. Linkage of congenital isolated adrenocorticotropic hormone deficiency to the corticotropin releasing hormone locus using simple sequence repeat polymorphisms

    Energy Technology Data Exchange (ETDEWEB)

    Kyllo, J.H.; Collins, M.M.; Vetter, K.L. [Univ. of Iowa College of Medicine, Iowa City, IA (United States)] [and others

    1996-03-29

    Genetic screening techniques using simple sequence repeat polymorphisms were applied to investigate the molecular nature of congenital isolated adrenocorticotropic hormone (ACTH) deficiency. We hypothesize that this rare cause of hypocortisolism shared by a brother and sister with two unaffected sibs and unaffected parents is inherited as an autosomal recessive single gene mutation. Genes involved in the hypothalamic-pituitary axis controlling cortisol sufficiency were investigated for a causal role in this disorder. Southern blotting showed no detectable mutations of the gene encoding pro-opiomelanocortin (POMC), the ACTH precursor. Other candidate genes subsequently considered were those encoding neuroendocrine convertase-1, and neuroendocrine convertase-2 (NEC-1, NEC-2), and corticotropin releasing hormone (CRH). Tests for linkage were performed using polymorphic di- and tetranucleotide simple sequence repeat markers flanking the reported map locations for POMC, NEC-1, NEC-2, and CRH. The chromosomal haplotypes determined by the markers flanking the loci for POMC, NEC-1, and NEC-2 were not compatible with linkage. However, 22 individual markers defining the chromosomal haplotypes flanking CRH were compatible with linkage of the disorder to the immediate area of this gene of chromosome 8. Based on these data, we hypothesize that the ACTH deficiency in this family is due to an abnormality of CRH gene structure or expression. These results illustrate the useful application of high density genetic maps constructed with simple sequence repeat markers for inclusion/exclusion studies of candidate genes in even very small nuclear families segregating for unusual phenotypes. 25 refs., 5 figs., 2 tabs.

  13. Early detection of response in small cell bronchogenic carcinoma by changes in serum concentrations of creatine kinase, neuron specific enolase, calcitonin, ACTH, serotonin and gastrin releasing peptide

    DEFF Research Database (Denmark)

    Bork, E; Hansen, M; Urdal, P;

    1988-01-01

    determined within 4-8 weeks. The results indicate that serum CK-BB and NSE are potential markers for SCC at the time of diagnosis and that changes in the concentrations during the first course of cytostatic therapy are promising as biochemical tests for early detection of response to chemotherapy.......Creatine kinase (CK-BB), neuron specific enolase (NSE), ACTH, calcitonin, serotonin and gastrin releasing peptide (GRP) were measured in serum or plasma before and immediately after initiation of treatment in patients with small cell lung cancer (SCC). Pretherapeutic elevated concentrations of CK...... stage patients and 71% in limited stage patients. Frequent initial monitoring of the substances showed an increase in the concentrations of pretherapeutic elevated CK-BB and NSE on day 1 or 2 followed by a sharp decrease within 1 week. These changes were correlated to objective clinical response...

  14. Mild Adrenal Steroidogenic Defects and ACTH-Dependent Aldosterone Secretion in High Blood Pressure: Preliminary Evidence

    Directory of Open Access Journals (Sweden)

    João Martin Martins

    2014-01-01

    Full Text Available Introduction. Adrenal glands play a major role in the control of blood pressure and mild defects of steroidogenesis and/or inappropriate control of mineralocorticoid production have been reported in high blood pressure (HBP. Patients and Methods. We used a specific protocol for the evaluation of 100 consecutive patients with inappropriate or recent onset HBP. Specific methods were used to confirm HBP and to diagnose secondary forms of HBP. In addition we tested adrenal steroidogenesis with the common cosyntropin test, modified to include the simultaneous measurement of renin and aldosterone besides 17-hydroxyprogesterone (17OHP and 11-deoxycortisol (S. Results. Secondary forms of HBP were diagnosed in 32 patients, including 14 patients with primary hyperaldosteronism (PA (14% and 10 patients with pheochromocytoma (10%. Mild defects of the 21-hydroxylase (21OHD and 11-hydroxylase (11OHD enzymes were common (42%. ACTH-dependent aldosterone secretion was found in most patients (54% and characteristically in those with mild defects of adrenal steroidogenesis (>60%, PA (>75%, and otherwise in patients with apparent essential HBP (EHBP (32%. Discussion. Mild defects of adrenal steroidogenesis are common in patients with HBP, occurring in almost half of the patients. In those patients as well as in patients with apparent EHBP, aldosterone secretion is commonly dependent on ACTH.

  15. Corticotropin (ACTH)-reactive immunoglobulins in adolescents in relation to antisocial behavior and stress-induced cortisol response : The TRAILS study

    NARCIS (Netherlands)

    Schaefer, Johanna M.; Fetissov, Serguei O.; Legrand, Romain; Claeyssens, Sophie; Hoekstra, Pieter J.; Verhulst, Frank C.; Van Oort, Floor V. A.

    2013-01-01

    Elevated levels of corticotropin (ACTH)-reactive immunoglobulins (ACTH IgG) were found in mates with conduct disorder, suggesting their involvement in the biology of antisocial behavior. We first aimed to confirm these findings in a large general population sample of adolescents. Secondly, we studie

  16. Comparative Evaluation of Pain, Stress, Neuropeptide Y, ACTH, and Cortisol Levels Between a Conventional Postoperative Care Protocol and a Fast-Track Recovery Program in Patients Undergoing Major Abdominal Surgery.

    Science.gov (United States)

    Kapritsou, Maria; Papathanassoglou, Elizabeth D; Bozas, Evangelos; Korkolis, Dimitrios P; Konstantinou, Evangelos A; Kaklamanos, Ioannis; Giannakopoulou, Margarita

    2017-03-01

    Fast-track (FT) postoperative protocol in oncological patients after major abdominal surgery reduces complications and length of postoperative stay compared to the conventional (CON) protocol. However, stress and pain responses have not been compared between the two protocols. To compare stress, pain, and related neuropeptidic responses (adrenocorticotropic hormone [ACTH], cortisol, and neuropeptide Y [NPY]) between FT and CON protocols. A clinical trial with repeated measurements was conducted (May 2012 to May 2014) with a sample of 63 hepatectomized or pancreatectomized patients randomized into two groups: FT ( n = 29) or CON ( n = 34). Demographic and clinical data were collected, and pain (Visual Analog Scale [VAS] and Behavioral Pain Scale [BPS]) and stress responses (3 self-report questions) assessed. NPY, ACTH, and cortisol plasma levels were measured at T1 = day of admission, T2 = day of surgery, and T3 = prior to discharge. ACTHT1 and ACTHT2 levels were positively correlated with self-reported stress levels (ρ = .43 and ρ = .45, respectively, p levels in the FT group were higher than those in the CON group at all time points ( p ≤ .004); this difference remained significant after adjusting for T1 levels through analysis of covariance for age, gender, and body mass index ( F = .003, F = .149, F = .015, respectively, p > .05). Neuropeptidic levels were higher in the FT group. Future research should evaluate this association further, as these biomarkers might serve as objective indicators of postoperative pain and stress.

  17. Repeated morphine treatment alters polysialylated neural cell adhesion molecule, glutamate decarboxylase-67 expression and cell proliferation in the adult rat hippocampus.

    Science.gov (United States)

    Kahn, Laëtitia; Alonso, Gérard; Normand, Elisabeth; Manzoni, Olivier J

    2005-01-01

    Altered synaptic transmission and plasticity in brain areas involved in reward and learning are thought to underlie the long-lasting effects of addictive drugs. In support of this idea, opiates reduce neurogenesis [A.J. Eisch et al. (2000) Proceedings of the National Academy of Sciences USA, 97, 7579-7584] and enhance long-term potentiation in adult rodent hippocampus [J.M. Harrison et al. (2002) Journal of Neurophysiology, 87, 2464-2470], a key structure of learning and memory processes. Here we studied how repeated morphine treatment and withdrawal affect cell proliferation and neuronal phenotypes in the dentate gyrus-CA3 region of the adult rat hippocampus. Our data showed a strong reduction of cellular proliferation in morphine-dependent animals (54% of control) that was followed by a rebound increase after 1 week withdrawal and a return to normal after 2 weeks withdrawal. Morphine dependence was also associated with a drastic reduction in the expression levels of the polysialylated form of neural cell adhesion molecule (68% of control), an adhesion molecule expressed by newly generated neurons and involved in cell migration and structural plasticity. Polysialylated neural cell adhesion molecule levels quickly returned to normal following withdrawal. In morphine-dependent rats, we found a significant increase of glutamate decarboxylase-67 mRNA transcription (170% of control) in dentate gyrus granular cells which was followed by a marked rebound decrease after 1 week withdrawal and a return to normal after 4 weeks withdrawal. Together, the results show, for the first time, that, in addition to reducing cell proliferation and neurogenesis, chronic exposure to morphine dramatically alters neuronal phenotypes in the dentate gyrus-CA3 region of the adult rat hippocampus.

  18. Repeated PTZ treatment at 25-day intervals leads to a highly efficient accumulation of doublecortin in the dorsal hippocampus of rats.

    Directory of Open Access Journals (Sweden)

    Ana-Maria Buga

    Full Text Available BACKGROUND: Neurogenesis persists throughout life in the adult mammalian brain. Because neurogenesis can only be assessed in postmortem tissue, its functional significance remains undetermined, and identifying an in vivo correlate of neurogenesis has become an important goal. By studying pentylenetetrazole-induced brain stimulation in a rat model of kindling we accidentally discovered that 25±1 days periodic stimulation of Sprague-Dawley rats led to a highly efficient increase in seizure susceptibility. METHODOLOGY/PRINCIPAL FINDINGS: By EEG, RT-PCR, western blotting and immunohistochemistry, we show that repeated convulsive seizures with a periodicity of 25±1 days led to an enrichment of newly generated neurons, that were BrdU-positive in the dentate gyrus at day 25±1 post-seizure. At the same time, there was a massive increase in the number of neurons expressing the migratory marker, doublecortin, at the boundary between the granule cell layer and the polymorphic layer in the dorsal hippocampus. Some of these migrating neurons were also positive for NeuN, a marker for adult neurons. CONCLUSION/SIGNIFICANCE: Our results suggest that the increased susceptibility to seizure at day 25±1 post-treatment is coincident with a critical time required for newborn neurons to differentiate and integrate into the existing hippocampal network, and outlines the importance of the dorsal hippocampus for seizure-related neurogenesis. This model can be used as an in vivo correlate of neurogenesis to study basic questions related to neurogenesis and to the neurogenic mechanisms that contribute to the development of epilepsy.

  19. The active sequence in the acth molecule responsible for inhibition of the extinction of conditioned avoidance behaviour in rats

    NARCIS (Netherlands)

    Greven, H.M.; Wied, D. de

    1967-01-01

    The effect of structural analogues of the N-terminal decapeptide of ACTH on inhibition of extinction of a conditioned avoidance response in rats has been studied. Studies involving the relation between chain length and behavioural activity revealed that the sequence 4–10 is the shortest peptide whic

  20. [Effect of dalargin on the content of endorphins, leucine-enkephalin ACTH and corticosterone of the blood of stressed rats].

    Science.gov (United States)

    Bobkov, A I; Polonskiĭ, V M; Vinogradov, V A; Demina, D G; Smagin, V G

    1985-12-01

    Stress caused by acute cysteamine duodenal ulcer was induced in Wistar male rats. All the endogenous opioides under study were involved in the stress-reaction mechanism. Protective dalargin (synthetic enkephalin analogue) administration revealed a tendency towards normalization of endorphin, L-enkephalin and ACTH blood levels.

  1. A patient with recurrent hypercortisolism after removal of an ACTH-secreting pituitary adenoma due to an adrenal macronodule.

    NARCIS (Netherlands)

    Timmers, H.J.L.M.; Ginneken, E.E.M. van; Wesseling, P.; Sweep, C.G.J.; Hermus, A.R.M.M.

    2006-01-01

    A 41-yr-old female was referred for signs and symptoms of Cushing's syndrome. Cortisol was not suppressed by 1 mg dexamethasone (0.41 micromol/l). Midnight cortisol and ACTH were 0.44 micromol/l and 18 pmol/l, respectively. Urinary cortisol excretion was 250 nmol/24 h (normal between 30 and 150 nmol

  2. Adiponectin regulates ACTH secretion and the HPAA in an AMPK-dependent manner in pituitary corticotroph cells.

    Science.gov (United States)

    Chen, Maopei; Wang, Zhiquan; Zhan, Ming; Liu, Ruixin; Nie, Aifang; Wang, Jiqiu; Ning, Guang; Ma, Qinyun

    2014-03-05

    It is known that adipokines can regulate the hypothalamic-pituitary-adrenal axis (HPAA). In this study, we confirmed that adiponectin regulates the HPAA by affecting pituitary corticotroph cells. Using RT-PCR and immunofluorescence, we determined that adiponectin receptors were expressed in pituitary corticotroph tumour cells (AtT-20 cells and human corticotroph tumours). Adiponectin stimulated calcium influx and increased basal ACTH secretion without affecting corticotrophin-releasing hormone (CRH)-stimulated ACTH secretion, which was most likely due to the expression of adiponectin repressing CRH receptor 1 (CRHR1). Adiponectin also acutely stimulated ACTH release in primary culture pituitary cells. Lastly, adiponectin directly phosphorylated 5' AMP-activated protein kinase (AMPK) in AtT-20 cells. The effects of adiponectin were mimicked by AICAR, which was blocked by compound C. Taken together, our results suggested that adiponectin stimulated ACTH secretion and down-regulated CRHR1, possibly via an AMPK-dependent mechanism in pituitary corticotroph cells. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  3. Burnout and Hypocortisolism - A Matter of Severity? A Study on ACTH and Cortisol Responses to Acute Psychosocial Stress.

    Science.gov (United States)

    Lennartsson, Anna-Karin; Sjörs, Anna; Währborg, Peter; Ljung, Thomas; Jonsdottir, Ingibjörg H

    2015-01-01

    Common consequences of long-term psychosocial stress are fatigue and burnout. It has been suggested that burnout could be associated with hypocortisolism, thus, inability to produce sufficient amounts of cortisol. This study aimed to investigate whether patients with clinical burnout exhibit aberrant ACTH and cortisol responses under acute psychosocial stress compared with healthy individuals. Nineteen patients (9 men and 10 women) and 37 healthy subjects (20 men and 17 women), underwent the Trier Social Stress Test. Blood samples and saliva samples were collected before, after, and during the stress test for measurements of plasma ACTH, serum cortisol, and salivary cortisol. Several statistical analyses were conducted to compare the responses between patients and controls. In addition, in order to investigate the possibility that burnout patients with more severe symptoms would respond differently, sub-groups of patients reporting higher and lower burnout scores were compared. In both patients and healthy controls, we observed elevated levels of ACTH and cortisol after exposure to the stressor. There were no differences in responses of ACTH, serum cortisol, or salivary cortisol between patients and controls. Patients reporting higher burnout scores had lower salivary cortisol responses than controls, indicating that patients with more severe burnout symptoms may be suffering from hypocortisolism. In addition, patients with more severe burnout symptoms tended to have smaller ACTH responses than the other patients. However, there was no corresponding difference in serum cortisol. This study indicates that hypocortisolism is not present in a clinical burnout patient group as a whole but may be present in the patients with more severe burnout symptoms.

  4. Burnout and hypocortisolism – a matter of severity? A study on ACTH and cortisol responses to acute psychosocial stress

    Directory of Open Access Journals (Sweden)

    Anna-Karin eLennartsson

    2015-02-01

    Full Text Available Background: Common consequences of long-term psychosocial stress are fatigue and burnout. It has been suggested that burnout could be associated with hypocortisolism, thus, inability to produce sufficient amounts of cortisol. This study aimed to investigate whether patients with clinical burnout exhibit aberrant ACTH and cortisol responses under acute psychosocial stress compared with healthy individuals. Methods: Nineteen patients (9 men and 10 women and 37 healthy subjects (20 men and 17 women, underwent the Trier Social Stress Test. Blood samples and saliva samples were collected before, after and during the stress test for measurements of plasma ACTH, serum cortisol and salivary cortisol. Several statistical analyses were conducted to compare the responses between patients and controls. In addition, in order to investigate the possibility that burnout patients with more severe symptoms would respond differently, sub-groups of patients reporting higher and lower burnout scores were compared. Results: In both patients and healthy controls, we observed elevated levels of ACTH and cortisol after exposure to the stressor. There were no differences in responses of ACTH, serum cortisol or salivary cortisol between patients and controls. Patients reporting higher burnout scores had lower salivary cortisol responses than controls, indicating that patients with more severe burnout symptoms may be suffering from hypocortisolism. In addition patients with more severe burnout symptoms tended to have smaller ACTH responses than the other patients. There was no corresponding difference in serum cortisol however. Conclusion: This study indicates that hypocortisolism is not present in a clinical burnout patient group as a whole but may be present in the patients with more severe burnout symptoms.

  5. Effects of ACTH on RNA synthesis and migration in the adrenal cortex cells of the young rat, as shown by radioautography

    Energy Technology Data Exchange (ETDEWEB)

    Magalhaes, M.C.; Vitor, A.B.; Magalhaes, M.M.

    1986-01-01

    The effect of ACTH on the RNA synthesis in adrenal zona fasciculata cells of the young rat were studied by light and electron microscope radioautography. Two units of ACTH were administered sc to animals and immediately followed by an iv injection of (/sup 3/)uridine. ACTH-injected and control rats, which received the isotope alone, were sacrificed at various time intervals. Labelling over extranucleolar areas was higher in the ACTH-treated animals at 20 min, then becoming lower than in the controls at 60 min and 24 h. Nucleolar radioactivity, however, was consistently decreased by ACTH at all experimental times. Apart from these changes in the rate of synthesis, the over-all curves of labelling were similar to those in the control animals with a striking peak at 1 h. The short-term increase in extranucleolar RNA synthesis observed after ACTH injection was considered to be consistent with the hypothesis that an enhanced extranucleolar synthesis of mRNA takes place early in stimulated animals and is associated with the synthesis of steroidogenic proteins. On the other hand, the relatively decreased uridine uptake of the label by the nucleolus in ACTH-treated animals, suggests an inhibition of nucleolar transcription with diminished pre-rRNA formation in treated animals.

  6. O retratamento da tuberculose no município do Recife, 1997: uma abordagem epidemiológica Repeated treatment of tuberculosis in the city of Recife, 1997: an epidemiological approach

    Directory of Open Access Journals (Sweden)

    HERMIRA MARIA AMORIM CAMPOS

    2000-09-01

    Full Text Available Objetivo: Este estudo descreve as características e analisa o acompanhamento de casos de retratamento ocorridos em residentes no município do Recife, no ano de 1997, com o objetivo de avaliar a importância deste grupo de doentes para a vigilância da tuberculose nos sistemas locais de saúde. Casuística e métodos: Foi realizado um estudo transversal com uma amostra de 240 casos de retratamento que representaram 16,2% dos casos de tuberculose notificados à Secretaria Estadual de Saúde do Estado de Pernambuco, em 1997. Resultados: O abandono do tratamento anterior foi o principal motivo para o retratamento (55,8%, seguido por casos de recidiva da doença (39,2%. Os doentes eram predominantemente do sexo masculino, com idade entre 30 e 49 anos, com baixa ou nenhuma escolaridade, e apresentavam um predomínio da forma pulmonar. Chama a atenção que 42,7% dos casos de retratamento tinham história de dois ou mais tratamentos anteriores. Em relação ao desfecho do retratamento, 52,5% dos casos apresentaram resultado desfavorável. Entre estes, 44,2% dos indivíduos abandonaram o esquema terapêutico e 39,6% deles fizeram-no até o primeiro mês. Os casos que voltaram a tratar-se após recidiva apresentaram maior percentual de desfecho favorável de retratamento (64% quando comparados com os casos que voltaram a tratar-se após falência ou abandono do tratamento anterior e esta diferença foi estatisticamente significante (chi² = 19,55; p Objectives: This study describes the epidemiological profile of cases of repeated treatment of tuberculosis occurring among residents of the city of Recife in the year of 1997. Material and methods: A cross-sectional study was performed and 240 cases of repeated treatment were studied, representing 16.2% of all cases of tuberculosis. Results: Interruption of previous treatment was the principal reason for repeated treatments (55.8%, followed by cases of recurrence of the disease (39.2%. Patients undergoing

  7. Outcome of synthetic adrenocorticotropin hormone treatment in children with infantile spasm

    Directory of Open Access Journals (Sweden)

    I Gusti Ngurah Made Suwarba

    2011-04-01

    Full Text Available Background Infantile spasms (IS is an age-spedfic epilepsy syndrome characterized by flexor, extensor, and mixed flexor-extensor spasms which often occur in clusters during the first 2 years of life. IS is often difficult to manage 'With the usual anti-epilepsy drugs (AEDs. Therapy with adrenocorticotropin honnone (ACTH has been used since 1958. In Indonesia, ACTH usage is still rare. Objective This study aims to examine the effectiveness of ACTH as an anti-epileptic drug in managing IS. Methods This was descriptive retrospective cohort study. Subjects were IS patients who visited the neurology outpatient clinic in Sanglah Hospital, Bali, from January 2007 until June 2010. Each subject received AED(s plus either ACTH or methylprednisolone for 46 weeks. Results There were 19 IS patients over the four year duration of this study. They were mostly boys (11, aged 2 weeks to 17 months, with a mean age at treatment of 9 months. Eighteen patients received poly therapy, while one patient received only phenobarbital as monotherapy. Most patients who received ACTH (13/16 had a seizure-free period, while the 3 that did not receive ACTH continued having seizures. Patients who received ACTH showed a good response (seizure-free after 5-13 days therapy and their EEG pattern showed disappearance of burst suppression Mthin 1-2 weeks. ACTH side effects included weight gain and cushingoid appearance. One patient died from pneumonia. Conclusions Diagnosis of IS should be considered in patients pre-senting Mth spasms at less than 6 months old. IS treatment should begin as soon as possible. IS patients responded well to a short course of ACTH therapy.

  8. Quantum repeated games revisited

    CERN Document Server

    Frackiewicz, Piotr

    2011-01-01

    We present a scheme for playing quantum repeated 2x2 games based on the Marinatto and Weber's approach to quantum games. As a potential application, we study twice repeated Prisoner's Dilemma game. We show that results not available in classical game can be obtained when the game is played in the quantum way. Before we present our idea, we comment on the previous scheme of playing quantum repeated games.

  9. [Behavior of circadian rhythm of ACTH and cortisol in 16 normal subjects after a balanced normocaloric diet and after a high protein diet (Cosinor mean method)].

    Science.gov (United States)

    Sellini, M; Giovannini, C; Manzo, G; Barletta, C; Borboni, P

    1983-01-31

    In 16 normal subjects the circadian rhythm of ACTH has been studied during normal calories diet and after a 15 days period of high protein content diet (2 g/Kg body weight). The statistical study, according Cosinor method, has shown a significant increase of the mesor and of the amplitude, but has not shown any change of the ACTH and Cortisol rhythm, after hyperproteic diet. Data advise the increase of the tonic and fasic secretion of both hormones and shown the mantained acrophase. The action of the protein on the ACTH and Cortisol secretion does not seem related to mechanism like stress, neither to the probable mediation of intestinal like-ACTH messengers. On the contrary it seems related to a direct stimulus on the diencephalo-pituitary axis; it is possible that some amino-acids (tryptophan, arginine) act as a mediator, even if data concern just the effect of the over mentioned amino-acid in large doses.

  10. Ultrastructural, histochemical, and biochemical studies of two cases with amylase, ACTH, and beta-MSH producing tumor.

    Science.gov (United States)

    Gomi, K; Kameya, T; Tsumuraya, M; Shimosato, Y; Zeze, F; Abe, K; Yoneyama, T

    1976-10-01

    Two cases of intrathoracic tumor, different in histology and accompanied by hyperamylasemia, were studied ultrastructurally, histochemically, and biochemically. The ultrastructure of the tumor cell cytoplasm showed many zymogen granules in case 1 and smaller cored granules in addition to zymogen granules in case 2. Both tumors contained not only a large amount of amylase, which was electrophoretically of saliva type with three components, but also significant amounts of immunoreactive ACTH and beta-MSH. Starch film and immunofluorescence showed that the tumor cells stored amylase. It was concluded from these findings that the tumor cells ectopically producing amylase, which showed differentiation toward the cells with zymogen production, could differentiate toward the cells of ACTH-MSH system at the same time.

  11. Ectopic ACTH and CRH Co-secreting Tumor Localized by 68Ga-DOTA-TATE PET/CT.

    Science.gov (United States)

    Papadakis, Georgios Z; Bagci, Ulas; Sadowski, Samira M; Patronas, Nicholas J; Stratakis, Constantine A

    2015-07-01

    Diagnosis of ectopic adrenocorticotropic hormone (ACTH) and corticotropin-releasing hormone (CRH) co-secreting tumors causing Cushing syndrome (CS) is challenging because these tumors are rare and their diagnosis is frequently confused with Cushing disease (CD), caused by the effect of CRH on the pituitary. We report a case of a 21-year-old male patient who was referred to our institution with persistent hypercortisolemia and CS after undergoing unnecessary transsphenoidal surgery (TSS). ⁶⁸Ga-DOTA-TATE PET/CT revealed increased tracer uptake in the thymus, which was histologically proven to be a neuroendocrine tumor (NET) that stained positive for ACTH and CRH. Imaging with ¹⁸F-FDG PET/CT was not diagnostic.

  12. Metabolic responses to adrenocorticotropic hormone (ACTH) vary with life-history stage in adult male northern elephant seals.

    Science.gov (United States)

    Ensminger, David C; Somo, Derek A; Houser, Dorian S; Crocker, Daniel E

    2014-08-01

    Strong individual and life-history variation in serum glucocorticoids has been documented in many wildlife species. Less is known about variation in hypothalamic-pituitary-adrenal (HPA) axis responsiveness and its impact on metabolism. We challenged 18 free-ranging adult male northern elephant seals (NES) with an intramuscular injection of slow-release adrenocorticotropic hormone (ACTH) over 3 sample periods: early in the breeding season, after 70+ days of the breeding fast, and during peak molt. Subjects were blood sampled every 30 min for 2h post-injection. Breeding animals were recaptured and sampled at 48 h. In response to the ACTH injection, cortisol increased 4-6-fold in all groups, and remained elevated at 48 h in early breeding subjects. ACTH was a strong secretagogue for aldosterone, causing a 3-8-fold increase in concentration. Cortisol and aldosterone responses did not vary between groups but were correlated within individuals. The ACTH challenge produced elevations in plasma glucose during late breeding and molting, suppressed testosterone and thyroid hormone at 48 h in early breeding, and increased plasma non-esterified fatty acids and ketoacids during molting. These data suggest that sensitivity of the HPA axis is maintained but the metabolic impacts of cortisol and feedback inhibition of the axis vary with life history stage. Strong impacts on testosterone and thyroid hormone suggest the importance of maintaining low cortisol levels during the breeding fast. These data suggest that metabolic adaptations to extended fasting in NES include alterations in tissue responses to hormones that mitigate deleterious impacts of acute or moderately sustained stress responses.

  13. Adrenocortical steroid response to ACTH in different phenotypes of non-obese polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Cinar Nese

    2012-12-01

    Full Text Available Abstract Background Adrenal androgen excess is frequently observed in PCOS. The aim of the study was to determine whether adrenal gland function varies among PCOS phenotypes, women with hyperandrogenism (H only and healthy women. Methods The study included 119 non-obese patients with PCOS (age: 22.2 ± 4.1y, BMI:22.5 ± 3.1 kg/m2, 24 women with H only and 39 age and BMI- matched controls. Among women with PCOS, 50 had H, oligo-anovulation (O, and polycystic ovaries (P (PHO, 32 had O and H (OH, 23 had P and H (PH, and 14 had P and O (PO. Total testosterone (T, SHBG and DHEAS levels at basal and serum 17-hydroxprogesterone (17-OHP, androstenedione (A4, DHEA and cortisol levels after ACTH stimulation were measured. Results T, FAI and DHEAS, and basal and AUC values for 17-OHP and A4 were significantly and similarly higher in PCOS and H groups than controls (p  Conclusion PCOS patients and women with H only have similar and higher basal and stimulated adrenal androgen levels than controls. All three hyperandrogenic subphenotypes of PCOS exhibit similar and higher basal and stimulated adrenal androgen secretion patterns compared to non-hyperandrogenic subphenotype.

  14. Longitudinal changes in serum catecholamines, dopamine, serotonin, ACTH and cortisol in pregnant Spanish mares.

    Science.gov (United States)

    Marcilla, María; Muñoz, Ana; Satué, Katy

    2017-01-21

    Systemic physiological changes required for placental and fetal development during pregnancy are associated with an activation of the sympathetic nervous system (SNS) and the hypothalamus-pituitary-adrenal axis (HPA) in women, but this fact has not been investigated in mares. Venous blood samples were taken monthly from 31 successful Spanish mares during the 11months of pregnancy. During the first 4months of pregnancy, adrenaline (AD), dopamine (DOPA) and ACTH increases, whereas 5-hydroxitryptamine (5-HT) decreased, and noradrenaline (NAD) and cortisol (CORT) did not change. Serum NAD increased at 8th month, 5-HT at 5th, 7th months, and DOPA increased progressively between the 5th and 8th months and CORT concentrations peak at 5th month. During the three last months of pregnancy, NAD, 5-TH and DOPA decreased, particularly at the 11th month. These results confirmed an activation of the SNS and the HPA axis in pregnant mares during successful pregnancies. The next step would be to elucidate whether these changes also appear in unsuccessful pregnancies. Copyright © 2017. Published by Elsevier Ltd.

  15. Increasing Belief in the Effectiveness of HIV Treatment as Prevention : Results of Repeated, National Surveys of Australian Gay and Bisexual Men, 2013-15

    NARCIS (Netherlands)

    Holt, Martin; Lea, Toby; Schmidt, Heather-Marie; Murphy, Dean; Rosengarten, Marsha; Crawford, David; Ellard, Jeanne; Kolstee, Johann; de Wit, John

    2016-01-01

    We surveyed Australian gay and bisexual men, assessing belief in HIV treatment as prevention (TasP) and support for early treatment. We identified the characteristics of participants who believed in TasP and supported early treatment using multivariate logistic regression. In 2013, 1316 men particip

  16. Bioavailability of gallic acid and catechins from grape seed polyphenol extract is improved by repeated dosing in rats: implications for treatment in Alzheimer's disease.

    Science.gov (United States)

    Ferruzzi, Mario G; Lobo, Jessica K; Janle, Elsa M; Cooper, Bruce; Simon, James E; Wu, Qing-Li; Welch, Cara; Ho, Lap; Weaver, Connie; Pasinetti, Giulio M

    2009-01-01

    The present study explored the bioavailability and brain deposition of a grape seed polyphenolic extract (GSPE) previously found to attenuate cognitive deterioration in a mouse model of Alzheimer's disease (AD). Plasma pharmacokinetic response of major GSPE phenolic components was measured following intragastric gavage of 50, 100, and 150 mg GSPE per kg body weight. Liquid chromatography-mass spectrometry (LC-MS) analysis identified gallic acid (GA), catechin (C), and epicatechin (EC) in plasma of rats gavaged acutely with GSPE. Additionally, 4-methylgallic acid (4-OMeGA), 3'-methylcatechin (3'-OMeC), and 3'-methylepicatechin (3'-OMeEC) were identified as circulating metabolites of GSPE phenolic constituents. Cmax for individual GSPE constituents and their metabolites increased in a dose-dependent fashion (with increasing GSPE oral dose). Repeated daily exposure to GSPE was found to significantly increase bioavailability (defined as plasma AUC0-8h) of GA, C, and EC by 198, 253, and 282% relative to animals receiving only a single acute GSPE dose. EC and C were not detectable in brain tissues of rats receiving a single GSPE dose but reached levels of 290.7 +/-45.9 and 576.7 +/- 227.7 pg/g in brain tissues from rats administered GSPE for 10 days. This study suggests that brain deposition of GA, C, and EC is affected by repeated dosing of GSPE.

  17. Reconfigurable multiport EPON repeater

    Science.gov (United States)

    Oishi, Masayuki; Inohara, Ryo; Agata, Akira; Horiuchi, Yukio

    2009-11-01

    An extended reach EPON repeater is one of the solutions to effectively expand FTTH service areas. In this paper, we propose a reconfigurable multi-port EPON repeater for effective accommodation of multiple ODNs with a single OLT line card. The proposed repeater, which has multi-ports in both OLT and ODN sides, consists of TRs, BTRs with the CDR function and a reconfigurable electrical matrix switch, can accommodate multiple ODNs to a single OLT line card by controlling the connection of the matrix switch. Although conventional EPON repeaters require full OLT line cards to accommodate subscribers from the initial installation stage, the proposed repeater can dramatically reduce the number of required line cards especially when the number of subscribers is less than a half of the maximum registerable users per OLT. Numerical calculation results show that the extended reach EPON system with the proposed EPON repeater can save 17.5% of the initial installation cost compared with a conventional repeater, and can be less expensive than conventional systems up to the maximum subscribers especially when the percentage of ODNs in lightly-populated areas is higher.

  18. Revisiting the TALE repeat.

    Science.gov (United States)

    Deng, Dong; Yan, Chuangye; Wu, Jianping; Pan, Xiaojing; Yan, Nieng

    2014-04-01

    Transcription activator-like (TAL) effectors specifically bind to double stranded (ds) DNA through a central domain of tandem repeats. Each TAL effector (TALE) repeat comprises 33-35 amino acids and recognizes one specific DNA base through a highly variable residue at a fixed position in the repeat. Structural studies have revealed the molecular basis of DNA recognition by TALE repeats. Examination of the overall structure reveals that the basic building block of TALE protein, namely a helical hairpin, is one-helix shifted from the previously defined TALE motif. Here we wish to suggest a structure-based re-demarcation of the TALE repeat which starts with the residues that bind to the DNA backbone phosphate and concludes with the base-recognition hyper-variable residue. This new numbering system is consistent with the α-solenoid superfamily to which TALE belongs, and reflects the structural integrity of TAL effectors. In addition, it confers integral number of TALE repeats that matches the number of bound DNA bases. We then present fifteen crystal structures of engineered dHax3 variants in complex with target DNA molecules, which elucidate the structural basis for the recognition of bases adenine (A) and guanine (G) by reported or uncharacterized TALE codes. Finally, we analyzed the sequence-structure correlation of the amino acid residues within a TALE repeat. The structural analyses reported here may advance the mechanistic understanding of TALE proteins and facilitate the design of TALEN with improved affinity and specificity.

  19. Response of the Hypothalamic-Pituitary-Adrenal System to Repeated Moderate Psychoemotional Stress Exposure Is Associated with Behavioral Parameters.

    Science.gov (United States)

    Goncharova, N D; Chigarova, O A; Oganyan, T E

    2017-05-01

    Individual features of the response of the hypothalamic-pituitary-adrenal axis (HPAA) to repeated moderate stress exposure (daily 2-h restraint stress for 10 days) was studied in young female rhesus monkeys with healthy normal behavior and combined group of female rhesus monkeys with abnormal depression-like and anxious behavior. No between-group differences in the response of ACTH and cortisol were found on day 1. On day 10, a rapid and less pronounced increase in ACTH secretion was observed in all animals in comparison with day 1. Analysis of between-group differences in HPAA response showed higher increase in ACTH level and lower increase in cortisol concentration in animals with depression-like and anxious behavior. These changes were similar to the previously described differences in the response of the adenohypophysis and adrenal cortex to acute restraint stress in old monkeys with similar behavior. Thus, individuals with depression-like and anxious behavior demonstrate impaired stress-induced reactivity of HPAA as early as in young age.

  20. Successful Treatment of Hemifacial Myokymia and Dystonia Associated to Linear Scleroderma “En Coup de Sabre” with Repeated Botox Injections

    Directory of Open Access Journals (Sweden)

    Carlos A. Cañas

    2012-01-01

    Full Text Available Linear scleroderma “en coup de sabre” (LSCS is a form of localized scleroderma presents as band-like sclerotic lesions of the frontoparietal area. It has been reported in association with diverse neurological manifestations like seizures, migraine, neuromyotonia, dystonia and abnormalities in MRI and CT studies as cerebral atrophy, white matter lesions, intraparenchymal calcification, meningeocortical alterations, and skull atrophy. We describe a patient with LSCS associated with two abnormal movements: permanent myokimia of right masseter muscle and recurrent spasmodic retraction of right cigomatic and depressor labii inferioris muscles. He was initially treated with methotrexate and steroids without response, so later on he underwent repeated Botox injections with remarkable improvement.

  1. Recursive quantum repeater networks

    CERN Document Server

    Van Meter, Rodney; Horsman, Clare

    2011-01-01

    Internet-scale quantum repeater networks will be heterogeneous in physical technology, repeater functionality, and management. The classical control necessary to use the network will therefore face similar issues as Internet data transmission. Many scalability and management problems that arose during the development of the Internet might have been solved in a more uniform fashion, improving flexibility and reducing redundant engineering effort. Quantum repeater network development is currently at the stage where we risk similar duplication when separate systems are combined. We propose a unifying framework that can be used with all existing repeater designs. We introduce the notion of a Quantum Recursive Network Architecture, developed from the emerging classical concept of 'recursive networks', extending recursive mechanisms from a focus on data forwarding to a more general distributed computing request framework. Recursion abstracts independent transit networks as single relay nodes, unifies software layer...

  2. Adaptation of the pituitary-adrenal axis to daily repeated forced swim exposure in rats is dependent on the temperature of water.

    Science.gov (United States)

    Rabasa, Cristina; Delgado-Morales, Raúl; Gómez-Román, Almudena; Nadal, Roser; Armario, Antonio

    2013-11-01

    Comparison of exposure to certain predominantly emotional stressors reveals a qualitatively similar neuroendocrine response profile as well as a reduction of physiological responses after daily repeated exposure (adaptation). However, particular physical components of the stressor may interfere with adaptation. As defective adaptation to stress can enhance the probability to develop pathologies, we studied in adult male rats (n = 10/group) swimming behavior (struggling, immobility and mild swim) and physiological responses (ACTH, corticosterone and rectal temperature) to daily repeated exposure to forced swim (20 min, 13 d) at 25 or 36 °C (swim25 or swim36). Rats were repeatedly blood-sampled by tail-nick and hormones measured by radioimmunoassay. Some differences were observed between the two swim temperature groups after the first exposure to forced swim: (a) active behaviors were greater in swim25 than swim36 groups; (b) swim25 but not swim36 caused hypothermia; and (c) swim36 elicited the same ACTH response as swim25, but plasma corticosterone concentration was lower for swim36 at 30 min post-swim. After daily repeated exposure, adaptation in ACTH secretion was observed with swim36 already on day 4, whereas with swim25 adaptation was not observed until day 13 and was of lower magnitude. Nevertheless, after repeated exposure to swim25 a partial protection from hypothermia was observed and the two swim conditions resulted in progressive reduction of active behaviors. Thus, daily repeated swim at 25 °C impairs adaptation of the hypothalamic-pituitary-adrenal axis as compared to swim at 36 °C, supporting the hypothesis that certain physical components of predominantly emotional stressors can interfere with the process of adaptation.

  3. Increasing Belief in the Effectiveness of HIV Treatment as Prevention: Results of Repeated, National Surveys of Australian Gay and Bisexual Men, 2013-15.

    Science.gov (United States)

    Holt, Martin; Lea, Toby; Schmidt, Heather-Marie; Murphy, Dean; Rosengarten, Marsha; Crawford, David; Ellard, Jeanne; Kolstee, Johann; de Wit, John

    2016-07-01

    We surveyed Australian gay and bisexual men, assessing belief in HIV treatment as prevention (TasP) and support for early treatment. We identified the characteristics of participants who believed in TasP and supported early treatment using multivariate logistic regression. In 2013, 1316 men participated; 1251 participated in 2015. Belief in TasP increased from 2.6 % in 2013 to 13.1 % in 2015 (p HIV treatment was associated with being younger, living in New South Wales and being in paid employment. We recommend continued monitoring of the growing gap in belief about TasP between HIV-positive men and HIV-negative/untested men.

  4. Investigation of Repeat Client Drop-Out and Re-Enrolment Cycles in Fourteen Methadone Maintenance Treatment Clinics in Guangdong, China.

    Science.gov (United States)

    Zhang, Lei; Zou, Xia; Zhang, Di; Li, Xiaoling; Zhao, Peizhen; Ling, Li

    2015-01-01

    Client adherence is vital for effective methadone maintenance treatment (MMT). This study explores the pattern and associated factors of client adherence, drop-out and re-enrolment in the Chinese MMT programme over the period of 2006-2013. This retrospective study was conducted in 14 MMT clinics in Guangdong Province, China. We employed Kaplan-Meier survival analysis to estimate the rates of drop-out and re-enrolment of MMT clients and multivariate Cox regression to identify associated factors. Among 1,512 study participants, 79% have experienced 'drop-out' during the 7-year study period. However, 82% 'dropped-out' clients resumed treatment at a later time. Low education level (junior high or below versus otherwise, HR = 1.21, 1.05-1.40), low methadone dosage in the first treatment episode (drop-outs of the participants. Among the 'dropped-out' clients, being female (HR = 1.40, 1.23-1.60), being married (HR = 1.19, 1.09-1.30), and having a higher proportion of positive urine tests in the first treatment episode (≥50% versusdrop-out out of clients in MMT programmes is common. Insufficient dosage and higher proportion of positive urine samples in the first treatment episode are the key determinants for subsequent client drop-out and re-enrolment. Interventions should target clients in their early stage of treatment to improve retention in the long term.

  5. Optimal and safe treatment of spider leg veins measuring less than 1.5 mm on skin type IV patients, using repeated low-fluence Nd:YAG laser pulses after polidocanol injection.

    Science.gov (United States)

    Moreno-Moraga, Javier; Hernández, Esteban; Royo, Josefina; Alcolea, Justo; Isarría, M Jose; Pascu, Mihail Lucian; Smarandache, Adriana; Trelles, Mario

    2013-05-01

    Treatment of micro-veins of less than 1.5 mm with laser and with chemical sclerosis is technically challenging because of their difficulty to remedy. Laser treatment is even more difficult when dark phototypes are involved.Three groups of 30 patients each, skin type IV, and vessels measuring less than 1.5 mm in diameter, were enrolled for two treatment sessions 8 weeks apart: group A, polidocanol (POL) micro-foam injection; group B, Nd:YAG laser alone; and group C, laser after POL injection. Repeated 8-Hz low-fluence pulses, moving the hand piece over a 3-cm vein segment with an average of five laser passes maximum and with a total time irradiation of 1 s were used. Sixteen weeks after the second treatment, statistically, degree of clearance after examining photographs and patients satisfaction index, plotted on a visual analogue scale and comparing results of all three groups, results were significantly better for group C (p<0.0001). No significant differences in complications were noticed between the three groups. Efficacy of combining POL and laser proved safe and satisfactory in 96 % of patients using low-fluence laser pulses with a total cumulative energy in the 3 cm venous segment, lower than that of conventional treatment. Very few and transient complications were observed. POL foam injection followed by laser pulses is safe and efficient for vein treatment in dark-skinned patients.

  6. 非ACTH依赖性双侧肾上腺大结节增生患者的临床特点分析%A study on clinical features of ACTH-independent bilateral macronodular adrenal hyperplasia

    Institute of Scientific and Technical Information of China (English)

    张倩; 巴建明; 母义明; 陆菊明; 潘长玉; 窦京涛; 谷伟军; 杜锦; 王先令; 杨国庆; 郭清华; 杨丽娟; 吕朝晖

    2011-01-01

    Objective To study the clinical features of patients with ACTH-independent bilateral macronodular adrenal hyperplasia(AIMAH).Methods Eighteen cases with AIMAH diagnosed in Chinese PLA General Hospital from 1998 to 2010 were analyzed retrospectively.Results ( 1 ) AIMAH was equally distributed between genders,mean age at diagnosis was ( 51.4 ± 10.7 ) years,and average course was ( 9.9:t:2.7 ) years.( 2 )Most patients visited hospital because of adrenal incidentaloma; hypertension and impaired glucose tolerance/diabetes mellitius were the most common clinical presentations; typical signs of Cushing′s syndrome (CS) such as moon face and central obesity were less frequent.( 3 ) All cases′ laboratory findings met the diagnostic criteria of ACTH-independent CS,some cases with the features of subclinical CS.24 h dynamic plasma ACTH and cortisol monitoring had the advantage of revealing the features of subclinical CS for some AIMAH cases; there was remarkable elevation of plasma cortisol after exogenous ACTH stimulation in AIMAH patients.(4) Bilateral adrenal macronodular changes could be visualized on CT scan.( 5 ) Pathology identified bilateral macronodular adrenal hyperplasia.( 6 ) Bilateral adrenalectomy was the most useful treatment.Conclusions AIMAH is an infrequent cause of CS,and some patients present subclinical CS.Its marked clinical feature is ACTH-independent bilateral macronodular adrenal hyperplasia.%目的 探讨非ACTH依赖性双侧肾上腺大结节增生(AIMAH)患者的临床特点.方法 回顾性分析1998年至2010年解放军总医院内分泌科收治并确诊的18例非ACTH依赖性双侧肾上腺大结节增生患者的临床资料.结果 (1) AIMAH患者男女比例1∶1,平均就诊年龄(51.4±10.7)岁,平均病程(9.9±2.7)年;(2)部分患者因体检意外发现肾上腺占位就诊;高血压、糖代谢异常最常见,满月脸、向心性肥胖等典型的库欣综合征(CS)体征较少见;(3)实验室检查示患者均为非ACTH

  7. Using the human melanocortin-2 receptor as a model for analyzing hormone/receptor interactions between a mammalian MC2 receptor and ACTH(1-24).

    Science.gov (United States)

    Liang, Liang; Angleson, Joseph K; Dores, Robert M

    2013-01-15

    When considering the interactions between the melanocortin peptides (i.e., ACTH, α-MSH, β-MSH, γ-MSH) and the melanocortin receptors (i.e., MC1R, MC2R, MC3R, MC4R, MC5R), it appears that the structure/function relationship between ACTH and MC2R is the most complicated. Human ACTH(1-24) and the human melanocortin-2 receptor provide a useful model system for understanding how ACTH emerged as the sole ligand for the melanocortin-2 receptor of bony vertebrates. This review will discuss how studies utilizing analogs of hACTH(1-24) have revealed two critical amino acid motifs in this ligand (HFRW and KKRRP) which are required for activation of the melanocortin-2 receptor. In addition, observations on the unique activation features of the melanocortin-2 receptor, as revealed from studies on Familial Glucocorticoid Deficiency, will be considered. Finally, the evolutionary implications of the relationship between MC2R and MRAP1 will be discussed.

  8. Ovarian localization of 11β-hydroxysteroid dehydrogenase (11βHSD): effects of ACTH stimulation and its relationship with bovine cystic ovarian disease.

    Science.gov (United States)

    Amweg, A N; Salvetti, N R; Stangaferro, M L; Paredes, A H; Lara, H H; Rodríguez, F M; Ortega, H H

    2013-10-01

    Cystic ovarian disease (COD) is an important cause of infertility in cattle, and ACTH has been involved in regulatory mechanisms related to ovarian function associated with ovulation, steroidogenesis, and luteal function. Here, we examined the localization of 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) and 11βHSD2 proteins in the ovary of healthy cows and animals with spontaneous and ACTH-induced COD and the in vitro response of the follicular wall exposed to ACTH. After stimulation by ACTH, we documented changes in 11βHSD expression and cortisol secretion by the follicular wall of large antral and follicular cysts. Follicular cysts showed a higher constitutive expression of both enzymes, whereas ACTH induced an increase in 11βHSD1 in tertiary follicles and follicular cysts and a decrease in 11βHSD2 in follicular cysts. Moderate expression of 11βHSD1 was observed by immunohistochemistry in granulosa of control animals, with an increase (P cortisol in COD pathogenesis and in regulatory mechanisms of ovarian function.

  9. The child accident repeater: a review.

    Science.gov (United States)

    Jones, J G

    1980-04-01

    The child accident repeater is defined as one who has at least three accidents that come to medical attention within a year. The accident situation has features in common with those of the child who has a single accident through simple "bad luck", but other factors predispose him to repeated injury. In the child who has a susceptible personality, a tendency for accident repetition may be due to a breakdown in adjustment to a stressful environment. Prevention of repeat accidents should involve the usual measures considered appropriate for all children as well as an attempt to provide treatment of significant maladjustment and modification of a stressful environment.

  10. The Pentapeptide Repeat Proteins

    Energy Technology Data Exchange (ETDEWEB)

    Vetting,M.; Hegde, S.; Fajardo, J.; Fiser, A.; Roderick, S.; Takiff, H.; Blanchard, J.

    2006-01-01

    The Pentapeptide Repeat Protein (PRP) family has over 500 members in the prokaryotic and eukaryotic kingdoms. These proteins are composed of, or contain domains composed of, tandemly repeated amino acid sequences with a consensus sequence of [S, T,A, V][D, N][L, F]-[S, T,R][G]. The biochemical function of the vast majority of PRP family members is unknown. The three-dimensional structure of the first member of the PRP family was determined for the fluoroquinolone resistance protein (MfpA) from Mycobacterium tuberculosis. The structure revealed that the pentapeptide repeats encode the folding of a novel right-handed quadrilateral {beta}-helix. MfpA binds to DNA gyrase and inhibits its activity. The rod-shaped, dimeric protein exhibits remarkable size, shape and electrostatic similarity to DNA.

  11. Differential effects of repeated low dose treatment with the cannabinoid agonist WIN 55,212-2 in experimental models of bone cancer pain and neuropathic pain

    DEFF Research Database (Denmark)

    Hald, Andreas; Ding, Ming; Egerod, Kristoffer Lihme;

    2008-01-01

    . Furthermore, this treatment strategy was not found to induce measurable CNS related side effects or tolerance. Cancer cell viability assays and bone volume fraction assessed by micro computed tomography (microCT) demonstrated that these effects were not due to changes in cancer progression. The difference...

  12. The impact of repeated treatment with praziquantel of schistosomiasis in children under six years of age living in an endemic area for Schistosoma haematobium infection

    Directory of Open Access Journals (Sweden)

    T Mduluza

    2001-09-01

    Full Text Available Praziquantel was given every eight weeks for two years to children aged under six years of age, living in a Schistosoma haematobium endemic area. Infection with S. haematobium and haematuria were examined in urine and antibody profiles (IgA, IgE, IgM, IgG1, IgG2, IgG3, and IgG4 against S. haematobium adult worm and egg antigens were determined from sera collected before each treatment. Chemotherapy reduced infection prevalence and mean intensity from 51.8% and 110 eggs per 10 ml urine, respectively, before starting re-treatment programme to very low levels thereafter. Praziquantel is not accumulated after periodic administration in children. Immunoglobulin levels change during the course of treatment with a shift towards 'protective' mechanisms. The significant changes noted in some individuals were the drop in 'blocking' IgG2 and IgG4 whereas the 'protecting' IgA and IgG1 levels increased. The antibody profiles in the rest of the children remained generally unchanged throughout the study and no haematuria was observed after the second treatment. The removal of worms before production of large number of eggs, prevented the children from developing morbidity.

  13. Effect of a Mind-Body Therapeutic Program for Infertile Women Repeating In Vitro Fertilization Treatment on Uncertainty, Anxiety, and Implantation Rate

    Directory of Open Access Journals (Sweden)

    Miok Kim, PhD

    2014-03-01

    Conclusion: This study is meaningful as the first intervention program for alleviating uncertainty and anxiety provided during the IVF treatment process. The positive effects of the mind-body therapeutic program in alleviating both uncertainty and anxiety have direct meaning for clinical applications.

  14. Impact of ivermectin on onchocerciasis transmission: Assessing the empirical evidence that repeated ivermectin mass treatments may lead to elimination/eradication in West-Africa

    NARCIS (Netherlands)

    G.J.J.M. Borsboom (Gerard); B.A. Boatin (Boakye); N.J.D. Nagelkerke (Nico); H. Agoua (Hyacinthe); K.L.B. Akpoboua (Komlan); E.W. Soumbey Alley (E. William); Y. Bissan (Yeriba); A. Renz (Anna); L. Yameogo (Laurent); J.H.F. Remme (Jan); J.D.F. Habbema (Dik)

    2003-01-01

    markdownabstract__Background:__ The Onchocerciasis Control Program (OCP) in West Africa has been closed down at the end of 2002. All subsequent control will be transferred to the participating countries and will almost entirely be based on periodic mass treatment with ivermectin. This makes the ques

  15. Authors' reply to comment on "Are repeated assisted reproductive technology treatments and an unsuccessful outcome risk factors for unipolar depression in infertile women?"

    DEFF Research Database (Denmark)

    Sejbaek, Camilla S.; Pinborg, Anja; Hageman, Ida

    2016-01-01

    The aim of our national register-based study (1) was to investigate the risk of a new episode of unipolar depression among women treated with assisted reproductive technology (ART) in regards to whether they had achieved a live birth (as a result of treatment or spontaneous conception) or not. He...

  16. Usefulness of Time-Point Serum Cortisol and ACTH Measurements for the Adjustment of Glucocorticoid Replacement in Adrenal Insufficiency.

    Science.gov (United States)

    Rousseau, Elise; Joubert, Michael; Trzepla, Géraldine; Parienti, Jean Jacques; Freret, Thomas; Vanthygem, Marie Christine; Desailloud, Rachel; Lefebvre, Hervé; Coquerel, Antoine; Reznik, Yves

    2015-01-01

    Adjustment of daily hydrocortisone dose on clinical criteria lacks sensitivity for fine tuning. Long term hydrocortisone (HC) over-replacement may lead to increased morbidity and mortality in patients with adrenal insufficiency (AI). Biochemical criteria may help detecting over- or under-replacement but have been poorly evaluated. Multicenter, institutional, pharmacokinetic study on ACTH and cortisol plasma profiles during HC replacement in 27 AI patients compared to 29 matched controls. All AI patients were administered HC thrice daily at doses of 6, 10 and 14 mg/m2/d. Blood samples were drawn hourly from 0800h to 1900h. The main outcome measures were: i) plasma peak cortisol and cortisol area under the curve (AUC) in AI patients compared to controls, ii) correlations between cortisol AUC vs single-point cortisol or ACTH decrease from baseline (ΔACTH) and iii) the predictive value of the two latters for obtaining AI patients' cortisol AUC in the control range. Cortisol peaks were observed 1h after each HC intake and a dose response was demonstrated for cortisol peak and cortisol AUC. The comparison of AI patients' cortisol AUC to controls showed that 81.5% AI patients receiving 6mg/m2/d were adequately replaced, whereas most patients receiving higher doses were over-replaced. The correlation coefficient between 1000h/1400h cortisol concentrations and 0800-1900h cortisol AUC were 0.93/0.88 respectively, whereas the 0800-1200h ΔACTH fairly correlated with 0800-1900h cortisol AUC (R = 0.57). ROC curve analysis indicated that the 1000h and 1400h cortisol concentrations best predicted over-replacement. Patients receiving a 6mg/m2 hydrocortisone daily dose exhibited the most physiological daytime cortisol profile. Single point plasma cortisol correlated with daytime cortisol AUC in AI patients. Although hydrocortisone dose should be currently determined on clinical grounds, our data suggest that single point plasma cortisol may be an adjunct for further hydrocortisone

  17. [Influence, in normal subjects, of an isocaloric hyperprotein diet on cortisol, ACTH, GH and PRL response to lysine-8-vasopressin].

    Science.gov (United States)

    Giovannini, C; Sellini, M; Manzo, G; Barletta, C; Scavo, D

    1981-12-30

    The Lysin-8-Vasopressin test has been experimented in ten healthy subjects during normocaloric balanced diet and after hyperproteic-normocaloric diet. The levels of ACTH, Cortisol and GH are significantly more elevated after hyperproteic-normocaloric diet than in basal conditions. The levels of Prolactin do not show any remarkable change. These results can indicate the increased reactivity of the diencephalon-hypophysis-adrenal axis and of the hormones connected with the mechanisms of homeostasis and stress, probably correlated to more disposable proteic material and to the metabolic effects which follow.

  18. Repeating the Past

    Science.gov (United States)

    Moore, John W.

    1998-05-01

    As part of the celebration of the Journal 's 75th year, we are scanning each Journal issue from 25, 50, and 74 years ago. Many of the ideas and practices described are so similar to present-day "innovations" that George Santayana's adage (1) "Those who cannot remember the past are condemned to repeat it" comes to mind. But perhaps "condemned" is too strong - sometimes it may be valuable to repeat something that was done long ago. One example comes from the earliest days of the Division of Chemical Education and of the Journal.

  19. Burnout as a risk factor for antidepressant treatment - a repeated measures time-to-event analysis of 2936 Danish human service workers

    DEFF Research Database (Denmark)

    Madsen, Ida E H; Lange, Theis; Borritz, Marianne

    2015-01-01

    Burnout is a state of emotional exhaustion, feelings of reduced personal accomplishment, and withdrawal from work thought to occur as a consequence of prolonged occupational stress. The condition is not included in the diagnostic classifications, but is considered likely to develop into depressive...... disorder in some cases. We examined the prospective association between burnout and antidepressant treatment, as an indicator of clinically significant mental disorder. We further investigated potential effect-modifiers of the association, to identify factors that may prevent this progression of burnout...... modeling, examining the risk of entering antidepressant treatment in relation to the level of work-related burnout measured by the Copenhagen Burnout inventory. As effect-modifiers we examined both sociodemographic factors and a range of psychosocial work environment factors. The level of burnout predicted...

  20. Post-traumatic Stress Disorder Symptoms in a Female Patient Following Repeated Teasing: Treatment with Gabapentin and Lamotrigine and the Possible Role of Sensitization

    OpenAIRE

    Kishimoto, Akira; Goto, Yurie; Hashimoto, Kenji

    2014-01-01

    Post-traumatic stress disorder (PTSD) is a pathological response to trauma characterized by frequent recollections, recurrent nightmares, and flashbacks of the traumatic event(s). To date, the precise mechanisms underlying the development of PTSD remain unknown. Several studies have suggested that antiepileptic drugs, such as gabapentin and lamotrigine, may be effective in the treatment of PTSD symptoms. We report on a 15-year-old Japanese female junior high school student who developed PTSD ...

  1. Prefrontal cortical and striatal transcriptional responses to the reinforcing effect of repeated methylphenidate treatment in the spontaneously hypertensive rat, animal model of attention-deficit/hyperactivity disorder (ADHD)

    OpenAIRE

    dela Peña, Ike; Kim, Hee Jin; Sohn, Aeree; Kim, Bung-Nyun; Han, Doug Hyun; Ryu, Jong Hoon; Shin, Chan Young; Noh, Minsoo; Cheong, Jae Hoon

    2014-01-01

    Background Methylphenidate is the most commonly used stimulant drug for the treatment of attention-deficit/hyperactivity disorder (ADHD). Research has found that methylphenidate is a “reinforcer” and that individuals with ADHD also abuse this medication. Nevertheless, the molecular consequences of long-term recreational methylphenidate use or abuse in individuals with ADHD are not yet fully known. Methods Spontaneously hypertensive rats (SHR), the most validated and widely used ADHD animal mo...

  2. Treatment with an anti-CD11d integrin antibody reduces neuroinflammation and improves outcome in a rat model of repeated concussion

    OpenAIRE

    2013-01-01

    Background Concussions account for the majority of traumatic brain injuries (TBI) and can result in cumulative damage, neurodegeneration, and chronic neurological abnormalities. The underlying mechanisms of these detrimental effects remain poorly understood and there are presently no specific treatments for concussions. Neuroinflammation is a major contributor to secondary damage following more severe TBI, and recent findings from our laboratory suggest it may be involved in the cumulative pr...

  3. All-optical repeater.

    Science.gov (United States)

    Silberberg, Y

    1986-06-01

    An all-optical device containing saturable gain, saturable loss, and unsaturable loss is shown to transform weak, distorted optical pulses into uniform standard-shape pulses. The proposed device performs thresholding, amplification, and pulse shaping as required from an optical repeater. It is shown that such a device could be realized by existing semiconductor technology.

  4. Bidirectional Manchester repeater

    Science.gov (United States)

    Ferguson, J.

    1980-01-01

    Bidirectional Manchester repeater is inserted at periodic intervals along single bidirectional twisted pair transmission line to detect, amplify, and transmit bidirectional Manchester 11 code signals. Requiring only 18 TTL 7400 series IC's, some line receivers and drivers, and handful of passive components, circuit is simple and relatively inexpensive to build.

  5. Spectrum of Adrenal Dysfunction in Patients with Acquired Immunodeficiency Syndrome Evaluation of Adrenal and Pituitary Reserve with ACTH and Corticotropin-Releasing Hormone Testing.

    Science.gov (United States)

    Freda, P U; Papadopoulos, A D; Wardlaw, S L; Goland, R S

    1997-07-01

    Patients with acquired immunodeficiency syndrome (AIDS) have been reported to develop abnormalities of the endocrine system and in particular of the hypothalamic-pituitary-adrenal (HPA) axis. To define the abnormalities of HPA function in AIDS patients better, we performed ACTH and ovine corticotropin-releasing hormone (oCRH) testing in a group of AIDS patients and oCRH testing in a group of healthy subjects. Our study found that in AIDS patients with normal ACTH testing, oCRH testing revealed a variety of subclinical abnormalities of ACTH and cortisol responses. Although we did not find frank adrenal insufficiency in any of these AIDS patients, it remains to be determined if any of the subclinical abnormalities we identified are predictive of clinically significant adrenal insufficiency; it may be that as AIDS patients live longer, the subclinical abnormalities will progress to adrenal insufficiency. (Trends Endocrinol Metab 1997;8:173-180). (c) 1997, Elsevier Science Inc.

  6. Repeat Gamma Knife Radiosurgery for Trigeminal Neuralgia

    Energy Technology Data Exchange (ETDEWEB)

    Aubuchon, Adam C., E-mail: acaubuchon@gmail.com [Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Chan, Michael D. [Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Lovato, James F. [Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Balamucki, Christopher J. [Department of Radiation Oncology, University of Florida, Gainesville, FL (United States); Ellis, Thomas L.; Tatter, Stephen B. [Department of Neurosurgery, Wake Forest University School of Medicine, Winston-Salem, NC (United States); McMullen, Kevin P.; Munley, Michael T.; Deguzman, Allan F.; Ekstrand, Kenneth E.; Bourland, J. Daniel; Shaw, Edward G. [Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States)

    2011-11-15

    Purpose: Repeat gamma knife stereotactic radiosurgery (GKRS) for recurrent or persistent trigeminal neuralgia induces an additional response but at the expense of an increased incidence of facial numbness. The present series summarized the results of a repeat treatment series at Wake Forest University Baptist Medical Center, including a multivariate analysis of the data to identify the prognostic factors for treatment success and toxicity. Methods and Materials: Between January 1999 and December 2007, 37 patients underwent a second GKRS application because of treatment failure after a first GKRS treatment. The mean initial dose in the series was 87.3 Gy (range, 80-90). The mean retreatment dose was 84.4 Gy (range, 60-90). The dosimetric variables recorded included the dorsal root entry zone dose, pons surface dose, and dose to the distal nerve. Results: Of the 37 patients, 81% achieved a >50% pain relief response to repeat GKRS, and 57% experienced some form of trigeminal dysfunction after repeat GKRS. Two patients (5%) experienced clinically significant toxicity: one with bothersome numbness and one with corneal dryness requiring tarsorraphy. A dorsal root entry zone dose at repeat treatment of >26.6 Gy predicted for treatment success (61% vs. 32%, p = .0716). A cumulative dorsal root entry zone dose of >84.3 Gy (72% vs. 44%, p = .091) and a cumulative pons surface dose of >108.5 Gy (78% vs. 44%, p = .018) predicted for post-GKRS numbness. The presence of any post-GKRS numbness predicted for a >50% decrease in pain intensity (100% vs. 60%, p = .0015). Conclusion: Repeat GKRS is a viable treatment option for recurrent trigeminal neuralgia, although the patient assumes a greater risk of nerve dysfunction to achieve maximal pain relief.

  7. Repeated low-dose 17β-estradiol treatment prevents activation of apoptotic signaling both in the synaptosomal and cellular fraction in rat prefrontal cortex following cerebral ischemia.

    Science.gov (United States)

    Stanojlović, Miloš; Zlatković, Jelena; Guševac, Ivana; Grković, Ivana; Mitrović, Nataša; Zarić, Marina; Horvat, Anica; Drakulić, Dunja

    2015-01-01

    Disturbance in blood circulation is associated with numerous pathological conditions characterized by cognitive decline and neurodegeneration. Activation of pro-apoptotic signaling previously detected in the synaptosomal fraction may underlie neurodegeneration in the prefrontal cortex of rats submitted to permanent bilateral common carotid arteries occlusion (two-vessel occlusion, 2VO). 17β-Estradiol (E) exerts potent neuroprotective effects in the brain affecting, among other, ischemia-induced pathological changes. As most significant changes in rats submitted to 2VO were observed on 7th day following the insult, of interest was to examine whether 7 day treatment with low dose of E (33.3 µg/kg/day) prevents formerly reported neurodegeneration and may represent additional therapy during the early post-ischemic period. Role of E treatment on apoptotic pathway was monitored on Bcl-2 family members, cytochrome c, caspase 3 and PARP protein level in the synaptosomal (P2) fraction of the prefrontal cortex. Furthermore, changes of these proteins were examined in the cytosolic, mitochondrial and nuclear fraction, with the emphasis on potential involvement of extracellular signal-regulated kinases (ERK) and protein kinase B (Akt) activation and their role in nuclear translocation of transcriptional nuclear factor kappa B (NF-kB) associated with alteration of Bax and Bcl-2 gene expression. The extent of cellular damage was determined using DNA fragmentation and Fluoro-Jade B staining. The absence of activation of apoptotic cascade both in the P2 and cell accompanied with decreased DNA fragmentation and number of degenerating neurons clearly indicates that E treatment ensures the efficient protection against ischemic insult. Moreover, E-mediated modulation of pro-apoptotic signaling in the cortical cellular fractions involves cooperative activation of ERK and Akt, which may be implicated in the observed prevention of neurodegenerative changes.

  8. The adrenocortical response of greater sage grouse (Centrocercus urophasianus) to capture, ACTH injection, and confinement, as measured in fecal samples

    Science.gov (United States)

    Jankowski, M.D.; Wittwer, D.J.; Heisey, D.M.; Franson, J.C.; Hofmeister, E.K.

    2009-01-01

    Investigators of wildlife populations often utilize demographic indicators to understand the relationship between habitat characteristics and population viability. Assessments of corticosterone may enable earlier detection of populations at risk of decline because physiological adjustments to habitat disturbance occur before reproductive diminutions. Noninvasive methods to accomplish these assesments are important in species of concern, such as the greater sage grouse (GRSG). Therefore, we validated a radioimmunoassay that measures immunoreactive corticosterone metabolites (ICM) in fecal samples and used it to characterize the adrenocortical response of 15 GRSG exposed to capture, intravenous injection of 50 IU/kg adrenocorticotrophic hormone (ACTH) or saline, and 22 h of confinement. Those animals injected with ACTH exhibited a more sustained (P = 0.0139) and less variable (P = 0.0012) response than those injected with saline, indicating different levels of adrenocortical activity. We also found that potential field-collection protocols of fecal samples did not alter ICM concentrations: samples held at 4??C for up to 16 h contained similar levels of ICM as those frozen (-20??C) immediately. This study demonstrates a multiphasic adrenocortical response that varied with the level of stimulation and indicates that the assay used to measure this phenomenon is applicable for studies of wild GRSG. ?? 2009 by The University of Chicago. All rights reserved.

  9. [Correction by natural adaptogens of hormonal-metabolic status disorders in rats during the development of adaptation syndrome using functional tests with dexamethasone and ACTH].

    Science.gov (United States)

    Udintsev, S N; Krylova, S G; Konovalova, O N

    1991-12-01

    Rats exposed to stress by fixation develop a complex of hormonal metabolic homeostasis disturbances (as evidenced by changed levels of ACTH, insulin, 11-HOCS, urea, glucose). One of the major mechanisms of these disorders in reduced hypothalamus sensitivity to regulatory signals and exhausted adrenocortical functional activity, developing at the stages of anxiety and exhaustion of the adaptation syndrome, respectively, and detectable by functional tests with dexamethasone and ACTH. Administration of natural adaptogens (Scutellaria baicalensis extract and its active principle, baikalin flavonoid) was conducive to normalization of the majority of the examined parameters whatever the direction of changes.

  10. Object memory impairment at post-drug Day 15 but not at Day 1 after a regimen of repeated treatment with oral methylphenidate.

    Science.gov (United States)

    Taukulis, Harald K; Bigney, Erin E; Fry, Michael D; Hooper, Courtney

    2014-04-30

    Methylphenidate (MPH) is a dopamine and norepinephrine reuptake inhibitor that is widely used for the treatment of attention-deficit/hyperactivity disorder in children and adults. Its similarity to other psychostimulants suggests that, at certain doses, the drug may generate lasting neuroadaptations that can be detrimental to the recipient. Some investigators have found that, in rats, the residual effects of the drug (i.e., following a 10-14 day washout period) can interfere with memory for objects when the retention interval is 3h or more. The present experiment replicated this result and demonstrated the critical importance of the washout period. Long-Evans male rats treated with MPH (5.0mg/kg po b.i.d.) on 21 days (during a post-natal period ranging from Day 29 to Day 57) and then twice-assessed for their performance in an object recognition task were able to recognize a familiar object on Day 1 after the last dose of the drug had been administered, behaving the same as the untreated control group. However, on Day 15 post-drug, the same MPH group failed to distinguish between a familiar and a novel object, exploring both nearly equally, while the control group continued to investigate the novel object to a greater extent than the familiar one. This suggests that, if a test for object recognition is conducted too early after the MPH treatment period ceases, a memory impairment may not be detected. In general, this finding has implications for studies of other behavioral or neurophysiological consequences of MPH that may appear following a drug-free withdrawal period.

  11. 多次利培酮治疗致抗精神病药恶性综合征%Neuroleptic malignant syndrome after repeated treatment with risperidone

    Institute of Scientific and Technical Information of China (English)

    丁跃庆; 李华; 谢振强; 张伟娟; 代俊; 孔君; 吴洪军

    2012-01-01

    1例31岁女性患者因精神分裂症给予利培酮1 mg,2次/d口服,1周后剂量增至2 mg,2次/d.此前患者曾3次间断应用利培酮治疗.本次治疗规律服药49 d,患者精神症状缓解.第50~52天未遵医嘱规律服药.第54天患者出现大汗淋漓,体温达38.5 ℃.第55天出现意识障碍、心动过速、双上肢肌强直、肌张力增高.心电图示窦性心动过速.实验室检查示:白细胞计数12.3×109/L,胆碱酯酶 13 268 U /L,肌酸激酶 1447 U/L,利培酮血液浓度70.5 μg/L.诊断为抗精神病药恶性综合征(NMS).立即停用利培酮,进行物理降温、补液、抗心律失常、抗感染、纠正酸碱平衡、护肝等治疗.6 d后患者体温恢复正常,NMS症状消失.换用奥氮平治疗后,未再出现类似症状.%A 31-year-old woman with schizophrenia received risperidone 1 mg twice daily. One week later, the dose was increased to 2 mg twice daily. The patient had previously received risperidone intermittent treatment for three times. After a 49-day regular treatment, the psychiatric symptoms relieved. On days 50 to 52, she did not adhere to the instructions of the physician for regular use of the drug. On day 54, the patient experienced profuse sweating with a temperature of 38. 5 ℃. On day 55, she developed disturbance of consciousness, tachycardia, muscle rigidity of the upper limbs, and hypermyotonia. Her electrocardiograph showed sinus tachycardia. Laboratory tests showed the following findings: white blood cell count 12. 3 × 109/L, cholinesterase 13 268 U/L, creatine kinase 1447 U/L. The blood concentrations of risperidone was 70. 5 μg/L. Neuroleptic malignant syndrome ( NMS ) was diagnosed. The medication was stopped immediately. Physical methods for lowering body temperature, fluid supplement, antiarrhythmics, anti-infective therapy, correction of the acid-base imbalance, and liver-protective treatment were given. Six days later, the temperature returned to normal, the NMS symptoms

  12. Duct Leakage Repeatability Testing

    Energy Technology Data Exchange (ETDEWEB)

    Walker, Iain [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Sherman, Max [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2014-01-01

    Duct leakage often needs to be measured to demonstrate compliance with requirements or to determine energy or Indoor Air Quality (IAQ) impacts. Testing is often done using standards such as ASTM E1554 (ASTM 2013) or California Title 24 (California Energy Commission 2013 & 2013b), but there are several choices of methods available within the accepted standards. Determining which method to use or not use requires an evaluation of those methods in the context of the particular needs. Three factors that are important considerations are the cost of the measurement, the accuracy of the measurement and the repeatability of the measurement. The purpose of this report is to evaluate the repeatability of the three most significant measurement techniques using data from the literature and recently obtained field data. We will also briefly discuss the first two factors. The main question to be answered by this study is to determine if differences in the repeatability of these tests methods is sufficient to indicate that any of these methods is so poor that it should be excluded from consideration as an allowed procedure in codes and standards.

  13. Safety of Repeated Yttrium-90 Radioembolization

    Energy Technology Data Exchange (ETDEWEB)

    Lam, Marnix G. E. H.; Louie, John D. [Stanford University School of Medicine, Division of Interventional Radiology (United States); Iagaru, Andrei H.; Goris, Michael L. [Stanford University School of Medicine, Division of Nuclear Medicine (United States); Sze, Daniel Y., E-mail: dansze@stanford.edu [Stanford University School of Medicine, Division of Interventional Radiology (United States)

    2013-10-15

    Purpose: Repeated radioembolization (RE) treatments carry theoretically higher risk of radiation-induced hepatic injury because of the liver's cumulative memory of previous exposure. We performed a retrospective safety analysis on patients who underwent repeated RE. Methods: From 2004 to 2011, a total of 247 patients were treated by RE. Eight patients (5 men, 3 women, age range 51-71 years) underwent repeated treatment of a targeted territory, all with resin microspheres (SIR-Spheres; Sirtex, Lane Cove, Australia). Adverse events were graded during a standardized follow-up. In addition, the correlation between the occurrence of RE-induced liver disease (REILD) and multiple variables was investigated in univariate and multivariate analyses in all 247 patients who received RE. Results: Two patients died shortly after the second treatment (at 84 and 107 days) with signs and symptoms of REILD. Both patients underwent whole liver treatment twice (cumulative doses 3.08 and 2.66 GBq). The other 6 patients demonstrated only minor toxicities after receiving cumulative doses ranging from 2.41 to 3.88 GBq. All patients experienced objective tumor responses. In the whole population, multifactorial analysis identified three risk factors associated with REILD: repeated RE (p = 0.036), baseline serum total bilirubin (p = 0.048), and baseline serum aspartate aminotransferase (p = 0.043). Repeated RE proved to be the only independent risk factor for REILD in multivariate analysis (odds ratio 9.6; p = 0.002). Additionally, the administered activity per target volume (in GBq/L) was found to be an independent risk factor for REILD, but only in whole liver treatments (p = 0.033). Conclusion: The risk of REILD appears to be elevated for repeated RE. Objective tumor responses were observed, but establishment of safety limits will require improvement in dosimetric measurement and prediction.

  14. Prefrontal cortical and striatal transcriptional responses to the reinforcing effect of repeated methylphenidate treatment in the spontaneously hypertensive rat, animal model of attention-deficit/hyperactivity disorder (ADHD).

    Science.gov (United States)

    dela Peña, Ike; Kim, Hee Jin; Sohn, Aeree; Kim, Bung-Nyun; Han, Doug Hyun; Ryu, Jong Hoon; Shin, Chan Young; Noh, Minsoo; Cheong, Jae Hoon

    2014-05-06

    Methylphenidate is the most commonly used stimulant drug for the treatment of attention-deficit/hyperactivity disorder (ADHD). Research has found that methylphenidate is a "reinforcer" and that individuals with ADHD also abuse this medication. Nevertheless, the molecular consequences of long-term recreational methylphenidate use or abuse in individuals with ADHD are not yet fully known. Spontaneously hypertensive rats (SHR), the most validated and widely used ADHD animal model, were pretreated with methylphenidate (5 mg/kg, i.p.) during their adolescence (post-natal day [PND] 42-48) and tested for subsequent methylphenidate-induced conditioned place preference (CPP) and self-administration. Thereafter, the differentially expressed genes in the prefrontal cortex (PFC) and striatum of representative methylphenidate-treated SHRs, which showed CPP to and self-administration of methylphenidate, were analyzed. Genome-wide transcriptome profiling analyses revealed 30 differentially expressed genes in the PFC, which include transcripts involved in apoptosis (e.g. S100a9, Angptl4, Nfkbia), transcription (Cebpb, Per3), and neuronal plasticity (Homer1, Jam2, Asap1). In contrast, 306 genes were differentially expressed in the striatum and among them, 252 were downregulated. The main functional categories overrepresented among the downregulated genes include those involved in cell adhesion (e.g. Pcdh10, Ctbbd1, Itgb6), positive regulation of apoptosis (Perp, Taf1, Api5), (Notch3, Nsbp1, Sik1), mitochondrion organization (Prps18c, Letm1, Uqcrc2), and ubiquitin-mediated proteolysis (Nedd4, Usp27x, Ube2d2). Together, these changes indicate methylphenidate-induced neurotoxicity, altered synaptic and neuronal plasticity, energy metabolism and ubiquitin-dependent protein degradation in the brains of methylphenidate-treated SHRs, which showed methylphenidate CPP and self-administration. In addition, these findings may also reflect cognitive impairment associated with chronic

  15. ATRAZINE DOES NOT INDUCE GASTROINTESTINAL DISCOMFORT (PICA) IN RATS AT DOSES THAT INCREASE ACTH ANDCORTICOSTERONE RELEASE AND CAUSE CONDITIONED TASTE AVERSION.

    Science.gov (United States)

    Previous work has shown that a single oral administration of atrazine (ATR), a chlorotriazine herbicide, induces dose-dependent increases in plasma adrenocorticotropic hormone (ACTH) and serum corticosterone (CORT), with a LOEL of 12.5mg/kg. The mechanism for these effects is unk...

  16. NERVE REGENERATION THROUGH A 2-PLY BIODEGRADABLE NERVE GUIDE IN THE RAT AND THE INFLUENCE OF ACTH4-9 NERVE GROWTH-FACTOR

    NARCIS (Netherlands)

    ROBINSON, PH; VANDERLEI, B; HOPPEN, HJ; LEENSLAG, JW; PENNINGS, AJ; NIEUWENHUIS, P

    1991-01-01

    Biodegradable polyurethane-based (PU) nerve guides, instilled with or without ACTH4-9 analog (a melanocortin) were used for bridging an 8 mm gap in the rat sciatic nerve and were evaluated for function and histological appearance after 16 weeks of implantation. Autologous nerve grafts functioned as

  17. Cortisol Response to Low-Dose (1 μg ACTH Stimulation for the Prediction of Outcome in Patients with Systemic Inflammatory Response Syndrome

    Directory of Open Access Journals (Sweden)

    Bjekić-Macut Jelica

    2016-10-01

    Full Text Available Background: Systemic inflammatory response syndrome (SIRS changes cortisol dynamics and indicates dissociation between the adrenal cortex and the hypothalamo-pituitary unit. The aim of this study was to assess the cortisol response after stimulation with ACTH1-24 in patients with SIRS at admission to the Respiratory Intensive Care Unit (RICU and seven days later.

  18. Repeatability of Cryogenic Multilayer Insulation

    Science.gov (United States)

    Johnson, W. L.; Vanderlaan, M.; Wood, J. J.; Rhys, N. O.; Guo, W.; Van Sciver, S.; Chato, D. J.

    2017-01-01

    Due to the variety of requirements across aerospace platforms, and one off projects, the repeatability of cryogenic multilayer insulation has never been fully established. The objective of this test program is to provide a more basic understanding of the thermal performance repeatability of MLI systems that are applicable to large scale tanks. There are several different types of repeatability that can be accounted for: these include repeatability between multiple identical blankets, repeatability of installation of the same blanket, and repeatability of a test apparatus. The focus of the work in this report is on the first two types of repeatability. Statistically, repeatability can mean many different things. In simplest form, it refers to the range of performance that a population exhibits and the average of the population. However, as more and more identical components are made (i.e. the population of concern grows), the simple range morphs into a standard deviation from an average performance. Initial repeatability testing on MLI blankets has been completed at Florida State University. Repeatability of five GRC provided coupons with 25 layers was shown to be +/- 8.4 whereas repeatability of repeatedly installing a single coupon was shown to be +/- 8.0. A second group of 10 coupons have been fabricated by Yetispace and tested by Florida State University, through the first 4 tests, the repeatability has been shown to be +/- 16. Based on detailed statistical analysis, the data has been shown to be statistically significant.

  19. Repeated treatment of recurrent uncomplicated Plasmodium falciparum malaria in Senegal with fixed-dose artesunate plus amodiaquine versus fixed-dose artemether plus lumefantrine: a randomized, open-label trial

    Directory of Open Access Journals (Sweden)

    Barry Aichatou

    2011-08-01

    Full Text Available Abstract Background The use of artemisinin-based combination therapy (ACT is currently recommended for treating uncomplicated malaria. The objective was to assess the efficacy and safety of repeated administrations of two fixed-dose presentations of ACT - artesunate plus amodiaquine (ASAQ and artemether-lumefantrine (AL - in subsequent episodes of Plasmodium falciparum malaria. Methods A randomized comparative study was conducted in a rural community of central Senegal from August 2007 to January 2009. Children and adults with uncomplicated P. falciparum malaria were randomized to receive open-label ASAQ once daily or AL twice daily for three days. Drug doses were given according to body weight. Treatments for first episodes were supervised. For subsequent episodes, only the first intake of study drug was supervised. ECGs and audiograms were performed in patients ≥12 years of age. Primary outcome was adequate clinical and parasitological response rate (ACPR after polymerase chain reaction (PCR correction on day 28 for the first episode. Results A total of 366 patients were enrolled in the two groups (ASAQ 184, AL 182 and followed up during two malaria transmission seasons. In the intent-to-treat population, PCR-corrected ACPRs at day 28 for the first episode were 98.4% and 96.2%, respectively, in the ASAQ and AL groups. For the per-protocol population (ASAQ 183, AL 182, PCR-corrected ACPRs at day 28 for the first episode were 98.9% and 96.7%, respectively. A 100% ACPR rate was obtained at day 28 in the 60 and four patients, respectively, who experienced second and third episodes. Treatment-related adverse events were reported in 11.7% of the patients, without significant differences between the two groups. A better improvement of haemoglobin at day 28 was noted in the ASAQ versus the AL group (12.2 versus 11.8 g/dL; p = 0.03. No sign of ototoxicity was demonstrated. A prolongation of the QTc interval was observed in both groups during

  20. Concomitant detection of IFNα signature and activated monocyte/dendritic cell precursors in the peripheral blood of IFNα-treated subjects at early times after repeated local cytokine treatments

    Directory of Open Access Journals (Sweden)

    Rizza Paola

    2011-05-01

    Full Text Available Abstract Background Interferons alpha (IFNα are the cytokines most widely used in clinical medicine for the treatment of cancer and viral infections. Among the immunomodulatory activities possibly involved in their therapeutic efficacy, the importance of IFNα effects on dendritic cells (DC differentiation and activation has been considered. Despite several studies exploiting microarray technology to characterize IFNα mechanisms of action, there is currently no consensus on the core signature of these cytokines in the peripheral blood of IFNα-treated individuals, as well as on the existence of blood genomic and proteomic markers of low-dose IFNα administered as a vaccine adjuvant. Methods Gene profiling analysis with microarray was performed on PBMC isolated from melanoma patients and healthy individuals 24 hours after each repeated injection of low-dose IFNα, administered as vaccine adjuvant in two separate clinical trials. At the same time points, cytofluorimetric analysis was performed on CD14+ monocytes, to detect the phenotypic modifications exerted by IFNα on antigen presenting cells precursors. Results An IFNα signature was consistently observed in both clinical settings 24 hours after each repeated administration of the cytokine. The observed modulation was transient, and did not reach a steady state level refractory to further stimulations. The molecular signature observed ex vivo largely matched the one detected in CD14+ monocytes exposed in vitro to IFNα, including the induction of CXCL10 at the transcriptional and protein level. Interestingly, IFNα ex vivo signature was paralleled by an increase in the percentage and expression of costimulatory molecules by circulating CD14+/CD16+ monocytes, indicated as natural precursors of DC in response to danger signals. Conclusions Our results provide new insights into the identification of a well defined molecular signature as biomarker of IFNα administered as immune adjuvants, and

  1. Episodes of repeated sudden deafness following pregnancies.

    Science.gov (United States)

    Pawlak-Osinska, Katarzyna; Burduk, Pawel K; Kopczynski, Andrzej

    2009-04-01

    Sex hormones influence and provoke changes in hearing levels. Sudden deafness is rarely observed in pregnant women. The effective treatment of sudden deafness in pregnant women is a challenging problem. We present a case of repeatable, completely regressed sudden deafness in a woman during her first and second pregnancies.

  2. Technetium-99m methoxyisobutylisonitrile localizes an ectopic ACTH-producing tumour: case report and review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Jacobsson, H. (Dept. of Diagnostic Radiology, Karolinska Hospital, Stockholm (Sweden)); Wallin, G. (Dept. of Surgery, Karolinska Hospital, Stockholm (Sweden)); Werner, S. (Dept. of Endocrinology and Diabetology, Karolinska Hospital, Stockholm (Sweden)); Larsson, S.A. (Dept. of Hospital Physics, Karolinska Hospital, Stockholm (Sweden))

    1994-06-01

    Extensive investigation including whole-body examinations with computed tomography and magnetic resonance imaging did not detect the suspected ectopic ACTH-producing tumour in a patient with advanced Cushing's syndrome and hypokalemic alkalosis. Gamma camera examination with technetium-99m methoxyisobutylisonitrile (MIBI) depicted the tumour, which was localized in the anterior neck and mediastinum. This was later verified by surgery. [sup 99m]Tc-MIBI is normally used for myocardial scintigraphy. Its accumulation is unspecific and merely reflects metabolic activity. Despite this, the present case shows that examination with this agent can provide important information with regard to tumour localization in a given situation, thereby serving as a complement to other imaging modalities. The current literature on [sup 99m]Tc-MIBI for tumour diagnosis is reviewed. (orig.)

  3. The Value of Somatostatin Receptor Imaging with In-111 Octreotide and/or Ga-68 DOTATATE in Localizing Ectopic ACTH Producing Tumors

    Directory of Open Access Journals (Sweden)

    Zeynep Gözde Özkan

    2013-08-01

    Full Text Available Objective: We aimed to evaluate the value of somatostatin receptor imaging (SRI with In-111 octreotide and Ga-68 DOTATATE in localizing ectopic ACTH producing tumors. Methods: Nineteen patients who had In-111 octreotide somatostatin receptor scintigraphy (SRS and/or Ga-68 DOTATATE PET-CT to localize ectopic ACTH producing tumors between the years 2000 and 2012 were included retrospectively in our study. The results of SRI were compared with clinical onset, radiological findings and surgical data of the patients. Results: Sixteen In-111 octreotide SRS and five Ga-68 DOTATATE PET-CT were performed in 19 patients. In eight out of 19 patients, ectopic ACTH secretion site could be detected. In five patients, SRS showed pathologic uptake. In four of these patients, surgery revealed pulmonary carcinoid tumors and in one patient pancreatic neuroendocrine tumor. In one patient, Ga-68 DOTATATE PET-CT revealed pathologic uptake in lung nodule which came out to be pulmonary carcinoid tumor. In another patient who had resection of metastases of atypical carcinoid tumor prior to scans, new metastatic foci were detected both with SRS and Ga-68 DOTATATE PET-CT imaging. In one patient, although SRS was negative, CT which was performed three years later showed a lung nodule diagnosed as pulmonary carcinoid tumor. In 11 patients, ectopic ACTH secretion site could not be detected. In 10 of those patients, scintigraphic and radiological imaging did not show any lesions and in one patient, Ga-68 DOTATATE PET-CT was false positive. Conclusion: SRI has a complementary role with radiological imaging in localizing ectopic ACTH secretion sites. PET-CT imaging with Ga-68 peptide conjugates is a promising new modality for this indication.

  4. Effect of ACTH and CRH on Plasma Levels of Cortisol and Prostaglandin F2α Metabolite in Cycling Gilts and Castrated Boars

    Directory of Open Access Journals (Sweden)

    Madej A

    2006-12-01

    Full Text Available The present study was designed to evaluate the effects of synthetic ACTH (1–24, tetracosactid and porcine CRH on the plasma levels of cortisol and PGF2α metabolite in cycling gilts (n = 3 and castrated boars (n = 3. The experiments were designed as crossover studies for each gender separately. Each animal received, during three consecutive days; 1 ACTH (Synacthen® Depot at a dose of 10 μg/kg body weight in 5 ml physiological saline, 2 porcine CRH at a dose 0.6 μg/kg body weight in 5 ml physiological saline or 3 physiological saline (5 ml. The test substances were administered via an indwelling jugular cannula in randomized order according to a Latin square. The administration of ACTH to cycling gilts resulted in concomitant elevations of cortisol and PGF2α metabolite with peak levels reached at 70.0 ± 10.0 and 33.3 ± 6.7 min, respectively. Similarly, the administration of ACTH to castrated boars resulted in concomitant elevation of cortisol and PGF2α metabolite with peak levels reached at 60.0 ± 0.0 and 20.0 ± 0.0 min, respectively. Cortisol peaked at 20 min after administration of CRH in both cycling gilts and castrated boars with maximum levels of 149.3 ± 16.5 nmol/1 and 138.3 ± 10.1 nmol/1, respectively. It can be concluded that administration of synthetic ACTH (tetracosactid to pigs caused a concomitant elevation of cortisol and PGF2α metabolite levels in both cycling gilts as well as castrated boars. The administration of CRH to pigs resulted in an elevation of cortisol levels in both cycling gilts and castrated boars. Conversely, PGF2α metabolite levels were not influenced by the administration of CRH either in cycling gilts or in castrated boars.

  5. Effect of ACTH and CRH on Plasma Levels of Cortisol and Prostaglandin F2α Metabolite in Cycling Gilts and Castrated Boars

    Directory of Open Access Journals (Sweden)

    Kindahl H

    2005-12-01

    Full Text Available The present study was designed to evaluate the effects of synthetic ACTH (1–24, tetracosactid and porcine CRH on the plasma levels of cortisol and PGF2α metabolite in cycling gilts (n = 3 and castrated boars (n = 3. The experiments were designed as crossover studies for each gender separately. Each animal received, during three consecutive days; 1 ACTH (Synacthen® Depot at a dose of 10 μg/kg body weight in 5 ml physiological saline, 2 porcine CRH at a dose 0.6 μg/kg body weight in 5 ml physiological saline or 3 physiological saline (5 ml. The test substances were administered via an indwelling jugular cannula in randomized order according to a Latin square. The administration of ACTH to cycling gilts resulted in concomitant elevations of cortisol and PGF2α metabolite with peak levels reached at 70.0 ± 10.0 and 33.3 ± 6.7 min, respectively. Similarly, the administration of ACTH to castrated boars resulted in concomitant elevation of cortisol and PGF2α metabolite with peak levels reached at 60.0 ± 0.0 and 20.0 ± 0.0 min, respectively. Cortisol peaked at 20 min after administration of CRH in both cycling gilts and castrated boars with maximum levels of 149.3 ± 16.5 nmol/1 and 138.3 ± 10.1 nmol/1, respectively. It can be concluded that administration of synthetic ACTH (tetracosactid to pigs caused a concomitant elevation of cortisol and PGF2α metabolite levels in both cycling gilts as well as castrated boars. The administration of CRH to pigs resulted in an elevation of cortisol levels in both cycling gilts and castrated boars. Conversely, PGF2α metabolite levels were not influenced by the administration of CRH either in cycling gilts or in castrated boars.

  6. Resposta do ACTH plasmático ao estímulo com CRH ou CRH + desmopressina em pacientes com síndrome de Cushing ACTH- dependente submetidos a cateterismo bilateral simultâneo dos seios petrosos inferiores Response of plasmatic ACTH to CRH or combined CRH/desmopressin stimulation in patients with ACTHdependent Cushing's syndrome submitted to simultaneous bilateral petrosal sinuses sampling

    Directory of Open Access Journals (Sweden)

    Daniella Maria Carneiro do Rêgo

    2007-12-01

    Full Text Available OBJETIVO: Comparar a resposta do ACTH plasmático após estímulo com CRH ou CRH + desmopressina em pacientes com síndrome de Cushing ACTH-dependente que realizaram cateterismo bilateral simultâneo dos seios petrosos inferiores. MATERIAIS E MÉTODOS: O procedimento foi realizado em 21 pacientes - 14 mulheres e 7 homens - com síndrome de Cushing ACTH-dependente no período de janeiro de 1998 a dezembro de 2003. Após a cateterização de ambos os seios petrosos, amostras de sangue para ACTH foram colhidas, simultaneamente, nos seios petrosos e veia periférica, tanto no estado basal como após três e cinco minutos da administração de CRH humano (100 mg (6 pacientes ou CRH + desmopressina (100 mg + 10 mg (15 pacientes. RESULTADOS: Aos três minutos, houve aumento percentual do ACTH tanto no grupo CRH (257,77 ± 240,36 no seio petroso direito e 718,78 ± 1.358,82 no seio petroso esquerdo [média ± desvio-padrão] como no grupo CRH + desmopressina (1.263,35 ± 1.842,91 no seio petroso direito [p = 0,06] e 583,93 ± 1.020,03 no seio petroso esquerdo [p = 0,83]. Aos cinco minutos houve declínio percentual do ACTH no grupo do CRH (181,07 ± 217,39 no seio petroso direito e 188,25 ± 270,15 no seio petroso esquerdo e aumento progressivo no grupo do CRH + desmopressina (1.365,29 ± 1.832,31 no seio petroso direito [p = 0,03] e 866,43 ± 1.431,72 no seio petroso esquerdo [p = 0,11]. Nos três pacientes com secreção ectópica não houve gradiente. CONCLUSÃO: A estimulação combinada CRH + desmopressina induziu maior produção de ACTH em adenomas corticotróficos em comparação ao CRH, o que pode melhorar a sensibilidade diagnóstica deste procedimento.OBJECTIVE: To compare the responses of plasmatic ACTH to CRH or combined CRH/desmopressin stimulation in patients with ACTH-dependent Cushing's syndrome submitted to simultaneous, bilateral inferior petrosal sinuses sampling. MATERIALS AND METHODS: The procedure was performed in 21 patients - 14

  7. Repeated fecal microbiota transplantation in a child with ulcerative colitis.

    Science.gov (United States)

    Shimizu, Hirotaka; Arai, Katsuhiro; Abe, Jun; Nakabayashi, Kazuhiko; Yoshioka, Takako; Hosoi, Kenji; Kuroda, Makoto

    2016-08-01

    We report the case of an 11-year-old girl with ulcerative colitis refractory to conventional therapy, who was subsequently treated successfully with repeated fecal microbiota transplantation (FMT). The patient was steroid dependent despite several infliximab treatments, and colectomy was proposed to improve quality of life. After repeated FMT, she was able to maintain remission with on minimal dose of steroid. Although her fecal microbiota was dysbiotic before FMT, it was restored to a similar pattern as the donor after repeated FMT.

  8. Effect of DNA extraction procedure, repeated extraction and ethidium monoazide (EMA)/propidium monoazide (PMA) treatment on overall DNA yield and impact on microbial fingerprints for bacteria, fungi and archaea in a reference soil.

    Science.gov (United States)

    Wagner, Andreas O; Praeg, Nadine; Reitschuler, Christoph; Illmer, Paul

    2015-09-01

    Different DNA extraction protocols were evaluated on a reference soil. A wide difference was found in the total extractable DNA as derived from different extraction protocols. Concerning the DNA yield phenol-chloroform-isomyl alcohol extraction resulted in high DNA yield but also in a remarkable co-extraction of contaminants making PCR from undiluted DNA extracts impossible. By comparison of two different extraction kits, the Macherey&Nagel SoilExtract II kit resulted in the highest DNA yields when buffer SL1 and the enhancer solution were applied. The enhancer solution not only significantly increased the DNA yield but also the amount of co-extracted contaminates, whereas additional disintegration strategies did not. Although a three times repeated DNA extraction increased the total amount of extracted DNA, microbial fingerprints were merely affected. However, with the 5th extraction this changed. A reduction of total DGGE band numbers was observed for archaea and fungi, whereas for bacteria the diversity increased. The application of ethidium monoazide (EMA) or propidium monoazide (PMA) treatment aiming on the selective removal of soil DNA derived from cells lacking cell wall integrity resulted in a significant reduction of total extracted DNA, however, the hypothesized effect on microbial fingerprints failed to appear indicating the need for further investigations.

  9. Changes in plasma melanocyte-stimulating hormone, ACTH, prolactin, GH, LH, FSH, and thyroid-stimulating hormone in response to injection of sulpiride, thyrotropin-releasing hormone, or vehicle in insulin-sensitive and -insensitive mares.

    Science.gov (United States)

    Valencia, N Arana; Thompson, D L; Mitcham, P B

    2013-05-01

    Six insulin-sensitive and 6 insulin-insensitive mares were used in a replicated 3 by 3 Latin square design to determine the pituitary hormonal responses (compared with vehicle) to sulpiride and thyrotropin-releasing hormone (TRH), 2 compounds commonly used to diagnose pituitary pars intermedia dysfunction (PPID) in horses. Mares were classified as insulin sensitive or insensitive by their previous glucose responses to direct injection of human recombinant insulin. Treatment days were February 25, 2012, and March 10 and 24, 2012. Treatments were sulpiride (racemic mixture, 0.01 mg/kg BW), TRH (0.002 mg/kg BW), and vehicle (saline, 0.01 mL/kg BW) administered intravenously. Blood samples were collected via jugular catheters at -10, 0, 5, 10, 20, 30, 45, 60, 90, and 120 min relative to treatment injection. Plasma ACTH concentrations were variable and were not affected by treatment or insulin sensitivity category. Plasma melanocyte-stimulating hormone (MSH) concentrations responded (P sulpiride and TRH injection and were greater (P sulpiride and TRH injection, and the response was greater (P sulpiride; no effect of insulin sensitivity was observed. Plasma thyroid-stimulating hormone (TSH) concentrations responded (P sulpiride and TRH in insulin-insensitive mares were similar to, but not as exaggerated as, those observed by others for PPID horses. In addition, the reduced TSH concentrations in insulin-insensitive mares are consistent with our previous observation of elevated plasma triiodothyronine concentrations in hyperleptinemic horses (later shown to be insulin insensitive as well).

  10. Repeatability of Response to Asthma Medications

    Science.gov (United States)

    Wu, Ann; Tantisira, Kelan; Li, Lingling; Schuemann, Brooke; Weiss, Scott

    2010-01-01

    Background Pharmacogenetic studies of drug response in asthma assume that patients respond consistently to a treatment but that treatment response varies across patients, however, no formal studies have demonstrated this. Objective To determine the repeatability of commonly used outcomes for treatment response to asthma medications: bronchodilator response, forced expiratory volume in 1 second (FEV1), and provocative concentration of methacholine producing a 20% decline in FEV1 (PC20). Methods The Childhood Asthma Management Program (CAMP) was a multi-center clinical trial of children randomized to receiving budesonide, nedocromil, or placebo. We determined the intraclass correlation coefficient (ICC) for each outcome over repeated visits over four years in CAMP using mixed effects regression models. We adjusted for the covariates: age, race/ethnicity, height, family income, parental education, and symptom score. We incorporated each outcome for each child as repeated outcome measurements and stratified by treatment group. Results The ICC for bronchodilator response was 0.31 in the budesonide group, 0.35 in the nedocromil group, and 0.40 in the placebo group, after adjusting for covariates. The ICC for FEV1 was 0.71 in the budesonide group, 0.60 in the nedocromil group, and 0.69 in the placebo group, after adjusting for covariates. The ICC for PC20 was 0.67 in the budesonide and placebo groups and 0.73 in the nedocromil group, after adjusting for covariates. Conclusion The within treatment group repeatability of FEV1 and PC20 are high; thus these phenotypes are heritable. FEV1 and PC20 may be better phenotypes than bronchodilator response for studies of treatment response in asthma. PMID:19064281

  11. Treatment of adrenocorticotropin-dependent cushing's syndrome: A consensus statement

    NARCIS (Netherlands)

    B.M.K. Biller; A. Grossman (Ashley Barry); P.M. Stewart; S. Melmed (Shlomo); X. Bertagna; J. Bertherat (Jerome); M. Buchfelder; A. Colao (Annamaria); A.R. Hermus (Ad); L.J. Hofland (Leo); A. Klibanski; A. Lacroix; J.R. Lindsay; J. Newell-Price; L.K. Nieman; S. Petersenn; N. Sonino; G.K. Stalla (Günter); B. Swearingen; M.L. Vance; J.A.H. Wass (John); M. Boscaro

    2008-01-01

    textabstractObjective: Our objective was to evaluate the published literature and reach a consensus on the treatment of patients with ACTH-dependent Cushing's syndrome, because there is no recent consensus on the management of this rare disorder. Participants: Thirty-two leading endocrinologists,

  12. Treatment of adrenocorticotropin-dependent Cushing's syndrome: a consensus statement.

    NARCIS (Netherlands)

    Grossman, A.B.; Stewart, P.M.; Melmed, S.; Bertagna, X.; Bertherat, J.; Buchfelder, M.; Colao, A.; Hermus, A.R.M.M.; Hofland, L.J.; Klibanski, A.; Lacroix, A.; Lindsay, J.R.; Newell-Price, J.; Nieman, L.K.; Petersenn, S.; Sonino, N.; Stalla, G.K.; Swearingen, B.; Vance, M.L.; Wass, J.A.; Boscaro, M.

    2008-01-01

    OBJECTIVE: Our objective was to evaluate the published literature and reach a consensus on the treatment of patients with ACTH-dependent Cushing's syndrome, because there is no recent consensus on the management of this rare disorder. PARTICIPANTS: Thirty-two leading endocrinologists, clinicians,

  13. Treatment of Nelson's syndrome with temozolomide.

    Science.gov (United States)

    Moyes, V J; Alusi, G; Sabin, H I; Evanson, J; Berney, D M; Kovacs, K; Monson, J P; Plowman, P N; Drake, W M

    2009-01-01

    A 64-year-old woman was previously treated for Cushing's disease with trans-sphenoidal surgery, external beam radiotherapy and bilateral adrenalectomy. Progression of an aggressive corticotroph adenoma was evident 3 years post-adrenalectomy; involvement of the clivus was treated with surgery and gamma knife radiosurgery. Tumour spread through the skull base, occiput and left ear with persistent facial pain and left ear discharge; progression continued despite second gamma knife treatment. ACTH levels peaked at 2472 and 2265 pmol/l pre- and post-hydrocortisone respectively. Treatment with temozolomide resulted in a significant improvement in symptoms, a reduction of plasma ACTH to 389 pmol/l and regression of tumour on magnetic resonance imaging scan after four cycles of treatment. We propose that temozolomide is an effective and well-tolerated therapeutic tool for the treatment of Nelson's syndrome and a useful addition to the range of therapies available to treat this condition.

  14. On balanced minimal repeated measurements designs

    Directory of Open Access Journals (Sweden)

    Shakeel Ahmad Mir

    2014-10-01

    Full Text Available Repeated Measurements designs are concerned with scientific experiments in which each experimental unit is assigned more than once to a treatment either different or identical. This class of designs has the property that the unbiased estimators for elementary contrasts among direct and residual effects are obtainable. Afsarinejad (1983 provided a method of constructing balanced Minimal Repeated Measurements designs p < t , when t is an odd or prime power, one or more than one treatment may occur more than once in some sequences and  designs so constructed no longer remain uniform in periods. In this paper an attempt has been made to provide a new method to overcome this drawback. Specifically, two cases have been considered                RM[t,n=t(t-t/(p-1,p], λ2=1 for balanced minimal repeated measurements designs and  RM[t,n=2t(t-t/(p-1,p], λ2=2 for balanced  repeated measurements designs. In addition , a method has been provided for constructing              extra-balanced minimal designs for special case RM[t,n=t2/(p-1,p], λ2=1.

  15. Expansion of protein domain repeats.

    Directory of Open Access Journals (Sweden)

    Asa K Björklund

    2006-08-01

    Full Text Available Many proteins, especially in eukaryotes, contain tandem repeats of several domains from the same family. These repeats have a variety of binding properties and are involved in protein-protein interactions as well as binding to other ligands such as DNA and RNA. The rapid expansion of protein domain repeats is assumed to have evolved through internal tandem duplications. However, the exact mechanisms behind these tandem duplications are not well-understood. Here, we have studied the evolution, function, protein structure, gene structure, and phylogenetic distribution of domain repeats. For this purpose we have assigned Pfam-A domain families to 24 proteomes with more sensitive domain assignments in the repeat regions. These assignments confirmed previous findings that eukaryotes, and in particular vertebrates, contain a much higher fraction of proteins with repeats compared with prokaryotes. The internal sequence similarity in each protein revealed that the domain repeats are often expanded through duplications of several domains at a time, while the duplication of one domain is less common. Many of the repeats appear to have been duplicated in the middle of the repeat region. This is in strong contrast to the evolution of other proteins that mainly works through additions of single domains at either terminus. Further, we found that some domain families show distinct duplication patterns, e.g., nebulin domains have mainly been expanded with a unit of seven domains at a time, while duplications of other domain families involve varying numbers of domains. Finally, no common mechanism for the expansion of all repeats could be detected. We found that the duplication patterns show no dependence on the size of the domains. Further, repeat expansion in some families can possibly be explained by shuffling of exons. However, exon shuffling could not have created all repeats.

  16. DWI Repeaters and Non-Repeaters: A Comparison.

    Science.gov (United States)

    Weeber, Stan

    1981-01-01

    Discussed how driving-while-intoxicated (DWI) repeaters differed signigicantly from nonrepeaters on 4 of 23 variables tested. Repeaters were more likely to have zero or two dependent children, attend church frequently, drink occasionally and have one or more arrests for public intoxication. (Author)

  17. To Repeat or Not to Repeat a Course

    Science.gov (United States)

    Armstrong, Michael J.; Biktimirov, Ernest N.

    2013-01-01

    The difficult transition from high school to university means that many students need to repeat (retake) 1 or more of their university courses. The authors examine the performance of students repeating first-year core courses in an undergraduate business program. They used data from university records for 116 students who took a total of 232…

  18. Persistent hypokalemia after successful adrenalectomy in a patient with Cushing's syndrome due to ectopic ACTH secretion: possible role of 11beta-hydroxysteroid dehydrogenase inhibition.

    Science.gov (United States)

    Arteaga, E; Fardella, C; Campusano, C; Cárdenas, I; Martinez, P

    1999-12-01

    Ectopic ACTH secretion is characterized by a high incidence of hypokalemia. The pathophysiology of hypokalemia has not been totally clarified, although it has been postulated that excessive amounts of adrenal steroids may play a role, as well as a possible role of the inhibition of the enzyme 11beta-hydroxysteroid dehydrogenase (11beta-OHSD). This enzyme normally converts cortisol to cortisone avoiding the mineralocorticoid action of cortisol. We present a patient with ectopic ACTH secretion due to a metastatic carcinoid tumor. The clinical picture was characterized by maintained hypokalemia (1.4 mmol/l) resistant to potassium, spironolactone and ketoconazole administration. A bilateral adrenalectomy was performed but the hypokalemia persisted while he was receiving a physiological dose of cortisol. Eight days after adrenalectomy cortisol was replaced by an equivalent dose of dexamethasone. This change was followed by a rapid and persistent normalization of hypokalemia suggesting a mineralocorticoid effect of cortisol. In conclusion, the origin of hypokalemia in our patient with ectopic ACTH secretion was secondary to cortisol. We postulate that this peculiar effect of cortisol could have happened if an inhibition of 11beta-OHSD occurred.

  19. Effect of dopamine, dopamine D-1 and D-2 receptor modulation on ACTH and cortisol levels in normal men and women

    DEFF Research Database (Denmark)

    Boesgaard, S; Hagen, C; Andersen, A N;

    1990-01-01

    The regulation of the hypothalamic-pituitary-adrenal axis by dopamine is not fully understood. Therefore, we have studied the effect of dopamine, metoclopramide, a D-2 receptor antagonist, and fenoldopam, a specific D-1 receptor agonist, on ACTH and cortisol levels in normal subjects. Normal women...... received 5-h infusions of either glucose (N = 6) or dopamine at rates of 0.04 (N = 6), 0.4 (N = 6) and 4.0 micrograms.kg-1.min-1 (N = 8). After 3 h, 10 mg metoclopramide was given iv. No intergroup differences regarding ACTH and cortisol levels were observed (p greater than 0.05). In a second study six...... women received dopamine (4.0 micrograms.kg-1.min-1) or glucose for 18 h. During the infusions cortisol and ACTH levels were similar on the two study days. Administration of metoclopramide (10 mg) after 17 h induced a significant increase in cortisol levels during dopamine infusion (p less than 0...

  20. Analysis of glucose dysbolism in patients with ectopic ACTH syndrome%异位ACTH综合征患者糖代谢异常的特点分析

    Institute of Scientific and Technical Information of China (English)

    赵蕾; 母义明; 窦京涛; 陆菊明; 潘长玉

    2008-01-01

    通过对经病理证实的117例库欣综合征患者临床资料的分析,探讨异位ACTH综合征(EAS)糖代谢异常的特点.117例患者分为3组:EAS组9例,库欣病组(CD)67例,肾上腺皮质腺瘤组(AA)41例.与CD组和AA组相比,EAS组继发性糖尿病发生率高,血糖水平高,HbAlc水平低,原发病灶根治术后,血糖降至正常.%The characteristics of glucose dysbolism in ectopic ACTH syndrome (EAS) were investigated by analysing the clinical data of 117 patients with Cushing syndrome (CS). The patients with CS were divided into 3 groups : EAS group (n = 9) , Cushing's disease (CD) group (n = 67) and adrenocortical adenoma (AA) group (n =41). Retrospective analysis of the data covered the prevalence of secondary diabetes, blood glucose, HbAlc, blood potassium, and blood ACTH and 24 h urinary-free cortisol (UFC) levels. Compared with CD and AA groups, the prevalence of secondary diabetes and blood glucose level were higher in EAS group, while HbAlc level was lower. Blood glucose level in patients with ectopic ACTH syndrome decreased to normal after tumor removal.

  1. Unilateral adrenalectomy can be an alternative therapy for infantile onset Cushing' s syndrome caused by ACTH-independent macronodular adrenal hyperplasia with McCune-Albright syndrome.

    Science.gov (United States)

    Hamajima, Takashi; Maruwaka, Kaori; Homma, Keiko; Matsuo, Kumihiro; Fujieda, Kenji; Hasegawa, Tomonobu

    2010-01-01

    We report herein the case of a 1-year-old boy with McCune-Albright syndrome (MAS) who presented with infantile-onset Cushing' s syndrome caused by ACTH independent macronodular adrenal hyperplasia (AIMAH). Abdominal CT, MRI, and adrenal scintigraphy with (131)I-adosterol identified bilateral adrenal involvement with the left adrenal gland being larger and functionally more active. Unilateral adrenalectomy of the left gland was performed and ameliorated many clinical symptoms, such as Cushingoid appearance and height restriction, and it also normalized many endocrinological data, such as diurnal rhythms of ACTH and cortisol, ACTH and cortisol responses to CRH, and urinary 24 hr free cortisol. Glucocorticoid was replaced for the first 1 year and 6 months after the operation. One adrenal crisis episode occurred at 3 weeks after the operation, but none have occurred since. These results suggest that unilateral adrenalectomy of the larger gland can be an alternative therapy for infantile onset Cushing' s syndrome caused by AIMAH with MAS, when asymmetric involvement is evident and the smaller gland is not markedly enlarged.

  2. Blunted ACTH and cortisol responses to systemic injection of corticotropin-releasing hormone (CRH) in fibromyalgia: role of somatostatin and CRH-binding protein.

    Science.gov (United States)

    Riedel, Walter; Schlapp, Ulrike; Leck, Stefanie; Netter, Petra; Neeck, Gunther

    2002-06-01

    Thirteen female patients suffering from fibromyalgia (FM) and thirteen female age-matched controls were intravenously injected with a bolus dose of 100 microg corticotropin-releasing hormone (CRH), and the evoked secretion pattern of ACTH, cortisol, somatostatin, and growth hormone (GH) was followed up for two hours, together with the plasma levels of CRH. The increases of ACTH and cortisol following CRH were not significantly different between controls and FM patients. The increase of plasma CRH following its injection was significantly higher in FM patients and lasted about 45 min, paralleled by an increase of somatostatin with a similar time course. Basal GH levels were significantly lower in FM patients. GH increased in FM patients 90 min after injection of CRH, coincident with decreasing CRH and somatostatin levels, while GH levels in controls rather decreased with the lowest values occurring 90 min after CRH. The results support the concept that the hormonal secretion pattern frequently observed in FM patients is primarily caused by CRH, possibly as a response to chronic pain and stress. The elevated levels of CRH in the circulation of FM patients suggest elevated levels of CRH-binding protein, which could explain why the levels of ACTH and cortisol between controls and FM following CRH do not differ.

  3. Long-term effects of repeated maternal separation and ethanol intake on HPA axis responsiveness in adult rats.

    Science.gov (United States)

    Odeon, María Mercedes; Yamauchi, Laura; Grosman, Mauricio; Acosta, Gabriela Beatriz

    2017-02-15

    It has been shown that early life manipulations produce behavioral, neural, and hormonal effects. The long term consequences of repeated maternal separation (RMS) plus cold stress and ethanol intake were evaluated during adolescence and adult rats on hypothalamic-pituitary-adrenal (HPA) axis in male adult Wistar rats. RMS+ cold stress was applied from postnatal day (PD) 2 in which the pups were separated from their mothers and exposed to cold stress (4°C) 1h per day for 20days; controls remained with their mothers. Then they were exposed to either voluntary ethanol (6%) or dextrose (1%) intake for 7days: PD22-29 and PD59-66. Half of the animals were sacrificed, while the others were exposed to acute stress (AS) for 2h and then they were killed. RMS+ cold stress: a) increased voluntary ethanol intake in adolescent and adult rats; b) reduced protein expression (Western measurements) in corticotropin-releasing hormone (CRH) in hypothalamus (Hyp) and mineralocorticoid receptor (MR) in hippocampus (Hic) while increased glucocorticoid receptor (GR) in Hic; c) decreased plasmatic levels of adrenocorticotropic hormone (ACTH) and increased corticosterone (COR) levels in HPA axis, d) adult rats exposure a new AS incremented ACTH and COR levels. However, this modification did not alter the HPA axis capacity to respond to a new type of stressor. These results demonstrate the consequences of early life stress on the vulnerability of ethanol consumption and HPA axis responsiveness to a stressor in adult rats.

  4. Nifty Nines and Repeating Decimals

    Science.gov (United States)

    Brown, Scott A.

    2016-01-01

    The traditional technique for converting repeating decimals to common fractions can be found in nearly every algebra textbook that has been published, as well as in many precalculus texts. However, students generally encounter repeating decimal numerals earlier than high school when they study rational numbers in prealgebra classes. Therefore, how…

  5. Nifty Nines and Repeating Decimals

    Science.gov (United States)

    Brown, Scott A.

    2016-01-01

    The traditional technique for converting repeating decimals to common fractions can be found in nearly every algebra textbook that has been published, as well as in many precalculus texts. However, students generally encounter repeating decimal numerals earlier than high school when they study rational numbers in prealgebra classes. Therefore, how…

  6. Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents.

    Science.gov (United States)

    Eremin, Kirill O; Kudrin, Vladimir S; Saransaari, Pirjo; Oja, Simo S; Grivennikov, Igor A; Myasoedov, Nikolay F; Rayevsky, Kirill S

    2005-12-01

    Corticotrophin (ACTH) and its analogues, particularly Semax (Met-Glu-His-Phe-Pro-Gly-Pro), demonstrate nootropic activity. Close functional and anatomical links have been established between melanocortinergic and monoaminergic brain systems. The aim of present work was to investigate the effects of Semax on neurochemical parameters of dopaminergic- and serotonergic systems in rodents. The tissue content of 5-hydroxyindoleacetic acid (5-HIAA) in the striatum was significantly increased (+25%) 2 h after Semax administration. The extracellular striatal level of 5-HIAA gradually increased up to 180% within 1-4 h after Semax (0.15 mg/kg, ip) administration. This peptide alone failed to alter the tissue and extracellular concentrations of dopamine and its metabolites. Semax injected 20 min prior D: -amphetamine dramatically enhanced the effects of the latter on the extracellular level of dopamine and on the locomotor activity of animals. Our results reveal the positive modulatory effect of Semax on the striatal serotonergic system and the ability of Semax to enhance both the striatal release of dopamine and locomotor behavior elicited by D-amphetamine.

  7. Cerebrospinal fluid rhinorrhea as a complication of ACTH-secreting pituitary macroadenoma in a patient with morbid obesity

    Directory of Open Access Journals (Sweden)

    Dar'ya Viktorovna Petrova

    2014-11-01

    Full Text Available Cushing's disease (CD is a progressive neuroendocrine disease caused by a pituitary tumor producing excessive amounts of ACTH. In most cases (80-85% the cause of the disease is a pituitary corticotroph microadenomas (located within the sella, measuring 3–10 mm, rarely multiple microadenomas and only 15% of cases are presented as corticotroph hyperplasia or pituitary macroadenoma extending beyond the sella. The macroadenomas in CD usually extend suprasellar (10%, infrasellar tumor growth is relatively rare (5%. If the clinical picture is subtle, the symptoms are caused by the development "mass effect" of the tumor as it propagates to the surrounding pituitary structures. Suprasellar growth leads to compression of the optic chiasm with narrowing of visual fields, infrasellar growth destructs the bottom of the sella turcica and may cause nasal cerebrospinal fluid leak, which is dangerous due depressurization of the cranial cavity and its communication with environmental pathogens, development of life-threatening conditions such as meningitis, meningoencephalitis, ventriculitis. Leading life-threatening complications of the CD are infectious and cardiovascular. But in the case of nasal liquorrhea with expansion of the tumor in sphenoid sinus with destruction of the bottom of the sella, there is an immediate threat to the life of the patient. This article presents an example of a patient with morbid obesity and lack of specific clinical manifestations of CD, in whom the diagnosis of disease CD was made on the results of laboratory and instrumental examination, which experienced a spontaneous nasal cerebrospinal fluid leak.

  8. All-photonic quantum repeaters

    Science.gov (United States)

    Azuma, Koji; Tamaki, Kiyoshi; Lo, Hoi-Kwong

    2015-01-01

    Quantum communication holds promise for unconditionally secure transmission of secret messages and faithful transfer of unknown quantum states. Photons appear to be the medium of choice for quantum communication. Owing to photon losses, robust quantum communication over long lossy channels requires quantum repeaters. It is widely believed that a necessary and highly demanding requirement for quantum repeaters is the existence of matter quantum memories. Here we show that such a requirement is, in fact, unnecessary by introducing the concept of all-photonic quantum repeaters based on flying qubits. In particular, we present a protocol based on photonic cluster-state machine guns and a loss-tolerant measurement equipped with local high-speed active feedforwards. We show that, with such all-photonic quantum repeaters, the communication efficiency scales polynomially with the channel distance. Our result paves a new route towards quantum repeaters with efficient single-photon sources rather than matter quantum memories. PMID:25873153

  9. Zinc-finger directed double-strand breaks within CAG repeat tracts promote repeat instability in human cells.

    Science.gov (United States)

    Mittelman, David; Moye, Christopher; Morton, Jason; Sykoudis, Kristen; Lin, Yunfu; Carroll, Dana; Wilson, John H

    2009-06-16

    Expanded triplet repeats have been identified as the genetic basis for a growing number of neurological and skeletal disorders. To examine the contribution of double-strand break repair to CAG x CTG repeat instability in mammalian systems, we developed zinc finger nucleases (ZFNs) that recognize and cleave CAG repeat sequences. Engineered ZFNs use a tandem array of zinc fingers, fused to the FokI DNA cleavage domain, to direct double-strand breaks (DSBs) in a site-specific manner. We first determined that the ZFNs cleave CAG repeats in vitro. Then, using our previously described tissue culture assay for identifying modifiers of CAG repeat instability, we found that transfection of ZFN-expression vectors induced up to a 15-fold increase in changes to the CAG repeat in human and rodent cell lines, and that longer repeats were much more sensitive to cleavage than shorter ones. Analysis of individual colonies arising after treatment revealed a spectrum of events consistent with ZFN-induced DSBs and dominated by repeat contractions. We also found that expressing a dominant-negative form of RAD51 in combination with a ZFN, dramatically reduced the effect of the nuclease, suggesting that DSB-induced repeat instability is mediated, in part, through homology directed repair. These studies identify a ZFN as a useful reagent for characterizing the effects of DSBs on CAG repeats in cells.

  10. Contagem de células somáticas e produção leiteira em cabras Saanen estressadas via aplicação de ACTH Somatic cell count and milk production of Saanen goats stressed via application of ACTH

    Directory of Open Access Journals (Sweden)

    Ana Paula Rodrigues Gaiato

    2012-05-01

    Full Text Available Avaliou-se neste estudo o efeito do estresse, via administração de ACTH (hormônio adrenocorticotrófico, sobre a quantidade e qualidade do leite produzido e a indicação de estresse pela alteração no nível de cortisol. Assim, 12 cabras lactantes foram distribuídas em dois grupos: seis animais receberam aplicação de 0,06 UI de ACTH/kg de PV (desafiadas e seis receberam solução placebo (controle, todas via intravenosa. O desafio ocorreu ao longo da lactação, com aplicação do protocolo aos 30, 60, 120 e 180 dias do início da lactação, avaliando-se em cada data os níveis de cortisol 30 minutos antes, no ato da aplicação, 60, 120 e 300 minutos depois. A produção leiteira foi mensurada diariamente durante 270 dias e, a cada 20 dias, o leite foi colhido para contagem de células somáticas (CCS pelo método direto. Os teores de cortisol mensurados em -30 e 0 minuto antes da aplicação de ACTH foram baixos e semelhantes entre os grupos. Entretanto, a partir de 60 minutos, constatou-se efeito da aplicação de ACTH, com teor de cortisol de 61,37±6,65 versus 5,47±1,21 ng/mL e de 51,17±10,21 versus 4,67±1,21 ng/mL aos 120 minutos. Aos 300 minutos, o cortisol retornou ao nível basal. Não houve diferença na produção de leite, no teor de proteína e de gordura do leite, cujos valores nos grupos ACTH e Placebo foram 1,37±0,59 e 1,38±0,63 kg de leite, respectivamente. A contagem de células somáticas não foi influenciada pelo estresse e apresentou valores situados na faixa indicada para animais sadios. Constatou-se estresse pontual em decorrência da aplicação de ACTH, porém sem alterações de natureza quantitativa e qualitativa do leite produzido, e isso indica que atividades de manejo que estressam os animais pontualmente não trazem prejuízos ao sistema produtivo.The objective of this study was to analyze the stress effect, via administration of ACTH (adrenocorticotropic hormone, on quantity and quality of milk

  11. Analysis of repeated outcome measures from longitudinal studies

    Institute of Scientific and Technical Information of China (English)

    Yuanjia WANG; Naihua DUAN

    2011-01-01

    @@ In many clinical studies repeated measurements of an outcome are collected over time.For example,in an 8-week study of treatment for obsessive compulsive disorder,the severity of the disorder may be measured weekly using the Yale-Brown-Obsessive-Compulsive-Disorder-Scale (YBOCS).For each study participant who completes the study,there will be nine repeated measures of YBOCS (a baseline assessment plus eight assessments during the course of treatment).Such a study in which participants are followed and measured repeatedly over time is called a longitudinal study and the resulting data are called longitudinal data.

  12. Evidence against a critical role of CB1 receptors in adaptation of the hypothalamic-pituitary-adrenal axis and other consequences of daily repeated stress.

    Science.gov (United States)

    Rabasa, Cristina; Pastor-Ciurana, Jordi; Delgado-Morales, Raúl; Gómez-Román, Almudena; Carrasco, Javier; Gagliano, Humberto; García-Gutiérrez, María S; Manzanares, Jorge; Armario, Antonio

    2015-08-01

    There is evidence that endogenous cannabinoids (eCBs) play a role in the control of the hypothalamic-pituitary-adrenal (HPA) axis, although they appear to have dual, stimulatory and inhibitory, effects. Recent data in rats suggest that eCBs, acting through CB1 receptors (CB1R), may be involved in adaptation of the HPA axis to daily repeated stress. In the present study we analyze this issue in male mice and rats. Using a knock-out mice for the CB1 receptor (CB1-/-) we showed that mutant mice presented similar adrenocorticotropic hormone (ACTH) response to the first IMO as wild-type mice. Daily repeated exposure to 1h of immobilization reduced the ACTH response to the stressor, regardless of the genotype, demonstrating that adaptation occurred to the same extent in absence of CB1R. Prototypical changes observed after repeated stress such as enhanced corticotropin releasing factor (CRH) gene expression in the paraventricular nucleus of the hypothalamus, impaired body weight gain and reduced thymus weight were similarly observed in both genotypes. The lack of effect of CB1R in the expression of HPA adaptation to another similar stressor (restraint) was confirmed in wild-type CD1 mice by the lack of effect of the CB1R antagonist AM251 just before the last exposure to stress. Finally, the latter drug did not blunt the HPA, glucose and behavioral adaptation to daily repeated forced swim in rats. Thus, the present results indicate that CB1R is not critical for overall effects of daily repeated stress or proper adaptation of the HPA axis in mice and rats.

  13. Ectopic ACTH-secreting pituitary adenoma of the sphenoid sinus: case report of endoscopic endonasal resection and systematic review of the literature.

    Science.gov (United States)

    Seltzer, Justin; Lucas, Joshua; Commins, Deborah; Lerner, Olga; Lerner, Alexander; Carmichael, John D; Zada, Gabriel

    2015-02-01

    Ectopic pituitary adenomas are exceedingly rare entities that are often misdiagnosed. The resulting delay in diagnosis may be particularly concerning in the case of Cushing syndrome caused by an ectopic adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma. Although the total resection of ectopic adenomas results in rapid and durable remission, persistent Cushing syndrome is often associated with permanently damaging invasive procedures and significantly higher risk of mortality. The authors report the case of a 48-year-old man with ACTH-dependent Cushing syndrome. On the morning before surgery, his serum cortisol measured 51 μg/dl, his ACTH level was 195.7 pg/ml, and his urinary free cortisol level was 2109 μg/day. Serum cortisol was not suppressed with the administration of high-dose dexamethasone. Imaging showed separate masses in both the sphenoid sinus and the pituitary gland, complicating the diagnostic process and requiring pathological assessment of both masses. No other abnormalities were found on thoracic, abdominal, or pelvic scans. Gross-total resection of both lesions was accomplished via an endoscopic endonasal transsphenoidal approach. Pathology confirmed an ectopic ACTH pituitary adenoma of the sphenoid sinus and a Crooke hyaline change of the pituitary gland. The patient achieved stable hormonal remission without significant postoperative complications, returned to full activity within 3 months, and remained disease free nearly 1 year after tumor resection. In a systematic literature review, the authors identified 41 cases of ectopic ACTH-secreting pituitary adenomas, including 18 arising in the sphenoid sinus without direct involvement of the sella. Including the case described here, the total number of ectopic ACTH pituitary adenomas arising in the sphenoid sinus was 19, and the total number of ectopic ACTH pituitary adenomas without regard to location was 42. For the 19 patients with adenomas found in the sphenoid sinus, ages ranged

  14. Analysis of repeated measures data

    CERN Document Server

    Islam, M Ataharul

    2017-01-01

    This book presents a broad range of statistical techniques to address emerging needs in the field of repeated measures. It also provides a comprehensive overview of extensions of generalized linear models for the bivariate exponential family of distributions, which represent a new development in analysing repeated measures data. The demand for statistical models for correlated outcomes has grown rapidly recently, mainly due to presence of two types of underlying associations: associations between outcomes, and associations between explanatory variables and outcomes. The book systematically addresses key problems arising in the modelling of repeated measures data, bearing in mind those factors that play a major role in estimating the underlying relationships between covariates and outcome variables for correlated outcome data. In addition, it presents new approaches to addressing current challenges in the field of repeated measures and models based on conditional and joint probabilities. Markov models of first...

  15. Mouse repeated electroconvulsive seizure (ECS) does not reverse social stress effects but does induce behavioral and hippocampal changes relevant to electroconvulsive therapy (ECT) side-effects in the treatment of depression

    Science.gov (United States)

    Sigrist, Hannes; Seifritz, Erich; Fikse, Lianne; Bosker, Fokko J.; Schoevers, Robert A.; Klein, Hans C.

    2017-01-01

    Electroconvulsive therapy (ECT) is an effective treatment for depression, but can have negative side effects including amnesia. The mechanisms of action underlying both the antidepressant and side effects of ECT are not well understood. An equivalent manipulation that is conducted in experimental animals is electroconvulsive seizure (ECS). Rodent studies have provided valuable insights into potential mechanisms underlying the antidepressant and side effects of ECT. However, relatively few studies have investigated the effects of ECS in animal models with a depression-relevant manipulation such as chronic stress. In the present study, mice were first exposed to chronic social stress (CSS) or a control procedure for 15 days followed by ECS or a sham procedure for 10 days. Behavioral effects were investigated using an auditory fear conditioning (learning) and expression (memory) test and a treadmill-running fatigue test. Thereafter, immunohistochemistry was conducted on brain material using the microglial marker Iba-1 and the cholinergic fibre marker ChAT. CSS did not increase fear learning and memory in the present experimental design; in both the control and CSS mice ECS reduced fear learning and fear memory expression. CSS induced the expected fatigue-like effect in the treadmill-running test; ECS induced increased fatigue in CSS and control mice. In CSS and control mice ECS induced inflammation in hippocampus in terms of increased expression of Iba-1 in radiatum of CA1 and CA3. CSS and ECS both reduced acetylcholine function in hippocampus as indicated by decreased expression of ChAT in several hippocampal sub-regions. Therefore, CSS increased fatigue and reduced hippocampal ChAT activity and, rather than reversing these effects, a repeated ECS regimen resulted in impaired fear learning-memory, increased fatigue, increased hippocampal Iba-1 expression, and decreased hippocampal ChAT expression. As such, the current model does not provide insights into the

  16. Cushing Disease After Treatment of Nonfunctional Pituitary Adenoma: A Case Report and Literature Review.

    Science.gov (United States)

    Fang, Hongjuan; Tian, Rui; Wu, Huanwen; Xu, Jian; Fan, Hong; Zhou, Jian; Zhong, Liyong

    2015-12-01

    We describe a very rare case of nonfunctional pituitary adenoma (NFPA) that exhibited corticotrophic activity after resection and radiotherapy. The possible mechanisms of the transformation from NFPA to Cushing disease (CD) are discussed.A 43-year-old man presented with impaired vision, bilateral frontal headaches, and hyposexuality. He had no symptoms suggestive of hypercortisolism, and 8 am plasma cortisol concentration was 67.88 ng/mL. Brain imaging revealed a 15 × 15 × 21-mm sellar mass suggestive of a macroadenoma. The tumor was resected by transsphenoidal surgery and identified by immunohistochemical analysis as a chromophobic adenoma that did not stain for pituitary hormones. The patient was treated with prednisone and levothyroxine replacement therapy. After a third recurrence, the patient presented with clinical features and physical signs of Cushing syndrome. Plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations were elevated, and there was a loss of circadian rhythms. Inferior petrosal sinus sampling after desmopressin showed the central-peripheral ACTH ratio was greater than 3:1. A repeat transsphenoidal resection was undertaken. Immunohistochemistry revealed ACTH positivity. Three months following surgery, imaging showed little residual tumor, but plasma ACTH remained elevated. He was referred for postoperative Gamma Knife radiotherapy.The immunological activity and biological features of the hormones secreted from a pituitary adenoma vary with time. Because long-term outcomes are unpredictable, postoperative follow-up is essential to detect postoperative transformation from NFPA to CD.

  17. Treatment of acute gout: a systematic review.

    Science.gov (United States)

    Khanna, Puja P; Gladue, Heather S; Singh, Manjit K; FitzGerald, John D; Bae, Sangmee; Prakash, Shraddha; Kaldas, Marian; Gogia, Maneesh; Berrocal, Veronica; Townsend, Whitney; Terkeltaub, Robert; Khanna, Dinesh

    2014-08-01

    Acute gout is traditionally treated with NSAIDs, corticosteroids, and colchicine; however, subjects have multiple comorbidities that limit the use of some conventional therapies. We systematically reviewed the published data on the pharmacologic and non-pharmacologic agents used for the treatment of acute gouty arthritis. A systematic search was performed using PubMed and Cochrane database through May 2013. We included only randomized controlled trials (RCTs) that included NSAIDs, corticosteroids, colchicine, adrenocorticotropic hormone (ACTH), interleukin-1 (IL-1) inhibitors, topical ice, or herbal supplements. Thirty articles were selected for systematic review. The results show that NSAIDs and COX-2 inhibitors are effective agents for the treatment of acute gout attacks. Systemic corticosteroids have similar efficacy to therapeutic doses of NSAIDs, with studies supporting oral and intramuscular use. ACTH is suggested to be efficacious in acute gout. Oral colchicine demonstrated to be effective, with low-dose colchicine demonstrating a comparable tolerability profile as placebo and a significantly lower side effect profile to high-dose colchicine. The IL-1β inhibitory antibody, canakinumab, was effective for the treatment of acute attacks in subjects refractory to and in those with contraindications to NSAIDs and/or colchicine. However, rilonacept was demonstrated to be not as effective, and there are no RCTs for the use of anakinra. NSAIDs, COX-2 selective inhibitors, corticosteroids, colchicine, ACTH, and canakinumab have evidence to suggest efficacy in treatment of acute gout. Published by Elsevier Inc.

  18. Temozolomide and pasireotide treatment for aggressive pituitary adenoma: expertise at a tertiary care center.

    Science.gov (United States)

    Ceccato, Filippo; Lombardi, Giuseppe; Manara, Renzo; Emanuelli, Enzo; Denaro, Luca; Milanese, Laura; Gardiman, Marina Paola; Bertorelle, Roberta; Scanarini, Massimo; D'Avella, Domenico; Occhi, Gianluca; Boscaro, Marco; Zagonel, Vittorina; Scaroni, Carla

    2015-03-01

    Aggressive pituitary adenomas (PAs) are clinically challenging for endocrinologists and neurosurgeons due to their locally invasive nature and resistance to standard treatment (surgery, medical or radiotherapy). Two pituitary-directed drugs have recently been proposed: temozolomide (TMZ) for aggressive PA, and pasireotide for ACTH-secreting PA. We describe the experience of our multidisciplinary team of endocrinologists, neurosurgeons, neuroradiologists, oncologists, otolaryngologists and pathologists with TMZ and pasireotide treatment for aggressive PAs in terms of their radiological shrinkage and genetic features. We considered five patients with aggressive PA, three of them non-secreting (two ACTH-silent and one becoming ACTH secreting), and two secreting (one GH and one ACTH). TMZ was administrated orally at 150-200 mg/m(2) daily for 5 days every 28 days to all 5 patients, and 2 of them also received pasireotide 600-900 µg bid sc. We assessed the MRI at the baseline and during TMZ or pasireotide treatment. We also checked for MGMT promoter methylation and IDH, BRAF and kRAS mutations. Considering TMZ, two patients showed PA progression, one stable disease and two achieved radiological and clinical response. Pasireotide was effective in reducing hypercortisolism and mass volume, combined with TMZ in one case. Both treatments were generally well tolerated; one patient developed a grade 2 TMZ-induced thrombocytopenia. None of patients developed hypopituitarism while taking TMZ or pasireotide treatment. No genetic anomalies were identified in the adenoma tissue. TMZ and pasireotide may be important therapies for aggressive PA, alone or in combination.

  19. Microsurgery treatment of Nelsons syndrome(report of 23 cases)%Nelson综合征的显微外科治疗(附23例报告)

    Institute of Scientific and Technical Information of China (English)

    任祖渊; 幸兵; 苏长保; 王任直; 杨义; 马文斌; 连伟; 李永宁; 杨众

    2001-01-01

    Objective To discuss the etiology, diagnosis criteria and treatment of Nelsons syndrome. Methods 23 cases of Nelsons syndrome operated in our department in last 19 years were analyzed retrospectively. The clinical features included increasing cutaneous pigmentation after bilateral adrenalectomy, markedly elevated ACTH level, pituitary adenoma in CT or/and MRI. Transsphenoidal surgery was done in 21 cases, transfrontal craniotomy in 2 cases. A follow-up period ranged from half a year to 9 years. Results The incidence of Nelsons syndrome was 7.7% in series of 300 patients with Cushings disease treated by surgery in the same period. Hyperpigmentation was relived in all cases and ACTH level decreased. 8 cases with visual disturbance improved after surgery. Curative ratio was 56.5%, remission ratio was 26.1%. Conclusions Transsphenoidal microsurgical removal of pituitary ACTH adenoma is the first choice in prevention and treatment of Nelsons syndrome. Follow-up examinations should be repeated at intervals.%目的 分析和探讨Nelson综合征的病因、诊断标准和治疗方法。方法 对我科手术治疗的23例该病病例进行回顾性研究,临床特点包括肾上腺切除手术后皮肤粘膜色素沉着,血ACTH水平升高,影像学检查发现垂体腺瘤,21例经蝶窦手术,2例经额开颅,随访时间从半年至9年。 结果 本组23例Nelson综合征,占同期手术治疗的库欣病的7.7%,经蝶窦手术后皮肤色素沉着减轻,血ACTH水平下降,8例视力视野障碍术后均改善,治愈率56.5%,缓解率26.1%。结论 经蝶窦垂体ACTH腺瘤切除是预防和治疗Nelson综合征的首选方法,术后应定期随访。

  20. Repeat Gamma Knife surgery for vestibular schwannomas

    Science.gov (United States)

    Lonneville, Sarah; Delbrouck, Carine; Renier, Cécile; Devriendt, Daniel; Massager, Nicolas

    2015-01-01

    Background: Gamma Knife (GK) surgery is a recognized treatment option for the management of small to medium-sized vestibular schwannoma (VS) associated with high-tumor control and low morbidity. When a radiosurgical treatment fails to stop tumor growth, repeat GK surgery can be proposed in selected cases. Methods: A series of 27 GK retreatments was performed in 25 patients with VS; 2 patients underwent three procedures. The median time interval between GK treatments was 45 months. The median margin dose used for the first, second, and third GK treatments was 12 Gy, 12 Gy, and 14 Gy, respectively. Six patients (4 patients for the second irradiation and 2 patients for the third irradiation) with partial tumor regrowth were treated only on the growing part of the tumor using a median margin dose of 13 Gy. The median tumor volume was 0.9, 2.3, and 0.7 cc for the first, second, and third treatments, respectively. Stereotactic positron emission tomography (PET) guidance was used for dose planning in 6 cases. Results: Mean follow-up duration was 46 months (range 24–110). At the last follow-up, 85% of schwannomas were controlled. The tumor volume decreased, remained unchanged, or increased after retreatment in 15, 8, and 4 cases, respectively. Four patients had PET during follow-up, and all showed a significant metabolic decrease of the tumor. Hearing was not preserved after retreatment in any patients. New facial or trigeminal palsy did not occur after retreatment. Conclusions: Our results support the long-term efficacy and low morbidity of repeat GK treatment for selected patients with tumor growth after initial treatment. PMID:26500799

  1. 不同针刺方法对慢性应激抑郁大鼠下丘脑CRH基因表达及血清ACTH、CORT的影响%Influences of different acupuncture methods on hypothalamic CRH mRNA expression and serum ACTH and CORT in rats with chronic stress depression

    Institute of Scientific and Technical Information of China (English)

    梁佳; 卢峻; 王俊仁; 崔善福; 阿英格; 图娅

    2012-01-01

    Objective To compare and observe the differences between the influences of acupuncture and electroacupuncture on the expression of hypothalamic corticotrophin-releasing hormone ( CRH) mRNA and content of serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) in rat model of chronic stress depression, and investigate the mechanism of acupuncture and electroacupuncture in intervene and treatment of depression. Methods All SD rats were randomly divided into Wank group, model group, acupuncture group and electroacupuncture group. The expression of hypothalamic CRH mRNA was detected by using real-time fluorescence quantitative polymerase chain reaction (RT-PCR), and content of serum ACTH and CORT were detected by applying enzyme-linked immunosorbent assay (ELJSA). Results Compared with blank group, the expression of CRH mRNA and content of serum ACTH and CORT increased significantly in model group (P 0.05) , and ACTH expression decreased significantly (P 0. 05). Conclusion The rat model of chronic stress depression had a hyperactivity of HPA axis. Acupuncture and electroacupuncture can down-regulate the function of HPA axis. It may be one of ways to treat depression with acupuncture and electroacupuncture that they have antagonism to the hyperactivity of HPA axis.%目的 对比观察手针与电针对慢性应激抑郁模型大鼠下丘脑促肾上腺皮质激素释放激素(CRH)mRNA表达及血清促肾上腺皮质激素(ACTH)、皮质酮(CORT)影响的差异,探讨手针与电针干预治疗抑郁症的机制.方法 将SD大鼠随机分为4组:空白组、模型组、手针组、电针组,采用实时荧光定量PCR (RT-PCR)方法检测下丘脑CRH mRNA含量,酶联免疫吸附法(ELISA)检测大鼠血清ACTH、CORT含量.结果 与空白组相比,模型组大鼠下丘脑CRH mRNA的含量显著升高(P<0.01),血清CORT和ACTH含量显著升高(P<0.01).与模型组相比,手针组与电针组大鼠下丘脑CRH mRNA的含量均明显降低(P<0.05

  2. Tentativa de controle de Hymenolepis nana através de tratamentos clínicos repetidos, com praziquantel, em uma comunidade fechada The use of repeated praziquantel treatments in an attempt to control Hymenolepis nana in an orphanage

    Directory of Open Access Journals (Sweden)

    R. S. Rocha

    1981-08-01

    controle da himenolepíase.Praziquantel was used repeatedly in an orphanage to determine its effectiveness in controlling hymenolepis. At the same time, the possible mechanisms of the transmission of this parasitosis were studied. The first group examined consisted of 161 people of which 109 were the orphanage children, who varied in age from days or months to eight years, and 52 adults, employees of the institution. Stool tests of all were made about every two months, using the Hoffman, Pons and Janer method; cure control was carried out by the same method seven to fourteen days after treatment. Every two weeks, H. nana eggs were searched for under the finger nails of the children, in insects, in domestic wastes, on door knobs and refrigerator handles, and on toilet flush knobs and strings. Water collected from rinsed urinals and shower floors was also tested. Eggs and larva of helminths and protozoa cysts were found in domestic waste and cockroaches and on door knobs. H. nana eggs were found in puddles of water left on shower floors and the rinse water of urinals. Every patient whose feces had H. nana eggs was treated with a single oral 25mg/kg dose of praziquantel, taken after lunch. In the four groups treated (66 patients in all, no important side effects were observed, and follow-up indicated 100% cure. For the 5th and last treatment, a group of both positive and negative (for H. nana people was divided into sub-groups and treated with one (25mg/kg or two doses of the medicine for a period of four days (total: 50mg/kg. Follow-up examination two months after treatment showed that only six patients were still eliminating eggs of the parasite; all belonged to the sub-group treated with a single dose of the drug. In spite of the treatments given an of the high percentage of cure, control of hymenolepiasis was not achieved.

  3. Life-threatening Pneumocystis jiroveci pneumonia following treatment of severe Cushing's syndrome

    NARCIS (Netherlands)

    Oosterhuis, J. K.; van den Berg, G.; Monteban-Kooistra, W. E.; Ligtenberg, J. J. M.; Tulleken, J. E.; Zijlstra, J. G.; Meertens, John

    We describe two patients with a severe Cushing's syndrome due to ectopic production of ACTH. Both patients developed a life-threatening Pneumocystis jiroveci pneumonia (PCP) shortly after treatment of the hypercortisolism was started by means of inhibition of production of glucocorticoids and

  4. Limitations on quantum key repeaters.

    Science.gov (United States)

    Bäuml, Stefan; Christandl, Matthias; Horodecki, Karol; Winter, Andreas

    2015-04-23

    A major application of quantum communication is the distribution of entangled particles for use in quantum key distribution. Owing to noise in the communication line, quantum key distribution is, in practice, limited to a distance of a few hundred kilometres, and can only be extended to longer distances by use of a quantum repeater, a device that performs entanglement distillation and quantum teleportation. The existence of noisy entangled states that are undistillable but nevertheless useful for quantum key distribution raises the question of the feasibility of a quantum key repeater, which would work beyond the limits of entanglement distillation, hence possibly tolerating higher noise levels than existing protocols. Here we exhibit fundamental limits on such a device in the form of bounds on the rate at which it may extract secure key. As a consequence, we give examples of states suitable for quantum key distribution but unsuitable for the most general quantum key repeater protocol.

  5. Hysteresis of magnetostructural transitions: Repeatable and non-repeatable processes

    Energy Technology Data Exchange (ETDEWEB)

    Provenzano, Virgil [National Institute of Standards and Technology, Gaithersburg, MD 20899 (United States); Della Torre, Edward; Bennett, Lawrence H. [Department of Electrical and Computer Engineering, The George Washington University, Washington, DC 20052 (United States); ElBidweihy, Hatem, E-mail: Hatem@gwmail.gwu.edu [Department of Electrical and Computer Engineering, The George Washington University, Washington, DC 20052 (United States)

    2014-02-15

    The Gd{sub 5}Ge{sub 2}Si{sub 2} alloy and the off-stoichiometric Ni{sub 50}Mn{sub 35}In{sub 15} Heusler alloy belong to a special class of metallic materials that exhibit first-order magnetostructural transitions near room temperature. The magnetic properties of this class of materials have been extensively studied due to their interesting magnetic behavior and their potential for a number of technological applications such as refrigerants for near-room-temperature magnetic refrigeration. The thermally driven first-order transitions in these materials can be field-induced in the reverse order by applying a strong enough field. The field-induced transitions are typically accompanied by the presence of large magnetic hysteresis, the characteristics of which are a complicated function of temperature, field, and magneto-thermal history. In this study we show that the virgin curve, the major loop, and sequentially measured MH loops are the results of both repeatable and non-repeatable processes, in which the starting magnetostructural state, prior to the cycling of field, plays a major role. Using the Gd{sub 5}Ge{sub 2}Si{sub 2} and Ni{sub 50}Mn{sub 35}In{sub 15} alloys, as model materials, we show that a starting single phase state results in fully repeatable processes and large magnetic hysteresis, whereas a mixed phase starting state results in non-repeatable processes and smaller hysteresis.

  6. Cataractogenesis after Repeat Laser in situ Keratomileusis

    Directory of Open Access Journals (Sweden)

    Ahmad M. Mansour

    2012-08-01

    Full Text Available There has been the unsubstantiated clinical impression that laser refractive surgery accelerates cataract development along with solid experimental data about the cataractogenic effects of excimer laser treatment. We present the first documented case of significant cataract formation in a young myope after repeat excimer laser ablation necessitating phacoemulsification with a posterior chamber implant. Proposed explanations include focusing of the ablation wave on the posterior capsule (acoustic wave lens epithelial damage, photooxidative stress of the lens (ultraviolet and inflammatory oxidative stress, and corticosteroid-induced cataract (lens toxicity.

  7. An influence of mental stress, related to parachute jumping, on ACTH and cortizol hormones concentration in blood serum [Wpływ stresu związanego ze skokami spadochronowymi na stężenie ACTH i kortyzolu w surowicy krwi

    Directory of Open Access Journals (Sweden)

    Kowalczyk, Edward

    2012-10-01

    Full Text Available Aim. The purpose of this research was to estimate an influence of parachute jumps on the level of ACTH and cortizol hormones among professional soldiers from air-borne forces. Methods. The investigation was carried out on 46 professional soldiers from 16 Air-Borne Battalion, patients of the outpatient department – SPZOZ JW. 4495, men at 20 to 45 age, healthy – admitted to parachute jumping in air-borne forces. They were divided into groups according to their knowledge and an experience in parachuting. Venous blood samples were taken to examine the level of ACTH and cortizol hormones three times during experiment: on a free day, day of parachute jumping and 24hrs after jump. Additionally in order to estimate the level of nervous tension and mental stress, in every stage of the experiment, personal questionnaires in accordance with STAI were carried out. Results. The results show the influence of psychological stress related to parachute jumps on the level of ACTH and cortizol hormones depending on experience in parachuting.

  8. EAMJ Dec. Repeatability.indd

    African Journals Online (AJOL)

    2008-12-12

    Dec 12, 2008 ... Results:Kappa values for four-week repeatability for the wheeze and asthma questions were 0.61 ... for logistic, cultural and ethical reasons, to use ... individual with baseline forced expiratory volume in .... period is likely to also include the effects of true ... data, the writing of the manuscript or the decision.

  9. ACTH (cosyntropin) stimulation test

    Science.gov (United States)

    ... you have an adrenal gland problem, such as Addison disease , or pituitary insufficiency . It is also used to ... that occurs when there is not enough cortisol) Addison disease (adrenal glands do not produce enough cortisol) Hypopituitarism ( ...

  10. ACTH (Adrenocorticotropic Hormone) Test

    Science.gov (United States)

    ... the arms and legs Fat collection between the shoulders Rounded, red face Fragile and thin skin Purple lines on the abdomen Muscle weakness Acne Skin infections Increased body hair Fatigue These ...

  11. Value of repeat biopsy in lupus nephritis flares

    Science.gov (United States)

    Greloni, G; Scolnik, M; Marin, J; Lancioni, E; Quiroz, C; Zacariaz, J; De la Iglesia Niveyro, P; Christiansen, S; Pierangelo, M A; Varela, C F; Rosa-Diez, G J; Catoggio, L J; Soriano, E R

    2014-01-01

    Objectives Renal flares are common in lupus nephritis (LN), and class switch is thought to be characteristic. There is no agreement on indications for performing a repeat renal biopsy. Our objective was to retrospectively review patients who had more than one renal biopsy performed on clinical indications, and analyse clinical, pathological and treatment changes after successive biopsies. Methods Forty-five patients with LN and one or more repeat renal biopsies were included, with a total of 116 biopsies. Results Of the 71 repeat biopsies, pathological transition occurred in 39 (54.9%). When having a previous biopsy with a proliferative lesion, class switch occurred in 55.6%, with 24.4% evolving into non-proliferative classes. When previous biopsy was class V, transition to other classes occurred in 58.3% and changes were all into proliferative classes. Conversion from one pure proliferative form to another (class III to class IV or vice versa) happened in 11.3% of the rebiopsies, with 62 rebiopsies (87.3%) leading to a change in the treatment regimen. Conclusions Histological transformations were common, and they occurred when the previous biopsy had non-proliferative lesions as well as when lesions were proliferative. Treatments were modified after repeat renal biopsy in the majority of patients. In this experience, kidney repeat biopsies were useful in guiding treatment of LN flares. PMID:25396056

  12. Valoración de Cortisol y ACTH postoperatorios en enfermedad de Cushing y su correlación con características clínicas a largo plazo

    OpenAIRE

    Abellán Galiana, Pablo

    2017-01-01

    La enfermedad de Cushing (EC) es un raro trastorno con una incidencia de 0,7-2,4 casos por millón de habitantes al año. La EC se caracteriza por un estado de hipercortisolismo, ocasionado por un adenoma hipofisario secretor de ACTH. Los adenomas hipofisarios productores de ACTH son la causa más frecuente de hipercortisolismo endógeno, suponiendo el 65-70% de los casos de síndrome de Cushing endógeno. La EC da lugar a obesidad, diabetes mellitus, hipertensión arterial, debilidad muscular, oste...

  13. Effects of repeated ether stress on the hypothalamic-pituitary-testes axis in adult rats with special reference to inhibin secretion.

    Science.gov (United States)

    Tohei, A; Tomabechi, T; Mamada, M; Akai, M; Watanabe, G; Taya, K

    1997-05-01

    Effects of ether stress on the hypothalamo-hypophysial-gonadal axis in adult male rats were examined. To clarify the role of adrenal glucocorticoids in gonadal function, the effects of adrenalectomy and Dexamethasone treatment were also investigated. Ether stress increased the plasma concentrations of ACTH and corticosterone, but decreased the plasma concentrations of LH, FSH, inhibin and testosterone. The pituitary responsiveness to LH-RH for LH release and testicular responsiveness to the endogenous LH for testosterone release were maintained in stressed rats. Adrenalectomy caused an increase in the plasma concentrations of ACTH, but decreased the plasma concentrations of LH, FSH and testosterone. Dexamethasone treatment in adrenalectomized rats recovered the levels of plasma gonadotropins to control levels. The concentration of plasma inhibin did not change in adrenalectomized rats, but it was decreased compared to control rats by Dexamethasone treatment. Treatments of Dexamethasone in intact male rats resulted in a decline in plasma levels of testosterone and inhibin without a decrease in the levels of LH and FSH, indicating the direct effect of Dexamethasone on the testes. These results indicate that increased ACTH secretion in stressed rats is probably due to hypersecretion of CRH from the hypothalamus, which suppresses gonadotropin secretion via the inhibition of LH-RH. The decreased levels of testosterone may be caused by a stress-induced decrease in plasma LH concentrations and increased secretion of corticosterone in the ether stressed rats. The low levels of plasma inhibin in stressed rats was also probably due to the direct effect of corticosterone on the Sertoli cells.

  14. Directionality switchable gain stabilized linear repeater

    Science.gov (United States)

    Ota, Takayuki; Ohmachi, Tadashi; Aida, Kazuo

    2004-10-01

    We propose a new approach to realize a bidirectional linear repeater suitable for future optical internet networks and fault location in repeater chain with OTDR. The proposed approach is the linear repeater of simple configuration whose directionality is rearranged dynamically by electrical control signal. The repeater is composed of a magneto-optical switch, a circulator, a dynamically gain stabilized unidirectional EDFA, and control circuits. The repeater directionality is rearranged as fast as 0.1ms by an electrical control pulse. It is experimentally confirmed that OTDR with the directionality switchable repeater is feasible for repeater chain. The detailed design and performance of the repeater are also discussed, including the multi-pass interference (MPI) which may arise in the proposed repeater, the effect of the MPI on SNR degradation of the repeater chain and the feed-forward EDFA gain control circuit.

  15. Measurement-based quantum repeaters

    CERN Document Server

    Zwerger, M; Briegel, H J

    2012-01-01

    We introduce measurement-based quantum repeaters, where small-scale measurement-based quantum processors are used to perform entanglement purification and entanglement swapping in a long-range quantum communication protocol. In the scheme, pre-prepared entangled states stored at intermediate repeater stations are coupled with incoming photons by simple Bell-measurements, without the need of performing additional quantum gates or measurements. We show how to construct the required resource states, and how to minimize their size. We analyze the performance of the scheme under noise and imperfections, with focus on small-scale implementations involving entangled states of few qubits. We find measurement-based purification protocols with significantly improved noise thresholds. Furthermore we show that already resource states of small size suffice to significantly increase the maximal communication distance. We also discuss possible advantages of our scheme for different set-ups.

  16. A Repeating Fast Radio Burst

    CERN Document Server

    Spitler, L G; Hessels, J W T; Bogdanov, S; Brazier, A; Camilo, F; Chatterjee, S; Cordes, J M; Crawford, F; Deneva, J; Ferdman, R D; Freire, P C C; Kaspi, V M; Lazarus, P; Lynch, R; Madsen, E C; McLaughlin, M A; Patel, C; Ransom, S M; Seymour, A; Stairs, I H; Stappers, B W; van Leeuwen, J; Zhu, W W

    2016-01-01

    Fast Radio Bursts are millisecond-duration astronomical radio pulses of unknown physical origin that appear to come from extragalactic distances. Previous follow-up observations have failed to find additional bursts at the same dispersion measures (i.e. integrated column density of free electrons between source and telescope) and sky position as the original detections. The apparent non-repeating nature of the fast radio bursts has led several authors to hypothesise that they originate in cataclysmic astrophysical events. Here we report the detection of ten additional bursts from the direction of FRB121102, using the 305-m Arecibo telescope. These new bursts have dispersion measures and sky positions consistent with the original burst. This unambiguously identifies FRB121102 as repeating and demonstrates that its source survives the energetic events that cause the bursts. Additionally, the bursts from FRB121102 show a wide range of spectral shapes that appear to be predominantly intrinsic to the source and wh...

  17. Repeatability of Harris Corner Detector

    Institute of Scientific and Technical Information of China (English)

    HU Lili

    2003-01-01

    Interest point detectors are commonly employed to reduce the amount of data to be processed. The ideal interest point detector would robustly select those features which are most appropriate or salient for the application and data at hand. This paper shows that interest points are geometrically stable under different transformations.This property makes interest points very successful in the context of image matching. To measure this property quantatively, we introduce a evaluation criterion: repeatability rate.

  18. Origin and fate of repeats in bacteria.

    Science.gov (United States)

    Achaz, G; Rocha, E P C; Netter, P; Coissac, E

    2002-07-01

    We investigated 53 complete bacterial chromosomes for intrachromosomal repeats. In previous studies on eukaryote chromosomes, we proposed a model for the dynamics of repeats based on the continuous genesis of tandem repeats, followed by an active process of high deletion rate, counteracted by rearrangement events that may prevent the repeats from being deleted. The present study of long repeats in the genomes of Bacteria and Archaea suggests that our model of interspersed repeats dynamics may apply to them. Thus the duplication process might be a consequence of very ancient mechanisms shared by all three domains. Moreover, we show that there is a strong negative correlation between nucleotide composition bias and the repeat density of genomes. We hypothesise that in highly biased genomes, non-duplicated small repeats arise more frequently by random effects and are used as primers for duplication mechanisms, leading to a higher density of large repeats.

  19. ACTH-independent macronodular adrenocortical hyperplasia reveals prevalent aberrant in vivo and in vitro responses to hormonal stimuli and coupling of arginine-vasopressin type 1a receptor to 11 beta-hydroxylase

    NARCIS (Netherlands)

    Hofland, Johannes; Hofland, Leo J.; van Koetsveld, Peter M.; Steenbergen, Jacobie; de Herder, Wouter W.; van Eijck, Casper H.; de Krijger, Ronald R.; van Nederveen, Francien H.; van Aken, Maarten O.; de Groot, Johannes W.; Links, Thera P.; de Jong, Frank H.; Feelders, Richard A.

    2013-01-01

    Background: Adrenal Cushing's syndrome caused by ACTH-independent macronodular adrenocortical hyperplasia (AIMAH) can be accompanied by aberrant responses to hormonal stimuli. We investigated the prevalence of adrenocortical reactions to these stimuli in a large cohort of AIMAH patients, both in viv

  20. Improving repeatability by improving quality

    Energy Technology Data Exchange (ETDEWEB)

    Ronen, Shuki; Ackers, Mark; Schlumberger, Geco-Prakla; Brink, Mundy

    1998-12-31

    Time lapse (4-D) seismic is a promising tool for reservoir characterization and monitoring. The method is apparently simple: to acquire data repeatedly over the same reservoir, process and interpret the data sets, then changes between the data sets indicate changes in the reservoir. A problem with time lapse seismic data is that reservoirs are a relatively small part of the earth and important reservoir changes may cause very small differences to the time lapse data. The challenge is to acquire and process economical time lapse data such that reservoir changes can be detected above the noise of varying acquisition and environment. 7 refs., 9 figs.

  1. Coordinated hybrid automatic repeat request

    KAUST Repository

    Makki, Behrooz

    2014-11-01

    We develop a coordinated hybrid automatic repeat request (HARQ) approach. With the proposed scheme, if a user message is correctly decoded in the first HARQ rounds, its spectrum is allocated to other users, to improve the network outage probability and the users\\' fairness. The results, which are obtained for single- and multiple-antenna setups, demonstrate the efficiency of the proposed approach in different conditions. For instance, with a maximum of M retransmissions and single transmit/receive antennas, the diversity gain of a user increases from M to (J+1)(M-1)+1 where J is the number of users helping that user.

  2. Proteomic analysis of adrenocorticotropic hormone treatment of an infantile spasm model induced by N-methyl-D-aspartic acid and prenatal stress.

    Directory of Open Access Journals (Sweden)

    Jing Wang

    Full Text Available Infantile spasms is an age-specific epileptic syndrome associated with poor developmental outcomes and poor response to nearly all traditional antiepileptic drugs except adrenocorticotropic hormone (ACTH. We investigated the protective mechanism of ACTH against brain damage. An infantile spasm rat model induced by N-methyl-D-aspartate (NMDA in neonate rats was used. Pregnant rats were randomly divided into the stress-exposed and the non-stress exposed groups, and their offspring were randomly divided into ACTH-treated spasm model, untreated spasm model, and control groups. A proteomics-based approach was used to detect the proteome differences between ACTH-treated and untreated groups. Gel image analysis was followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometric protein identification and bioinformatics analysis. Prenatal stress exposure resulted in more severe seizures, and ACTH treatment reduced and delayed the onset of seizures. The most significantly up-regulated proteins included isoform 1 of tubulin β-5 chain, cofilin-1 (CFL1, synaptosomal-associated protein 25, malate dehydrogenase, N(G,N(G-dimethylarginine dimethylaminohydrolase 1, annexin A3 (ANXA3, and rho GDP-dissociation inhibitor 1 (ARHGDIA. In contrast, tubulin α-1A chain was down-regulated. Three of the identified proteins, ARHGDIA, ANXA3, and CFL1, were validated using western blot analysis. ARHGDIA expression was assayed in the brain samples of five infantile spasm patients. These proteins are involved in the cytoskeleton, synapses, energy metabolism, vascular regulation, signal transduction, and acetylation. The mechanism underlying the effects of ACTH involves the molecular events affected by these proteins, and protein acetylation is the mechanism of action of the drug treatment.

  3. Considerations on repeated repairing of weldments in Inconel 718 alloy

    Science.gov (United States)

    Bayless, E. O.; Lovoy, C. V.; Mcilwain, M. C.; Munafo, P.

    1981-01-01

    The effects of repeated weld repairs on the metallurgical characteristics, high cycle fatigue (HCF), and tensile properties of Inconel 718 butt weld joints were determined. A 1/4 in thick plate and a 1/2 in thick plate were used as well as tungsten inert gas welding, and Inconel 718 filler wire. Weld panels were subjected to 2, 6, and 12 repeated repairs and were made in a highly restrained condition. Post weld heat treatments were also conducted with the welded panel in the highly restrained condition. Results indicate that no significant metallurgical anomaly is evident as a result of up to twelve repeated weld repairs. No degradation in fatigue life is noted for up to twelve repeated repairs. Tensile results from specimens which contained up to twelve repeated weld repairs revealed no significant degradation in UTS and YS. However, a significant decrease in elongation is evident with specimens (solution treated and age hardened after welding) which contained twelve repeated repairs. The elongation loss is attributed to the presence of a severe notch on each side (fusion line) of the repair weld bead reinforcement.

  4. Comparative analysis of repeated skin dilation in the treatment of scarring baldness%重复皮肤扩张术治疗瘢痕性秃发的对比分析

    Institute of Scientific and Technical Information of China (English)

    李继洋; 惠雷; 盖亚; 郭力

    2014-01-01

    Objective To investigate the clinical effect of repeated skin expansion technique on scarring alopecia. Methods Twenty-eight cases of scarring alopecia underwent repeated relay skin ex-pansion technique were chosen,and 21 cases of scarring alopecia underwent repeated delay skin expan-sion technique were chose. The times of operations,length of hospital stay,expenses and times of anes-thesia were compared between the two methods. Results Relay dilatation was used to repair scarring al-opecia in 28 cases,26 patients had good repairment,the average length of hospital stay was(24 ± 6)d, the average hospitalization expenses were(26 ± 3)thousand yuan. Delay skin expansion was used to re-pair scarring alopecia in 21 cases,20 cases of had good reparrment,the average length of hospital stay was(32 ± 4)d,the average hospitalization expenses were(38 ± 4)thousand yuan. There were signifi-cant differences in the average length of hospital stay and the average hospitalization expenses between the two methods( P<0 . 01 ). Conclusions Delayed skin expansion and relayed expansion both can better repair scarring alopecia,but relayed expansion is feasible,and has fewer operation times,shorter length of hospital stay,little costs and pain.%目的:探讨重复皮肤扩张术治疗瘢痕性秃发的临床效果。方法选择本科重复接力皮肤扩张术治疗瘢痕性秃发28例,重复延期皮肤扩张术治疗瘢痕性秃发21例,对两种治疗方法的手术次数、住院时间、手术费用、麻醉次数等进行比较分析。结果接力扩张术修复瘢痕性秃发28例,修复良好26例,平均住院时间(24±6)d,平均住院费用(2.6±0.3)万元;延期皮肤扩张修复瘢痕秃发21例,修复良好20例,平均住院时间(32±4)d,平均住院费用(3.8±0.4)万元。两种治疗方式的平均住院时间及平均住院费比较差异有统计学意义(P<0.01)。结论延期皮肤扩张和接力扩

  5. An influence of mental stress, related to parachute jumping, on ACTH and cortizol hormones concentration in blood serum [Wpływ stresu związanego ze skokami spadochronowymi na stężenie ACTH i kortyzolu w surowicy krwi

    OpenAIRE

    Kowalczyk, Edward; Kura, Marcin

    2012-01-01

    Aim. The purpose of this research was to estimate an influence of parachute jumps on the level of ACTH and cortizol hormones among professional soldiers from air-borne forces. Methods. The investigation was carried out on 46 professional soldiers from 16 Air-Borne Battalion, patients of the outpatient department – SPZOZ JW. 4495, men at 20 to 45 age, healthy – admitted to parachute jumping in air-borne forces. They were divided into groups according to their knowledge and an experience in par...

  6. An unusual case of an ACTH-secreting macroadenoma with a germline variant in the aryl hydrocarbon receptor-interacting protein (AIP) gene

    DEFF Research Database (Denmark)

    Dinesen, Pia T; Dal, Jakob; Gabrovska, Plamena;

    2015-01-01

    was diagnosed with a large pituitary tumor by magnetic resonance imaging (MRI). His visual fields were intact and he exhibited no features of CD. Owing to an exuberant response to synacthen, an overnight dexamethasone suppression test was performed revealing inadequate suppression of plasma cortisol (419 nmol...... test demonstrated high basal and stimulated cortisol levels; an overnight dexamethasone suppression test showed no suppression (791 nmol/l) and elevated plasma ACTH levels (135 ng/l). A transcranial operation was performed followed by radiotherapy. Two months after radiotherapy, he developed secondary...... growth rather than symptoms of hypersecretion. The particular AIP gene variant identified in our patient is shared by four other reported cases of CD. Future studies are needed to assess whether the reported AIP gene variant is more than just coincidental. LEARNING POINTS: CD is occasionally dominated...

  7. ACTH-producing carcinoma of the pituitary with refractory Cushing's Disease and hepatic metastases: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Sippel Rebecca

    2009-04-01

    Full Text Available Abstract Background Pituitary carcinomas are rare neuroendocrine tumors affecting the adenohypophysis. The hallmark of these lesions is the demonstration of distant metastatic spread. To date, few well-documented cases have been reported in the literature. Case presentation Here, we report the case of a fatal pituitary carcinoma evolving within two years from an adrenocorticotrophic hormone (ACTH-secreting macroadenoma and review the global literature regarding this rare neuroendocrine tumor. Conclusion Pituitary carcinomas are extremely rare neoplasms, representing only 0.1% to 0.2% of all pituitary tumors. To date, little is understood about the molecular basis of malignant transformation. The latency period between initial presentation of a pituitary adenoma and the development of distal metastases marking carcinoma is extremely variable, and some patients may live well over 10 years with pituitary carcinoma.

  8. Síndrome de Guillain-Barré: a propósito de 5 casos tratados com ACTH e cortisona

    Directory of Open Access Journals (Sweden)

    José Lamartine de Assis

    1953-12-01

    Full Text Available São registrados 5. casos de síndrome de Guillain-Barré (polirradiculoneurite tratados com ACTH ou cortisona. Foi observada melhora rápida em todos êles, em tempo variável de um para outro caso, mas menor que o tempo médio de evolução da moléstia quando tais hormônios não são empregados. Em vista da evolução observada é discutida a teoria da patogenia alérgica da doença e sua inclusão no grupo das doenças desmielinizantes do sistema nervoso.

  9. Crowding by a repeating pattern.

    Science.gov (United States)

    Rosen, Sarah; Pelli, Denis G

    2015-01-01

    Theinability to recognize a peripheral target among flankers is called crowding. For a foveal target, crowding can be distinguished from overlap masking by its sparing of detection, linear scaling with eccentricity, and invariance with target size.Crowding depends on the proximity and similarity of the flankers to the target. Flankers that are far from or dissimilar to the target do not crowd it. On a gray page, text whose neighboring letters have different colors, alternately black and white, has enough dissimilarity that it might escape crowding. Since reading speed is normally limited by crowding, escape from crowding should allow faster reading. Yet reading speed is unchanged (Chung & Mansfield, 2009). Why? A recent vernier study found that using alternating-color flankers produces strong crowding (Manassi, Sayim, & Herzog, 2012). Might that effect occur with letters and reading? Critical spacing is the minimum center-to-center target-flanker spacing needed to correctly identify the target. We measure it for a target letter surrounded by several equidistant flanker letters of the same polarity, opposite polarity, or mixed polarity: alternately white and black. We find strong crowding in the alternating condition, even though each flanker letter is beyond its own critical spacing (as measured in a separate condition). Thus a periodic repeating pattern can produce crowding even when the individual elements do not. Further, in all conditions we find that, once a periodic pattern repeats (two cycles), further repetition does not affect critical spacing of the innermost flanker.

  10. Repeat microvascular decompression for recurrent idiopathic trigeminal neuralgia

    NARCIS (Netherlands)

    Bakker, Nicolaas A.; van Dijk, J. Marc C.; Immenga, Steven; Wagemakers, Michiel; Metzemaekers, Jan D. M.

    2014-01-01

    Object. Microvascular decompression (MVD) is considered the method of choice to treat idiopathic trigeminal neuralgia (TN) refractory to medical treatment. However, repeat MVD for recurrent TN is not well established. In this paper, the authors describe a large case series in which patients underwen

  11. Effectiveness of Repeated Gonorrhea Cultures in the Third Trimester

    Directory of Open Access Journals (Sweden)

    Juan G. Torres

    1993-01-01

    Full Text Available Objective: With the high cost of health care today, the universal prophylactic measures recommended, and the availability of effective treatment should infection occur, the practice of routinely repeating the endocervical gonorrhea (GC culture in the third trimester of pregnancy may be unwarranted.

  12. Repeat microvascular decompression for recurrent idiopathic trigeminal neuralgia

    NARCIS (Netherlands)

    Bakker, Nicolaas A.; van Dijk, J. Marc C.; Immenga, Steven; Wagemakers, Michiel; Metzemaekers, Jan D. M.

    2014-01-01

    Object. Microvascular decompression (MVD) is considered the method of choice to treat idiopathic trigeminal neuralgia (TN) refractory to medical treatment. However, repeat MVD for recurrent TN is not well established. In this paper, the authors describe a large case series in which patients

  13. Automatization and familiarity in repeated checking

    NARCIS (Netherlands)

    Dek, Eliane C P; van den Hout, Marcel A.; Giele, Catharina L.; Engelhard, Iris M.

    2014-01-01

    Repeated checking paradoxically increases memory uncertainty. This study investigated the underlying mechanism of this effect. We hypothesized that as a result of repeated checking, familiarity with stimuli increases, and automatization of the checking procedure occurs, which should result in decrea

  14. CDC Vital Signs: Preventing Repeat Teen Births

    Science.gov (United States)

    ... file Error processing SSI file Preventing Repeat Teen Births Recommend on Facebook Tweet Share Compartir On this ... Too many teens, ages 15–19, have repeat births. Nearly 1 in 5 births to teens, ages ...

  15. Gradual loss of ACTH due to a novel mutation in LHX4: comprehensive mutation screening in Japanese patients with congenital hypopituitarism.

    Science.gov (United States)

    Takagi, Masaki; Ishii, Tomohiro; Inokuchi, Mikako; Amano, Naoko; Narumi, Satoshi; Asakura, Yumi; Muroya, Koji; Hasegawa, Yukihiro; Adachi, Masanori; Hasegawa, Tomonobu

    2012-01-01

    Mutations in transcription factors genes, which are well regulated spatially and temporally in the pituitary gland, result in congenital hypopituitarism (CH) in humans. The prevalence of CH attributable to transcription factor mutations appears to be rare and varies among populations.This study aimed to define the prevalence of CH in terms of nine CH-associated genes among Japanese patients. We enrolled 91 Japanese CH patients for DNA sequencing of POU1F1, PROP1, HESX1, LHX3, LHX4, SOX2, SOX3, OTX2, and GLI2. Additionally, gene copy numbers for POU1F1, PROP1, HESX1, LHX3, and LHX4 were examined by multiplex ligation-dependent probe amplification. The gene regulatory properties of mutant LHX4 proteins were characterized in vitro. We identified two novel heterozygous LHX4 mutations, namely c.249-1G>A, p.V75I, and one common POU1F1 mutation, p.R271W. The patient harboring the c.249-1G>A mutation exhibited isolated growth hormone deficiency at diagnosis and a gradual loss of ACTH, whereas the patient with the p.V75I mutation exhibited multiple pituitary hormone deficiency. In vitro experiments showed that both LHX4 mutations were associated with an impairment of the transactivation capacities of POU1F1 andαGSU, without any dominant-negative effects. The total mutation prevalence in Japanese CH patients was 3.3%. This study is the first to describe, a gradual loss of ACTH in a patient carrying an LHX4 mutation. Careful monitoring of hypothalamic-pituitary -adrenal function is recommended for CH patients with LHX4 mutations.

  16. Treatment

    National Research Council Canada - National Science Library

    Safaa M. Raghab; Ahmed M. Abd El Meguid; Hala A. Hegazi

    2013-01-01

    .... This paper presents the results of the analyses of leachate treatment from the solid waste landfill located in Borg El Arab landfill in Alexandria using an aerobic treatment process which was applied...

  17. Expanded complexity of unstable repeat diseases

    OpenAIRE

    Polak, Urszula; McIvor, Elizabeth; Dent, Sharon Y.R.; Wells, Robert D.; Napierala, Marek.

    2012-01-01

    Unstable Repeat Diseases (URDs) share a common mutational phenomenon of changes in the copy number of short, tandemly repeated DNA sequences. More than 20 human neurological diseases are caused by instability, predominantly expansion, of microsatellite sequences. Changes in the repeat size initiate a cascade of pathological processes, frequently characteristic of a unique disease or a small subgroup of the URDs. Understanding of both the mechanism of repeat instability and molecular consequen...

  18. 47 CFR 97.205 - Repeater station.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Repeater station. 97.205 Section 97.205... SERVICE Special Operations § 97.205 Repeater station. (a) Any amateur station licensed to a holder of a Technician, General, Advanced or Amateur Extra Class operator license may be a repeater. A holder of...

  19. 47 CFR 22.1015 - Repeater operation.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Repeater operation. 22.1015 Section 22.1015... Offshore Radiotelephone Service § 22.1015 Repeater operation. Offshore central stations may be used as repeater stations provided that the licensee is able to maintain control of the station, and in...

  20. ProtRepeatsDB: a database of amino acid repeats in genomes

    Directory of Open Access Journals (Sweden)

    Chauhan Virander S

    2006-07-01

    Full Text Available Abstract Background Genome wide and cross species comparisons of amino acid repeats is an intriguing problem in biology mainly due to the highly polymorphic nature and diverse functions of amino acid repeats. Innate protein repeats constitute vital functional and structural regions in proteins. Repeats are of great consequence in evolution of proteins, as evident from analysis of repeats in different organisms. In the post genomic era, availability of protein sequences encoded in different genomes provides a unique opportunity to perform large scale comparative studies of amino acid repeats. ProtRepeatsDB http://bioinfo.icgeb.res.in/repeats/ is a relational database of perfect and mismatch repeats, access to which is designed as a resource and collection of tools for detection and cross species comparisons of different types of amino acid repeats. Description ProtRepeatsDB (v1.2 consists of perfect as well as mismatch amino acid repeats in the protein sequences of 141 organisms, the genomes of which are now available. The web interface of ProtRepeatsDB consists of different tools to perform repeat s; based on protein IDs, organism name, repeat sequences, and keywords as in FASTA headers, size, frequency, gene ontology (GO annotation IDs and regular expressions (REGEXP describing repeats. These tools also allow formulation of a variety of simple, complex and logical queries to facilitate mining and large-scale cross-species comparisons of amino acid repeats. In addition to this, the database also contains sequence analysis tools to determine repeats in user input sequences. Conclusion ProtRepeatsDB is a multi-organism database of different types of amino acid repeats present in proteins. It integrates useful tools to perform genome wide queries for rapid screening and identification of amino acid repeats and facilitates comparative and evolutionary studies of the repeats. The database is useful for identification of species or organism specific

  1. Pentatricopeptide repeat proteins in plants.

    Science.gov (United States)

    Barkan, Alice; Small, Ian

    2014-01-01

    Pentatricopeptide repeat (PPR) proteins constitute one of the largest protein families in land plants, with more than 400 members in most species. Over the past decade, much has been learned about the molecular functions of these proteins, where they act in the cell, and what physiological roles they play during plant growth and development. A typical PPR protein is targeted to mitochondria or chloroplasts, binds one or several organellar transcripts, and influences their expression by altering RNA sequence, turnover, processing, or translation. Their combined action has profound effects on organelle biogenesis and function and, consequently, on photosynthesis, respiration, plant development, and environmental responses. Recent breakthroughs in understanding how PPR proteins recognize RNA sequences through modular base-specific contacts will help match proteins to potential binding sites and provide a pathway toward designing synthetic RNA-binding proteins aimed at desired targets.

  2. Two-dimensional quantum repeaters

    Science.gov (United States)

    Wallnöfer, J.; Zwerger, M.; Muschik, C.; Sangouard, N.; Dür, W.

    2016-11-01

    The endeavor to develop quantum networks gave rise to a rapidly developing field with far-reaching applications such as secure communication and the realization of distributed computing tasks. This ultimately calls for the creation of flexible multiuser structures that allow for quantum communication between arbitrary pairs of parties in the network and facilitate also multiuser applications. To address this challenge, we propose a two-dimensional quantum repeater architecture to establish long-distance entanglement shared between multiple communication partners in the presence of channel noise and imperfect local control operations. The scheme is based on the creation of self-similar multiqubit entanglement structures at growing scale, where variants of entanglement swapping and multiparty entanglement purification are combined to create high-fidelity entangled states. We show how such networks can be implemented using trapped ions in cavities.

  3. General benchmarks for quantum repeaters

    CERN Document Server

    Pirandola, Stefano

    2015-01-01

    Using a technique based on quantum teleportation, we simplify the most general adaptive protocols for key distribution, entanglement distillation and quantum communication over a wide class of quantum channels in arbitrary dimension. Thanks to this method, we bound the ultimate rates for secret key generation and quantum communication through single-mode Gaussian channels and several discrete-variable channels. In particular, we derive exact formulas for the two-way assisted capacities of the bosonic quantum-limited amplifier and the dephasing channel in arbitrary dimension, as well as the secret key capacity of the qubit erasure channel. Our results establish the limits of quantum communication with arbitrary systems and set the most general and precise benchmarks for testing quantum repeaters in both discrete- and continuous-variable settings.

  4. Hungarian repeat station survey, 2010

    Directory of Open Access Journals (Sweden)

    Péter Kovács

    2013-03-01

    Full Text Available The last Hungarian repeat station survey was completed between October 2010 and February 2011. Declination, inclination and the total field were observed using one-axial DMI fluxgate magnetometer mounted on Zeiss20A theodolite and GSM 19 Overhauser magnetometer. The magnetic elements of the sites were reduced to the epoch of 2010.5 on the basis of the continuous recordings of Tihany Geophysical Observatory. In stations located far from the reference observatory, the observations were carried out in the morning and afternoon in order to decrease the effect of the distant temporal correction. To further increase the accuracy, on-site dIdD variometer has also been installed near the Aggtelek station, in the Baradla cave, during the survey of the easternmost sites. The paper presents the technical details and the results of our last campaign. The improvement of the accuracy of the temporal reduction by the use of the local variometer is also reported.

  5. Quality control during repeated fryings

    Directory of Open Access Journals (Sweden)

    Cuesta, C.

    1998-08-01

    Full Text Available Most of the debate ¡s about how the slow or frequent turnover of fresh fat affects the deterioration, of fat used in frying. Then, the modification of different oils used in repeated fryings of potatoes without or with turnover of fresh oil, under similar frying conditions, was evaluated by two criteria: by measuring the total polar component isolated by column chromatography and by the evaluation of the specific compounds related to thermoxidative and hydrolytic alteration by High Performance Size Exclusion Chromatography (HPSEC. The results indicate that with frequent turnover of fresh oil, the critical level of 25% of polar material is rarely reached, and there are fewer problems with fat deterioration because the frying tended to increase the level of polar material and thermoxidative compounds (polymers and dimers of triglycerides and oxidized triglycerides in the fryer oil during the first fryings, followed by minor changes and a tendency to reach a near-steady state in successive fryings. However, in repeated frying of potatoes using a null turnover the alteration rate was higher being linear the relationship found between polar material or the different thermoxidative compounds and the number of fryings. On the other hand chemical reactions produced during deep-fat frying can be minimized by using proper oils. In addition the increased level of consumers awareness toward fat composition and its impact on human health could had an impact on the selection of fats for snacks and for industry. In this way monoenic fats are the most adequate from a nutritional point of view and for its oxidative stability during frying.

  6. Mouse repeated electroconvulsive seizure (ECS) does not reverse social stress effects but does induce behavioral and hippocampal changes relevant to electroconvulsive therapy (ECT) side-effects in the treatment of depression

    NARCIS (Netherlands)

    van Buel, Erin M; Sigrist, Hannes; Seifritz, Erich; Fikse, Lianne; Bosker, Fokko J; Schoevers, Robert A; Klein, Hans C; Pryce, Christopher R; Eisel, Ulrich Lm

    2017-01-01

    Electroconvulsive therapy (ECT) is an effective treatment for depression, but can have negative side effects including amnesia. The mechanisms of action underlying both the antidepressant and side effects of ECT are not well understood. An equivalent manipulation that is conducted in experimental

  7. Efficacy and tolerance of repeated oral doses of tolperisone hydrochloride in the treatment of painful reflex muscle spasm: results of a prospective placebo-controlled double-blind trial.

    Science.gov (United States)

    Pratzel, H G; Alken, R G; Ramm, S

    1996-10-01

    The efficacy and safety of oral tolperisone hydrochloride (Mydocalm) in the treatment of painful reflex muscle spasm was assessed in a prospective, randomized, double-blind, placebo-controlled trial. A total of 138 patients, aged between 20 and 75 years, with painful reflex muscle spasm associated with diseases of the spinal column or proximal joints were enrolled in eight rehabilitation centers. Patients were randomized to receive either 300 mg tolperisone hydrochloride or placebo for a period of 21 days. Both treatment groups recovered during the 3 weeks rehabilitation program. However, tolperisone hydrochloride proved to be significantly superior to placebo: the change score of the pressure pain threshold as the primary target parameter significantly increased during therapy with tolperisone hydrochloride (P = 0.03, valid-case-analysis) compared to the results obtained on placebo treatment. The overall assessment of efficacy by the patient also demonstrated significant differences in favor of tolperisone hydrochloride. Best results were seen in patients aged between 40 and 60 years with a history of complaints shorter than 1 year and with concomitant physical therapy. The evaluation of safety data, i.e., adverse events, biochemical and hematological laboratory parameters, demonstrated no differences between tolperisone hydrochloride and placebo. As a conclusion tolperisone hydrochloride represents an effective and safe treatment of painful reflex muscle spasm without the typical side effects of centrally active muscle relaxants.

  8. A Preliminary Study of the Effects of Repeated Massage on Hypothalamic–Pituitary–Adrenal and Immune Function in Healthy Individuals: A Study of Mechanisms of Action and Dosage

    Science.gov (United States)

    Schettler, Pamela; Bresee, Catherine

    2012-01-01

    Abstract Objectives This study gathers preliminary data about the biologic effects of repeated Swedish massage therapy compared to a light-touch control condition. Design The study design was a 5-week comparison of repeated Swedish massage and light touch on oxytocin (OT), arginine-vasopressin (AVP), adrenal corticotropin hormone (ACTH), cortisol (CORT), circulating phenotypic lymphocyte markers, and mitogen-stimulated cytokine function. Setting The setting was an outpatient research unit in an academic medical center. Participants The study subjects were medically and psychiatrically healthy young adults. Intervention The study comprised 45 minutes of Swedish massage or light touch, using highly specified and identical protocols, either weekly or twice weekly for 5 weeks. Outcome measures The outcome measures were mean differences between massage and light touch on OT, AVP, ACTH, CORT, lymphocyte markers, and cytokine levels. Results Compared to the touch control condition, weekly Swedish massage stimulated a sustained pattern of increased circulating phenotypic lymphocyte markers and decreased mitogen-stimulated cytokine production, similar to what was previously reported for a single massage session, while having minimal effect on hypothalamic–pituitary–adrenal function. Twice-weekly massage produced a different response pattern with increased OT levels, decreased AVP, and decreased CORT but little effect on circulating lymphocyte phenotypic markers and a slight increase in mitogen-stimulated interferon-γ, tumor necrosis factor-α, interleukin (IL)-1b and IL-2 levels, suggesting increased production of pro-inflammatory cytokines. Conclusions There are sustained cumulative biologic actions for the massage and touch interventions that persist for several days or a week, and these differ profoundly depending on the dosage (frequency) of sessions. Confirmatory studies in larger samples are needed. PMID:22775448

  9. Decomposition of Straw in Soil after Stepwise Repeated Additions

    DEFF Research Database (Denmark)

    Sørensen, Lasse Holst

    1979-01-01

    of laboratory incubation, following the first repeated application, by determination of the total amount of labelled C in the soils and labelled C in the soil amino acids. The overall pattern of decomposition was similar whether the soil was amended with one or with several successive applications. Four years...... after the first repeated addition of labelled straw the soils were subjected to a number of “stress” treatments: addition of unlabelled glucose, air-drying, oven-drying, grinding and fumigation with vapour of chloroform, respectively. The CO2 that developed during the first 10 days after the treatments...... accounted for 2.6% of the labelled C in the soil amended with one repeated addition, and 1.0% in the soil amended with 4 repeated additions. The increase in the evolution of labelled CO2-C caused by the stress treatments ranged from 0.3 to 1.7% of the labelled C in the soil: air-drying had the least effect...

  10. 成人特发性孤立性ACTH缺乏症三例临床分析并文献复习%Analysis of three patients with adult idiopathic isolated ACTH deficiency and literature review

    Institute of Scientific and Technical Information of China (English)

    郭清华; 陈康; 陆菊明; 母义明; 窦京涛; 吕朝晖; 巴建明; 李江源; 潘长玉

    2014-01-01

    Objective Adult idiopathic isolated ACTH deficiencv(AIIAD) is an underestimated disorder which is frequently misdiagnosed.In this paper,we presented 3 new cases of AIIAD and summarized the clinical characteristics by analyzing these cases and available literature for further understanding this disease.Methods Three cases of AIIAD in our hospital from 1998 to 2003 were retrospectively identified.Data of clinical features,laboratory findings,and response to treatment were collected.The clinical characteristics and pertinent literature were reviewed and analysed.Results These 3 cases of AIIAD aged 52-68 years old were misdiagnosed and incorrectly treated for 7 months to 4 years.All three cases presented the symptoms of fatigue and loss of weight at the onset,and were misdiagnosed as climacteric syndrome,thyroiditis,and gastrointestinal disease.The prevalence of AIIAD was very low,and it was thought to be an underestimated disorder.Through analyzing the 3 cases and literature review,the clinical features of this disease were summarized as follows:(1) Most patients were aged over 40 years and had no history of glucocorticoid medication.(2) Clinical presentations were insidious,with symptoms such as fatigue and weight loss.(3) Patients usually had no excessive pigmentation.(4) Hypogonadism in men and amenorrhea in women could be present.(5) Blood chemistry usually revealed hyponatremia but rarely hyperkalemia.(6) Blood lymphocytosis and eosinophilia were common.(7) Plasma ACTH and cortisol levels markedly decreased with normal secretion of other pituitary hormones.(8) High prevalence of thvroid disorder or positive anti-thyroid autoantibodv.(9) Usually the other accompanied autoimmune diseases might be ameliorated with glucocorticoid replacement.(10) MRI revealed no structural pituitary defects except for empty sella.(11) No evidence of infiltration,trauma,surgery,infection,and radiotherapy of the pituitary gland was found.Conclusions AIIAD is an unspecified and

  11. A Prospective Study of Psychiatric Comorbidity and Recidivism Among Repeat DUI Offenders

    OpenAIRE

    Nelson, Sarah E.; Belkin, Katerina; LaPlante, Debi A.; Bosworth, Leslie; Shaffer, Howard J.

    2015-01-01

    Psychiatric comorbidity has emerged as a key element distinguishing DUI offenders from others, and, in some cases, distinguishing repeat offenders from first-time offenders. This paper utilizes a prospective design to determine whether the comorbid disorders identified among repeat DUI offenders can predict recidivism. Seven hundred forty-three repeat DUI offenders were recruited from a two-week inpatient treatment program at which they received a standardized mental health assessment and fol...

  12. [Study of personal best value of peak expiratory flow in patients with asthma--comparison of the highest value of daily PEF under good control and the highest value of daily PEF obtained after using repeated inhaled beta2-agonist during high-dose inhaled steroid treatment].

    Science.gov (United States)

    Watanabe, Naoto; Makino, Sohei; Kihara, Norio; Fukuda, Takeshi

    2008-12-01

    In the guideline for asthma management, it is important to find the personal best value of peak expiratory flow (best PEF). Recently, we have substituted the highest value of PEF in daily life under good control (daily highest PEF) for the best PEF. In the present study, we considered whether the daily highest PEF could be used as the best PEF or not. Subjects were 30 asthmatics who were well controlled but whose baseline PEF values were less than 80 percent of predicted values. We compared the daily highest PEF and the highest of PEF obtained after repeated inhaled beta2-agonist (salbutamol MDI every 20 minutes three times). All subjects then received 1600 microg/day of beclomethasone dipropionate (BDP) for 4 to 8 weeks. We studied the effect of high-dose inhaled steroid treatment on each PEF value and compared the daily highest PEF and the highest PEF obtained after using repeated salbutamol MDI during high dose inhaled steroid therapy on the examination day again. The baseline PEF, daily highest PEF and the highest PEF obtained after salbutamol MDI were significantly less than the each values obtained after high-dose BDP. The best PEF value of them was the value obtained after repeated salbutamol MDI during high dose BDP. We suggest that the daily highest PEF under good control is not a substitute for best PEF because it changes according to the degree of improvement of airway inflammation. We recommend that a course of high dose inhaled steroid is effective in finding the best value of PEF for each individual with moderate asthma.

  13. Repeat urine cultures in children with urinary tract infection

    Directory of Open Access Journals (Sweden)

    Risky Vitria Prasetyo

    2012-05-01

    Full Text Available Background Urinary tract infections (UTIs are the second leading cause of infection in children, following respiratory tract infections. Repeat urine cultures after antibiotic treatment are routinely obtained in clinical practice to verify proof of bacteriologic cure. The American Academy of Pediatrics does not recommended repeat cultures, due to increased cost and discomfort to patients. Objective To determine the frequency of positive repeat urine cultures after 3 days of antibiotics in children with UTIs. Methods We conducted a retrospective study on children with UTIs who visited the Division of Pediatric Nephrology, Department of Child Health at Dr. Soetomo Hospital, Surabaya from January 2006 to December 2011. Results of repeat urine cultures were obtained after 3 days of antibiotic treatment. Descriptive statistics were used to analyze the data. Results Of the 779 pediatric UTI cases, repeat urine cultures were performed in 264 (33.9% cases. Of the 264 patients who comprised our study, there were similar numbers of girls and boys (50.4% vs. 49.6%, respectively. The mean age of patients was 43.9 (SD 1.59 months and 35.5% of subjects were aged under 1 year. In the initial urine cultures of our subjects, Escherichia coli was the most common organism found, with 92 cases (34.8%, compared to 58 cases (21.9% of Klebsiella pneumoniae and 29 cases (10.9% of Pseudomonas aeruginosa. Rrepeat urine cultures showed no bacterial growth in 168 cases (63.6%. Conclusion Mostly negative repeat urine cultures will probably obviate the need of this test in daily routine practice. [Paediatr Indones. 2012;52:170-4].

  14. Permanent upregulation of hippocampal mineralocorticoid receptors after neonatal administration of ACTH-(4-9) analog ORG 2766 in rats

    NARCIS (Netherlands)

    Nyakas, C; Felszeghy, K; Bohus, B; Luiten, PGM

    1997-01-01

    The development of brain corticosteroid receptors may be permanently modified by perinatal hormone treatments, in particular by hormones of the hypothalamic-pituitary-adrenal axis. Changes in binding characteristics of corticosteroid receptors were investigated in rats treated subcutaneously with 1

  15. Strengthening concept learning by repeated testing.

    Science.gov (United States)

    Wiklund-Hörnqvist, Carola; Jonsson, Bert; Nyberg, Lars

    2014-02-01

    The aim of this study was to examine whether repeated testing with feedback benefits learning compared to rereading of introductory psychology key-concepts in an educational context. The testing effect was examined immediately after practice, after 18 days, and at a five-week delay in a sample of undergraduate students (n = 83). The results revealed that repeated testing with feedback significantly enhanced learning compared to rereading at all delays, demonstrating that repeated retrieval enhances retention compared to repeated encoding in the short- and the long-term. In addition, the effect of repeated testing was beneficial for students irrespectively of working memory capacity. It is argued that teaching methods involving repeated retrieval are important to consider by the educational system.

  16. A Comparison of Two Reading Fluency Methods: Repeated Readings to a Fluency Criterion and Interval Sprinting

    Science.gov (United States)

    Kostewicz, Douglas E.; Kubina, Richard M., Jr.

    2010-01-01

    Teachers have used the method of repeated readings to build oral reading fluency in students with and without special needs. A new fluency building intervention called interval sprinting uses shorter timing intervals (i.e., sprints) across a passage. This study used an alternating treatment design to compare repeated readings and interval…

  17. Repeat concussions in the national football league.

    Science.gov (United States)

    Casson, Ira R; Viano, David C; Powell, John W; Pellman, Elliot J

    2011-01-01

    Repeat concussion is an important issue in the National Football League (NFL). An initial description of repeat injuries was published for 6 years (1996-2001). The characteristics and frequency of repeat concussion in the NFL have not changed in the subsequent 6 years (2002-2007). Case control. From 1996 to 2007, concussions were reported using a standardized form documenting signs and symptoms, loss of consciousness and medical action taken. Data on repeat concussions were analyzed for the 12 years and compared between the 2 periods. In 2002-2007, 152 players had repeat concussions (vs 160 in 1996-2001); 44 had 3+ head injuries (vs 52). The positions most often associated with repeat concussion in 2002-2007 were the defensive secondary, kick unit, running back, and linebacker. The odds for repeat concussion were elevated for wide receivers, tight ends, and linebackers but lower than in the earlier period. During 2002-2007, over half of players with repeat concussion were removed from play, and fewer immediately returned (vs 1996-2001). The average duration between concussions was 1.25 years for 2002-2007 and 1.65 years for the 12-year period. Over 12 years, 7.6% of all repeat concussions occurred within 2 weeks of the prior concussion. The defensive secondary, kick unit, running back, and linebacker have the highest incidence of repeat concussion. During 2002-2007, more than half of players with repeat concussion were removed from play, and only a fraction immediately returned. Although concussion was managed more conservatively by team physicians in the recent 6 years, repeat concussions occurred at similar rates during both periods.

  18. Automated quality checks on repeat prescribing.

    OpenAIRE

    Rogers, Jeremy E; Wroe, Christopher J; Roberts, Angus; Swallow, Angela; Stables, David; Cantrill, Judith A; Rector, Alan L.

    2003-01-01

    BACKGROUND: Good clinical practice in primary care includes periodic review of repeat prescriptions. Markers of prescriptions that may need review have been described, but manually checking all repeat prescriptions against the markers would be impractical. AIM: To investigate the feasibility of computerising the application of repeat prescribing quality checks to electronic patient records in United Kingdom (UK) primary care. DESIGN OF STUDY: Software performance test against benchmark manual...

  19. Short Tandem Repeat DNA Internet Database

    Science.gov (United States)

    SRD 130 Short Tandem Repeat DNA Internet Database (Web, free access)   Short Tandem Repeat DNA Internet Database is intended to benefit research and application of short tandem repeat DNA markers for human identity testing. Facts and sequence information on each STR system, population data, commonly used multiplex STR systems, PCR primers and conditions, and a review of various technologies for analysis of STR alleles have been included.

  20. Síndrome de Guillain-Barré: a propósito de três casos, sendo um tratado pelo ACTH

    Directory of Open Access Journals (Sweden)

    José Lamartine de Assis

    1953-06-01

    Full Text Available O autor tece considerações sôbre a posição atual da síndrome de Guillain-Barré em face dos progressos recentes da virulogia, da experimentação e da terapêutica. Ao mesmo tempo procura justificar a aproximação daquela síndrome do grupo das afecçÕes desmielinizantes do sistema nervoso, com base nas observações próprias e naquelas encontradas na literatura; estas são de ordem clínica, anátomo-clínica e terapêutica, enquanto as primeiras são de ordem clínica e terapêutica. Dos três casos apresentados, os dois primeiros eram crônicos e com seqüelas irreversíveis, enquanto o terceiro era agudo e foi tratado pelo ACTH na dose de 15 mg em sôro glicosado isotônico, em gôta a gôta, por via intravenosa, durante 8 horas, diàriamente. Nos dois primeiros casos foi conseguida a recuperação da marcha sem apôio, sendo que, no primeiro, conseguiu-se, também, a recuperação satisfatória da movimentação ativa dos membros superiores, permitindo ao enfêrmo desincumbir-se sòzinho das suas atividades habituais indispensáveis. No caso 1 havia edema de papila bilateral que regrediu muito lentamente, além de bloqueio parcial transitório do canal raquidiano com líquor xantocrômico ; no caso 2 era de notar uma síndrome cordonal posterior dominante; no caso 3 havia, como fato digno de realce, comprometimento do miocárdio. Neste caso a remissão da sintomatologia clínica e a melhora progressiva das alterações eletrocardiográficas coincidiram com o emprêgo do ACTH.

  1. Fatal Renal Failure in a Spinal Cord Injury Patient with Vesicoureteric Reflux Who Underwent Repeated Ureteric Reimplantations Unsuccessfully: Treatment Should Focus on Abolition of High Intravesical Pressures rather than Surgical Correction of Reflux

    Directory of Open Access Journals (Sweden)

    Subramanian Vaidyanathan

    2012-01-01

    Full Text Available A 29-year-old man developed paraplegia at T-10 level due to road traffic accident in 1972. Both kidneys were normal and showed good function on intravenous urography. Division of external urethral sphincter was performed in 1973. In 1974, cystogram showed retrograde filling of left renal tract, which was hydronephrotic. Left ureteric reimplantation was performed. Following surgery, cystogram revealed marked retrograde filling of left renal tract as before. Penile sheath drainage was continued. In 1981, intravenous urography revealed bilateral severe hydronephrosis. Left ureteric reimplantation was performed again in 1983. Blood pressure was 220/140 mm Hg; this patient was prescribed atenolol. Cystogram showed gross left vesicoureteral reflux. Intermittent catheterisation was commenced in 2001. In 2007, proteinuria was 860 mg/day. This patient developed progressive renal failure and expired in 2012. In a spinal cord injury patient with vesicoureteral reflux, the treatment should focus on abolition of high intravesical pressures rather than surgical correction of vesicoureteric reflux. Detrusor hyperactivity and high intravesical pressures are the basic causes for vesicoureteral reflux in spinal cord injury patients. Therefore, it is important to manage spinal cord injury patients with neuropathic bladder by intermittent catheterisations along with antimuscarinic drug therapy in order to abolish high detrusor pressures and prevent vesicoureteral reflux. Angiotensin-converting enzyme inhibitors or angiotensin-receptor-blocking agents should be prescribed even in the absence of hypertension when a spinal cord injury patient develops vesicoureteral reflux and proteinuria.

  2. Repeated Nrf2 stimulation using sulforaphane protects fibroblasts from ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Mathew, Sherin T.; Bergström, Petra; Hammarsten, Ola, E-mail: ola.hammarsten@clinchem.gu.se

    2014-05-01

    Most of the cytotoxicity induced by ionizing radiation is mediated by radical-induced DNA double-strand breaks. Cellular protection from free radicals can be stimulated several fold by sulforaphane-mediated activation of the transcription factor Nrf2 that regulates more than 50 genes involved in the detoxification of reactive substances and radicals. Here, we report that repeated sulforaphane treatment increases radioresistance in primary human skin fibroblasts. Cells were either treated with sulforaphane for four hours once or with four-hour treatments repeatedly for three consecutive days prior to radiation exposure. Fibroblasts exposed to repeated-sulforaphane treatment showed a more pronounced dose-dependent induction of Nrf2-regulated mRNA and reduced amount of radiation-induced free radicals compared with cells treated once with sulforaphane. In addition, radiation- induced DNA double-strand breaks measured by gamma-H2AX foci were attenuated following repeated sulforaphane treatment. As a result, cellular protection from ionizing radiation measured by the 5-ethynyl-2′-deoxyuridine (EdU) assay was increased, specifically in cells exposed to repeated sulforaphane treatment. Sulforaphane treatment was unable to protect Nrf2 knockout mouse embryonic fibroblasts, indicating that the sulforaphane-induced radioprotection was Nrf2-dependent. Moreover, radioprotection by repeated sulforaphane treatment was dose-dependent with an optimal effect at 10 uM, whereas both lower and higher concentrations resulted in lower levels of radioprotection. Our data indicate that the Nrf2 system can be trained to provide further protection from radical damage. - Highlights: • Repeated treatment with sulforaphane protects fibroblasts from ionizing radiation • Repeated sulforaphane treatment attenuates radiation induced ROS and DNA damage • Sulforaphane mediated protection is Nrf2 dependent.

  3. Modelling repeatedly flaring delta-sunspots

    CERN Document Server

    Chatterjee, Piyali; Carlsson, Mats

    2016-01-01

    Active regions (AR) appearing on the surface of the Sun are classified into $\\alpha$, $\\beta$, $\\gamma$, and $\\delta$ by the rules of the Mount Wilson Observatory, California on the basis of their topological complexity. Amongst these, the $\\delta$-sunspots are known to be super-active and produce the most X-ray flares. Here, we present results from a simulation of the Sun by mimicking the upper layers and the corona, but starting at a more primitive stage than any earlier treatment. We find that this initial state consisting of only a thin sub-photospheric magnetic sheet breaks into multiple flux-tubes which evolve into a colliding-merging system of spots of opposite polarity upon surface emergence, similar to those often seen on the Sun. The simulation goes on to produce many exotic $\\delta$-sunspot associated phenomena: repeated flaring in the range of typical solar flare energy release and ejective helical flux ropes with embedded cool-dense plasma filaments resembling solar coronal mass ejections.

  4. The measurement of glucocorticoid concentrations in the serum and faeces of captive African elephants (Loxodonta africana after ACTH stimulation : research communication

    Directory of Open Access Journals (Sweden)

    S.K. Stead

    2000-07-01

    Full Text Available Conventionally, the assessment of adrenal responses to stress relies on blood sample collection. However, blood collection from animals is impossible without restraint or immobilisation that influences results. This study was undertaken to validate recently established enzyme immunoassays that measure faecal glucocorticoid metabolites in elephants, and to perform a preliminary investigation into the biological relevance of this non-invasive method for use in assessing the degree of stress in this species. Four juvenile African elephants were injected i.m. with 2.15 mg synthetic adrenocorticotrophic hormone (Synacthén, Novartis, Switzerland. Blood and faecal samples were collected over 4 h and 7 d respectively. Concentrations of serum cortisol and faecal cortisol metabolites were determined using immunoassay. Variability of basal and peak values in blood and faeces was observed among the elephants. After ACTH injection, serum cortisol concentrations increased by 400-700 %. An 11-oxoaetiocholanolone enzyme immunoassay (EIA proved best suited to measure cortisol metabolites (11,17-dioxoandrostanes when compared to a cortisol and corticosterone EIA in faecal samples. Concentrations of faecal 11,17-dioxoandrostanes increased by 570-1070 %, reaching peak levels after 20.0-25.5 h. Greater levels of glucocorticoid metabolites were measured in faecal samples from elephants kept in small enclosures compared to levels in the faeces of animals ranging over a larger area. The results of this preliminary study suggest that non-invasive faecal monitoring of glucocorticoid metabolites is useful in investigating adrenal activity in African elephants.

  5. Complicações neurológicas no decurso de tratamento pelo ACTH: A propósito de um caso de agnosia visual

    Directory of Open Access Journals (Sweden)

    O. Freitas Julião

    1953-12-01

    Full Text Available Os autores relatam a observação de um menino de 8 anos de idade, portador de síndrome nefrótica tratada pelo ACTH e que apresentou uma série de graves distúrbios neurológicos conseqüentes a uma crise hipertensiva (a pressão arterial elevou-se a 220-130 mm Hg, ocorrida por ocasião desse tratamento. Manifestando-se inicialmente por cefaléia intensa, depois por crise convulsiva generalizada, à qual se seguiu estado comatoso e posteriormente síndrome confusional, a encefalopatía hipertensiva condicionou, como seqüelas neurológicas mais importantes, distúrbios visuais. Êstes, que se apresentaram, a princípio, sob a forma de amaurose total, assumiram depois o aspecto de distúrbios da percepção, tipo agnóstico, persistentes ainda hoje. A agnosia visual refere-se aos objetos, pessoas, figuras simbólicas e côres.

  6. Increased anxiety induced by listening to unpleasant music during stress exposure is associated with reduced blood pressure and ACTH responses in healthy men.

    Science.gov (United States)

    Jezova, Daniela; Hlavacova, Natasa; Makatsori, Aikaterini; Duncko, Roman; Loder, Ingrid; Hinghofer-Szalkay, Helmut

    2013-01-01

    The relationship between anxiety and the neuroendocrine response to stress stimuli is still not fully understood. The aim of this study was to evaluate the contribution of an acute increase in state anxiety to neuroendocrine activation under stress conditions. To do so, it was necessary to find a stress condition of the same character and intensity with and without a rise in state anxiety. We decided to examine the effects of listening to music on anxiety and to apply a new methodological approach. A group of 14 healthy volunteers participated in a counterbalanced crossover design study. The stress procedure consisted of mental (Stroop test, mental arithmetic) and physical (handgrip exercise) tasks combined with listening to music played forward (pleasant) or backwards (unpleasant). The results confirmed our hypothesis, namely the condition with listening to unpleasant music was anxiogenic, while the other was not. In case of increased state anxiety, the rise in ACTH concentrations in response to mental challenge and the increase in systolic blood pressure induced by handgrip exercise was reduced compared to the situation with unchanged anxiety. Concentrations of testosterone, oxytocin, vasopressin and aldosterone were slightly increased in response to the stress paradigm accompanied with increased anxiety. In conclusion, the present data demonstrate that an acute increase in state anxiety contributes to neuroendocrine activation under stress conditions. Moreover, the results show that listening to music may both positively and negatively influence the perception of stress and the level of anxiety, which might have functional consequences.

  7. Semax, an ACTH4-10 peptide analog with high affinity for copper(II) ion and protective ability against metal induced cell toxicity.

    Science.gov (United States)

    Tabbì, Giovanni; Magrì, Antonio; Giuffrida, Alessandro; Lanza, Valeria; Pappalardo, Giuseppe; Naletova, Irina; Nicoletti, Vincenzo Giuseppe; Attanasio, Francesco; Rizzarelli, Enrico

    2015-01-01

    Heptapeptide Semax, encompassing the sequence 4-7 of N-terminal domain of the adrenocorticotropic hormone (ACTH) and a C-terminal Pro-Gly-Pro tripeptide, belongs to a short regulatory peptides family. This compound has been found to affect learning processes and to exert marked neuroprotective activities on cognitive brain functions. Dys-homeostasis of metal ions is involved in several neurodegenerative disorders and growing evidences have showed that brain is a specialized organ able to concentrate metal ions. In this work, the metal binding ability and protective activity of Semax and its metal complexes were studied. The equilibrium study clearly demonstrated the presence of three complex species. Two minor species [CuL] and [CuLH-1]- co-exist together with the [CuLH-2]2- in the pH range from 3.6 to 5. From pH5 the [CuLH-2]2- species becomes predominant with the donor atoms around copper arranged in a 4N planar coordination mode. Noteworthy, a reduced copper induced cytotoxicity was observed in the presence of Semax by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay on a SHSY5Y neuroblastoma and RBE4 endothelial cell lines.

  8. Proteolytic processing of pro-ACTH/endorphin begins in the Golgi complex of pituitary corticotropes and AtT-20 cells.

    Science.gov (United States)

    Schnabel, E; Mains, R E; Farquhar, M G

    1989-08-01

    The intracellular sites where proteolytic processing of pro-ACTH/endorphin or POMC take place have not yet been reliably identified. We have used affinity-purified antisera that recognize only the products of POMC processing and immunoelectron microscopy to identify the compartments of rat pituitary corticotropes and mouse AtT-20 cells in which cleavage occurs. Immunoperoxidase labeling of cryostat sections and immunogold labeling of ultrathin frozen sections were used for localization of the processing sites. By both procedures we detected processed peptides in Golgi cisternae and secretion granules. Within the Golgi, labeling was limited to the last or transmost cisterna and was most concentrated in its dilated rims which contain condensing secretory protein. No labeling of other Golgi cisternae was seen. All Golgi cisternae were labeled, however, when antisera that recognize unprocessed POMC were used for immunolabeling. We conclude that in AtT-20 and rat pituitary cells: 1) processing of POMC through at least two endo- and exoproteolytic cleavage steps and alpha-amidation of joining peptide begin in the trans Golgi subcompartment; 2) no detectable processing takes place before POMC reaches the trans Golgi cisterna; and 3) this Golgi cisterna as well as secretion granules contain the active enzymes necessary for proteolytic processing and alpha-amidation.

  9. Repeatability & Workability Evaluation of SIGMOD 2009

    KAUST Repository

    Manegold, Stefan

    2010-12-15

    SIGMOD 2008 was the first database conference that offered to test submitters\\' programs against their data to verify the repeatability of the experiments published [1]. Given the positive feedback concerning the SIGMOD 2008 repeatability initiative, SIGMOD 2009 modified and expanded the initiative with a workability assessment.

  10. 19 CFR 10.474 - Repeated false or unsupported preference claims.

    Science.gov (United States)

    2010-04-01

    ... States-Chile Free Trade Agreement Origin Verifications and Determinations § 10.474 Repeated false or... qualifies as originating, CBP may deny subsequent claims for preferential tariff treatment on...

  11. Reward modulation of contextual cueing: Repeated context overshadows repeated target location.

    Science.gov (United States)

    Sharifian, Fariba; Contier, Oliver; Preuschhof, Claudia; Pollmann, Stefan

    2017-08-07

    Contextual cueing can be enhanced by reward. However, there is a debate if reward is associated with the repeated target-distractor configurations or with the repeated target locations that occur in both repeated and new displays. Based on neuroimaging evidence, we hypothesized that reward becomes associated with the target location only in new displays, but not in repeated displays, where the repeated target location is overshadowed by the more salient repeated target-distractor configuration. To test this hypothesis, we varied the reward value associated with the same target location in repeated and new displays. The results confirmed the overshadowing hypothesis in that search facilitation in repeated target-distractor configurations was modulated by the variable value associated with the target location. This effect was observed mainly in early learning.

  12. Childhood experiences and repeated suicidal behavior

    DEFF Research Database (Denmark)

    Krarup, Gertrud; Nielsen, Bent; Rask, P

    1991-01-01

    The aim of this study was to elucidate the influence of various events in childhood on suicidal behavior in adult age. For this purpose, 99 patients admitted to the Department of Psychiatry of Odense University Hospital after making a suicide attempt were followed for 5 years, to register repeated...... suicidal behavior. The results showed that three fourths of the patients attempted suicide more than once (62% nonfatal and 14% fatal outcome). The sex distribution was about the same among the first-evers as among the repeaters. Most repeaters were younger people in their twenties and thirties......, and the first-evers on average were past the age of 40. Somewhat unexpectedly, significantly more repeaters than first-evers had grown up with both their parents. However, the results also showed that significantly more repeaters than first-evers had had an unhappy childhood. This indicates...

  13. UK 2009-2010 repeat station report

    Directory of Open Access Journals (Sweden)

    Thomas J.G. Shanahan

    2013-03-01

    Full Text Available The British Geological Survey is responsible for conducting the UK geomagnetic repeat station programme. Measurements made at the UK repeat station sites are used in conjunction with the three UK magnetic observatories: Hartland, Eskdalemuir and Lerwick, to produce a regional model of the local field each year. The UK network of repeat stations comprises 41 stations which are occupied at approximately 3-4 year intervals. Practices for conducting repeat station measurements continue to evolve as advances are made in survey instrumentation and as the usage of the data continues to change. Here, a summary of the 2009 and 2010 UK repeat station surveys is presented, highlighting the measurement process and techniques, density of network, reduction process and recent results.

  14. A Prospective Study of Psychiatric Comorbidity and Recidivism Among Repeat DUI Offenders.

    Science.gov (United States)

    Nelson, Sarah E; Belkin, Katerina; LaPlante, Debi A; Bosworth, Leslie; Shaffer, Howard J

    2015-04-13

    Psychiatric comorbidity has emerged as a key element distinguishing DUI offenders from others, and, in some cases, distinguishing repeat offenders from first-time offenders. This paper utilizes a prospective design to determine whether the comorbid disorders identified among repeat DUI offenders can predict recidivism. Seven hundred forty-three repeat DUI offenders were recruited from a two-week inpatient treatment program at which they received a standardized mental health assessment and followed across five years post-treatment to track DUI offense, motor vehicle-related offenses, and general criminal offenses. Psychiatric comorbidity, though it did not predict DUI recidivism specifically, predicted criminal re-offense more generally. In addition, there was a specific relationship between lifetime attention deficit disorder and repeated motor vehicle-related offenses. These findings suggest that for many repeat offenders, DUI is one outlet in a constellation of criminal behavior, and that psychiatric comorbidity increases vulnerability for criminal re-offense.

  15. Temozolomide treatment in aggressive pituitary tumors and pituitary carcinomas: a French multicenter experience.

    Science.gov (United States)

    Raverot, Gérald; Sturm, Nathalie; de Fraipont, Florence; Muller, Marie; Salenave, Sylvie; Caron, Philippe; Chabre, Olivier; Chanson, Philippe; Cortet-Rudelli, Christine; Assaker, Richard; Dufour, Henry; Gaillard, Stephan; François, Patrick; Jouanneau, Emmanuel; Passagia, Jean-Guy; Bernier, Michèle; Cornélius, Aurélie; Figarella-Branger, Dominique; Trouillas, Jacqueline; Borson-Chazot, Françoise; Brue, Thierry

    2010-10-01

    To date only 18 patients with aggressive pituitary tumors or carcinomas treated with temozolomide have been reported. Increased expression of O6-methylguanine-DNA-methyltranferase (MGMT) has been suggested to predict resistance to temozolomide. The objective of the study was to describe the antitumoral efficacy and toxicity of temozolomide in patients with aggressive pituitary tumors or carcinomas and evaluate the possible prognostic value of MGMT promoter methylation and protein expression. Eight patients, five with pituitary carcinomas (three prolactin (PRL) and two ACTH) and three with aggressive pituitary tumors (one PRL and two ACTH), all treated with temozolomide administered orally for four to 24 cycles, were included in our French multicenter study. MGMT expression was assessed by immunohistochemistry and MGMT promoter methylation by pyrosequencing. Three of the eight patients (two ACTH adenomas and one PRL carcinoma) responded to temozolomide as demonstrated by significant tumor shrinkage and reduced hormone secretion. Three cycles of temozolomide were sufficient to identify treatment-responsive patients. Additional cycles did not improve treatment efficacy in those not responding, even when associated with carboplatin and vepeside. MGMT expression did not predict tumoral response to temozolomide because it was positive in one responder and negative in two nonresponders. Similarly, MGMT promoter methylation (three of seven tumors) did not predict clinical response. Toxicity remained mild in all patients. Temozolomide treatment may be an effective option for some aggressive pituitary tumors or carcinomas. Response to a trial of three cycles of treatment seems sufficient to identify responders and more reliable than patient MGMT status.

  16. Hiperplasia adrenal congênita: dosagem da 17-hidroxiprogesterona basal para seleção e casos para realização do teste de estímulo com ACTH sintético Congenital adrenal hyperplasia: measurement of basal 17-hydroxyprogesterone as a screening test to select patients for the synthetic ACTH provocative test

    Directory of Open Access Journals (Sweden)

    Lúcia Helena Coelho Nóbrega

    2004-05-01

    Full Text Available OBJETIVOS: avaliar se os níveis de 17-hidroxiprogesterona podem predizer o resultado do teste de estímulo como diagnóstico de hiperplasia adrenal congênita, forma tardia. MÉTODOS: foram incluídas no estudo e avaliadas retrospectivamente 122 pacientes com suspeita clínica de hiperplasia adrenal congênita forma tardia. Essa suspeita clínica incluía sinais e/ou sintomas de hiperandrogenismo (hirsutismo, acne, pele oleosa, irregularidade menstrual, etc.. Todas as pacientes foram submetidas ao teste de estímulo da adrenal com ACTH sintético 0,25 mg (Synacthen®. Após repouso de 60 minutos as amostras foram colhidas nos tempos basal e 60 minutos após a administração de 0,25 mg de ACTH sintético para dosagem de 17-hidroxiprogesterona, sendo mantido o acesso venoso com catéter heparinizado. Foi utilizado o método de radioimunoensaio para realizar as dosagens séricas da 17-hidroxiprogesterona. A sensibilidade e a especificidade da 17-hidroxiprogesterona basal como teste de rastreamento para hiperplasia adrenal congênita foram medidas, avaliando vários pontos de corte. Curvas ROC foram feitas para analisar a performance do teste, utilizando o software Medcalc®. RESULTADOS: a análise por curva ROC mostrou um ponto de corte de 181 ng/dl acima do qual dever-se-ia realizar o teste de estímulo, bem próximo a 200 ng/dl, mais comumente aceito pela literatura. Níveis séricos da 17-hidroxiprogesterona mais altos que 200 ng/dl têm valores preditivo positivo e negativo de 75% e 100% e acurácia de 98,4% como diagnóstico de hiperplasia adrenal não-clássica. CONCLUSÕES: considerando os dados, sugerimos que pacientes com hiperandrogenismo clínico devam iniciar a investigação com 17-hidroxiprogesterona basal e, caso esta se mostre acima de 181 ng/dl, sigam a investigação com o teste de estímulo com ACTH sintético.INTRODUCTION: adrenal hyperplasia is a common genetic disorder and 95% of the cases are due to a 21-hydroxylase

  17. Evidence from studies on co-cultures of TtT/GF and AtT20 cells that Annexin 1 acts as a paracrine or juxtacrine mediator of the early inhibitory effects of glucocorticoids on ACTH release.

    Science.gov (United States)

    Tierney, T; Christian, H C; Morris, J F; Solito, E; Buckingham, J C

    2003-12-01

    Annexin 1 (ANXA1) is a key mediator of the inhibitory effects of glucocorticoids on adrenocorticotropic hormone (ACTH) release, which develop within 1-2 h of a steroid challenge. Our previous studies, which showed that (i) ANXA1 is expressed principally by the nonsecretory folliculo-stellate cells in the pituitary gland; (ii) glucocorticoids cause the exportation of ANXA1 from these cells; and (iii) corticotrophs express specific ANXA1 binding sites, led us to propose that ANXA1 serves as a paracrine or juxtacrine mediator of glucocorticoids. To address this hypothesis, we examined ANXA1-dependent glucocorticoid actions in co-cultures of murine corticotroph (AtT20 clone D1) and folliculo-stellate (TtT/GF) cell lines. ANXA1 mRNA and protein were found in abundance in TtT/GF cells but neither was detectable in the AtT20 cells. AtT20 cells (alone and in co-culture with TtT/GF cells) responded to corticotropin-releasing hormone (CRH) (0.1-1 micro m) with increased ACTH release. The CRH-stimulated release of ACTH from AtT20 cells cultured alone was unaffected by preincubation with dexamethasone (Dex, 100 nm); by contrast, in co-cultures of AtT20 and TtT/GF cells, the steroid readily inhibited the secretory response to CRH. The effects of Dex on ACTH release were mimicked by N-terminal ANXA1 fragments (ANXA1Ac2-26, 2 micro g/ml and ANXA11-188, 0.1 ng/ml) and reversed by mifepristone (1 micro m) and by an antisense oligodeoxynucleotide (ODN) to ANXA1 (50 nm) but not by control ODNs. The antisense ODN also specifically blocked the Dex-induced externalization of ANXA1 from TtT/GF cells. Immunofluorescence imaging of the co-cultures localized the exported protein to the vicinity of the AtT20 cells and identified ANXA1 binding sites on these cells. These results provide functional and histological evidence to support our premise that the early inhibitory effects of glucocorticoids on ACTH release are dependent upon paracrine/juxtacrine actions of ANXA1 derived from folliculo

  18. Improving Oral Reading Fluency through Response Opportunities: A Comparison of Phrase Drill Error Correction with Repeated Readings

    Science.gov (United States)

    Begeny, John C.; Daly, Edward J., III; Valleley, Rachel J.

    2006-01-01

    The purpose of this study was to compare two oral reading fluency treatments (repeated readings and phrase drill error correction) which differ in the way they prompt student responding. Repeated readings (RR) and phrase drill (PD) error correction were alternated with a baseline and a reward condition within an alternating treatments design with…

  19. 亚硒酸钠对实验性胃癌大鼠垂体 ACTH、GH和 TSH细胞的影响%Effect of sodium selenite on ACTH, GH and TSH positive cells of experimental gastric cancer rat pituitary

    Institute of Scientific and Technical Information of China (English)

    陈瑶瑶; 唐军民; 唐岩; 柯嘉; 毛卓; 孙红亚; 甄昱; 苏衍萍

    2014-01-01

    metaplasia in selenium group was remarkably higher than that in experiment control group (P<0. 05). ACTH, GH and TSH positive cells were labeled using immunohistochemical method. The mean optical densities (MOD) of ACTH pos-itive cells in MNNG experiment control group, MNNG low-selenium group, and MNNG high-selenium group were 0. 0623±0. 02024, 0. 0680±0. 08948, and 0. 0574±0. 01949 respectively;the MOD of GH positive cells were 0. 0380±0. 01311, 0. 0415±0. 01559 and 0. 0293±0. 01323 respectively;and the MOD of TSH positive cells were 0. 0943±0. 18606, 0. 1272±0. 05389 and 0. 1044±0. 04166 respectively. Conclusions:During the carcinogenesis of gastric cancer in experimental animal models, the reactivity of ACTH, GH, TSH positive cells located in pars distalis of pituitary increase after the treatment of sodium selenite in a low dosage;however, a high dosage of sodium selenite exerts opposite effects.

  20. Differential regulation of parvocellular neuronal activity in the paraventricular nucleus of the hypothalamus following single vs. repeated episodes of water restriction-induced drinking.

    Science.gov (United States)

    Arnhold, Michelle M; Wotus, Cheryl; Engeland, William C

    2007-07-01

    Acute activation of the hypothalamic-pituitary-adrenal (HPA) axis releases glucocorticoids to maintain homeostasis, whereas prolonged exposure to elevated glucocorticoids has deleterious effects. Due to the potential benefits of limiting stress-induced glucocorticoid secretion, the present study uses drinking in dehydrated rats as a model to delineate mechanisms mobilized to rapidly inhibit HPA activity during stress. Using Fos expression as an indicator of neuronal activation, the effect of a single or repeated episode of dehydration-induced drinking on the activity of magnocellular and parvocellular neurons in the paraventricular nucleus (PVN) of the hypothalamus was examined. Adult male rats underwent a single episode or repeated (six) episodes of water restriction and were sacrificed before or after drinking water in the AM. Plasma osmolality, vasopressin (AVP), adrenocorticotropic hormone (ACTH) and corticosterone were elevated by water restriction and reduced after drinking in both models. Fos expression was elevated in AVP-positive magnocellular PVN neurons and AVP- and corticotropin releasing hormone (CRH)-positive parvocellular PVN neurons after water restriction. Fos expression was reduced in magnocellular AVP neurons after both models of restriction-induced drinking. In contrast, Fos expression did not change in AVP and CRH parvocellular neurons after a single episode of restriction-induced drinking, but was reduced after repeated episodes of restriction-induced drinking. These data indicate that drinking-induced decreases in glucocorticoids in dehydrated rats involve multiple factors including reduction in magnocellular release of vasopressin and reduction in parvocellular neuronal activity. The differential inhibition of PVN parvocellular neurons after repeated rehydration may reflect a conditioned response to repeated stress reduction.

  1. Differential regulation of parvocellular neuronal activity in the paraventricular nucleus of the hypothalamus following single versus repeated episodes of water restriction-induced drinking

    Science.gov (United States)

    Arnhold, Michelle M.; Wotus, Cheryl; Engeland, William C.

    2007-01-01

    Acute activation of the hypothalamic-pituitary-adrenal (HPA) axis releases glucocorticoids to maintain homeostasis, whereas prolonged exposure to elevated glucocorticoids has deleterious effects. Due to the potential benefits of limiting stress-induced glucocorticoid secretion, the present study uses drinking in dehydrated rats as a model to delineate mechanisms mobilized to rapidly inhibit HPA activity during stress. Using Fos expression as an indicator of neuronal activation, the effect of a single or repeated episode of dehydration-induced drinking on the activity of magnocellular and parvocellular neurons in the paraventricular nucleus (PVN) of the hypothalamus was examined. Adult male rats underwent a single episode or repeated (six) episodes of water restriction and were sacrificed before or after drinking water in the AM. Plasma osmolality, vasopressin (AVP), adrenocorticotropic hormone (ACTH) and corticosterone were elevated by water restriction and reduced after drinking in both models. Fos expression was elevated in AVP-positive magnocellular PVN neurons and AVP- and corticotropin releasing hormone (CRH)-positive parvocellular PVN neurons after water restriction. Fos expression was reduced in magnocellular AVP neurons after both models of restriction-induced drinking. In contrast, Fos expression did not change in AVP and CRH parvocellular neurons after a single episode of restriction-induced drinking, but was reduced after repeated episodes of restriction-induced drinking. These data indicate that drinking-induced decreases in glucocorticoids in dehydrated rats involve multiple factors including reduction in magnocellular release of vasopressin and reduction in parvocellular neuronal activity. The differential inhibition of PVN parvocellular neurons after repeated rehydration may reflect a conditioned response to repeated stress reduction. PMID:17537436

  2. Strabismus: Botox Treatment

    Medline Plus

    Full Text Available ... 4 months. However, after repeat treatments the effect can be longer lasting. The reason why the effect ... restored. In adults and cooperative teenagers Botox treatment can be carried out in clinic using anesthetic drops ...

  3. Strabismus: Botox Treatment

    Medline Plus

    Full Text Available ... treatment. The muscle will normally regain its normal function after 3-4 months. However, after repeat treatments ... 2017 Stargardt Disease (STGD) Aug 21, 2017 Surgical Management of Strabismus Jun 10, 2017 Binocular Vision and ...

  4. Mid-Childhood Bone Mass After Exposure to Repeat Doses of Antenatal Glucocorticoids: A Randomized Trial.

    Science.gov (United States)

    McKinlay, Christopher J D; Cutfield, Wayne S; Battin, Malcolm R; Dalziel, Stuart R; Crowther, Caroline A; Harding, Jane E

    2017-05-01

    Treatment of women at risk for preterm birth with repeat doses of glucocorticoids reduces neonatal morbidity, but could have adverse effects on skeletal development. We assessed whether exposure to repeat antenatal betamethasone alters bone mass in children whose mothers participated in the Australasian Collaborative Trial of Repeat Doses of Corticosteroids. Women were randomized to a single dose of betamethasone or placebo, ≥7 days after an initial course of glucocorticoids, repeated each week that they remained at risk for preterm birth at children underwent whole-body dual-energy radiograph absorptiometry at 6 to 8 years' corrected age. Of 212 eligible childhood survivors, 185 were studied (87%; 91 repeat betamethasone group; 94 placebo [single course] group). Children exposed to repeat antenatal betamethasone and those exposed to placebo had similar whole-body bone mineral content (median repeat betamethasone: 553 g, interquartile range: 442-712 g; placebo: 567 g, interquartile range: 447-750 g; geometric mean ratio: 0.99; 95% confidence interval: 0.94-1.03, P = .55) and bone area (median repeat betamethasone 832 cm(2), interquartile range: 693-963 cm(2); placebo: 822 cm(2), interquartile range: 710-1020 cm(2); geometric mean ratio: 0.99, 95% confidence interval: 0.92-1.07, P = .75). Exposure to repeat doses of antenatal betamethasone compared with a single course of glucocorticoids does not alter bone mass in mid-childhood. Copyright © 2017 by the American Academy of Pediatrics.

  5. The Moral Maturity of Repeater Delinquents.

    Science.gov (United States)

    Petronio, Richard J.

    1980-01-01

    Differences in moral development (as conceived by Kohlberg) were examined in a sample of delinquent teenagers. The repeater group was not found, as had been hypothesized, to be lower on moral maturity than those who engaged in less delinquency. (GC)

  6. Star repeaters for fiber optic links.

    Science.gov (United States)

    McMahon, D H; Gravel, R L

    1977-02-01

    A star repeater combines the functions of a passive star coupler and a signal regenerating amplifier. By more effectively utilizing the light power radiated by a light emitting diode, the star repeater can, when used with small diameter channels, couple as much power to all receivers of a multiterminal link as would be coupled to the single receiver of a simple point-to-point link.

  7. Effects of Balance-acupuncture Stimulation of“Back Pain” and “Hip Pain”Points on Plasma β-endorphin and ACTH Contents in Rats with Lumbar Disc Herniation%平衡针对腰椎神经根压迫模型大鼠血浆β-内啡肽、促肾上腺皮质激素的影响

    Institute of Scientific and Technical Information of China (English)

    马文珠; 张艺萌; 袁红; 王文远

    2011-01-01

    Objective To observe the effect of balance acupuncture on the thermal pain threshold and plasma β-endor-phin (p-EP) and adrenocorticotrophic hormone (ACTH) levels in lumbar disc herniation rats so as to research its mechanisms underlying improvement of lumbar disc protrusion. Methods A total of 120 male rats were randomly divided into blank control (control) group, model group. Sham-operation(sham)group, and acupuncture group (n = 30) which were further divided into 7-days (d) and 14-d subgroups. Rats in the acupuncture group were treated with balance acupuncture of "Back Pain" point (the midpoint between two eyes) and "Hip Pain"point (the midpoint between the acromial process and the axillary furrow). Thermal pain threshold was detected by using radiant heat detector. Plasma p-EP and ACTH levels were determined by radioimmunoassay. Results Compared with the control group and pre-operation and sham group, the thermal pain reaction was increased significantly in the model group (P0. 05). Conclusion Balance acupuncture treatment can lower plasma ACTH level in lumbar disc herniation rats, which may contribute to its effect in easing lumbar disc herniation pain in clinic practice.%目的:初步探求平衡针治疗腰椎间盘突出神经根压迫症状的作用机制.方法:将SD雄性大鼠随机分为空白组、假手术组、模型组、治疗组,每组30只,各组中又分为7d取材组和14d取材组各15只.用肠线环扎L4神经根造模.治疗组针刺“腰痛穴”“臀痛穴”,每日2次.用热痛测试仪检测各组大鼠造模前及造模后第4、7、10、14天的缩爪潜伏期,采用放射免疫分析法测定血浆β-内啡肽(EP)及促肾上腺皮质激素(ACTH)的变化.结果:模型组大鼠痛敏现象明显增强(P<0.05),血浆β-EP、ACTH的含量呈增高趋势;经过平衡针治疗,治疗组痛敏现象至治疗第10天起较模型组明显降低(P<0.05),血浆中β-EP的含量第7天时就较模型组显著降低(P<0.05),

  8. Digital repeat analysis; setup and operation.

    Science.gov (United States)

    Nol, J; Isouard, G; Mirecki, J

    2006-06-01

    Since the emergence of digital imaging, there have been questions about the necessity of continuing reject analysis programs in imaging departments to evaluate performance and quality. As a marketing strategy, most suppliers of digital technology focus on the supremacy of the technology and its ability to reduce the number of repeats, resulting in less radiation doses given to patients and increased productivity in the department. On the other hand, quality assurance radiographers and radiologists believe that repeats are mainly related to positioning skills, and repeat analysis is the main tool to plan training needs to up-skill radiographers. A comparative study between conventional and digital imaging was undertaken to compare outcomes and evaluate the need for reject analysis. However, digital technology still being at its early development stages, setting a credible reject analysis program became the major task of the study. It took the department, with the help of the suppliers of the computed radiography reader and the picture archiving and communication system, over 2 years of software enhancement to build a reliable digital repeat analysis system. The results were supportive of both philosophies; the number of repeats as a result of exposure factors was reduced dramatically; however, the percentage of repeats as a result of positioning skills was slightly on the increase for the simple reason that some rejects in the conventional system qualifying for both exposure and positioning errors were classified as exposure error. The ability of digitally adjusting dark or light images reclassified some of those images as positioning errors.

  9. Quantum Key Distribution over Probabilistic Quantum Repeaters

    CERN Document Server

    Amirloo, Jeyran; Majedi, A Hamed

    2010-01-01

    A feasible route towards implementing long-distance quantum key distribution (QKD) systems relies on probabilistic schemes for entanglement distribution and swapping as proposed in the work of Duan, Lukin, Cirac, and Zoller (DLCZ) [Nature 414, 413 (2001)]. Here, we calculate the conditional throughput and fidelity of entanglement for DLCZ quantum repeaters, by accounting for the DLCZ self-purification property, in the presence of multiple excitations in the ensemble memories as well as loss and other sources of inefficiency in the channel and measurement modules. We then use our results to find the generation rate of secure key bits for QKD systems that rely on DLCZ quantum repeaters. We compare the key generation rate per logical memory employed in the two cases of with and without a repeater node. We find the cross-over distance beyond which the repeater system outperforms the non-repeater one. That provides us with the optimum inter-node distancing in quantum repeater systems. We also find the optimal exci...

  10. Remarkable selective constraints on exonic dinucleotide repeats.

    Science.gov (United States)

    Haasl, Ryan J; Payseur, Bret A

    2014-09-01

    Long dinucleotide repeats found in exons present a substantial mutational hazard: mutations at these loci occur often and generate frameshifts. Here, we provide clear and compelling evidence that exonic dinucleotides experience strong selective constraint. In humans, only 18 exonic dinucleotides have repeat lengths greater than six, which contrasts sharply with the genome-wide distribution of dinucleotides. We genotyped each of these dinucleotides in 200 humans from eight 1000 Genomes Project populations and found a near-absence of polymorphism. More remarkably, divergence data demonstrate that repeat lengths have been conserved across the primate phylogeny in spite of what is likely considerable mutational pressure. Coalescent simulations show that even a very low mutation rate at these loci fails to explain the anomalous patterns of polymorphism and divergence. Our data support two related selective constraints on the evolution of exonic dinucleotides: a short-term intolerance for any change to repeat length and a long-term prevention of increases to repeat length. In general, our results implicate purifying selection as the force that eliminates new, deleterious mutants at exonic dinucleotides. We briefly discuss the evolution of the longest exonic dinucleotide in the human genome--a 10 x CA repeat in fibroblast growth factor receptor-like 1 (FGFRL1)--that should possess a considerably greater mutation rate than any other exonic dinucleotide and therefore generate a large number of deleterious variants. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

  11. Dynamic combinatorial libraries of artificial repeat proteins.

    Science.gov (United States)

    Eisenberg, Margarita; Shumacher, Inbal; Cohen-Luria, Rivka; Ashkenasy, Gonen

    2013-06-15

    Repeat proteins are found in almost all cellular systems, where they are involved in diverse molecular recognition processes. Recent studies have suggested that de novo designed repeat proteins may serve as universal binders, and might potentially be used as practical alternative to antibodies. We describe here a novel chemical methodology for producing small libraries of repeat proteins, and screening in parallel the ligand binding of library members. The first stage of this research involved the total synthesis of a consensus-based three-repeat tetratricopeptide (TPR) protein (~14 kDa), via sequential attachment of the respective peptides. Despite the effectiveness of the synthesis and ligation steps, this method was found to be too demanding for the production of proteins containing variable number of repeats. Additionally, the analysis of binding of the individual proteins was time consuming. Therefore, we designed and prepared novel dynamic combinatorial libraries (DCLs), and show that their equilibration can facilitate the formation of TPR proteins containing up to eight repeating units. Interestingly, equilibration of the library building blocks in the presence of the biologically relevant ligands, Hsp90 and Hsp70, induced their oligomerization into forming more of the proteins with large recognition surfaces. We suggest that this work presents a novel simple and rapid tool for the simultaneous screening of protein mixtures with variable binding surfaces, and for identifying new binders for ligands of interest.

  12. Effects of repeated regrouping on horse behaviour and injuries

    DEFF Research Database (Denmark)

    Christensen, Janne Winther; Søndergaard, Eva; Thodberg, Karen;

    2011-01-01

    Domestic horses are faced with social challenges throughout their lives due to limitations in social contact, space restrictions and frequent changes in social companionship. This is in contrast to natural conditions where horses live in relatively stable harem bands. Currently, little is known...... about how repeated regrouping affect horse behaviour and welfare, and it is unknown whether horses may adapt to regrouping. In this study, we aimed to investigate the effects of an unstable group structure, caused by weekly regroupings, on behaviour and frequency of injuries in young horses. Forty......, to repeated regrouping. Compared to horses in Stable groups, more agonistic behaviour was shown by horses in Unstable groups (i.e. non-contact agonistic; F1,65 = 5.60, P = 0.02), whereas there was no treatment effect on other variables. The level of play behaviour appeared, however, to be more variable...

  13. Caffeine Ingestion Improves Repeated Freestyle Sprints in Elite Male Swimmers

    Directory of Open Access Journals (Sweden)

    Paul S.R. Goods, Grant Landers, Sacha Fulton

    2017-03-01

    Full Text Available The purpose of this investigation was to determine the efficacy of a moderate dose of caffeine to improve repeat-sprint performance in elite freestyle sprinters. Nine highly trained male swimmers performed 6 x 75 m freestyle sprints on two occasions 1-h after consuming either 3 mg·kg-1 caffeine (CAF, or placebo, in a cross-over manner. Capillary blood samples for the analysis of blood lactate concentration and pH were collected after the 1st, 3rd, and 5th sprint, while heart rate and perceived exertion (RPE were collected after every sprint. There was a moderate effect for improved mean sprint time in the CAF condition (0.52 s; 1.3%; d = 0.50. When assessed individually, there was a large effect for improved performance in sprints 3 (1.00 s; 2.5%; d = 1.02 and 4 (0.84 s; 2.1%; d = 0.84 in CAF compared to placebo, with worthwhile performance improvement found for each of the first 5 sprints. There was a significant treatment effect for higher blood lactate concentration for CAF (p = 0.029, and a significant treatment*time effect for reduced pH in the CAF condition (p = 0.004. Mean heart rate (167 ± 9 bpm vs 169 ± 7 bpm and RPE (17 ± 1 vs 17 ± 1 were not different between placebo and CAF trials, respectively. This investigation is the first to demonstrate enhanced repeat-sprint ability in swimmers following acute caffeine ingestion. It appears likely that the combination of a moderate dose of caffeine (3-6 mg·kg-1 with trained athletes is most likely to enhance repeat-sprint ability in various athletic populations; however, the exact mechanism(s for an improved repeat-sprint ability following acute caffeine ingestion remain unknown.

  14. Metabolic rate variation over adult lifetime in the butterfly Vanessa cardui (Nymphalidae: Nymphalinae): aging, feeding, and repeatability.

    Science.gov (United States)

    Woods, William A; Wood, C A L; Ebersole, John; Stevenson, R D

    2010-01-01

    Questions about the adaptive importance of metabolic rate can be approached only when measurements of differences between individuals are repeatable. We made daily measurements of CO(2) production, body mass, and food uptake over the adult life span of unmated Vanessa cardui kept under constant environmental conditions in both fed and unfed treatments. Mass and CO(2) production generally declined with age in both treatments, though with much day-to-day variability in the fed treatment. For the full samples, metabolic rate was repeatable for the unfed treatment (repeatability r = 0.60) but not for the fed treatment (r = 0.03). Differences between fed and unfed individuals of the same age range were repeatable for the unfed treatment (r = 0.39) but not for the fed treatment (r = -0.20). Removing age effects on CO(2) production yielded still higher repeatability in the unfed treatment (r = 0.83), though not in fed butterflies of the same age range (r = -0.02). However, repeatability of CO(2) production of fed butterflies increased sharply with age, rising to 0.82 for butterflies age 8-10 d. Although food uptake mass was repeatable (r = 0.52), feeding history explained little variation in CO(2) production. We conclude that for V. cardui and possibly for other insects of similar feeding habit, variation in metabolic rate between individuals is best represented by measurements of unfed individuals of the same age or of older fed individuals.

  15. Automated genotyping of dinucleotide repeat markers

    Energy Technology Data Exchange (ETDEWEB)

    Perlin, M.W.; Hoffman, E.P. [Carnegie Mellon Univ., Pittsburgh, PA (United States)]|[Univ. of Pittsburgh, PA (United States)

    1994-09-01

    The dinucleotide repeats (i.e., microsatellites) such as CA-repeats are a highly polymorphic, highly abundant class of PCR-amplifiable markers that have greatly streamlined genetic mapping experimentation. It is expected that over 30,000 such markers (including tri- and tetranucleotide repeats) will be characterized for routine use in the next few years. Since only size determination, and not sequencing, is required to determine alleles, in principle, dinucleotide repeat genotyping is easily performed on electrophoretic gels, and can be automated using DNA sequencers. Unfortunately, PCR stuttering with these markers generates not one band for each allele, but a pattern of bands. Since closely spaced alleles must be disambiguated by human scoring, this poses a key obstacle to full automation. We have developed methods that overcome this obstacle. Our model is that the observed data is generated by arithmetic superposition (i.e., convolution) of multiple allele patterns. By quantitatively measuring the size of each component band, and exploiting the unique stutter pattern associated with each marker, closely spaced alleles can be deconvolved; this unambiguously reconstructs the {open_quotes}true{close_quotes} allele bands, with stutter artifact removed. We used this approach in a system for automated diagnosis of (X-linked) Duchenne muscular dystrophy; four multiplexed CA-repeats within the dystrophin gene were assayed on a DNA sequencer. Our method accurately detected small variations in gel migration that shifted the allele size estimate. In 167 nonmutated alleles, 89% (149/167) showed no size variation, 9% (15/167) showed 1 bp variation, and 2% (3/167) showed 2 bp variation. We are currently developing a library of dinucleotide repeat patterns; together with our deconvolution methods, this library will enable fully automated genotyping of dinucleotide repeats from sizing data.

  16. Macronodular Adrenal Hyperplasia due to Mutations in an Armadillo Repeat Containing 5 (ARMC5) Gene: A Clinical and Genetic Investigation

    Science.gov (United States)

    Faucz, Fabio R.; Zilbermint, Mihail; Lodish, Maya B.; Szarek, Eva; Trivellin, Giampaolo; Sinaii, Ninet; Berthon, Annabel; Libé, Rossella; Assié, Guillaume; Espiard, Stéphanie; Drougat, Ludivine; Ragazzon, Bruno; Bertherat, Jerome

    2014-01-01

    Context: Inactivating germline mutations of the probable tumor suppressor gene, armadillo repeat containing 5 (ARMC5), have recently been identified as a genetic cause of macronodular adrenal hyperplasia (MAH). Objective: We searched for ARMC5 mutations in a large cohort of patients with MAH. The clinical phenotype of patients with and without ARMC5 mutations was compared. Methods: Blood DNA from 34 MAH patients was genotyped using Sanger sequencing. Diurnal serum cortisol measurements, plasma ACTH levels, urinary steroids, 6-day Liddle's test, adrenal computed tomography, and weight of adrenal glands at adrenalectomy were assessed. Results: Germline ARMC5 mutations were found in 15 of 34 patients (44.1%). In silico analysis of the mutations indicated that seven (20.6%) predicted major implications for gene function. Late-night cortisol levels were higher in patients with ARMC5-damaging mutations compared with those without and/or with nonpathogenic mutations (14.5 ± 5.6 vs 6.7 ± 4.3, P < .001). All patients carrying a pathogenic ARMC5 mutation had clinical Cushing's syndrome (seven of seven, 100%) compared with 14 of 27 (52%) of those without or with mutations that were predicted to be benign (P = .029). Repeated-measures analysis showed overall higher urinary 17-hydroxycorticosteroids and free cortisol values in the patients with ARMC5-damaging mutations during the 6-day Liddle's test (P = .0002). Conclusions: ARMC5 mutations are implicated in clinically severe Cushing's syndrome associated with MAH. Knowledge of a patient's ARMC5 status has important clinical implications for the diagnosis of Cushing's syndrome and genetic counseling of patients and their families. PMID:24601692

  17. Repeated Renal Biopsy - A Predictive Tool to Assess the Probability of Renal Flare in Lupus Nephritis.

    Science.gov (United States)

    Piñeiro, Gastón J; Arrizabalaga, Pilar; Solé, Manel; Abellana, Rosa M; Espinosa, Gerard; Cervera, Ricard

    2016-01-01

    How one responds to treatment of lupus nephritis (LN) is based on clinical features, but the activity in renal biopsy (RB) is uncertain. We have described the therapeutic decisions after performing a repeated RB on the assessment of response to intravenous cyclophosphamide (IC) and the possible prognostic role of this repeated RB. Clinical, laboratory and histological features at the initial RB and repeated RB were analyzed in 35 patients. Data in the initial versus the repeated RB were serum creatinine 1.23 ± 1.08 and 0.96 ± 0.45 mg/dl (p < 0.05), glomerular filtration rate <60 ml/min in 12 and 5% patients and proteinuria 4.1 ± 2.8 vs. 0.6 1.1 g/day (p < 0.05). Significant differences were detected in hematuria, nephrotic syndrome and serological immune features. Complete renal remission was reached in 60% (n = 21) at the time of the repeated RB, partial remission in 31.4% (n = 11), and no response IC in 8.6% (n = 3). Nine patients showed proliferative forms in the repeated RB, 3 of them had proteinuria <1 g/day. Just after the repeated RB, 34.3% increased or started a new immunosuppressive therapy, 17.1% remained with the same complementary IST, and 14.3% decreased or stopped it. In the follow-up post repeated RB, 34.5% without active lesions showed a renal flare versus 77.8% with active lesions (p = 0.04). The mean time was 120 and 45 months, respectively. A repeated biopsy in LN distinguishes patients in true remission from those in apparent remission. By doing this, we can identify patients who could benefit from intensified treatment and for whom unnecessary treatment methods can be modified or eliminated. © 2016 S. Karger AG, Basel.

  18. Establishment and characterization of a human ovarian small cell carcinoma, hypercalcemic type, cell line (OS-1) secreting PTH, PthrP and ACTH--special reference to the susceptibility of anti-cancer drugs.

    Science.gov (United States)

    Ohi, Satoshi; Niimi, Shigeki; Okada, Naoya; Yamada, Kyosuke; Tachibana, Toshiaki; Hashimoto, Hisashi; Nakajima, Masako; Yasuda, Mitsuru; Tanaka, Tadao; Sato, Kahei; Ishikawa, Hiroshi

    2004-12-01

    We successfully established a novel cell line (OS-1) derived from human ovarian small cell carcinoma, hypercalcemic type secreted PTH, PTH-rP and ACTH. The OS-1 cell line was established from metastatic focus of uterus. A patient was 25-year-old Japanese woman. The first she received left ovariectomy on April 2002. The histopathological diagnosis was ovarian small cell carcinoma, pT2c, Nx, Mx. Then on June 2003, metastatic focus of uterus was ectomied. A part of the recurrent tumor of uterus was cut into small pieces with razor blades, and dissociated with 0.1% trypsin-0.02% EDTA/ PBS(-) solution at room temperature. The single cells and small cell clusters were seeded into 60mm dishes and cultured in growth medium (GM: DMEM/F12 supplemented with 20% fetal bovine serum and 0.1% non-essential amino acids solution) at 37 degrees C, 4.7% CO2 in humidified air. Medium was exchanged twice a week. The OS-1 cells grew as floating cultures in the dishes. Radioimmunoassay of the conditioned media was revealed that the cultures secreted large amount of PTH, PTHrP and ACTH simultaneously. Susceptibilities of anti-cancer drugs to the OS-1 cells were examined using oxygen electrode meter (Daikin), and the results suggested VLB and TXL were effective, and CDDP, CPT-11, VP-16, VCR, CPA, MMC and CBDCA were not effective. In our knowledge, it is the first report that the cell line secreting PTH, PTHrP and ACTH was successfully established from ovarian small cell carcinoma, hypercalcemic type. We expect that OS-1 cell line contribute to study on the mechanism of ectopic hormone secretion and susceptibility of anti cancer drugs to the small cell carcinoma.

  19. Genome-Wide Demethylation Promotes Triplet Repeat Instability Independently of Homologous Recombination

    Science.gov (United States)

    Dion, Vincent; Lin, Yunfu; Price, Brandee A.; Fyffe, Sharyl L.; Seluanov, Andrei; Gorbunova, Vera; Wilson, John H.

    2008-01-01

    Trinucleotide repeat instability is intrinsic to a family of human neurodegenerative diseases. The mechanism leading to repeat length variation is unclear. We previously showed that treatment with the demethylating agent 5-aza-2′-deoxycytidine (5-aza-CdR) dramatically increases triplet repeat instability in mammalian cells. Based on previous reports that demethylation increases homologous recombination (HR), and our own observations that HR destabilizes triplet repeats, we hypothesized that demethylation alters repeat stability by stimulating HR. Here, we test that hypothesis at the Aprt (adenosine phosphoribosyl transferase) locus in CHO cells, where CpG demethylation and HR have both been shown to increase CAG repeat instability. We find that the rate of HR at the Aprt locus is not altered by demethylation. The spectrum of recombinants, however, was shifted from the usual 6:1 ratio of conversions to crossovers to more equal proportions in 5-aza-CdR-treated cells. The subtle influences of demethylation on HR at the Aprt locus are not sufficient to account for its dramatic effects on repeat instability. We conclude that 5-aza-CdR promotes triplet repeat instability independently of HR. PMID:18083071

  20. Mining of simple sequence repeats in the Genome of Gentianaceae

    Directory of Open Access Journals (Sweden)

    R Sathishkumar

    2011-01-01

    Full Text Available Simple sequence repeats (SSRs or short tandem repeats are short repeat motifs that show high level of length polymorphism due to insertion or deletion mutations of one or more repeat types. Here, we present the detection and abundance of microsatellites or SSRs in nucleotide sequences of Gentianaceae family. A total of 545 SSRs were mined in 4698 nucleotide sequences downloaded from the National Center for Biotechnology Information (NCBI. Among the SSR sequences, the frequency of repeat type was about 429 -mono repeats, 99 -di repeats, 15 -tri repeats, and 2 --hexa repeats. Mononucleotide repeats were found to be abundant repeat types, about 78%, followed by dinucleotide repeats (18.16% among the SSR sequences. An attempt was made to design primer pairs for 545 identified SSRs but these were found only for 169 sequences.

  1. ACTH非依赖性Cushing综合征的分子生物学研究进展%Research advance in molecular biochemistry of ACTH-independent Cushing syndrome

    Institute of Scientific and Technical Information of China (English)

    蒋怡然; 王卫庆

    2010-01-01

    促肾上腺皮质激素(ACTH)非依赖性Cushing综合征包括肾上腺皮质腺瘤、肾上腺皮质癌和肾上腺皮质结节样增生,其发病机制主要与基因突变(GNAS1、PRKAR1A和PDE11A)、异位受体表达、WNT通路异常激活及抑癌基因杂合丢失等诸多因素相关,该文就上述发病机制作一综述.

  2. Distúrbios neurológicos e electrolíticos em nefrótico após diurese rápida provocada pelo ACTH

    Directory of Open Access Journals (Sweden)

    Hedda Arminante de Oliveira Penna

    1960-03-01

    Full Text Available Os autores apresentam o caso de criança de 10 anos, portadora de síndrome nefrótica, que, durante a fase de diurese rápida conseqüente à administração de ACTH, apresentou crises convulsivas, coma, alterações do electrencefalograma, do electrocardiograma, hiponatremia, hipocalemia, hipocloremia e alcalose. Como principais seqüelas, o paciente apresentava, ao ter alta hospitalar, síndrome convulsiva e hemianopsia homônima lateral direita. Os autores comentam o possível mecanismo dessas alterações.

  3. PolyQ repeat expansions in ATXN2 associated with ALS are CAA interrupted repeats.

    Directory of Open Access Journals (Sweden)

    Zhenming Yu

    Full Text Available Amyotrophic lateral sclerosis (ALS is a devastating, rapidly progressive disease leading to paralysis and death. Recently, intermediate length polyglutamine (polyQ repeats of 27-33 in ATAXIN-2 (ATXN2, encoding the ATXN2 protein, were found to increase risk for ALS. In ATXN2, polyQ expansions of ≥ 34, which are pure CAG repeat expansions, cause spinocerebellar ataxia type 2. However, similar length expansions that are interrupted with other codons, can present atypically with parkinsonism, suggesting that configuration of the repeat sequence plays an important role in disease manifestation in ATXN2 polyQ expansion diseases. Here we determined whether the expansions in ATXN2 associated with ALS were pure or interrupted CAG repeats, and defined single nucleotide polymorphisms (SNPs rs695871 and rs695872 in exon 1 of the gene, to assess haplotype association. We found that the expanded repeat alleles of 40 ALS patients and 9 long-repeat length controls were all interrupted, bearing 1-3 CAA codons within the CAG repeat. 21/21 expanded ALS chromosomes with 3CAA interruptions arose from one haplotype (GT, while 18/19 expanded ALS chromosomes with <3CAA interruptions arose from a different haplotype (CC. Moreover, age of disease onset was significantly earlier in patients bearing 3 interruptions vs fewer, and was distinct between haplotypes. These results indicate that CAG repeat expansions in ATXN2 associated with ALS are uniformly interrupted repeats and that the nature of the repeat sequence and haplotype, as well as length of polyQ repeat, may play a role in the neurological effect conferred by expansions in ATXN2.

  4. Repeatability and heritability of response to superovulation in Holstein cows.

    Science.gov (United States)

    Tonhati, H; Lôbo, R B; Oliveira, H N

    1999-04-15

    The objective of this study was to estimate the relative effects of genetic and phenotypic factors on the efficacy and efficiency of superovulation for Holstein-Friesian cows reared in Brazil. A database, established by the Associacao Brasileira de Criadores de Bovinos da Raca Holandesa, consisting of a total of 5387 superovulations of 2941 cows distributed over 473 herds and sired by 690 bulls was used for the analysis. The records were analyzed by MTDFREML (Multiple Trait Derivative-Free Restricted Maximum Likelihood), using a repeatability animal model. The fixed effects included in the model were contemporaneous group (veterinarian, herd, year and season of the superovulation); number of semen doses; cow age; and superovulation order. The estimated repeatability of the number of the transferable embryos was low (0.13), and the estimated heritability was 0.03. These results indicate that environmental factors play a critical role in the response of a cow to a superovulation treatment. There is little evidence that future responses to superovulation by individual females can be predicted by previous treatment(s) or that superovulation response is an heritable trait.

  5. Repeatability of peripheral aberrations in young emmetropes.

    Science.gov (United States)

    Baskaran, Karthikeyan; Theagarayan, Baskar; Carius, Staffan; Gustafsson, Jörgen

    2010-10-01

    The purpose of this study is to assess the intrasession repeatability of ocular aberration measurements in the peripheral visual field with a commercially available Shack-Hartmann aberrometer (complete ophthalmic analysis system-high definition-vision research). The higher-order off-axis aberrations data in young healthy emmetropic eyes are also reported. The aberrations of the right eye of 18 emmetropes were measured using an aberrometer with an open field of view that allows peripheral measurements. Five repeated measures of ocular aberrations were obtained and assessed in steps of 10° out to ±40° in the horizontal visual field (nasal + and temporal -) and -20° in the inferior visual field. The coefficient of repeatability, coefficient of variation, and the intraclass correlation coefficient were calculated as a measure of intrasession repeatability. In all eccentric angles, the repeatability of the third- and fourth-order aberrations was better than the fifth and sixth order aberrations. The coefficient of variation was coefficient was >0.90 for the third and fourth order but reduced gradually for higher orders. There was no statistical significant difference in variance of total higher-order root mean square between on- and off-axis measurements (p > 0.05). The aberration data in this group of young emmetropes showed that the horizontal coma (C(3)(1)) was most positive at 40° in the temporal field, decreasing linearly toward negative values with increasing off-axis angle into the nasal field, whereas all other higher-order aberrations showed little or no change. The complete ophthalmic analysis system-high definition-vision research provides fast, repeatable, and valid peripheral aberration measurements and can be used efficiently to measure off-axis aberrations in the peripheral visual field.

  6. Repeat Descemetopexy after Descemet's Membrane Detachment following Phacoemulsification

    Directory of Open Access Journals (Sweden)

    Sameer Datar

    2014-07-01

    Full Text Available Descemet's membrane detachment (DMD is an uncommon condition with a wide range of possible etiologies. Probably the commonest cause is a localized detachment occurring after cataract extraction surgery. Descemetopexy gives good anatomic attachment rates and visual outcomes and has become the standard treatment for DMD. However, in cases with failed initial descemetopexy, the next step in the management of such cases remains unclear. Before initiating a complex surgical procedure like keratoplasty, which requires good postoperative care and regular follow-ups, repeat descemetopexy with a long-term tamponade using 14% C3F8 gas for recurrent DMD is definitely a worthwhile attempt.

  7. Caffeine Ingestion Improves Repeated Freestyle Sprints in Elite Male Swimmers

    Science.gov (United States)

    Goods, Paul S.R.; Landers, Grant; Fulton, Sacha

    2017-01-01

    The purpose of this investigation was to determine the efficacy of a moderate dose of caffeine to improve repeat-sprint performance in elite freestyle sprinters. Nine highly trained male swimmers performed 6 x 75 m freestyle sprints on two occasions 1-h after consuming either 3 mg·kg-1 caffeine (CAF), or placebo, in a cross-over manner. Capillary blood samples for the analysis of blood lactate concentration and pH were collected after the 1st, 3rd, and 5th sprint, while heart rate and perceived exertion (RPE) were collected after every sprint. There was a moderate effect for improved mean sprint time in the CAF condition (0.52 s; 1.3%; d = 0.50). When assessed individually, there was a large effect for improved performance in sprints 3 (1.00 s; 2.5%; d = 1.02) and 4 (0.84 s; 2.1%; d = 0.84) in CAF compared to placebo, with worthwhile performance improvement found for each of the first 5 sprints. There was a significant treatment effect for higher blood lactate concentration for CAF (p = 0.029), and a significant treatment*time effect for reduced pH in the CAF condition (p = 0.004). Mean heart rate (167 ± 9 bpm vs 169 ± 7 bpm) and RPE (17 ± 1 vs 17 ± 1) were not different between placebo and CAF trials, respectively. This investigation is the first to demonstrate enhanced repeat-sprint ability in swimmers following acute caffeine ingestion. It appears likely that the combination of a moderate dose of caffeine (3-6 mg·kg-1) with trained athletes is most likely to enhance repeat-sprint ability in various athletic populations; however, the exact mechanism(s) for an improved repeat-sprint ability following acute caffeine ingestion remain unknown. Key points A moderate dose of caffeine (3 mg·kg-1) ingested 1 h before a repeat-sprint freestyle set significantly improves mean sprint time in elite swimmers. The combination of at least a moderate dose of caffeine (>3 mg·kg-1) with trained athletes appears the most likely to result in ergogenic benefit to anaerobic

  8. Copy number of tandem direct repeats within the inverted repeats of Marek's disease virus DNA.

    Science.gov (United States)

    Kanamori, A; Nakajima, K; Ikuta, K; Ueda, S; Kato, S; Hirai, K

    1986-12-01

    We previously reported that DNA of the oncogenic strain BC-1 of Marek's disease virus serotype 1 (MDV1) contains three units of tandem direct repeats with 132 base pair (bp) repeats within the inverted repeats of the long regions of the MDV1 genome, whereas the attenuated, nononcogenic viral DNA contains multiple units of tandem direct repeats (Maotani et al., 1986). In the present study, the difference in the copy numbers of 132 bp repeats of oncogenic and nononcogenic MDV1 DNAs in other strains of MDV1 was investigated by Southern blot hybridization. The main copy numbers in different oncogenic MDV1 strains differed: those of BC-1, JM and highly oncogenic Md5 were 3, 5 to 12 and 2, respectively. The viral DNA population with two units of repeats was small, but detectable, in cells infected with either the oncogenic BC-1 or JM strain. The MDV1 DNA in various MD cell lines contained either two units or both two and three units of repeats. The significance of the copy number of repeats in oncogenicity of MDV1 is discussed.

  9. 再次置入药物洗脱支架治疗经皮冠状动脉支架置入术后早期与晚期支架内再狭窄的对比研究%Comparison of repeated drug eluting stent for treatment of early and late in-stent restenosis after drug eluting stent implantation

    Institute of Scientific and Technical Information of China (English)

    朱玮玮; 赵林; 郭成军; 方冬平; 何东方; 张晓江; 迟云鹏; 刘梅颜; 吴小凡

    2014-01-01

    目的 比较再次置入药物洗脱支架(DES)治疗置入DES后早期(≤1年)与晚期(>1年)支架内再狭窄(ISR)患者的临床疗效.方法 收集2008年10月至2011年12月在北京安贞医院因DES置入术后ISR接受再次DES置人治疗并完成临床随访的患者资料.根据DES置入术后发生ISR的时间分为早期ISR组和晚期ISR组.对比2组随访期间的主要不良心血管事件(MACE)[包括全因死亡、心肌梗死和靶病变血运重建(TLR)].结果 总计107例患者入选本研究,其中早期ISR组43例,晚期ISR组64例.2组的患者基线资料、靶病变部位、类型、长度、置入支架特征及ISR类型、再次置入支架特征差异均无统计学意义(P>0.05).早期ISR组糖尿病患病率明显低于晚期ISR组[22.7% (10/44)比42.9% (27/63),P<0.01].晚期ISR组MACE发生率明显低于早期ISR组[15.9% (10/63)比47.7% (21/44),P<0.01];晚期ISR组TLR率明显低于早期ISR组[12.7% (8/63))比43.2% (19/44),P<0.01].Logistic回归分析显示,DES术后早期ISR(OR=6.47,95% CI:2.26~18.50,P<0.01)是DES治疗ISR后再次TLR的唯一预测因素.结论 再次DES置入治疗DES置入后ISR安全有效,但治疗早期ISR时TLR明显升高.%Objective To compare the efficiency and safety of repeated drug eluting stent (DES) for treatment of early and late DES in-stent restenosis(ISR).Methods Patients treated with repeated DES for DES ISR in Beijing anzhen hospital between October 2008 and December 2011 were followed up.All lesions were divided into early ISR group(within 1 year) (43 cases)and late ISR group (in > 1 year) (64 cases) by the period ISR occurring after initial DES implantation.Major adverse cardiovascular events (MACE) including all-cause death,myocardial infarction and clinical target lesion revascularization (TLR) were the primary endpoints.Results There were not differences between early ISR group and late ISR group in clinical and angiographic characteristics(P >0

  10. Efficacy and safety of long-term repeated treatment of facial wrinkles with botulinum toxin A%长期重复应用A型肉毒毒素面部除皱的疗效和安全性评价

    Institute of Scientific and Technical Information of China (English)

    潘卫利; 陆威; 陶小华

    2010-01-01

    目的 评价长期重复多次应用A型肉毒毒素(botulinum toxin A,BTXA)进行面部除皱的疗效和安全性.方法 对52例多次使用国产A型肉毒毒素注射面部除皱者进行了回顾性分析总结.每次注射除皱部位均包括额纹、鱼尾纹、眉间纹、鼻背横纹.于注射前和注射后1周、1个月、3个月及再次注射时,分别进行疗效和安全性评价.结果 每例均注射除皱共8次,每次注射后开始起效时间都在3~4 d,1个月左右是最佳表现时间.疗效评价1级为很好的比例依次是额纹100%、鱼尾纹97.1%、眉间纹99.8%、鼻背横纹99.0%,评价2级为好的比例依次是额纹0、鱼尾纹2.9%、眉间纹0.2%、鼻背横纹1.0%,评价为一般、较差、差这3个等级者为0.随着注射次数增多,疗效等级不断提高.平均疗效维持时间有所延长(r=0.256,P=0.02),为(7.8±1.1)个月,呈正态分布.随着注射次数增加后,不良反应轻微,仅部分受注射者个别注射部位出现瘀斑、额部紧绷感、一定程度的表情僵化和鱼尾纹注射后下眼睑邻近部位皱纹加重.不良反应发生率随注射次数下降(r=0.850,P=0.01).所有被注射者均未出现严重不良反应.结论 长期多次应用A型肉毒毒素除皱安全可靠,且疗效不受影响,因此可以多次使用.%Objective To evaluate the clinical efficacy and safety of long-term repeated treatment of facial wrinkles with application of botulinum toxin A (BTXA). Methods A total of 52 patients had received 8 injections in seven years with BTXA against facial wrinkles, including forehead wrinkles, fishtail lines, glabellas wrinkles, and nasal dorsum transverse wrinkles. Besides day 1 (baseline) and day for the next injection (end-point), follow-up visits were scheduled on 1 week, 1 month, and 3 months after every injection. The therapy effect and safety were evaluated. Results For all the patients, it began to take effect on day 3 or 4 after the treatment and best effect

  11. Y Se Repite = And It Repeats Itself

    Science.gov (United States)

    Katzew, Adriana

    2010-01-01

    In this article, the author discusses Y Se Repite [And It Repeats Itself], a project she conceptualized due to the growing number of Latino/a Mexican migrant workers in dairy farms in the state of Vermont. In 2006, approximately 2,000 Latinos/as--most of them undocumented Mexican migrant workers--worked throughout the state's dairy farms, yet…

  12. Repeater For A Digital-Communication Bus

    Science.gov (United States)

    Torres-Guzman, Esteban; Olson, Stephen; Heaps, Tim

    1993-01-01

    Digital repeater circuit designed to extend range of communication on MIL-STD-1553 bus beyond original maximum allowable length of 300 ft. Circuit provides two-way communication, one way at time, and conforms to specifications of MIL-STD-1553. Crosstalk and instability eliminated.

  13. Repeated sprint training in normobaric hypoxia.

    Science.gov (United States)

    Galvin, Harvey M; Cooke, Karl; Sumners, David P; Mileva, Katya N; Bowtell, Joanna L

    2013-12-01

    Repeated sprint ability (RSA) is a critical success factor for intermittent sport performance. Repeated sprint training has been shown to improve RSA, we hypothesised that hypoxia would augment these training adaptations. Thirty male well-trained academy rugby union and rugby league players (18.4 ± 1.5 years, 1.83 ± 0.07 m, 88.1 ± 8.9 kg) participated in this single-blind repeated sprint training study. Participants completed 12 sessions of repeated sprint training (10 × 6 s, 30 s recovery) over 4 weeks in either hypoxia (13% FiO₂) or normoxia (21% FiO₂). Pretraining and post-training, participants completed sports specific endurance and sprint field tests and a 10 × 6 s RSA test on a non-motorised treadmill while measuring speed, heart rate, capillary blood lactate, muscle and cerebral deoxygenation and respiratory measures. Yo-Yo Intermittent Recovery Level 1 test performance improved after RS training in both groups, but gains were significantly greater in the hypoxic (33 ± 12%) than the normoxic group (14 ± 10%, prepeated aerobic high intensity workout than an equivalent normoxic training. Performance gains are evident in the short term (4 weeks), a period similar to a preseason training block.

  14. Adaptation and complexity in repeated games

    DEFF Research Database (Denmark)

    Maenner, Eliot Alexander

    2008-01-01

    The paper presents a learning model for two-player infinitely repeated games. In an inference step players construct minimally complex inferences of strategies based on observed play, and in an adaptation step players choose minimally complex best responses to an inference. When players randomly ...

  15. A Structured Group Program for Repeat Dieters.

    Science.gov (United States)

    McNamara, Kathleen

    1989-01-01

    Describes a structured group program for women who repeatedly diet and may be at risk of developing more serious eating disorders. Discusses sessions focusing on eating behavior as well as internal factors that contribute to low body esteem and food and weight preoccupation. Evaluates effectiveness of program by self-reports of members of two…

  16. Why Do Students Repeat Admissions Tests?

    Science.gov (United States)

    Jones, Martha S.

    Attitudes and beliefs about the admissions process, especially the role of standardized testing in admissions, were examined for students who took a standardized admissions test more than once. Their attitudes were compared with those of students who did not repeat the test. About 200 preveterinary students who had taken the Veterinary Aptitude…

  17. The Effect of Repeaters on Equating

    Science.gov (United States)

    Kim, HeeKyoung; Kolen, Michael J.

    2010-01-01

    Test equating might be affected by including in the equating analyses examinees who have taken the test previously. This study evaluated the effect of including such repeaters on Medical College Admission Test (MCAT) equating using a population invariance approach. Three-parameter logistic (3-PL) item response theory (IRT) true score and…

  18. Triggering of repeating earthquakes in central California

    Science.gov (United States)

    Wu, Chunquan; Gomberg, Joan; Ben-Naim, Eli; Johnson, Paul

    2014-01-01

    Dynamic stresses carried by transient seismic waves have been found capable of triggering earthquakes instantly in various tectonic settings. Delayed triggering may be even more common, but the mechanisms are not well understood. Catalogs of repeating earthquakes, earthquakes that recur repeatedly at the same location, provide ideal data sets to test the effects of transient dynamic perturbations on the timing of earthquake occurrence. Here we employ a catalog of 165 families containing ~2500 total repeating earthquakes to test whether dynamic perturbations from local, regional, and teleseismic earthquakes change recurrence intervals. The distance to the earthquake generating the perturbing waves is a proxy for the relative potential contributions of static and dynamic deformations, because static deformations decay more rapidly with distance. Clear changes followed the nearby 2004 Mw6 Parkfield earthquake, so we study only repeaters prior to its origin time. We apply a Monte Carlo approach to compare the observed number of shortened recurrence intervals following dynamic perturbations with the distribution of this number estimated for randomized perturbation times. We examine the comparison for a series of dynamic stress peak amplitude and distance thresholds. The results suggest a weak correlation between dynamic perturbations in excess of ~20 kPa and shortened recurrence intervals, for both nearby and remote perturbations.

  19. A Repeater in the Language Laboratory

    Science.gov (United States)

    Griffiths, B. T.

    1969-01-01

    Discusses the feasilility of the use of repeater devices in the language laboratory in order to enable the student to "recapitulate effortlessly and and indefinitely any utterance of any length which is causing him difficulty or is of special interest. (FWB)

  20. The Differential Effects of Repeating Kindergarten

    Science.gov (United States)

    Burkam, David T.; LoGerfo, Laura; Ready, Doug; Lee, Valerie E.

    2007-01-01

    We use the Early Childhood Longitudinal Study to investigate national patterns addressing (a) who repeats kindergarten, and (b) the subsequent cognitive effects of this event. Using OLS regression techniques, we investigate 1st-time kindergartners who are promoted, 1st-time kindergartners who are retained, and children who are already repeating…

  1. Preventing Repeat Teen Births PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2013-04-02

    This 60 second public service announcement is based on the April 2013 CDC Vital Signs report, which discusses repeat teen births and ways teens, parents and guardians, health care providers, and communities can help prevent them.  Created: 4/2/2013 by Centers for Disease Control and Prevention (CDC).   Date Released: 4/2/2013.

  2. Epigenetics and triplet repeat neurological diseases

    Directory of Open Access Journals (Sweden)

    Sathiji eNageshwaran

    2015-12-01

    Full Text Available The term ‘junk DNA’ has been reconsidered following the delineation of the functional significance of repetitive DNA regions. Typically associated with centromeres and telomeres, DNA repeats are found in nearly all organisms throughout their genomes. Repetitive regions are frequently heterchromatinised resulting in silencing of intrinsic and nearby genes. However, this is not a uniform rule, with several genes known to require such an environment to permit transcription. Repetitive regions frequently exist as dinucleotide, trinucleotide and tetranucleotide repeats. The association between repetitive regions and disease was emphasised following the discovery of abnormal trinucleotide repeats underlying spinal and bulbar muscular atrophy (Kennedy’s disease and fragile X syndrome of mental retardation (FRAXA in 1991. In this review we provide a brief overview of epigenetic mechanisms and then focus on several diseases caused by DNA triplet-repeat expansions, which exhibit diverse epigenetic effects. It is clear that the emerging field of epigenetics is already generating novel potential therapeutic avenues for this group of largely incurable diseases.

  3. Costly renegotiation in repeated Bertand games

    DEFF Research Database (Denmark)

    Andersson, Ola; Wengström, Erik Roland

    2010-01-01

    This paper extends the concept of weak renegotiation-proof equilibrium (WRP) to allow for costly renegotiation and shows that even small renegotiation costs can have dramatic effects on the set of equilibria. More specifically, the paper analyzes the infinitely repeated Bertrand game. It is shown...

  4. EVOLUTION AND RECOMBINATION OF BOVINE DNA REPEATS

    NARCIS (Netherlands)

    JOBSE, C; BUNTJER, JB; HAAGSMA, N; BREUKELMAN, HJ; BEINTEMA, JJ; LENSTRA, JA

    The history of the abundant repeat elements in the bovine genome has been studied by comparative hybridization and PCR. The Bov-A and Bov-B SINE elements both emerged just after the divergence of the Camelidae and the true ruminants. A 31-bp subrepeat motif in satellites of the Bovidae species

  5. Building Fluency through the Repeated Reading Method

    Science.gov (United States)

    Cohen, Joshua

    2011-01-01

    For the last two years the author has used Repeated Reading (RR) to teach reading fluency in English as a Foreign Language classrooms in colleges and universities in Japan. RR is a method where the student reads and rereads a text silently or aloud from two to four times to reach a predetermined level of speed, accuracy, and comprehension. RR…

  6. History repeats itself: genomic divergence in copepods.

    Science.gov (United States)

    Renaut, Sébastien; Dion-Côté, Anne-Marie

    2016-04-01

    Press stop, erase everything from now till some arbitrary time in the past and start recording life as it evolves once again. Would you see the same tape of life playing itself over and over, or would a different story unfold every time? The late Steven Jay Gould called this experiment replaying the tape of life and argued that any replay of the tape would lead evolution down a pathway radically different from the road actually taken (Gould 1989). This thought experiment has puzzled evolutionary biologists for a long time: how repeatable are evolutionary events? And if history does indeed repeat itself, what are the factors that may help us predict the path taken? A powerful means to address these questions at a small evolutionary scale is to study closely related populations that have evolved independently, under similar environmental conditions. This is precisely what Pereira et al. (2016) set out to do using marine copepods Tigriopus californicus, and present their results in this issue of Molecular Ecology. They show that evolution can be repeatable and even partly predictable, at least at the molecular level. As expected from theory, patterns of divergence were shaped by natural selection. At the same time, strong genetic drift due to small population sizes also constrained evolution down a similar evolutionary road, and probably contributed to repeatable patterns of genomic divergence.

  7. Costly renegotiation in repeated Bertand games

    DEFF Research Database (Denmark)

    Andersson, Ola; Wengström, Erik Roland

    2010-01-01

    This paper extends the concept of weak renegotiation-proof equilibrium (WRP) to allow for costly renegotiation and shows that even small renegotiation costs can have dramatic effects on the set of equilibria. More specifically, the paper analyzes the infinitely repeated Bertrand game. It is shown...

  8. Photometric Repeatability of Scanned Imagery: UVIS

    Science.gov (United States)

    Shanahan, Clare E.; McCullough, Peter; Baggett, Sylvia

    2017-08-01

    We provide the preliminary results of a study on the photometric repeatability of spatial scans of bright, isolated white dwarf stars with the UVIS channel of the Wide Field Camera 3 (WFC3) on the Hubble Space Telescope (HST). We analyze straight-line scans from the first pair of identical orbits of HST program 14878 to assess if sub 0.1% repeatability can be attained with WFC3/UVIS. This study is motivated by the desire to achieve better signal-to-noise in the UVIS contamination and stability monitor, in which observations of standard stars in staring mode have been taken from the installation of WFC3 in 2009 to the present to assess temporal photometric stability. Higher signal to noise in this program would greatly benefit the sensitivity to detect contamination, and to better characterize the observed small throughput drifts over time. We find excellent repeatability between identical visits of program 14878, with sub 0.1% repeatability achieved in most filters. These! results support the initiative to transition the staring mode UVIS contamination and photometric stability monitor from staring mode images to spatial scans.

  9. Repeat surgery after failed midurethral slings

    DEFF Research Database (Denmark)

    Foss Hansen, Margrethe; Lose, Gunnar; Kesmodel, Ulrik Schiøler

    2016-01-01

    MUS from 1998 through 2007. The outcome was repeat surgery with any subsequent procedure code for urinary incontinence within a 5-year period of the first procedure. RESULTS: A total of 5,820 women (mean age 55.4 years, ± 12.1) were registered with a synthetic MUS, and 354 (6 %) underwent reoperation...

  10. EVOLUTION AND RECOMBINATION OF BOVINE DNA REPEATS

    NARCIS (Netherlands)

    JOBSE, C; BUNTJER, JB; HAAGSMA, N; BREUKELMAN, HJ; BEINTEMA, JJ; LENSTRA, JA

    1995-01-01

    The history of the abundant repeat elements in the bovine genome has been studied by comparative hybridization and PCR. The Bov-A and Bov-B SINE elements both emerged just after the divergence of the Camelidae and the true ruminants. A 31-bp subrepeat motif in satellites of the Bovidae species cattl

  11. Multivariate linear models and repeated measurements revisited

    DEFF Research Database (Denmark)

    Dalgaard, Peter

    2009-01-01

    Methods for generalized analysis of variance based on multivariate normal theory have been known for many years. In a repeated measurements context, it is most often of interest to consider transformed responses, typically within-subject contrasts or averages. Efficiency considerations leads...

  12. One repeat of the cell wall binding domain is sufficient for anchoring the Lactobacillus acidophilus surface layer protein

    NARCIS (Netherlands)

    Smit, E.; Pouwels, P.H.

    2002-01-01

    The N-terminal repeat (SAC1) of the S-protein of Lactobacillus acidophilus bound efficiently and specifically to cell wall fragments (CWFs) when fused to green fluorescent protein, whereas the C-terminal repeat (SAC2) did not. Treatment of CWFs with hydrofluoric acid, but not phenol, prevented bindi

  13. Repeated Nrf2 stimulation using sulforaphane protects fibroblasts from ionizing radiation.

    Science.gov (United States)

    Mathew, Sherin T; Bergström, Petra; Hammarsten, Ola

    2014-05-01

    Most of the cytotoxicity induced by ionizing radiation is mediated by radical-induced DNA double-strand breaks. Cellular protection from free radicals can be stimulated several fold by sulforaphane-mediated activation of the transcription factor Nrf2 that regulates more than 50 genes involved in the detoxification of reactive substances and radicals. Here, we report that repeated sulforaphane treatment increases radioresistance in primary human skin fibroblasts. Cells were either treated with sulforaphane for four hours once or with four-hour treatments repeatedly for three consecutive days prior to radiation exposure. Fibroblasts exposed to repeated-sulforaphane treatment showed a more pronounced dose-dependent induction of Nrf2-regulated mRNA and reduced amount of radiation-induced free radicals compared with cells treated once with sulforaphane. In addition, radiation- induced DNA double-strand breaks measured by gamma-H2AX foci were attenuated following repeated sulforaphane treatment. As a result, cellular protection from ionizing radiation measured by the 5-ethynyl-2'-deoxyuridine (EdU) assay was increased, specifically in cells exposed to repeated sulforaphane treatment. Sulforaphane treatment was unable to protect Nrf2 knockout mouse embryonic fibroblasts, indicating that the sulforaphane-induced radioprotection was Nrf2-dependent. Moreover, radioprotection by repeated sulforaphane treatment was dose-dependent with an optimal effect at 10 uM, whereas both lower and higher concentrations resulted in lower levels of radioprotection. Our data indicate that the Nrf2 system can be trained to provide further protection from radical damage. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Tratamento dos casos graves de miastenia: ação do ACTH e cortisona. Considerações a propósito de três casos

    Directory of Open Access Journals (Sweden)

    José Lamartine de Assis

    1956-03-01

    Full Text Available São apresentados 3 casos de miastenia grave em que os recursos terapêuticos clássicos não deram resultado favorável. Os 3 pacientes foram, então, submetidos ao tratamento pelo ACTH e cortisona; em todos houve remissão da sintomatologia, remissão que perdurou até cêrca de um mês após a suspensão da hormonioterapia. O tratamento foi repetido várias vêzes de acôrdo com a evolução da doença. É de notar que em 2 pacientes (casos 1 e 2, foram estabelecidas doses mínimas de manutenção controladas durante cerca de 40 dias. O ACTH foi usado por via intravenosa em doses variáveis de 2,5 a 25 mg, diluído em 250 a 1000 ml de sôro glicosado isotônico, na velocidade de 20 a 25 gotas por minuto. Em todos os casos, durante a hormonioterapia, foi administrada prostigmina em doses muito pequenas.

  15. RepeatsDB 2.0: improved annotation, classification, search and visualization of repeat protein structures

    Science.gov (United States)

    Paladin, Lisanna; Hirsh, Layla; Piovesan, Damiano; Andrade-Navarro, Miguel A.; Kajava, Andrey V.; Tosatto, Silvio C.E.

    2017-01-01

    RepeatsDB 2.0 (URL: http://repeatsdb.bio.unipd.it/) is an update of the database of annotated tandem repeat protein structures. Repeat proteins are a widespread class of non-globular proteins carrying heterogeneous functions involved in several diseases. Here we provide a new version of RepeatsDB with an improved classification schema including high quality annotations for ∼5400 protein structures. RepeatsDB 2.0 features information on start and end positions for the repeat regions and units for all entries. The extensive growth of repeat unit characterization was possible by applying the novel ReUPred annotation method over the entire Protein Data Bank, with data quality is guaranteed by an extensive manual validation for >60% of the entries. The updated web interface includes a new search engine for complex queries and a fully re-designed entry page for a better overview of structural data. It is now possible to compare unit positions, together with secondary structure, fold information and Pfam domains. Moreover, a new classification level has been introduced on top of the existing scheme as an independent layer for sequence similarity relationships at 40%, 60% and 90% identity. PMID:27899671

  16. Successful Pregnancies after the Treatment of a Thymic Carcinoid

    Directory of Open Access Journals (Sweden)

    Wiebren A. A. Tjalma

    2015-01-01

    Full Text Available The present report describes the case of a woman diagnosed with an adrenocorticotropic hormone- (ACTH- secreting thymic carcinoid associated with Cushing’s syndrome. Treatment consisted of tumour resection and 131-I-meta-iodobenzylguanidine (MIBG therapy. In spite of her iatrogenic menopausal state she twice became pregnant and delivered two healthy babies but developed recurrences during both pregnancies. The last recurrence presented as a primary breast cancer. Despite poor prognosis our patient survived for eleven years. To our knowledge this is the first report of successful pregnancy and delivery in a patient with a thymic carcinoid.