WorldWideScience

Sample records for narcolepsy pharmacological studies

  1. Pharmacological management of narcolepsy with and without cataplexy.

    Science.gov (United States)

    Kallweit, Ulf; Bassetti, Claudio L

    2017-06-01

    Narcolepsy is an orphan neurological disease and presents with sleep-wake, motoric, neuropsychiatric and metabolic symptoms. Narcolepsy with cataplexy is most commonly caused by an immune-mediated process including genetic and environmental factors, resulting in the selective loss of hypocretin-producing neurons. Narcolepsy has a major impact on workableness and quality of life. Areas covered: This review provides an overview of the temporal available treatment options for narcolepsy (type 1 and 2) in adults, including authorization status by regulatory agencies. First- and second-line options are discussed as well as combination therapies. In addition, treatment options for frequent coexisting co-morbidities and different phenotypes of narcolepsy are presented. Finally, this review considers potential future management strategies. Non-pharmacological approaches are important in the management of narcolepsy but will not be covered in this review. Expert opinion: Concise evaluation of symptoms and type of narcolepsy, coexisting co-morbidities and patients´ distinct needs is mandatory in order to identify a suitable, individual pharmacological treatment. First-line options include Modafinil/Armodafinil (for excessive daytime sleepiness, EDS), Sodium Oxybate (for EDS and/with cataplexy), Pitolisant (for EDS and cataplexy) and Venlafaxine (for cataplexy (off-label) and co-morbid depression). New symptomatic and causal treatment most probably will be completed by hypocretin-replacement and immune-modifying strategies.

  2. Clinical and practical considerations in the pharmacologic management of narcolepsy.

    Science.gov (United States)

    Thorpy, Michael J; Dauvilliers, Yves

    2015-01-01

    Despite published treatment recommendations and the availability of approved and off-label pharmacologic therapies for narcolepsy, the clinical management of this incurable, chronic neurologic disorder remains challenging. While treatment is generally symptomatically driven, decisions regarding which drug(s) to use need to take into account a variety of factors that may affect adherence, efficacy, and tolerability. Type 1 narcolepsy (predominantly excessive daytime sleepiness with cataplexy) or type 2 narcolepsy (excessive daytime sleepiness without cataplexy) may drive treatment decisions, with consideration given either to a single drug that targets multiple symptoms or to multiple drugs that each treat a specific symptom. Other drug-related characteristics that affect drug choice are dosing regimens, tolerability, and potential drug-drug interactions. Additionally, the patient should be an active participant in treatment decisions, and the main symptomatic complaints, treatment goals, psychosocial setting, and use of lifestyle substances (ie, alcohol, nicotine, caffeine, and cannabis) need to be discussed with respect to treatment decisions. Although there is a lack of narcolepsy-specific instruments for monitoring therapeutic effects, clinically relevant subjective and objective measures of daytime sleepiness (eg, Epworth Sleepiness Scale and Maintenance of Wakefulness Test) can be used to provide guidance on whether treatment goals are being met. These considerations are discussed with the objective of providing clinically relevant recommendations for making treatment decisions that can enhance the effective management of patients with narcolepsy. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Narcolepsy

    DEFF Research Database (Denmark)

    Kornum, Birgitte R; Knudsen, Stine; Ollila, Hanna M

    2017-01-01

    Narcolepsy is a chronic sleep disorder that has a typical onset in adolescence and is characterized by excessive daytime sleepiness, which can have severe consequences for the patient. Problems faced by patients with narcolepsy include social stigma associated with this disease, difficulties...... and safety profiles. However, to date, no treatment hinders or slows disease development. Improved diagnostic tools and increased understanding of the pathogenesis of narcolepsy type 1 are needed and might lead to therapeutic or even preventative interventions....

  4. Narcolepsy

    Science.gov (United States)

    Mitler, Merrill M.; Hajdukovic, Roza; Erman, Milton; Koziol, James A.

    2008-01-01

    Summary Narcolepsy is a neurological condition with a prevalence of up to 1 per 1,000 that is characterized by irresistible bouts of sleep. Associated features include the pathological manifestations of rapid-eye-movement (REM) sleep: cataplexy, sleep paralysis, hypnagogic hallucinations, and abnormal sleep-onset REM periods and disturbed nocturnal sleep. The condition is strongly associated with the HLA-DR2 and DQw1 phenotype. The phenomenology of narcolepsy is discussed, and diagnostic procedures are reviewed. Treatment modalities involving central nervous system stimulants for somnolence and tricyclic drugs for REM-sleep abnormalities are discussed. Sleep laboratory studies on the treatment efficacy of methylphenidate, pemoline, dextroamphetamine, protriptyline, and viloxazine are presented. Data suggest that: (1) methylphenidate and dextro-amphetamine objectively improve somnolence; (2) pemoline, at doses up to 112.5 mg, is less effective in controlling somnolence but may improve certain aspects of performance; and (3) protriptyline and viloxazine are effective anticataplectic agents that produce little improvement in somnolence. PMID:1968069

  5. Efficiency of a Combination of Pharmacological Treatment and Nondrug Interventions in Childhood Narcolepsy.

    Science.gov (United States)

    Kacar Bayram, Ayşe; Per, Hüseyin; Ismailoğullari, Sevda; Canpolat, Mehmet; Gumus, Hakan; Aksu, Murat

    2016-12-01

    Objective  Narcolepsy is a chronic sleep disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic and/or hypnopompic hallucinations, and sleep paralysis. It is one of the most important causes of excessive daytime sleepiness in the pediatric population. The aim of this study is to present the clinical and laboratory findings, and treatment results of pediatric patients with narcolepsy. Materials and Methods  We studied five unrelated consecutive children with narcolepsy, focusing on clinical and laboratory features, the therapy and outcome over the 33-month follow-up period. Results  The study subjects included two boys and three girls. The mean age at diagnosis was 11.8 ± 3.3 years (range: 8-16 years). Three patients had cataplexy. There were no hypnagogic hallucinations and/or sleep paralysis in any patients. All patients were educated about sleep hygiene, appropriate nutrition, and regular exercise. Three patients were treated with modafinil, while two patients received methylphenidate. Sodium oxybate was added to existing treatment in patients with cataplexy. Cataplexy attacks did not respond well to the treatment in one patient; therefore intravenous immunoglobulin therapy was given. Conclusions  Early diagnosis is important to help narcoleptic patients in improving their quality of life. A combination of pharmacological treatment and nondrug interventions can greatly improve children's clinical symptoms. Georg Thieme Verlag KG Stuttgart · New York.

  6. Narcolepsy

    Science.gov (United States)

    ... nih.gov/pubmed/25700880 . Mignot E. Narcolepsy: genetics, immunology, and pathophysiology. In: Kryger M, Roth T, Dement ... Read more NIH MedlinePlus Magazine Read more Health Topics A-Z Read more A.D.A.M., ...

  7. A Global View on Narcolepsy - A Review Study.

    Science.gov (United States)

    Klimova, Blanka; Maresova, Petra; Novotny, Michal; Kuca, Kamil

    2018-02-14

    Narcolepsy is an incurable neurological disorder when the brain is not able to regulate a sleep and wakefulness cycle correctly. The affected person suddenly falls asleep during the day or he/she suffers from excessive day sleepiness. In addition, people may also suffer from cataplexy, hypnagogic hallucinations, sleep paralysis, and disturbed nighttime sleep. The purpose of this review study is to provide the latest information on both clinical and socioeconomic issues in the field of narcolepsy treatment and emphasize its benefits and limitations. The methodological approaches include a method of literature review of available sources exploring the issue of narcolepsy, both from a global and specific perspective point of view. On the basis of evaluation of these literature sources, the researched issue is examined. The main benefits (e.g., new drugs are being tested or non-invasive cognitive behavioral therapies are being applied) and limitations (e.g., late diagnosis of the disease or lifelong and costly treatment) of the treatment of narcolepsy are highlighted. The findings call for more research in the field of the development of novel drugs reflecting understanding of the neurological basis of narcolepsy and early diagnosis in order to eliminate the symptoms of narcolepsy and prevent the development of this disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Anxiety and mood disorders in narcolepsy: a case-control study.

    NARCIS (Netherlands)

    Fortuyn, H.A.; Lappenschaar, M.A.; Furer, J.W.; Hodiamont, P.P.G.; Rijnders, C.A.T.; Renier, W.O.; Buitelaar, J.K.; Overeem, S.

    2010-01-01

    INTRODUCTION: Narcolepsy is a primary sleeping disorder with excessive daytime sleepiness and cataplexy as core symptoms. There is increasing interest in the psychiatric phenotype of narcolepsy. Although many authors suggest an overrepresentation of mood disorders, few systematic studies have been

  9. Anxiety and mood disorders in narcolepsy: A case-control study

    NARCIS (Netherlands)

    Droogleever Fortuyn, H.A.; Lappenschaar, G.A.M.; Furer, J.W.; Hodiamont, P.P.G.; Rijnders, C.A.T.; Renier, W.O.; Buitelaar, J.K.; Overeem, S.

    2010-01-01

    Introduction: Narcolepsy is a primary sleeping disorder with excessive daytime sleepiness and cataplexy as core symptoms. There is increasing interest in the psychiatric phenotype of narcolepsy. Although many authors suggest an overrepresentation of mood disorders, few systematic studies have been

  10. Modafinil : A Review of its Pharmacology and Clinical Efficacy in the Management of Narcolepsy.

    Science.gov (United States)

    McClellan, K J; Spencer, C M

    1998-04-01

    volunteers. Modafinil reduced the impairment of cognitive performance induced by sleep deprivation in volunteers, suppressed microsleeps and reduced the length of recovery sleep required. However, volunteers treated with modafinil reported recovery sleep patterns which were similar to those of placebo recipients. Studies in volunteers indicate that modafinil has less abuse potential than dexamphetamine or methylphenidate. Peak plasma concentrations of modafinil (mean 4.82 mg/L) were reached 2.3 hours after a single 200mg oral dose in healthy volunteers. Over the dose range 200 to 600mg, the pharmacokinetics of modafinil were linear and dose dependent. Orally administered modafinil is extensively biotransformed in the liver to the inactive metabolites modafinil acid and modafinil sulphone, before being eliminated primarily in the urine (elimination half-life 9 to 14 hours). The pharmacokinetics of modafinil are not affected to a clinically significant extent by volunteer age or food intake, but both the maximum plasma concentration and the elimination half-life of the drug are increased in patients with hepatic or renal impairment. The efficacy of modafinil 200 or 400 mg/day was rated as good or excellent (using a 4-point scale) in 84 of 131 evaluable patients (64%) with excessive daytime sleepiness treated for 1 to 114 months in a noncomparative study. 53 patients withdrew from the study (43 because of loss of efficacy). In another study, 1 or 2 months' treatment with modafinil reduced or eliminated symptoms of excessive daytime sleepiness in 17 of 24 patients with narcolepsy. Modafinil 200 or 400 mg/day for 9 weeks significantly increased daytime sleep latency and reduced daytime sleepiness compared with placebo in patients with narcolepsy, but did not suppress cataplexy. It tended to improve psychomotor performance, although this effect was variable. Importantly, modafinil did not affect patients' nocturnal sleep parameters, ability to nap when necessary or feelings on

  11. Conditional ablation of orexin/hypocretin neurons: a new mouse model for the study of narcolepsy and orexin system function.

    Science.gov (United States)

    Tabuchi, Sawako; Tsunematsu, Tomomi; Black, Sarah W; Tominaga, Makoto; Maruyama, Megumi; Takagi, Kazuyo; Minokoshi, Yasuhiko; Sakurai, Takeshi; Kilduff, Thomas S; Yamanaka, Akihiro

    2014-05-07

    The sleep disorder narcolepsy results from loss of hypothalamic orexin/hypocretin neurons. Although narcolepsy onset is usually postpubertal, current mouse models involve loss of either orexin peptides or orexin neurons from birth. To create a model of orexin/hypocretin deficiency with closer fidelity to human narcolepsy, diphtheria toxin A (DTA) was expressed in orexin neurons under control of the Tet-off system. Upon doxycycline removal from the diet of postpubertal orexin-tTA;TetO DTA mice, orexin neurodegeneration was rapid, with 80% cell loss within 7 d, and resulted in disrupted sleep architecture. Cataplexy, the pathognomic symptom of narcolepsy, occurred by 14 d when ∼5% of the orexin neurons remained. Cataplexy frequency increased for at least 11 weeks after doxycycline. Temporary doxycycline removal followed by reintroduction after several days enabled partial lesion of orexin neurons. DTA-induced orexin neurodegeneration caused a body weight increase without a change in food consumption, mimicking metabolic aspects of human narcolepsy. Because the orexin/hypocretin system has been implicated in the control of metabolism and addiction as well as sleep/wake regulation, orexin-tTA; TetO DTA mice are a novel model in which to study these functions, for pharmacological studies of cataplexy, and to study network reorganization as orexin input is lost.

  12. Narcolepsy: a review

    Directory of Open Access Journals (Sweden)

    Akintomide GS

    2011-09-01

    Full Text Available Gbolagade Sunmaila Akintomide1, Hugh Rickards21Department of Neuropsychiatry, University of Birmingham, 2Department of Neuropsychiatry, The Barberry, Edgbaston, Birmingham, UKAbstract: Narcolepsy is a lifelong sleep disorder characterized by a classic tetrad of excessive daytime sleepiness with irresistible sleep attacks, cataplexy (sudden bilateral loss of muscle tone, hypnagogic hallucination, and sleep paralysis. There are two distinct groups of patients, ie, those having narcolepsy with cataplexy and those having narcolepsy without cataplexy. Narcolepsy affects 0.05% of the population. It has a negative effect on the quality of life of its sufferers and can restrict them from certain careers and activities. There have been advances in the understanding of the pathogenesis of narcolepsy. It is thought that narcolepsy with cataplexy is secondary to loss of hypothalamic hypocretin neurons in those genetically predisposed to the disorder by possession of human leukocyte antigen DQB1*0602. The diagnostic criteria for narcolepsy are based on symptoms, laboratory sleep tests, and serum levels of hypocretin. There is no cure for narcolepsy, and the present mainstay of treatment is pharmacological treatment along with lifestyle changes. Some novel treatments are also being developed and tried. This article critically appraises the evidence for diagnosis and treatment of narcolepsy.Keywords: narcolepsy, cataplexy, hypocretin, modafinil, gamma hydroxybutyrate

  13. Epigenome-wide association study of DNA methylation in narcolepsy: an integrated genetic and epigenetic approach.

    Science.gov (United States)

    Shimada, Mihoko; Miyagawa, Taku; Toyoda, Hiromi; Tokunaga, Katsushi; Honda, Makoto

    2018-04-01

    Narcolepsy with cataplexy, which is a hypersomnia characterized by excessive daytime sleepiness and cataplexy, is a multifactorial disease caused by both genetic and environmental factors. Several genetic factors including HLA-DQB1*06:02 have been identified; however, the disease etiology is still unclear. Epigenetic modifications, such as DNA methylation, have been suggested to play an important role in the pathogenesis of complex diseases. Here, we examined DNA methylation profiles of blood samples from narcolepsy and healthy control individuals and performed an epigenome-wide association study (EWAS) to investigate methylation loci associated with narcolepsy. Moreover, data from the EWAS and a previously performed narcolepsy genome-wide association study were integrated to search for methylation loci with causal links to the disease. We found that (1) genes annotated to the top-ranked differentially methylated positions (DMPs) in narcolepsy were associated with pathways of hormone secretion and monocarboxylic acid metabolism. (2) Top-ranked narcolepsy-associated DMPs were significantly more abundant in non-CpG island regions and more than 95 per cent of such sites were hypomethylated in narcolepsy patients. (3) The integrative analysis identified the CCR3 region where both a single methylation site and multiple single-nucleotide polymorphisms were found to be associated with the disease as a candidate region responsible for narcolepsy. The findings of this study suggest the importance of future replication studies, using methylation technologies with wider genome coverage and/or larger number of samples, to confirm and expand on these results.

  14. Narcolepsy: a review

    Science.gov (United States)

    Akintomide, Gbolagade Sunmaila; Rickards, Hugh

    2011-01-01

    Narcolepsy is a lifelong sleep disorder characterized by a classic tetrad of excessive daytime sleepiness with irresistible sleep attacks, cataplexy (sudden bilateral loss of muscle tone), hypnagogic hallucination, and sleep paralysis. There are two distinct groups of patients, ie, those having narcolepsy with cataplexy and those having narcolepsy without cataplexy. Narcolepsy affects 0.05% of the population. It has a negative effect on the quality of life of its sufferers and can restrict them from certain careers and activities. There have been advances in the understanding of the pathogenesis of narcolepsy. It is thought that narcolepsy with cataplexy is secondary to loss of hypothalamic hypocretin neurons in those genetically predisposed to the disorder by possession of human leukocyte antigen DQB1*0602. The diagnostic criteria for narcolepsy are based on symptoms, laboratory sleep tests, and serum levels of hypocretin. There is no cure for narcolepsy, and the present mainstay of treatment is pharmacological treatment along with lifestyle changes. Some novel treatments are also being developed and tried. This article critically appraises the evidence for diagnosis and treatment of narcolepsy. PMID:21931493

  15. Narcolepsy and pregnancy

    DEFF Research Database (Denmark)

    Maurovich-Horvat, Eszter; Kemlink, David; Högl, Birgit

    2013-01-01

    In a retrospective cohort study undertaken in 12 European countries, 249 female narcoleptic patients with cataplexy (n = 216) and without cataplexy (n = 33) completed a self-administrated questionnaire regarding pregnancy and childbirth. The cohort was divided further into patients whose symptoms...... of narcolepsy started before or during pregnancy (308 pregnancies) and those in whom the first symptoms of narcolepsy appeared after delivery (106 pregnancies). Patients with narcolepsy during pregnancy were older during their first pregnancy (P ...

  16. Association Study of HLA-DQB1*0602 Allele in Iranian Patients with Narcolepsy.

    Science.gov (United States)

    Geremew, Demeke; Rahimi-Golkhandan, Ania; Sadeghniiat-Haghighi, Khosro; Shakiba, Yadollah; Khajeh-Mehrizi, Ahmad; Ansaripour, Bita; Izad, Maryam

    2017-10-01

    Narcolepsy is a rare, disabling disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucinations and sleep paralysis. Several studies demonstrated its association with HLA-DQB1*0602 in various ethnic groups. Our study aimed to determine the prevalence of HLA-DQB1*0602 allele in Iranian patients with narcolepsy and assess its predictive parameters for diagnosing narcolepsy. In addition, car accidents and job problems were assessed among narcoleptic patients. We studied 44 narcoleptic patients, 30 patients with other types of excessive daytime sleepiness (EDS)  and 50 healthy age and sex matched individuals in this case-control study. Patients and controls filled out a questionnaire including items about car accidents due to sleepiness and job problems. International classification of sleep disorders-2 criteria was used as the gold standard for diagnosis of narcolepsy. The DNAs isolated from whole blood samples were collected from the patients and controls to assess the presence of HLA-DQB1*0602. The results showed that HLA DQB1*0602 was present in 4 (8%) individual of controls and 20 (45.5%) patients with higher prevalence in patients with cataplexy (78.9%) than patients without cataplexy (p<0.001). The sensitivities of the DQB1*0602 for diagnosing narcolepsy with cataplexy and narcolepsy without cataplexy were 78.9 and 20; specificities were 88 and 72.4, respectively. 18.2% of patients had car accidents due to sleepiness and 68.2% suffered from job problems. Our study shows that evaluation of DQB1*0602 in patients suspected to narcolepsy could be helpful especially in complex cases with atypical cataplexy and indistinguishable multiple sleep latency test MSLT results. Moreover, high rates of car accidents and job problems are found among narcoleptic patients.

  17. Attention-Deficit/Hyperactivity Disorder (ADHD) Symptoms in Pediatric Narcolepsy: A Cross-Sectional Study.

    Science.gov (United States)

    Lecendreux, Michel; Lavault, Sophie; Lopez, Régis; Inocente, Clara Odilia; Konofal, Eric; Cortese, Samuele; Franco, Patricia; Arnulf, Isabelle; Dauvilliers, Yves

    2015-08-01

    To evaluate the frequency, severity, and associations of symptoms of attention-deficit/hyperactivity disorder (ADHD) in children with narcolepsy with and without cataplexy. Cross-sectional survey. Four French national reference centers for narcolepsy. One hundred eight consecutively referred children aged younger than 18 y with narcolepsy, with (NwC, n = 86) or without cataplexy (NwoC, n = 22), and 67 healthy controls. The participants, their families, and sleep specialists completed a structured interview and questionnaires about sleep, daytime sleepiness, fatigue, and ADHD symptoms (ADHD-rating scale based upon Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision [DSM-IV-TR] symptoms), and use of psychostimulants for the treatment of narcolepsy (administered in 68.2%). Polysomnographic measures were collected. Clinically significant levels of ADHD symptoms were found in 4.8% of controls compared with 35.3% in patients with NwoC (P ADHD scores were 6.4 (95% confidence interval [CI]: 4.5, 9.0) in controls compared with 14.2 (95% CI: 10.6, 18.9; P hyperactivity/impulsivity were also significantly higher in both narcolepsy groups compared with controls. No difference was found between the NwC and NwoC groups for any ADHD measure. ADHD symptom severity was associated with increased levels of sleepiness, fatigue, and insomnia. Compared with the 34 untreated patients, the 73 patients treated with psychostimulants (modafinil in 91%) showed a trend toward lower narcolepsy symptoms but not lower ADHD symptoms. Pediatric patients with narcolepsy have high levels of treatment-resistant attention-deficit/hyperactivity disorder (ADHD) symptoms. The optimal treatment for ADHD symptoms in these patients warrants further evaluation in longitudinal intervention studies. © 2015 Associated Professional Sleep Societies, LLC.

  18. Frequencies and Associations of Narcolepsy-Related Symptoms: A Cross-Sectional Study.

    Science.gov (United States)

    Kim, Lenise Jihe; Coelho, Fernando Morgadinho; Hirotsu, Camila; Araujo, Paula; Bittencourt, Lia; Tufik, Sergio; Andersen, Monica Levy

    2015-12-15

    Narcolepsy is a disabling disease with a delayed diagnosis. At least 3 years before the disorder identification, several comorbidities can be observed in patients with narcolepsy. The early recognition of narcolepsy symptoms may improve long-term prognosis of the patients. Thus, we aimed to investigate the prevalence of the symptoms associated with narcolepsy and its social and psychological association in a sample of Sao Paulo city inhabitants. We performed a cross-sectional evaluation with 1,008 individuals from the Sao Paulo Epidemiologic Sleep Study (EPISONO). Excessive daytime sleepiness (EDS) was assessed by the Epworth Sleepiness Scale. Volunteers were also asked about the occurrence of cataplectic-like, hypnagogic or hypnopompic hallucinations, and sleep paralysis symptoms. The participants underwent a full-night polysomnography and completed questionnaires about psychological, demographic, and quality of life parameters. We observed a prevalence of 39.2% of EDS, 15.0% of cataplectic-like symptom, 9.2% of hypnagogic or hypnopompic hallucinations, and 14.9% of sleep paralysis in Sao Paulo city inhabitants. A frequency of 6.9% was observed when EDS and cataplectic-like symptoms were grouped. The other associations were EDS + hallucinations (4.7%) and EDS + sleep paralysis (7.5%). Symptomatic participants were predominantly women and younger compared with patients without any narcolepsy symptom (n = 451). Narcolepsy symptomatology was also associated with a poor quality of life and symptoms of depression, anxiety, and fatigue. Narcolepsy-related symptoms are associated with poor quality of life and worse psychological parameters. © 2015 American Academy of Sleep Medicine.

  19. Update on therapy for narcolepsy.

    Science.gov (United States)

    Thorpy, Michael J

    2015-05-01

    Narcolepsy is a severe, incurable, neurological disorder that is treated by pharmacological management of its symptoms. The main symptoms are excessive daytime sleepiness (EDS) and cataplexy, although addition symptoms that may require treatment include sleep paralysis, hypnagogic hallucinations, and disturbed nocturnal sleep. Sodium oxybate and modafinil/armodafinil are the first-line treatments for EDS, and sodium oxybate for cataplexy. Sodium oxybate treats all the symptoms of narcolepsy, whereas modafinil is effective for EDS only. Alternative medications for EDS include methylphenidate or amphetamines such as dextroamphetamine, lisdexamfetamine, methamphetamine, or combination amphetamine salts. Non-FDA approved medications for cataplexy include norepinephrine reuptake inhibitors such as venlafaxine or atomoxetine. Combination therapy can be more effective for sleepiness such as sodium oxybate and modafinil/armodafinil. Medication for narcolepsy is generally well tolerated and usually required life-long although does not eliminate all symptoms of narcolepsy.

  20. Lucid Dreaming in Narcolepsy

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    Dodet, Pauline; Chavez, Mario; Leu-Semenescu, Smaranda; Golmard, Jean-Louis; Arnulf, Isabelle

    2015-01-01

    Objective: To evaluate the frequency, determinants and sleep characteristics of lucid dreaming in narcolepsy Settings: University hospital sleep disorder unit Design: Case-control study Participants: Consecutive patients with narcolepsy and healthy controls Methods: Participants were interviewed regarding the frequency and determinants of lucid dreaming. Twelve narcolepsy patients and 5 controls who self-identified as frequent lucid dreamers underwent nighttime and daytime sleep monitoring after being given instructions regarding how to give an eye signal when lucid. Results: Compared to 53 healthy controls, the 53 narcolepsy patients reported more frequent dream recall, nightmares and recurrent dreams. Lucid dreaming was achieved by 77.4% of narcoleptic patients and 49.1% of controls (P dreams/month (P dreaming. Seven of 12 narcoleptic (and 0 non-narcoleptic) lucid dreamers achieved lucid REM sleep across a total of 33 naps, including 14 episodes with eye signal. The delta power in the electrode average, in delta, theta, and alpha powers in C4, and coherences between frontal electrodes were lower in lucid than non-lucid REM sleep in spectral EEG analysis. The duration of REM sleep was longer, the REM sleep onset latency tended to be shorter, and the percentage of atonia tended to be higher in lucid vs. non-lucid REM sleep; the arousal index and REM density and amplitude were unchanged. Conclusion: Narcoleptics have a high propensity for lucid dreaming without differing in REM sleep characteristics from people without narcolepsy. This suggests narcolepsy patients may provide useful information in future studies on the nature of lucid dreaming. Citation: Dodet P, Chavez M, Leu-Semenescu S, Golmard JL, Arnulf I. Lucid dreaming in narcolepsy. SLEEP 2015;38(3):487–497. PMID:25348131

  1. Narcolepsy as an autoimmune disease

    DEFF Research Database (Denmark)

    Partinen, Markku; Kornum, Birgitte Rahbek; Plazzi, Giuseppe

    2014-01-01

    in the incidence of narcolepsy after the pandemic AS03 adjuvanted H1N1 vaccination in 2010 from Sweden and Finland supports the immune-mediated pathogenesis. Epidemiological observations from studies in China also suggest a role for H1N1 virus infections as a trigger for narcolepsy. Although the pathological...

  2. Lucid dreaming in narcolepsy.

    Science.gov (United States)

    Dodet, Pauline; Chavez, Mario; Leu-Semenescu, Smaranda; Golmard, Jean-Louis; Arnulf, Isabelle

    2015-03-01

    To evaluate the frequency, determinants and sleep characteristics of lucid dreaming in narcolepsy. University hospital sleep disorder unit. Case-control study. Consecutive patients with narcolepsy and healthy controls. Participants were interviewed regarding the frequency and determinants of lucid dreaming. Twelve narcolepsy patients and 5 controls who self-identified as frequent lucid dreamers underwent nighttime and daytime sleep monitoring after being given instructions regarding how to give an eye signal when lucid. Compared to 53 healthy controls, the 53 narcolepsy patients reported more frequent dream recall, nightmares and recurrent dreams. Lucid dreaming was achieved by 77.4% of narcoleptic patients and 49.1% of controls (P dreamers achieved lucid REM sleep across a total of 33 naps, including 14 episodes with eye signal. The delta power in the electrode average, in delta, theta, and alpha powers in C4, and coherences between frontal electrodes were lower in lucid than non-lucid REM sleep in spectral EEG analysis. The duration of REM sleep was longer, the REM sleep onset latency tended to be shorter, and the percentage of atonia tended to be higher in lucid vs. non-lucid REM sleep; the arousal index and REM density and amplitude were unchanged. Narcolepsy is a novel, easy model for studying lucid dreaming. © 2015 Associated Professional Sleep Societies, LLC.

  3. A child with narcolepsy

    Directory of Open Access Journals (Sweden)

    Silvério Macedo

    2016-02-01

    Full Text Available Introduction: Narcolepsy is a chronic disease characterized by sleep attacks, excessive daytime sleepiness and nocturnal sleep fragmentation. It can be associated cataplexy and other disturbance of REM sleep (sleep paralysis and hypnagogic hallucinations and hypnopompic. Case report: A 10-year old boy was referred to Pedopsychiatry because of behavioural disturbance, irritability, sleepiness and distraction, being interpreted as an “ill-mannered child.” After clinical evaluation and comprehensive laboratory studies we concluded that he presented narcolepsy with cataplexy. Discussion/conclusion: Patients with narcolepsy face several problems due to the disease which, if left untreated or ineffectively treated, cause embarrassing or distressing symptoms, affecting their quality of life. The purpose of this paper is to draw attention to this problem since it is a rare condition and therefore seldom not recognized by the general public or even by health professionals.

  4. Narcolepsy: Pathophysiology and Neuropsychological Changes

    Directory of Open Access Journals (Sweden)

    Angela Naumann

    2003-01-01

    Full Text Available Narcolepsy is now recognized as a distinctive disorder with specific pathophysiology and neurochemical abnormalities. Findings on the role of the neuropeptide hypocretin are opening new avenues of research and new strategies for therapy. Recently, neuropsychological and electrophysiological studies have provided evidence for reduced memory performance on standard memory tests in addition to subjective complaints of forgetfulness which may be related to changes in attentional processing. Further studies are, however, necessary to clarify the neuropsychological profile in narcolepsy. This review focuses on the recent advances in understanding narcolepsy.

  5. Clinical and Neurobiological Aspects of Narcolepsy

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    Nishino, Seiji

    2007-01-01

    Narcolepsy is characterized by excessive daytime sleepiness (EDS), cataplexy and/or other dissociated manifestations of rapid eye movement (REM) sleep (hypnagogic hallucinations and sleep paralysis). Narcolepsy is currently treated with amphetamine-like central nervous system (CNS) stimulants (for EDS) and antidepressants (for cataplexy). Some other classes of compounds such as modafinil (a non-amphetamine wake-promoting compound for EDS) and gamma-hydroxybutyrate (GHB, a short-acting sedative for EDS/fragmented nighttime sleep and cataplexy) given at night are also employed. The major pathophysiology of human narcolepsy has been recently elucidated based on the discovery of narcolepsy genes in animals. Using forward (i.e., positional cloning in canine narcolepsy) and reverse (i.e., mouse gene knockout) genetics, the genes involved in the pathogenesis of narcolepsy (hypocretin/orexin ligand and its receptor) in animals have been identified. Hypocretins/orexins are novel hypothalamic neuropeptides also involved in various hypothalamic functions such as energy homeostasis and neuroendocrine functions. Mutations in hypocretin-related genes are rare in humans, but hypocretin-ligand deficiency is found in many narcolepsy-cataplexy cases. In this review, the clinical, pathophysiological and pharmacological aspects of narcolepsy are discussed. PMID:17470414

  6. Quality management of pharmacology and safety pharmacology studies

    DEFF Research Database (Denmark)

    Spindler, Per; Seiler, Jürg P

    2002-01-01

    to safety pharmacology studies, and, when indicated, to secondary pharmacodynamic studies, does not influence the scientific standards of studies. However, applying formal GLP standards will ensure the quality, reliability and integrity of studies, which reflect sound study management. It is important...... to encourage a positive attitude among researchers and academics towards these lines, whenever possible. GLP principles applied to the management of non-clinical safety studies are appropriate quality standards when studies are used in the context of protecting public health, and these quality standards...... of pharmacology studies (ICH S7A): primary pharmacodynamic, secondary pharmacodynamic and safety pharmacology studies, and guidance on the quality standards (expectations for GLP conformity) for these study types have been provided. Primary pharmacodynamic studies are the only study types that are fully exempt...

  7. Increased lucid dreaming frequency in narcolepsy

    NARCIS (Netherlands)

    Rak, M.; Beitinger, P.; Steiger, A.; Schredl, M.; Dresler, M.

    2015-01-01

    STUDY OBJECTIVE: Nightmares are a frequent symptom in narcolepsy. Lucid dreaming, i.e., the phenomenon of becoming aware of the dreaming state during dreaming, has been demonstrated to be of therapeutic value for recurrent nightmares. Data on lucid dreaming in narcolepsy patients, however, is

  8. ImmunoChip study implicates antigen presentation to T cells in narcolepsy.

    Directory of Open Access Journals (Sweden)

    Juliette Faraco

    Full Text Available Recent advances in the identification of susceptibility genes and environmental exposures provide broad support for a post-infectious autoimmune basis for narcolepsy/hypocretin (orexin deficiency. We genotyped loci associated with other autoimmune and inflammatory diseases in 1,886 individuals with hypocretin-deficient narcolepsy and 10,421 controls, all of European ancestry, using a custom genotyping array (ImmunoChip. Three loci located outside the Human Leukocyte Antigen (HLA region on chromosome 6 were significantly associated with disease risk. In addition to a strong signal in the T cell receptor alpha (TRA@, variants in two additional narcolepsy loci, Cathepsin H (CTSH and Tumor necrosis factor (ligand superfamily member 4 (TNFSF4, also called OX40L, attained genome-wide significance. These findings underline the importance of antigen presentation by HLA Class II to T cells in the pathophysiology of this autoimmune disease.

  9. Paraneoplastic limbic encephalitis and possible narcolepsy in a patient with testicular cancer: case study.

    Science.gov (United States)

    Landolfi, Joseph C.; Nadkarni, Mangala

    2003-01-01

    We describe a patient who presented with a clinical syndrome of limbic encephalitis, narcolepsy, and cataplexy. The anti-Ma2 antibody was positive. Although there was no mass on imaging, orchiectomy was performed in this patient, and testicular carcinoma was found. This is the first known case of limbic encephalitis and anti-Ma2 antibody to be associated with cataplexy and possible narcolepsy. Neurological symptoms precede the diagnosis of cancer in 50% of patients with paraneoplastic syndromes, and clinicians are therefore strongly advised to evaluate patients with neurological symptoms for this condition. PMID:12816728

  10. Investigational therapies for the treatment of narcolepsy.

    Science.gov (United States)

    de Biase, Stefano; Nilo, Annacarmen; Gigli, Gian Luigi; Valente, Mariarosaria

    2017-08-01

    Narcolepsy is a chronic sleep disorder characterized by a pentad of excessive daytime sleepiness (EDS), cataplexy, sleep paralysis, hypnagogic/hypnopompic hallucinations, and disturbed nocturnal sleep. While non-pharmacological treatments are sometimes helpful, more than 90% of narcoleptic patients require a pharmacological treatment. Areas covered: The present review is based on an extensive Internet and PubMed search from 1994 to 2017. It is focused on drugs currently in development for the treatment of narcolepsy. Expert opinion: Currently there is no cure for narcolepsy, with treatment focusing on symptoms control. However, these symptomatic treatments are often unsatisfactory. The research is leading to a better understanding of narcolepsy and its symptoms. New classes of compounds with possible applications in the development of novel stimulant/anticataplectic medications are described. H3 receptor antagonists represent a new therapeutic option for EDS in narcolepsy. JZP-110, with its distinct mechanism of action, would be a new therapeutic option for the treatment of EDS in the coming years. In the future, hypocretin-based therapies and immune-based therapies, could modify the clinical course of the disease. However, more information would be necessary to completely understand the autoimmune process and also how this process can be altered for therapeutic benefits.

  11. Retrospective multicenter matched case-control study on the risk factors for narcolepsy with special focus on vaccinations (including pandemic influenza vaccination) and infections in Germany.

    Science.gov (United States)

    Oberle, Doris; Pavel, Jutta; Mayer, Geert; Geisler, Peter; Keller-Stanislawski, Brigitte

    2017-06-01

    Studies associate pandemic influenza vaccination with narcolepsy. In Germany, a retrospective, multicenter, matched case-control study was performed to identify risk factors for narcolepsy, particularly regarding vaccinations (seasonal and pandemic influenza vaccination) and infections (seasonal and pandemic influenza) and to quantify the detected risks. Patients with excessive daytime sleepiness who had been referred to a sleep center between April 2009 and December 2012 for multiple sleep latency test (MSLT) were eligible. Case report forms were validated according to the criteria for narcolepsy defined by the Brighton Collaboration (BC). Confirmed cases of narcolepsy (BC level of diagnostic certainty 1-4a) were matched with population-based controls by year of birth, gender, and place of residence. A second control group was established including patients in whom narcolepsy was definitely excluded (test-negative controls). A total of 103 validated cases of narcolepsy were matched with 264 population-based controls. The second control group included 29 test-negative controls. A significantly increased odd ratio (OR) to develop narcolepsy (crude OR [cOR] = 3.9, 95% confidence interval [CI] = 1.8-8.5; adjusted OR [aOR] = 4.5, 95% CI = 2.0-9.9) was detected in individuals immunized with pandemic influenza A/H1N1/v vaccine prior to symptoms onset as compared to nonvaccinated individuals. Using test-negative controls, in individuals immunized with pandemic influenza A/H1N1/v vaccine prior to symptoms onset, a nonsignificantly increased OR of narcolepsy was detected when compared to nonvaccinated individuals (whole study population, BC levels 1-4a: cOR = 1.9, 95% CI = 0.5-6.9; aOR = 1.8, 95% CI = 0.3-10.1). The findings of this study support an increased risk for narcolepsy after immunization with pandemic influenza A/H1N1/v vaccine. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. A comparative study of methods for automatic detection of rapid eye movement abnormal muscular activity in narcolepsy

    DEFF Research Database (Denmark)

    Olesen, Alexander Neergaard; Cesari, Matteo; Christensen, Julie Anja Engelhard

    2018-01-01

    atonia index (RAI), supra-threshold REM EMG activit ymetric (STREAM), and Frandsen method (FR) were calculated from polysomnography recordings of 20 healthy controls, 18 clinic controls (subjects suspected with narcolepsy but finally diagnosed without any sleep abnormality), 16 narcolepsy type 1 without...... REM sleep behavior disorder (RBD), 9 narcolepsy type 1 with RBD, and 18 narcolepsy type 2. Diagnostic value of metrics in differentiating between groups was quantified by area under the receiver operating characteristic curve (AUC). Correlations among the metrics and cerebrospinal fluid hypocretin-1...... in narcolepsy 1 compared to controls. This finding might play a supportive role in diagnosing narcolepsy and in discriminating narcolepsy subtypes. Moreover, the negative correlation between CSF-hcrt-1 level and REM muscular activity supported a role for hypocretin in the control of motor tone during REM sleep....

  13. ImmunoChip Study Implicates Antigen Presentation to T Cells in Narcolepsy

    DEFF Research Database (Denmark)

    Faraco, Juliette; Lin, Ling; Kornum, Birgitte Rahbek

    2013-01-01

    receptor alpha (TRA@), variants in two additional narcolepsy loci, Cathepsin H (CTSH) and Tumor necrosis factor (ligand) superfamily member 4 (TNFSF4, also called OX40L), attained genome-wide significance. These findings underline the importance of antigen presentation by HLA Class II to T cells...

  14. Quality of life and trust among young people with narcolepsy and their families, after the Pandemrix® vaccination: protocol for a case-control study.

    Science.gov (United States)

    Blomberg, Karin; Carlsson, Agneta Anderzén; Hagberg, Lars; Jonsson, Östen; Leissner, Lena; Eriksson, Mats H

    2017-08-23

    The extensive vaccination programme against swine flu resulted in an increased incidence of narcolepsy among children and adolescents. There is a need to explore if these young persons' experiences have affected their trust in healthcare, their willingness to participate in future prevention programmes, and their contacts with the healthcare system. The overall aim is to identify factors important for the life-situation of children and adolescents with narcolepsy and their families, and factors that correlate with trust in healthcare. Data will be collected via questionnaires from all available children with narcolepsy following the vaccination and their families, as well as a control group of children with diabetes and their families. Longitudinal descriptive interviews will also be conducted with a selection of 20-25 children and their families. Techniques from media research will be used for Internet-based data collection and analysis of information relating to narcolepsy from social media. This project will use the situation of young persons with narcolepsy after the swine flu vaccination as a case to build a model that can be used in situations where trust in healthcare is essential. This model will be based on findings from the included studies on how trust is influenced by support, quality of life, burden of disease, impact on family, and use of social media. The model developed in this project will be beneficial in future situations where trust in healthcare is essential, such as new pandemic outbreaks but also for "everyday" adherence to health advice.

  15. Challenges in the development of therapeutics for narcolepsy.

    Science.gov (United States)

    Black, Sarah Wurts; Yamanaka, Akihiro; Kilduff, Thomas S

    2017-05-01

    Narcolepsy is a neurological disorder that afflicts 1 in 2000 individuals and is characterized by excessive daytime sleepiness and cataplexy-a sudden loss of muscle tone triggered by positive emotions. Features of narcolepsy include dysregulation of arousal state boundaries as well as autonomic and metabolic disturbances. Disruption of neurotransmission through the hypocretin/orexin (Hcrt) system, usually by degeneration of the HCRT-producing neurons in the posterior hypothalamus, results in narcolepsy. The cause of Hcrt neurodegeneration is unknown but thought to be related to autoimmune processes. Current treatments for narcolepsy are symptomatic, including wake-promoting therapeutics that increase presynaptic dopamine release and anticataplectic agents that activate monoaminergic neurotransmission. Sodium oxybate is the only medication approved by the US Food and Drug Administration that alleviates both sleep/wake disturbances and cataplexy. Development of therapeutics for narcolepsy has been challenged by historical misunderstanding of the disease, its many disparate symptoms and, until recently, its unknown etiology. Animal models have been essential to elucidating the neuropathology underlying narcolepsy. These models have also aided understanding the neurobiology of the Hcrt system, mechanisms of cataplexy, and the pharmacology of narcolepsy medications. Transgenic rodent models will be critical in the development of novel therapeutics for the treatment of narcolepsy, particularly efforts directed to overcome challenges in the development of hypocretin replacement therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Pathophysiology, Clinical, and Therapeutic Aspects of Narcolepsy

    Directory of Open Access Journals (Sweden)

    Pinar Guzel Ozdemir

    2014-09-01

    Full Text Available Narcolepsy is a lifelong sleep disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucination, and sleep paralysis. The exact cause remains unknown, but there is significant evidence that hypocretin deficiency plays an integral role. There have been advances in the understanding of the pathogenesis of narcolepsy. It has a negative effect on the quality of life and can restrict the patients from certain careers and activities. Diagnosis relies on patient history and objective data gathered from polysomnography and multiple sleep latency testing. Treatment focuses on symptom relief through medication, education, and behavioral modification. Both classic pharmacological treatments as well as newer options have significant problems, especially because of side effects and abuse potential. Some novel modalities are being examined to expand options for treatment. In this review, the pathophysiological, clinical, and pharmacotherapeutic aspects of narcolepsy are discussed. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2014; 6(3.000: 271-283

  17. [NARCOLEPSY WITH CATAPLEXY: TYPE 1 NARCOLEPSY].

    Science.gov (United States)

    Dauvilliers, Yves; Lopez, Régis

    2016-06-01

    Narcolepsy with cataplexy or narcolepsy type 1 in a rare, disabling sleep disorder, with a prevalence of 20 to 30 per 100,000. Its onset peaks in the second decade. The main features are excessive daytime sleepiness and cataplexy or sudden less of muscle tone triggered by emotional situations. Other less consistent symptoms include hypnagogic hallucinations, sleep paralysis, disturbed nighttime sleep, and weight gain. Narcolepsy with cataplexy remains a clinical diagnosis but nighttime and daytime polysomnography (multiple sleep latency tests) are useful to document mean sleep latency below 8 min and at least two sleep-onset REM periods. HLA typing shows an association with HLA DQB1*0602 in more than 92% of cases but was not included in the new diagnostic criteria. In contrast, a low hypocretin-1/orexin-A levels (values below 110 pg/mL) in the cerebrospinal fluid was highly specific for narcolepsy with cataplexy and was included in the recent diagnostic criteria for narcolepsy. The deficiency of the hypocretin system is well-established in human narcoleptics with a reduction of cerebrospinal fluid hypocretin levels in relation with an early loss of hypocretin neurons. The cause of human narcolepsy remains unknown, however an autoimmune process in most probable acting on a highly genetic background with environmental factors such as streptococcal infections, and H1N1 AS03-adjuvanted vaccine named Pandemrix.

  18. Patients with narcolepsy in Slovenia

    Directory of Open Access Journals (Sweden)

    Leja Dolenc Grošelj

    2014-12-01

    Full Text Available Abstract Background: To determine the number of patients with narcolepsy in Slovenia, describe their typical clinical features and the diagnostic criteria they met on polysomnography (PSG, the mean sleep latency test (MSLT and HLA typing.Methods: Retrospective study of all narcolepsy patients referred to the National Sleep Disorder Centre at the Institute of Clinical Neurophysiology, University Medical Centre Ljubljana in the period from May 1994 to September 2013.Results: There are currently only 38 patients with narcolepsy in Slovenia. The average time lapse from onset to diagnosis is 17 years. The time lapse is much longer for older patients. The prevalence of narcolepsy in Slovenia is 1.85 to 100,000 inhabitants. All patients had EDS, 89% cataplexy, 66% hallucinations and 37% sleep paralysis at the time of diagnosis. Characteristic changes on PSG and MSLT were present in 97% of all tested patients. HLA DQB1*0602 is present in 88% of all tested patients. The most common differential diagnoses found were OSAS and hypersomnia.Conclusion: With a prevalence of 1.85/100,000 narcolepsy in Slovenia, it is seriously underdiagnosed and not recognized by general practitioners and neurologists alike. Both should be more aware of the disease and think about the possibility of it in patients with excessive daytime sleepiness and unexplained attacks, with additional symptoms such as hallucinations and paralysis during sleep. Such patients should be sent to the Sleep Disorder Centre, where the diagnosis can be confirmed and treatment started as soon as possible, thereby reducing the patient’s pathological symptoms and improve their quality of life.  

  19. Type 1 narcolepsy

    DEFF Research Database (Denmark)

    Degn, Matilda; Kornum, Birgitte Rahbek

    2015-01-01

    Type 1 narcolepsy is a sleep disorder characterized by excessive daytime sleepiness with unintentional sleep attacks and cataplexy. The disorder is caused by a loss of hypocretinergic neurons in the brain. The specific loss of these neurons in narcolepsy is thought to result from an autoimmune...

  20. Neuroimaging of Narcolepsy and Kleine-Levin Syndrome.

    Science.gov (United States)

    Hong, Seung Bong

    2017-09-01

    Narcolepsy is a chronic neurologic disorder with the abnormal regulation of the sleep-wake cycle, resulting in excessive daytime sleepiness, disturbed nocturnal sleep, and manifestations related to rapid eye movement sleep, such as cataplexy, sleep paralysis, and hypnagogic hallucination. Over the past decade, numerous neuroimaging studies have been performed to characterize the pathophysiology and various clinical features of narcolepsy. This article reviews structural and functional brain imaging findings in narcolepsy and Kleine-Levin syndrome. Based on the current state of research, brain imaging is a useful tool to investigate and understand the neuroanatomic correlates and brain abnormalities of narcolepsy and other hypersomnia. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. What Is Narcolepsy?

    Science.gov (United States)

    ... medical center. Support from family and friends also can help relieve stress and anxiety. Let your loved ones know how you feel and what they can do to help you. Narcolepsy in Special Groups School-Aged Children ...

  2. Hypocretin deficiency develops during onset of human narcolepsy with cataplexy

    DEFF Research Database (Denmark)

    Savvidou, Andri; Knudsen, Stine; Olsson-Engman, Mia

    2013-01-01

    Although hypothesized through animal studies, a temporal and causal association between hypocretin deficiency and the onset of narcolepsy with cataplexy (NC) has never been proven in humans.......Although hypothesized through animal studies, a temporal and causal association between hypocretin deficiency and the onset of narcolepsy with cataplexy (NC) has never been proven in humans....

  3. Treatment Options for Narcolepsy.

    Science.gov (United States)

    Barateau, Lucie; Lopez, Régis; Dauvilliers, Yves

    2016-05-01

    Narcolepsy type 1 and narcolepsy type 2 are central disorders of hypersomnolence. Narcolepsy type 1 is characterized by excessive daytime sleepiness and cataplexy and is associated with hypocretin-1 deficiency. On the other hand, in narcolepsy type 2, cerebrospinal fluid hypocretin-1 levels are normal and cataplexy absent. Despite major advances in our understanding of narcolepsy mechanisms, its current management is only symptomatic. Treatment options may vary from a single drug that targets several symptoms, or multiple medications that each treats a specific symptom. In recent years, narcolepsy treatment has changed with the widespread use of modafinil/armodafinil for daytime sleepiness, antidepressants (selective serotonin and dual serotonin and noradrenalin reuptake inhibitors) for cataplexy, and sodium oxybate for both symptoms. Other psychostimulants can also be used, such as methylphenidate, pitolisant and rarely amphetamines, as third-line therapy. Importantly, clinically relevant subjective and objective measures of daytime sleepiness are required to monitor the treatment efficacy and to provide guidance on whether the treatment goals are met. Associated symptoms and comorbid conditions, such as hypnagogic/hypnopompic hallucinations, sleep paralysis, disturbed nighttime sleep, unpleasant dreams, REM- and non REM-related parasomnias, depressive symptoms, overweight/obesity, and obstructive sleep apnea, should also be taken into account and managed, if required. In the near future, the efficacy of new wake-promoting drugs, anticataplectic agents, hypocretin replacement therapy and immunotherapy at the early stages of the disease should also be evaluated.

  4. Application of Probabilistic Multiple-Bias Analyses to a Cohort- and a Case-Control Study on the Association between Pandemrix™ and Narcolepsy.

    Directory of Open Access Journals (Sweden)

    Kaatje Bollaerts

    Full Text Available An increase in narcolepsy cases was observed in Finland and Sweden towards the end of the 2009 H1N1 influenza pandemic. Preliminary observational studies suggested a temporal link with the pandemic influenza vaccine Pandemrix™, leading to a number of additional studies across Europe. Given the public health urgency, these studies used readily available retrospective data from various sources. The potential for bias in such settings was generally acknowledged. Although generally advocated by key opinion leaders and international health authorities, no systematic quantitative assessment of the potential joint impact of biases was undertaken in any of these studies.We applied bias-level multiple-bias analyses to two of the published narcolepsy studies: a pediatric cohort study from Finland and a case-control study from France. In particular, we developed Monte Carlo simulation models to evaluate a potential cascade of biases, including confounding by age, by indication and by natural H1N1 infection, selection bias, disease- and exposure misclassification. All bias parameters were evidence-based to the extent possible.Given the assumptions used for confounding, selection bias and misclassification, the Finnish rate ratio of 13.78 (95% CI: 5.72-28.11 reduced to a median value of 6.06 (2.5th- 97.5th percentile: 2.49-15.1 and the French odds ratio of 5.43 (95% CI: 2.6-10.08 to 1.85 (2.5th-97.5th percentile: 0.85-4.08.We illustrate multiple-bias analyses using two studies on the Pandemrix™-narcolepsy association and advocate their use to better understand the robustness of study findings. Based on our multiple-bias models, the observed Pandemrix™-narcolepsy association consistently persists in the Finnish study. For the French study, the results of our multiple-bias models were inconclusive.

  5. Narcolepsy: current treatment options and future approaches

    Science.gov (United States)

    Billiard, Michel

    2008-01-01

    The management of narcolepsy is presently at a turning point. Three main avenues are considered in this review: 1) Two tendencies characterize the conventional treatment of narcolepsy. Modafinil has replaced methylphenidate and amphetamine as the first-line treatment of excessive daytime sleepiness (EDS) and sleep attacks, based on randomized, double blind, placebo-controlled clinical trials of modafinil, but on no direct comparison of modafinil versus traditional stimulants. For cataplexy, sleep paralysis, and hypnagogic hallucinations, new antidepressants tend to replace tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) in spite of a lack of randomized, double blind, placebo-controlled clinical trials of these compounds; 2) The conventional treatment of narcolepsy is now challenged by sodium oxybate, the sodium salt of gammahydroxybutyrate, based on a series of randomized, double-blind, placebo-controlled clinical trials and a long-term open label study. This treatment has a fairly good efficacy and is active on all symptoms of narcolepsy. Careful titration up to an adequate level is essential both to obtain positive results and avoid adverse effects; 3) A series of new treatments are currently being tested, either in animal models or in humans, They include novel stimulant and anticataplectic drugs, endocrine therapy, and, more attractively, totally new approaches based on the present state of knowledge of the pathophysiology of narcolepsy with cataplexy, hypocretine-based therapies, and immunotherapy. PMID:18830438

  6. Update on the treatment of narcolepsy: clinical efficacy of pitolisant

    Directory of Open Access Journals (Sweden)

    Calik MW

    2017-04-01

    Full Text Available Michael W Calik1,2 1Department of Biobehavioral Health Science, 2Center for Narcolepsy, Sleep and Health Research, University of Illinois at Chicago, Chicago, IL, United States Abstract: Narcolepsy is a neurological disease that affects 1 in 2,000 individuals and is characterized by excessive daytime sleepiness (EDS. In 60–70% of individuals with narcolepsy, it is also characterized by cataplexy or a sudden loss of muscle tone that is triggered by positive or negative emotions. Narcolepsy decreases the quality of life of the afflicted individuals. Currently used drugs treat EDS alone (modafinil/armodafinil, methylphenidate, and amphetamine, cataplexy alone (“off-label” use of antidepressants, or both EDS and cataplexy (sodium oxybate. These drugs have abuse, tolerability, and adherence issues. A greater diversity of drug options is needed to treat narcolepsy. The small molecule drug, pitolisant, acts as an inverse agonist/antagonist at the H3 receptor, thus increasing histaminergic tone in the wake promoting system of the brain. Pitolisant has been studied in animal models of narcolepsy and used in clinical trials as a treatment for narcolepsy. A comprehensive search of online databases (eg, Medline, PubMed, EMBASE, the Cochrane Library Database, Ovid MEDLINE, Europe PubMed Central, EBSCOhost CINAHL, ProQuest Research Library, Google Scholar, and ClinicalTrials.gov was performed. Nonrandomized and randomized studies were included. This review focuses on the outcomes of four clinical trials of pitolisant to treat narcolepsy. These four trials show that pitolisant is an effective drug to treat EDS and cataplexy in narcolepsy. Keywords: narcolepsy, pitolisant, histamine

  7. Autoimmunity and Immunotherapy in Narcolepsy

    Directory of Open Access Journals (Sweden)

    Min Jae Seong

    2017-06-01

    Full Text Available Narcolepsy is a neurological disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucination, and sleep paralysis. Narcolepsy is caused by damage of hypocretin producing neurons in the lateral hypothalamus. The association of narcolepsy with HLA DQB1*0602 and high incidence following H1N1 pandemic in china, vaccination with pandemrix and an adjuvanted H1N1 vaccine suggests that pathophysiology of narcolepsy is involved in the immune system. This review focused on immunological associations and immunotherapy in narcolepsy.

  8. National narcolepsy survey

    LENUS (Irish Health Repository)

    Doherty, L.

    2010-04-01

    Narcolepsy is characterised by excessive daytime sleepiness and cataplexy and has a prevalence of 25 per 100,000. We suspect this is higher than presently seen in the Republic of Ireland. We aimed to calculate the Irish prevalence of Narcolepsy and to examine current management practices. We conducted an online survey of respiratory physicians, neurologists, paediatric neurologists, and psychiatrists with an interest in sleep disorders (73% response rate). Of this group, a total of 16 physicians managed 180 patients prior to January 2009. A clinical diagnosis alone was reached in 67 (41%) patients, the remainder by polysomnography or multiple sleep latency testing. No patients were diagnosed by cerebro-spinal fluid analysis of hypocretin levels. While 70 (42%) patients received modafanil, only 7 (4%) were treated with sodium oxybate. Even allowing for missing data it is apparent that Narcolepsy is hugely under-diagnosed in Ireland, however, current practises adhere with new international guidelines.

  9. Narcolepsy: current treatment options and future approaches

    Directory of Open Access Journals (Sweden)

    Michel Billiard

    2008-06-01

    Full Text Available Michel BilliardDepartment of Neurology, Gui de Chauliac Hospital, Montpellier, FranceAbstract: The management of narcolepsy is presently at a turning point. Three main avenues are considered in this review: 1 Two tendencies characterize the conventional treatment of narcolepsy. Modafinil has replaced methylphenidate and amphetamine as the first-line treatment of excessive daytime sleepiness (EDS and sleep attacks, based on randomized, double blind, placebo-controlled clinical trials of modafinil, but on no direct comparison of modafinil versus traditional stimulants. For cataplexy, sleep paralysis, and hypnagogic hallucinations, new antidepressants tend to replace tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs in spite of a lack of randomized, double blind, placebo-controlled clinical trials of these compounds; 2 The conventional treatment of narcolepsy is now challenged by sodium oxybate, the sodium salt of gammahydroxybutyrate, based on a series of randomized, double-blind, placebo-controlled clinical trials and a long-term open label study. This treatment has a fairly good efficacy and is active on all symptoms of narcolepsy. Careful titration up to an adequate level is essential both to obtain positive results and avoid adverse effects; 3 A series of new treatments are currently being tested, either in animal models or in humans, They include novel stimulant and anticataplectic drugs, endocrine therapy, and, more attractively, totally new approaches based on the present state of knowledge of the pathophysiology of narcolepsy with cataplexy, hypocretine-based therapies, and immunotherapy.Keywords: narcolepsy, treatment, conventional drugs, modafinil, sodium oxybate, future treatments

  10. A consensus definition of cataplexy in mouse models of narcolepsy.

    Science.gov (United States)

    Scammell, Thomas E; Willie, Jon T; Guilleminault, Christian; Siegel, Jerome M

    2009-01-01

    People with narcolepsy often have episodes of cataplexy, brief periods of muscle weakness triggered by strong emotions. Many researchers are now studying mouse models of narcolepsy, but definitions of cataplexy-like behavior in mice differ across labs. To establish a common language, the International Working Group on Rodent Models of Narcolepsy reviewed the literature on cataplexy in people with narcolepsy and in dog and mouse models of narcolepsy and then developed a consensus definition of murine cataplexy. The group concluded that murine cataplexy is an abrupt episode of nuchal atonia lasting at least 10 seconds. In addition, theta activity dominates the EEG during the episode, and video recordings document immobility. To distinguish a cataplexy episode from REM sleep after a brief awakening, at least 40 seconds of wakefulness must precede the episode. Bouts of cataplexy fitting this definition are common in mice with disrupted orexin/hypocretin signaling, but these events almost never occur in wild type mice. It remains unclear whether murine cataplexy is triggered by strong emotions or whether mice remain conscious during the episodes as in people with narcolepsy. This working definition provides helpful insights into murine cataplexy and should allow objective and accurate comparisons of cataplexy in future studies using mouse models of narcolepsy.

  11. Narcolepsy and the hypocretins.

    Science.gov (United States)

    Wurtman, Richard J

    2006-10-01

    Narcolepsy is a chronic neurologic disease characterized by excessive daytime sleepiness and one or more of three additional symptoms (cataplexy, or sudden loss of muscle tone; vivid hallucinations; and brief periods of total paralysis) related to the occurrence of rapid eye movement (REM) sleep at inappropriate times. The daytime sleepiness typically presents as a sudden overwhelming urge to sleep, followed by periods of sleep that last for seconds or minutes, or even longer. During daytime sleep episodes, patients may exhibit "automatic behavior," performing conventionalized functions (eg, taking notes), but not remembering having done so once they are awake. About 10% of narcoleptics are members of familial clusters; however, genetic factors alone are apparently insufficient to cause the disease, inasmuch as the most common genetic disorder, a mutation in chromosome 6 controlling the HLA antigen immune complex, although seen in 90% to 100% of patients, also occurs in as many as 50% of people without narcolepsy. A dog model of narcolepsy exhibits a mutation on chromosome 12 that disrupts the processing of the peptide neurotransmitter hypocretin. No such mutation characterizes human narcolepsy; however, cerebrospinal fluid (CSF) hypocretin levels are profoundly depressed in narcoleptic patients, and a specific reduction in hypocretin-containing neurons has been described. One hypothesis concerning the pathophysiology of narcolepsy proposes that the HLA subtype resulting from the mutation on chromosome 6 increases the susceptibility of hypocretin-containing brain neurons to immune attack. Because hypocretin may normally participate in the maintenance of wakefulness, the loss of neurons that release this peptide might allow REM sleep to occur at inappropriate times, ie, while the patient is awake, in contrast to its normal cyclic appearance after a period of slow-wave sleep. The cataplexy, hallucinations, and/or paralysis associated with REM episodes normally are

  12. Anesthetic Management of Narcolepsy Patients During Surgery: A Systematic Review.

    Science.gov (United States)

    Hu, Sally; Singh, Mandeep; Wong, Jean; Auckley, Dennis; Hershner, Shelley; Kakkar, Rahul; Thorpy, Michael J; Chung, Frances

    2018-01-01

    Narcolepsy is a rare sleep disorder characterized by excessive daytime sleepiness, sleep paralysis, and/or hypnagogic/hypnopompic hallucinations, and in some cases cataplexy. The response to anesthetic medications and possible interactions in narcolepsy patients is unclear in the perioperative period. In this systematic review, we aim to evaluate the current evidence on the perioperative outcomes and anesthetic considerations in narcolepsy patients. Electronic literature search of Medline, Medline in-process, Embase, Cochrane Database of Systematic Reviews databases, international conference proceedings, and abstracts was conducted in November 2015 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols guideline. A total of 3757 articles were screened using a 2-stage strategy (title-abstract followed by full text). We included case studies/series, cohort studies, and randomized controlled trials of narcolepsy patients undergoing surgical procedures under anesthesia or sedation. Preoperative narcolepsy symptoms and sleep study data, anesthetic technique, and perioperative complications were extracted. Screening of articles, data extraction, and compilation were conducted by 2 independent reviewers and any conflict was resolved by the senior author. A total of 19 studies including 16 case reports and 3 case series were included and evaluated. The majority of these patients received general anesthesia, whereas a small percentage of patients received regional anesthesia. Reported complications of narcolepsy patients undergoing surgeries were mainly related to autonomic dysregulation, or worsening of narcolepsy symptoms intra/postoperatively. Narcolepsy symptoms worsened only in those patient populations where the preoperative medications were either discontinued or reduced (mainly in obstetric patients). In narcolepsy patients, use of depth of anesthesia monitoring and total intravenous technique may have some advantage in terms

  13. Causes of Hypersomnia – Narcolepsy

    Directory of Open Access Journals (Sweden)

    M V Padma Srivastav

    2014-03-01

    Full Text Available The causes of hypersomnia or excessive daytime sleepiness (EDS besides volitionalsleep deprivation and obstructive sleep apnea are principally due to primary centralnervous system abnormalities. Most common amongst these is Narcolepsy, a primarydisorder of the neural control of wakefulness and sleep. The recent discovery ofhypocretin/orexin deficiency as the main cause of narcolepsy will lead to importanttherapeutic advances for patients with narcolepsy and further to understanding of thecontrol of sleep and wakefulness in general. Importantly, the excessive daytimesleepiness is not due to psychiatric conditions, but rather is always due to sleepdeprivation or an underlying diagnosable and treatable sleep disorder.Key words : EDS, Sleep, Narcolepsy

  14. Pharmacological studies of the lung with PET

    International Nuclear Information System (INIS)

    Syrota, A.

    1986-10-01

    Positron emission tomography (PET), known to be used for lung ventilation and perfusion studies, can also be used in pharmacology to obtain information that is otherwise not available. The lung takes up biologically active substances which can be inactivated or activated, and synthesises and releases others. Such information in man has been obtained from samples of human lungs, or from in vivo first-pass studies, invasive or not, as well as from in vivo kinetic studies using external detection methods with scintillation cameras. PET provides now quantitative regional data in the human lung

  15. Narcolepsy as an Immune-Mediated Disease

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    Alberto K. De la Herrán-Arita

    2014-01-01

    Full Text Available Narcolepsy is a neurological disorder characterized by excessive daytime sleepiness, cataplexy, hypnagonic hallucinations, sleep paralysis, and disturbed nocturnal sleep patterns. This disease is secondary to the specific loss of hypothalamic hypocretin (orexin-producing neurons in the lateral hypothalamus. An autoimmune basis for the disease has long been suspected based on its strong association with the genetic marker DQB1*06:02, and current studies greatly support this hypothesis. Narcolepsy with hypocretin deficiency is associated with human leukocyte antigen (HLA and T cell receptor (TCR polymorphisms, suggesting that an autoimmune process targets a peptide unique to hypocretin-producing neurons via specific HLA-peptide-TCR interactions. This concept has gained a lot of notoriety after the increase of childhood narcolepsy in 2010 following the 2009 H1N1 pandemic (pH1N1 in China and vaccination with Pandemrix, an adjuvanted H1N1 vaccine that was used in Scandinavia. The surge of narcolepsy cases subsequent to influenza A H1N1 infection and H1N1 vaccination suggests that processes such as molecular mimicry or bystander activation might be crucial for disease development.

  16. Sleep transitions in hypocretin-deficient narcolepsy.

    Science.gov (United States)

    Sorensen, Gertrud Laura; Knudsen, Stine; Jennum, Poul

    2013-08-01

    Narcolepsy is characterized by instability of sleep-wake, tonus, and rapid eye movement (REM) sleep regulation. It is associated with severe hypothalamic hypocretin deficiency, especially in patients with cataplexy (loss of tonus). As the hypocretin neurons coordinate and stabilize the brain's sleep-wake pattern, tonus, and REM flip-flop neuronal centers in animal models, we set out to determine whether hypocretin deficiency and/or cataplexy predicts the unstable sleep-wake and REM sleep pattern of the human phenotype. We measured the frequency of transitions in patients with narcolepsy between sleep-wake states and to/from REM and NREM sleep stages. Patients were subdivided by the presence of +/- cataplexy and +/- hypocretin-1 deficiency. Sleep laboratory studies conducted from 2001-2011. In total 63 narcolepsy patients were included in the study. Cataplexy was present in 43 of 63 patients and hypocretin-1 deficiency was present in 37 of 57 patients. Hypocretin-deficient patients with narcolepsy had a significantly higher frequency of sleep-wake transitions (P = 0.014) and of transitions to/from REM sleep (P = 0.044) than patients with normal levels of hypocretin-1. Patients with cataplexy had a significantly higher frequency of sleep-wake transitions (P = 0.002) than those without cataplexy. A multivariate analysis showed that transitions to/from REM sleep were predicted mainly by hypocretin-1 deficiency (P = 0.011), whereas sleep-wake transitions were predicted mainly by cataplexy (P = 0.001). In human narcolepsy, hypocretin deficiency and cataplexy are both associated with signs of destabilized sleep-wake and REM sleep control, indicating that the disorder may serve as a human model for the sleep-wake and REM sleep flip-flop switches.

  17. Parkinson's disease and narcolepsy-like symptoms.

    Science.gov (United States)

    Ylikoski, Ari; Martikainen, Kirsti; Sarkanen, Tomi; Partinen, Markku

    2015-04-01

    Various sleep-related problems, for example, insomnia and symptoms of rapid eye movement behavior disorder (RBD), are common in patients with Parkinson's disease (PD). We studied the prevalence of symptoms of narcolepsy (NARC), hallucinations, and RBD and their association with other symptoms. Altogether, 1447 randomly selected patients with PD, aged 43-89 years, participated in a questionnaire study. A structured questionnaire with 207 items was based on the Basic Nordic Sleep Questionnaire. Questions on demographics, PD, RBD, and other issues were included. The response rate was 59.0%; of these patients, 73% had answered to all questions that were used in the analyses (N = 623). The occurrence of suspected narcolepsy (Ullanlinna Narcolepsy Scale ≥ 14 and Epworth Sleepiness Scale ≥ 11) was observed in 9.3% of the subjects (PD with NARC), RBD (REM Sleep Behavior Disorder Screening Questionnaire ≥ 6) in 39.2% of all patients with PD, and in 62.1% of those with PD and NARC. In patients with PD, hallucinations before going to bed in the evening occurred in 5.8%, hypnagogic hallucinations in 4.0%, hallucinations during night 8.3%, and hypnopompic hallucinations in 3.2%. Cataplexy symptoms occurred in 43.1% of subjects with PD and NARC. In a logistic regression analysis, PD with NARC was associated with RBD, all types of hallucinations, daytime sleepiness, fatigue, insomnia, and intense dreaming also when adjusted for age, sex, disease duration, and levodopa. Narcolepsy-like symptoms may be present in patients with PD. Symptoms of RBD were associated with symptoms of narcolepsy including symptoms of cataplexy. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Prostaglandin D2 Receptor DP1 Antibodies Predict Vaccine-induced and Spontaneous Narcolepsy Type 1: Large-scale Study of Antibody Profiling

    Directory of Open Access Journals (Sweden)

    Helle Sadam

    2018-03-01

    Full Text Available Background: Neuropathological findings support an autoimmune etiology as an underlying factor for loss of orexin-producing neurons in spontaneous narcolepsy type 1 (narcolepsy with cataplexy; sNT1 as well as in Pandemrix influenza vaccine-induced narcolepsy type 1 (Pdmx-NT1. The precise molecular target or antigens for the immune response have, however, remained elusive. Methods: Here we have performed a comprehensive antigenic repertoire analysis of sera using the next-generation phage display method - mimotope variation analysis (MVA. Samples from 64 children and adolescents were analyzed: 10 with Pdmx-NT1, 6 with sNT1, 16 Pandemrix-vaccinated, 16 H1N1 infected, and 16 unvaccinated healthy individuals. The diagnosis of NT1 was defined by the American Academy of Sleep Medicine international criteria of sleep disorders v3. Findings: Our data showed that although the immunoprofiles toward vaccination were generally similar in study groups, there were also striking differences in immunoprofiles between sNT1 and Pdmx-NT1 groups as compared with controls. Prominent immune response was observed to a peptide epitope derived from prostaglandin D2 receptor (DP1, as well as peptides homologous to B cell lymphoma 6 protein. Further validation confirmed that these can act as true antigenic targets in discriminating NT1 diseased along with a novel epitope of hemagglutinin of H1N1 to delineate exposure to H1N1. Interpretation: We propose that DP1 is a novel molecular target of autoimmune response and presents a potential diagnostic biomarker for NT1. DP1 is involved in the regulation of non-rapid eye movement (NREM sleep and thus alterations in its functions could contribute to the disturbed sleep regulation in NT1 that warrants further studies. Together our results also show that MVA is a helpful method for finding novel peptide antigens to classify human autoimmune diseases, possibly facilitating the design of better therapies. Keywords: Narcolepsy type 1

  19. DIVERSE POTENTIAL AND PHARMACOLOGICAL STUDIES OF ARGININE

    Directory of Open Access Journals (Sweden)

    Anju Meshram

    2015-09-01

    Full Text Available Arginine is metabolically flexible amino acid with major role in protein synthesis and detoxification of ammonia. It is involved in several metabolic pathways for the production of biologically active compounds such as creatine, nitric oxide, ornithine, glutamate, agmatine, citrulline and polyamines. Regarding this all, we review the crucial role of arginine in metabolism, diversified prospective uses and pharmacological applications. Arginine plays an important role in the treatment of tumorigenesis, asthama, gastric, erectile dysfunction, apoptosis, melanoma and congestive heart failure. Ability to produce nitric oxide offers various applications as in the prevention of age and hair loss. It serves as a precursor of creatine with ergogenic potential. The ability to increase endogenous growth hormone makes arginine a preferred supplement for the improvement of physical performance. In the present study details about the pharmacological applications of arginine based on modern scientific investigations have been discussed. There are immense properties hidden in arginine that need to be explored using the scientific investigations to make it beneficial for the medicine and human health. More research is needed to evaluate the role of arginine supplementation on exercise performance and training adaptations in healthy and diseased populations before taking any conclusions.

  20. Increased immune complexes of hypocretin autoantibodies in narcolepsy.

    Science.gov (United States)

    Deloumeau, Aude; Bayard, Sophie; Coquerel, Quentin; Déchelotte, Pierre; Bole-Feysot, Christine; Carlander, Bertrand; Cochen De Cock, Valérie; Fetissov, Sergueï O; Dauvilliers, Yves

    2010-10-13

    Hypocretin peptides participate in the regulation of sleep-wake cycle while deficiency in hypocretin signaling and loss of hypocretin neurons are causative for narcolepsy-cataplexy. However, the mechanism responsible for alteration of the hypocretin system in narcolepsy-cataplexy and its relevance to other central hypersomnias remain unknown. Here we studied whether central hypersomnias can be associated with autoantibodies reacting with hypocretin-1 peptide present as immune complexes. Serum levels of free and dissociated (total) autoantibodies reacting with hypocretin-1 peptide were measured by enzyme-linked immunosorbent assay and analyzed with regard to clinical parameters in 82 subjects with narcolepsy-cataplexy, narcolepsy without cataplexy or idiopathic hypersomnia and were compared to 25 healthy controls. Serum levels of total but not free IgG autoantibodies against hypocretin-1 were increased in narcolepsy-cataplexy. Increased levels of complexed IgG autoantibodies against hypocretin-1 were found in all patients groups with a further increase in narcolepsy-cataplexy. Levels of total IgM hypocretin-1 autoantibodies were also elevated in all groups of patients. Increased levels of anti-idiotypic IgM autoantibodies reacting with hypocretin-1 IgG autoantibodies affinity purified from sera of subjects with narcolepsy-cataplexy were found in all three groups of patients. Disease duration correlated negatively with serum levels of hypocretin-1 IgG and IgM autoantibodies and with anti-idiotypic IgM autoantibodies. Central hypersomnias and particularly narcolepsy-cataplexy are characterized by higher serum levels of autoantibodies directed against hypocretin-1 which are present as immune complexes most likely with anti-idiotypic autoantibodies suggesting their relevance to the mechanism of sleep-wake cycle regulation.

  1. Increased immune complexes of hypocretin autoantibodies in narcolepsy.

    Directory of Open Access Journals (Sweden)

    Aude Deloumeau

    Full Text Available BACKGROUND: Hypocretin peptides participate in the regulation of sleep-wake cycle while deficiency in hypocretin signaling and loss of hypocretin neurons are causative for narcolepsy-cataplexy. However, the mechanism responsible for alteration of the hypocretin system in narcolepsy-cataplexy and its relevance to other central hypersomnias remain unknown. Here we studied whether central hypersomnias can be associated with autoantibodies reacting with hypocretin-1 peptide present as immune complexes. METHODOLOGY: Serum levels of free and dissociated (total autoantibodies reacting with hypocretin-1 peptide were measured by enzyme-linked immunosorbent assay and analyzed with regard to clinical parameters in 82 subjects with narcolepsy-cataplexy, narcolepsy without cataplexy or idiopathic hypersomnia and were compared to 25 healthy controls. PRINCIPAL FINDINGS: Serum levels of total but not free IgG autoantibodies against hypocretin-1 were increased in narcolepsy-cataplexy. Increased levels of complexed IgG autoantibodies against hypocretin-1 were found in all patients groups with a further increase in narcolepsy-cataplexy. Levels of total IgM hypocretin-1 autoantibodies were also elevated in all groups of patients. Increased levels of anti-idiotypic IgM autoantibodies reacting with hypocretin-1 IgG autoantibodies affinity purified from sera of subjects with narcolepsy-cataplexy were found in all three groups of patients. Disease duration correlated negatively with serum levels of hypocretin-1 IgG and IgM autoantibodies and with anti-idiotypic IgM autoantibodies. CONCLUSION: Central hypersomnias and particularly narcolepsy-cataplexy are characterized by higher serum levels of autoantibodies directed against hypocretin-1 which are present as immune complexes most likely with anti-idiotypic autoantibodies suggesting their relevance to the mechanism of sleep-wake cycle regulation.

  2. Health-related stigma as a determinant of functioning in young adults with narcolepsy.

    Directory of Open Access Journals (Sweden)

    Mary C Kapella

    Full Text Available Symptoms of narcolepsy tend to arise during adolescence or young adulthood, a formative time in human development during which people are usually completing their education and launching a career. Little is known about the impact of narcolepsy on the social aspects of health-related quality of life in young adults. The purpose of this study was to examine relationships between health-related stigma, mood (anxiety and depression and daytime functioning in young adults with narcolepsy compared to those without narcolepsy. Young adults (age 18-35 with narcolepsy (N = 122 and without narcolepsy (N = 93 were mailed a packet that included questionnaires and a self-addressed postage paid envelope. The questionnaire included demographic information and a composite of instruments including the SF 36, Functional Outcomes of Sleep Questionnaire (FOSQ, Fife Stigma Scale (FSS, Epworth Sleepiness Scale (ESS and Hospital Anxiety and Depression Scale (HADS. Variable associations were assessed using descriptive statistics, ANOVA, Mann-Whitney U Test, correlations, stepwise multiple regression and path analysis. Young adults with narcolepsy perceived significantly more stigma and lower mood and health-related quality of life than young adults without narcolepsy (p<0.01. Health-related stigma was directly and indirectly associated with lower functioning through depressed mood. Fifty-two percent of the variance in functioning was explained by the final model in the young adults with narcolepsy. Health-related stigma in young adults with narcolepsy is at a level consistent with other chronic medical illnesses. Health-related stigma may be an important determinant of functioning in young adults with narcolepsy. Future work is indicated toward further characterizing stigma and developing interventions that address various domains of stigma in people with narcolepsy.

  3. Health-related stigma as a determinant of functioning in young adults with narcolepsy.

    Science.gov (United States)

    Kapella, Mary C; Berger, Barbara E; Vern, Boris A; Vispute, Sachin; Prasad, Bharati; Carley, David W

    2015-01-01

    Symptoms of narcolepsy tend to arise during adolescence or young adulthood, a formative time in human development during which people are usually completing their education and launching a career. Little is known about the impact of narcolepsy on the social aspects of health-related quality of life in young adults. The purpose of this study was to examine relationships between health-related stigma, mood (anxiety and depression) and daytime functioning in young adults with narcolepsy compared to those without narcolepsy. Young adults (age 18-35) with narcolepsy (N = 122) and without narcolepsy (N = 93) were mailed a packet that included questionnaires and a self-addressed postage paid envelope. The questionnaire included demographic information and a composite of instruments including the SF 36, Functional Outcomes of Sleep Questionnaire (FOSQ), Fife Stigma Scale (FSS), Epworth Sleepiness Scale (ESS) and Hospital Anxiety and Depression Scale (HADS). Variable associations were assessed using descriptive statistics, ANOVA, Mann-Whitney U Test, correlations, stepwise multiple regression and path analysis. Young adults with narcolepsy perceived significantly more stigma and lower mood and health-related quality of life than young adults without narcolepsy (p<0.01). Health-related stigma was directly and indirectly associated with lower functioning through depressed mood. Fifty-two percent of the variance in functioning was explained by the final model in the young adults with narcolepsy. Health-related stigma in young adults with narcolepsy is at a level consistent with other chronic medical illnesses. Health-related stigma may be an important determinant of functioning in young adults with narcolepsy. Future work is indicated toward further characterizing stigma and developing interventions that address various domains of stigma in people with narcolepsy.

  4. Delusional Confusion of Dreaming and Reality in Narcolepsy

    Science.gov (United States)

    Wamsley, Erin; Donjacour, Claire E.H.M.; Scammell, Thomas E.; Lammers, Gert Jan; Stickgold, Robert

    2014-01-01

    Study Objectives: We investigated a generally unappreciated feature of the sleep disorder narcolepsy, in which patients mistake the memory of a dream for a real experience and form sustained delusions about significant events. Design: We interviewed patients with narcolepsy and healthy controls to establish the prevalence of this complaint and identify its predictors. Setting: Academic medical centers in Boston, Massachusetts and Leiden, The Netherlands. Participants: Patients (n = 46) with a diagnosis of narcolepsy with cataplexy, and age-matched healthy healthy controls (n = 41). Interventions: N/A. Measurements and Results: “Dream delusions” were surprisingly common in narcolepsy and were often striking in their severity. As opposed to fleeting hypnagogic and hypnopompic hallucinations of the sleep/wake transition, dream delusions were false memories induced by the experience of a vivid dream, which led to false beliefs that could persist for days or weeks. Conclusions: The delusional confusion of dreamed events with reality is a prominent feature of narcolepsy, and suggests the possibility of source memory deficits in this disorder that have not yet been fully characterized. Citation: Wamsley E; Donjacour CE; Scammell TE; Lammers GJ; Stickgold R. Delusional confusion of dreaming and reality in narcolepsy. SLEEP 2014;37(2):419-422. PMID:24501437

  5. The Familial Risk and HLA Susceptibility among Narcolepsy Patients in Hong Kong Chinese

    Science.gov (United States)

    Chen, Lei; Fong, S.Y.Y.; Lam, Ching W.; Tang, Nelson L.S.; Ng, Margaret H. L.; Li, Albert M.; Ho, C.K.W.; Cheng, Suk-Hang; Lau, Kin-Mang; Wing, Yun Kwok

    2007-01-01

    Study Objectives: To explore the familial aggregation and HLA susceptibility of narcolepsy in Hong Kong Chinese by objective sleep measurements and HLA typing. Design: Case control design Participants: Twelve narcoleptic probands, 34 first-degree relatives, and 30 healthy controls. Interventions: N/A Measurements and Results: Each subject underwent a standardized nocturnal polysomnogram (PSG), followed by a daytime multiple sleep latency test (MSLT). HLA typing was performed for all subjects. One relative (2.9%) was diagnosed as suffering from narcolepsy with cataplexy. Nearly 30% of the relatives fulfilled the criteria of narcolepsy spectrum disorder (shortened mean sleep latency [MSL] and/or the presence of sleep onset REM periods [SOREMPs]). When using the population data for comparison, the relative risk of narcolepsy in first-degree relatives was 85.3. The odds ratio of narcolepsy spectrum disorder in first-degree relatives was 5.8 (95% CI: 1.2 – 29.3) when compared to healthy controls. There existed 6 multiplex families, in which all 10 relatives with narcolepsy spectrum disorders, including all 3 relatives with multiple SOREMPs, were positive for HLA DQB1*0602. Conclusions: Our study demonstrated a definitive familial aggregation of narcolepsy, narcolepsy spectrum disorders, and possibly cataplexy in Hong Kong Chinese. This familial aggregation supported an inherited basis for narcolepsy spectrum. The tight co-segregation of HLA DQB1*0602 and narcolepsy spectrum disorders might suggest that HLA typing, especially DQB1*0602, at least partly confer the familial risk of narcolepsy. In addition, our study suggested that the subjective questionnaire measurements including Ullanlinna Narcolepsy Scale and Epworth Sleepiness Scale were unable to detect the presence of narcolepsy spectrum disorders among the relatives. A stringent objective measurement-based design for family studies is suggested for future study. Further studies are indicated for the determination

  6. Misleading hallucinations in unrecognized narcolepsy.

    Science.gov (United States)

    Szucs, A; Janszky, J; Holló, A; Migléczi, G; Halász, P

    2003-10-01

    To describe psychosis-like hallucinatory states in unrecognized narcolepsy. Two patients with hypnagogic/hypnapompic hallucinations are presented. Both patients had realistic and complex - multi-modal and scenic-daytime sexual hallucinations leading, in the first case, to a legal procedure because of false accusation, and in the second, to serious workplace conflicts. Both patients were convinced of the reality of their hallucinatory experiences but later both were able to recognize their hallucinatory character. Clinical data, a multiple sleep latency test, polysomnography, and HLA typing revealed that both patients suffered from narcolepsy. We suggest that in unrecognized narcolepsy with daytime hypnagogic/hypnapompic hallucinations the diagnostic procedure may mistakenly incline towards delusional psychoses. Daytime realistic hypnagogic/hypnapompic hallucinations may also have forensic consequences and mislead legal evaluation. Useful clinical features in differentiating narcolepsy from psychoses are: the presence of other narcoleptic symptoms, features of hallucinations, and response to adequate medication.

  7. Genetic association, seasonal infections and autoimmune basis of narcolepsy

    Science.gov (United States)

    Singh, Abinav Kumar; Mahlios, Josh; Mignot, Emmanuel

    2014-01-01

    In recent years, a growing number of potential autoimmune disorders affecting neurons in the central nervous system have been identified, including narcolepsy. Narcolepsy is a lifelong sleep disorder characterized by excessive daytime sleepiness with irresistible sleep attacks, cataplexy (sudden bilateral loss of muscle tone), hypnagogic hallucinations, and abnormalities of Rapid Eye Movement sleep. Narcolepsy is generally a sporadic disorder and is caused by the loss of hypocretin (orexin)-producing neurons in the hypothalamus region of the brain. Studies have established that more than 90% of patients have a genetic association with HLA DQB1*06:02. Genome-wide association analysis shows a strong association between narcolepsy and polymorphisms in the TCRα locus and weaker associations within TNFSF4 (also called OX40L), Cathepsin H and the P2RY11-DNMT1 (purinergic receptor subtype P2Y11 to DNMT1, a DNA methytransferase) loci, suggesting an autoimmune basis. Mutations in DNMT1 have also been reported to cause narcolepsy in association with a complex neurological syndrome, suggesting the importance of DNA methylation in the pathology. More recently, narcolepsy was identified in association with seasonal streptococcus, H1N1 infections and following AS03-adjuvanted pH1N1 influenza vaccination in Northern Europe. Potential immunological pathways responsible for the loss of hypocretin producing neurons in these cases may be molecular mimicry or bystander activation. Specific autoantibodies or T cells cross-reactive with hypocretin neurons have not yet been identified, however, thus narcolepsy does not meet Witebsky’s criteria for an autoimmune disease. As the brain is not an easily accessible organ, mechanisms of disease initiation and progression remain a challenge to researchers. PMID:23497937

  8. Pharmacological Experimental Study Of The Anti-Depressant Effect ...

    African Journals Online (AJOL)

    Pharmacological Experimental Study Of The Anti-Depressant Effect Of Total Saikosaponins. Y Liu, C Cao, H Ding. Abstract. Background: Chai Hu has the hepato-protective, choleretic, anti-tussive, analgesic, anti-inflammatory, anti-viral, hypotensive, hypolipidemic, and anti-tumor pharmacological effects. In this study, the ...

  9. Cerebrospinal fluid hypocretin 1 deficiency, overweight, and metabolic dysregulation in patients with narcolepsy.

    Science.gov (United States)

    Heier, Mona S; Jansson, Tine S; Gautvik, Kaare M

    2011-12-15

    The possible relationship between cerebrospinal fluid (CSF) hypocretin and leptin levels, overweight, and association to risk factors for diabetes 2 in narcolepsy with cataplexy were compared to patients with idiopathic hypersomnia and controls. 26 patients with narcolepsy, cataplexy, and hypocretin deficiency; 23 patients with narcolepsy, cataplexy, and normal hypocretin values; 11 patients with idiopathic hypersomnia; and 43 controls. Body mass index (BMI), serum leptin, and HbA1C were measured in patients and controls; and CSF hypocretin 1 and leptin measured in all patients. Female and male patients with narcolepsy and hypocretin deficiency had the highest mean BMI (27.8 and 26.2, respectively), not statistically different from patients with narcolepsy and normal hypocretin or controls, but statistically higher than the patients with idiopathic hypersomnia (p 30) was increased in both narcolepsy groups. Serum and CSF leptin levels correlated positively to BMI in patients and controls, but not to CSF hypocretin concentrations. HbA1C was within normal levels and similar in all groups. The study confirms a moderate tendency to obesity (BMI > 30) and overweight in patients with narcolepsy and cataplexy. Obesity was not correlated to hypocretin deficiency or reduced serum or CSF leptin concentrations. We suggest that overweight and possible metabolic changes previously reported in narcolepsy, may be caused by other mechanisms.

  10. Rapid eye movement sleep behaviour disorder in patients with narcolepsy is associated with hypocretin-1 deficiency

    DEFF Research Database (Denmark)

    Knudsen, Stine; Gammeltoft, Steen; Jennum, Poul J

    2010-01-01

    Rapid eye movement sleep behaviour disorder is characterized by dream-enacting behaviour and impaired motor inhibition during rapid eye movement sleep. Rapid eye movement sleep behaviour disorder is commonly associated with neurodegenerative disorders, but also reported in narcolepsy with cataplexy....... Most narcolepsy with cataplexy patients lack the sleep-wake, and rapid eye movement sleep, motor-regulating hypocretin neurons in the lateral hypothalamus. In contrast, rapid eye movement sleep behaviour disorder and hypocretin deficiency are rare in narcolepsy without cataplexy. We hypothesized...... that rapid eye movement sleep behaviour disorder coexists with cataplexy in narcolepsy due to hypocretin deficiency. In our study, rapid eye movement sleep behaviour disorder was diagnosed by the International Classification of Sleep Disorders (2nd edition) criteria in 63 narcolepsy patients with or without...

  11. Comparison of driving simulator performance and neuropsychological testing in narcolepsy.

    Science.gov (United States)

    Kotterba, Sylvia; Mueller, Nicole; Leidag, Markus; Widdig, Walter; Rasche, Kurt; Malin, Jean-Pierre; Schultze-Werninghaus, Gerhard; Orth, Maritta

    2004-09-01

    Daytime sleepiness and cataplexy can increase automobile accident rates in narcolepsy. Several countries have produced guidelines for issuing a driving license. The aim of the study was to compare driving simulator performance and neuropsychological test results in narcolepsy in order to evaluate their predictive value regarding driving ability. Thirteen patients with narcolepsy (age: 41.5+/-12.9 years) and 10 healthy control patients (age: 55.1+/-7.8 years) were investigated. By computer-assisted neuropsychological testing, vigilance, alertness and divided attention were assessed. In a driving simulator patients and controls had to drive on a highway for 60 min (mean speed of 100 km/h). Different weather and daytime conditions and obstacles were presented. Epworth Sleepiness Scale-Scores were significantly raised (narcolepsy patients: 16.7+/-5.1, controls: 6.6+/-3.6, P divided attention (56.9+/-25.4) and vigilance (58.7+/-26.8) were in a normal range. There was, however, a high inter-individual difference. There was no correlation between driving performance and neuropsychological test results or ESS Score. Neuropsychological test results did not significantly change in the follow-up. The difficulties encountered by the narcolepsy patient in remaining alert may account for sleep-related motor vehicle accidents. Driving simulator investigations are closely related to real traffic situations than isolated neuropsychological tests. At the present time the driving simulator seems to be a useful instrument judging driving ability especially in cases with ambiguous neuropsychological results.

  12. Juvenile myoclonic epilepsy and narcolepsy: A series of three cases.

    Science.gov (United States)

    Joshi, Puja Aggarwal; Poduri, Annapurna; Kothare, Sanjeev V

    2015-10-01

    This paper sets out to demonstrate the coexistence of juvenile myoclonic epilepsy (JME) and narcolepsy that raises the possibility of a shared genetic predisposition to both conditions. The electronic medical records (EMRs) were searched for narcolepsy and JME over 10years. We identified three young adult women diagnosed with JME in their teenage years, with myoclonic, generalized tonic-clonic, and absence seizure semiologies, along with psychiatric comorbidity, well managed on lamotrigine and/or levetiracetam. Our patients were also found to have disturbed sleep preceding the diagnosis of JME by many years, including excessive daytime sleepiness (EDS), fragmented nocturnal sleep, hypnagogic vivid hallucinations, and REM behavior disorder along with daytime cataplexy. They were ultimately diagnosed with coexisting narcolepsy, confirmed by sleep studies and multiple sleep latency testing, along with positive genetic testing for HLA-DQB1*0602 in all three patients. Stimulants, selective serotonin receptor inhibitors, and/or sodium oxybate were used to successfully treat their narcolepsy. The coexistence of JME and narcolepsy has not been well recognized and may be clinically relevant. In addition, it raises the possibility of a shared genetic predisposition to both conditions. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Sleep spindle density in narcolepsy

    DEFF Research Database (Denmark)

    Christensen, Julie Anja Engelhard; Nikolic, Miki; Hvidtfelt, Mathias

    2017-01-01

    BACKGROUND: Patients with narcolepsy type 1 (NT1) show alterations in sleep stage transitions, rapid-eye-movement (REM) and non-REM sleep due to the loss of hypocretinergic signaling. However, the sleep microstructure has not yet been evaluated in these patients. We aimed to evaluate whether...... the sleep spindle (SS) density is altered in patients with NT1 compared to controls and patients with narcolepsy type 2 (NT2). METHODS: All-night polysomnographic recordings from 28 NT1 patients, 19 NT2 patients, 20 controls (C) with narcolepsy-like symptoms, but with normal cerebrospinal fluid hypocretin...... levels and multiple sleep latency tests, and 18 healthy controls (HC) were included. Unspecified, slow, and fast SS were automatically detected, and SS densities were defined as number per minute and were computed across sleep stages and sleep cycles. The between-cycle trends of SS densities in N2...

  14. Narcolepsy: Association with H1N1 Infection and Vaccination

    Directory of Open Access Journals (Sweden)

    Ji Hyun Song

    2016-12-01

    Full Text Available Epidemiological studies have demonstrated an association between H1N1 influenza infection and vaccinations. This article reviews the various studies, and suggests the biological mechanisms explaining why and how H1N1 influenza infection or vaccine stimulates the autoimmune response, thereby resulting in narcolepsy. Among the vaccines, the effect of Pandemrix was scrutinized more than other vaccines, due to its higher association with an increase of narcolepsy onset. The consequences of using other vaccines which contain same or different adjuvants as Pandemrix, were also analyzed.

  15. Risks of neurological and immune-related diseases, including narcolepsy, after vaccination with Pandemrix: a population- and registry-based cohort study with over 2 years of follow-up.

    Science.gov (United States)

    Persson, I; Granath, F; Askling, J; Ludvigsson, J F; Olsson, T; Feltelius, N

    2014-02-01

    To investigate the association between vaccination with Pandemrix and risk of selected neurological and immune-related diseases including narcolepsy. Population-based prospective cohort study using data from regional vaccination registries and national health registries. Seven healthcare regions in Sweden comprising 61% of the Swedish population. Study population of 3,347,467 vaccinated and 2,497,572 nonvaccinated individuals (vaccination coverage ≈ 60%) followed between 2009 and 2011 for 6.9 million person-years after exposure and 6.0 million person-years without exposure. First recorded diagnosis of neurological and immune-related diseases. Relative risks [hazard ratios (HRs) with 95% confidence intervals (CIs)] assessed using Cox regression, adjusted for covariates. For all selected neurological and immune-related outcomes under study, other than allergic vaccine reactions (for which we verified an expected increase in risk) and narcolepsy, HRs were close to 1.0 and always below 1.3. We observed a three-fold increased risk of a diagnosis of narcolepsy (HR: 2.92, 95% CI: 1.78-4.79; that is, four additional cases per 100,000 person-years) in individuals ≤ 20 years of age at vaccination and a two-fold increase (HR: 2.18, 95% CI: 1.00-4.75) amongst young adults between 21 and 30 years of age. The excess risk declined successively with increasing age at vaccination; no increase in risk was seen after 40 years of age. For a large number of selected neurological and immune-related diseases, we could neither confirm any causal association with Pandemrix nor refute entirely a small excess risk. We confirmed an increased risk for a diagnosis of narcolepsy in individuals ≤ 20 years of age and observed a trend towards an increased risk also amongst young adults between 21 and 30 years. © 2013 The Association for the Publication of the Journal of Internal Medicine.

  16. Antibodies Against Hypocretin Receptor 2 Are Rare in Narcolepsy.

    Science.gov (United States)

    Giannoccaro, Maria Pia; Waters, Patrick; Pizza, Fabio; Liguori, Rocco; Plazzi, Giuseppe; Vincent, Angela

    2017-02-01

    Recently, antibodies to the hypocretin receptor 2 (HCRTR2-Abs) were reported in a high proportion of narcolepsy patients who developed the disease following Pandemrix® vaccination. We tested a group of narcolepsy patients for the HCRTR2-Abs using a newly established cell-based assay. Sera from 50 narcolepsy type 1 (NT1) and 11 narcolepsy type 2 (NT2) patients, 22 patients with other sleep disorders, 15 healthy controls, and 93 disease controls were studied. Cerebrospinal fluid (CSFs) from three narcoleptic patients were subsequently included. Human embryonic kidney cells were transiently transfected with human HCRTR2, incubated with patients' sera for 1 hr at 1:20 dilution and then fixed. Binding of antibodies was detected by fluorescently labeled secondary antibodies to human immunoglobulin G (IgG) and the different IgG subclasses. A nonlinear visual scoring system was used from 0 to 4; samples scoring ≥1 were considered positive. Only 3 (5%) of 61 patients showed a score ≥1, one with IgG1- and two with IgG3-antibodies, but titers were low (1:40-1:100). CSFs from these patients were negative. The three positive patients included one NT1 case with associated psychotic features, one NT2 patient, and an NT1 patient with normal hypocretin CSF levels. Low levels of IgG1 or IgG3 antibodies against HCRTR2 were found in 3 of 61 patients with narcolepsy, although only 1 presented with full-blown NT1. HCRTR2-Abs are not common in narcolepsy unrelated to vaccination. © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  17. Obesity accompanies narcolepsy with cataplexy but not narcolepsy without cataplexy

    Czech Academy of Sciences Publication Activity Database

    Šonka, K.; Kemlink, D.; Bušková, J.; Pretl, M.; Srutková, Z.; Horvát, E. M.; Vodička, Pavel; Poláková, Veronika; Nevšímalová, S.

    2010-01-01

    Roč. 31, č. 5 (2010), s. 631-634 ISSN 0172-780X Grant - others:GA MŠk(CZ) 0021620816; GA MŠk(CZ) 0021620849 Keywords : narcolepsy with cataplexy * Body Mass Index * sleep iness Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.621, year: 2010

  18. Measurement of narcolepsy symptoms: The Narcolepsy Severity Scale.

    Science.gov (United States)

    Dauvilliers, Yves; Beziat, Severine; Pesenti, Carole; Lopez, Regis; Barateau, Lucie; Carlander, Bertrand; Luca, Gianina; Tafti, Mehdi; Morin, Charles M; Billiard, Michel; Jaussent, Isabelle

    2017-04-04

    To validate the Narcolepsy Severity Scale (NSS), a brief clinical instrument to evaluate the severity and consequences of symptoms in patients with narcolepsy type 1 (NT1). A 15-item scale to assess the frequency and severity of excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, sleep paralysis, and disrupted nighttime sleep was developed and validated by sleep experts with patients' feedback. Seventy untreated and 146 treated adult patients with NT1 were evaluated and completed the NSS in a single reference sleep center. The NSS psychometric properties, score changes with treatment, and convergent validity with other clinical parameters were assessed. The NSS showed good psychometric properties with significant item-total score correlations. The factor analysis indicated a 3-factor solution with good reliability, expressed by satisfactory Cronbach α values. The NSS total score temporal stability was good. Significant NSS score differences were observed between untreated and treated patients (dependent sample, 41 patients before and after sleep therapy; independent sample, 29 drug-free and 105 treated patients). Scores were lower in the treated populations (10-point difference between groups), without ceiling effect. Significant correlations were found among NSS total score and daytime sleepiness (Epworth Sleepiness Scale, Mean Sleep Latency Test), depressive symptoms, and health-related quality of life. The NSS can be considered a reliable and valid clinical tool for the quantification of narcolepsy symptoms to monitor and optimize narcolepsy management. © 2017 American Academy of Neurology.

  19. Imaging tools to study pharmacology: functional MRI on small rodents

    OpenAIRE

    Elisabeth eJonckers; Disha eShah; Julie eHamaide; Marleen eVerhoye; Annemie eVan Der Linden

    2015-01-01

    Functional Magnetic Resonance Imaging (fMRI) is an excellent tool to study the effect of pharmacological modulations on brain function in a non-invasive and longitudinal manner. We introduce several blood oxygenation level dependent (BOLD) fMRI techniques, including resting state (rsfMRI), stimulus-evoked (st-fMRI), and pharmacological MRI (phMRI). Respectively, these techniques permit the assessment of functional connectivity during rest as well as brain activation triggered by sensory stimu...

  20. Executive control of attention in narcolepsy.

    Directory of Open Access Journals (Sweden)

    Sophie Bayard

    Full Text Available BACKGROUND: Narcolepsy with cataplexy (NC is a disabling sleep disorder characterized by early loss of hypocretin neurons that project to areas involved in the attention network. We characterized the executive control of attention in drug-free patients with NC to determine whether the executive deficits observed in patients with NC are specific to the disease itself or whether they reflect performance changes due to the severity of excessive daytime sleepiness. METHODOLOGY: Twenty-two patients with NC compared to 22 patients with narcolepsy without cataplexy (NwC matched for age, gender, intellectual level, objective daytime sleepiness and number of sleep onset REM periods (SOREMPs were studied. Thirty-two matched healthy controls were included. All participants underwent a standardized interview, completed questionnaires, and neuropsychological tests. All patients underwent a polysomnography followed by multiple sleep latency tests (MSLT, with neuropsychological evaluation performed the same day between MSLT sessions. PRINCIPAL FINDINGS: Irrespective of diagnosis, patients reported higher self-reported attentional complaints associated with the intensity of depressive symptoms. Patients with NC performed slower and more variably on simple reaction time tasks than patients with NwC, who did not differ from controls. Patients with NC and NwC generally performed slower, reacted more variably, and made more errors than controls on executive functioning tests. Individual profile analyses showed a clear heterogeneity of the severity of executive deficit. This severity was related to objective sleepiness, higher number of SOREMPs on the MSLT, and lower intelligence quotient. The nature and severity of the executive deficits were unrelated to NC and NwC diagnosis. CONCLUSIONS: We demonstrated that drug-free patients with NC and NwC complained of attention deficit, with altered executive control of attention being explained by the severity of objective

  1. New developments in the management of narcolepsy

    Directory of Open Access Journals (Sweden)

    Abad VC

    2017-03-01

    Full Text Available Vivien C Abad, Christian Guilleminault Department of Psychiatry and Behavioral Sciences, Division of Sleep Medicine, Stanford University Outpatient Center, Redwood City, CA, USA Abstract: Narcolepsy is a life-long, underrecognized sleep disorder that affects 0.02%–0.18% of the US and Western European populations. Genetic predisposition is suspected because of narcolepsy’s strong association with HLA DQB1*06-02, and genome-wide association studies have identified polymorphisms in T-cell receptor loci. Narcolepsy pathophysiology is linked to loss of signaling by hypocretin-producing neurons; an autoimmune etiology possibly triggered by some environmental agent may precipitate hypocretin neuronal loss. Current treatment modalities alleviate the main symptoms of excessive daytime somnolence (EDS and cataplexy and, to a lesser extent, reduce nocturnal sleep disruption, hypnagogic hallucinations, and sleep paralysis. Sodium oxybate (SXB, a sodium salt of γ hydroxybutyric acid, is a first-line agent for cataplexy and EDS and may help sleep disruption, hypnagogic hallucinations, and sleep paralysis. Various antidepressant medications including norepinephrine serotonin reuptake inhibitors, selective serotonin reuptake inhibitors, and tricyclic antidepressants are second-line agents for treating cataplexy. In addition to SXB, modafinil and armodafinil are first-line agents to treat EDS. Second-line agents for EDS are stimulants such as methylphenidate and extended-release amphetamines. Emerging therapies include non-hypocretin-based therapy, hypocretin-based treatments, and immunotherapy to prevent hypocretin neuronal death. Non-hypocretin-based novel treatments for narcolepsy include pitolisant (BF2.649, tiprolisant; JZP-110 (ADX-N05 for EDS in adults; JZP 13-005 for children; JZP-386, a deuterated sodium oxybate oral suspension; FT 218 an extended-release formulation of SXB; and JNJ-17216498, a new formulation of modafinil. Clinical trials are

  2. New developments in the management of narcolepsy.

    Science.gov (United States)

    Abad, Vivien C; Guilleminault, Christian

    2017-01-01

    Narcolepsy is a life-long, underrecognized sleep disorder that affects 0.02%-0.18% of the US and Western European populations. Genetic predisposition is suspected because of narcolepsy's strong association with HLA DQB1*06-02, and genome-wide association studies have identified polymorphisms in T-cell receptor loci. Narcolepsy pathophysiology is linked to loss of signaling by hypocretin-producing neurons; an autoimmune etiology possibly triggered by some environmental agent may precipitate hypocretin neuronal loss. Current treatment modalities alleviate the main symptoms of excessive daytime somnolence (EDS) and cataplexy and, to a lesser extent, reduce nocturnal sleep disruption, hypnagogic hallucinations, and sleep paralysis. Sodium oxybate (SXB), a sodium salt of γ hydroxybutyric acid, is a first-line agent for cataplexy and EDS and may help sleep disruption, hypnagogic hallucinations, and sleep paralysis. Various antidepressant medications including norepinephrine serotonin reuptake inhibitors, selective serotonin reuptake inhibitors, and tricyclic antidepressants are second-line agents for treating cataplexy. In addition to SXB, modafinil and armodafinil are first-line agents to treat EDS. Second-line agents for EDS are stimulants such as methylphenidate and extended-release amphetamines. Emerging therapies include non-hypocretin-based therapy, hypocretin-based treatments, and immunotherapy to prevent hypocretin neuronal death. Non-hypocretin-based novel treatments for narcolepsy include pitolisant (BF2.649, tiprolisant); JZP-110 (ADX-N05) for EDS in adults; JZP 13-005 for children; JZP-386, a deuterated sodium oxybate oral suspension; FT 218 an extended-release formulation of SXB; and JNJ-17216498, a new formulation of modafinil. Clinical trials are investigating efficacy and safety of SXB, modafinil, and armodafinil in children. γ-amino butyric acid (GABA) modulation with GABA A receptor agonists clarithromycin and flumazenil may help daytime somnolence

  3. Plasma total ghrelin and leptin levels in human narcolepsy and matched healthy controls: Basal concentrations and response to sodium oxybate

    NARCIS (Netherlands)

    Donjacour, C.E.; Pardi, D.; Aziz, N.A.; Frolich, M.; Roelfsema, F.; Overeem, S.; Pijl, H.; Lammers, G.J.

    2013-01-01

    STUDY OBJECTIVES: Narcolepsy is caused by a selective loss of hypocretin neurons and is associated with obesity. Ghrelin and leptin interact with hypocretin neurons to influence energy homeostasis. Here, we evaluated whether human hypocretin deficiency, or the narcolepsy therapeutic agent sodium

  4. Nocturnal rapid eye movement sleep latency for identifying patients with narcolepsy/hypocretin deficiency.

    Science.gov (United States)

    Andlauer, Olivier; Moore, Hyatt; Jouhier, Laura; Drake, Christopher; Peppard, Paul E; Han, Fang; Hong, Seung-Chul; Poli, Francesca; Plazzi, Giuseppe; O'Hara, Ruth; Haffen, Emmanuel; Roth, Thomas; Young, Terry; Mignot, Emmanuel

    2013-07-01

    Narcolepsy, a disorder associated with HLA-DQB1*06:02 and caused by hypocretin (orexin) deficiency, is diagnosed using the Multiple Sleep Latency Test (MSLT) following nocturnal polysomnography (NPSG). In many patients, a short rapid eye movement sleep latency (REML) during the NPSG is also observed but not used diagnostically. To determine diagnostic accuracy and clinical utility of nocturnal REML measures in narcolepsy/hypocretin deficiency. Observational study using receiver operating characteristic curves for NPSG REML and MSLT findings (sleep studies performed between May 1976 and September 2011 at university medical centers in the United States, China, Korea, and Europe) to determine optimal diagnostic cutoffs for narcolepsy/hypocretin deficiency compared with different samples: controls, patients with other sleep disorders, patients with other hypersomnias, and patients with narcolepsy with normal hypocretin levels. Increasingly stringent comparisons were made. In a first comparison, 516 age- and sex-matched patients with narcolepsy/hypocretin deficiency were selected from 1749 patients and compared with 516 controls. In a second comparison, 749 successive patients undergoing sleep evaluation for any sleep disorders (low pretest probability for narcolepsy) were compared within groups by final diagnosis of narcolepsy/hypocretin deficiency. In the third comparison, 254 patients with a high pretest probability of having narcolepsy were compared within group by their final diagnosis. Finally, 118 patients with narcolepsy/hypocretin deficiency were compared with 118 age- and sex-matched patients with a diagnosis of narcolepsy but with normal hypocretin levels. Sensitivity and specificity of NPSG REML and MSLT as diagnostic tests for narcolepsy/hypocretin deficiency. This diagnosis was defined as narcolepsy associated with cataplexy plus HLA-DQB1*06:02 positivity (no cerebrospinal fluid hypocretin-1 results available) or narcolepsy with documented low (≤ 110 pg

  5. Recent Pharmacology Studies on the International Space Station

    Science.gov (United States)

    Wotring, Virginia

    2014-01-01

    The environment on the International Space Station (ISS) includes a variety of potential stressors including the absence of Earth's gravity, elevated exposure to radiation, confined living and working quarters, a heavy workload, and high public visibility. The effects of this extreme environment on pharmacokinetics, pharmacodynamics, and even on stored medication doses, are not yet understood. Dr. Wotring will discuss recent analyses of medication doses that experienced long duration storage on the ISS and a recent retrospective examination of medication use during long-duration spaceflights. She will also describe new pharmacology experiments that are scheduled for upcoming ISS missions. Dr. Virginia E. Wotring is a Senior Scientist in the Division of Space Life Sciences in the Universities Space Research Association, and Pharmacology Discipline Lead at NASA's Johnson Space Center, Human Heath and Countermeasures Division. She received her doctorate in Pharmacological and Physiological Science from Saint Louis University after earning a B.S. in Chemistry at Florida State University. She has published multiple studies on ligand gated ion channels in the brain and spinal cord. Her research experience includes drug mechanisms of action, drug receptor structure/function relationships and gene & protein expression. She joined USRA (and spaceflight research) in 2009. In 2012, her book reviewing pharmacology in spaceflight was published by Springer: Space Pharmacology, Space Development Series.

  6. Simulation in an Undergraduate Nursing Pharmacology Course: A Pilot Study.

    Science.gov (United States)

    Tinnon, Elizabeth; Newton, Rebecca

    This study examined the effectiveness of simulation as a method of teaching pharmacological concepts to nursing students; perceptions of satisfaction with simulation as a teaching strategy were also evaluated. Second-semester juniors participated in three simulations and completed the National League for Nursing Student Satisfaction and Self-Confidence in Learning Questionnaire and the Student Evaluation of Educational Quality Survey; a control group received traditional lectures. A unit exam on anticoagulant therapy content was administered to measure effectiveness. Findings support that simulation is as effective as traditional lecture for an undergraduate pharmacology course.

  7. Clinical Pharmacology Studies in Critically Ill Children

    Science.gov (United States)

    Thakkar, Nilay; Salerno, Sara; Hornik, Christoph P.; Gonzalez, Daniel

    2016-01-01

    Developmental and physiological changes in children contribute to variation in drug disposition with age. Additionally, critically ill children suffer from various life-threatening conditions that can lead to pathophysiological alterations that further affect pharmacokinetics (PK). Some factors that can alter PK in this patient population include variability in tissue distribution caused by protein binding changes and fluid shifts, altered drug elimination due to organ dysfunction, and use of medical interventions that can affect drug disposition (e.g., extracorporeal membrane oxygenation and continuous renal replacement therapy). Performing clinical studies in critically ill children is challenging because there is large inter-subject variability in the severity and time course of organ dysfunction; some critical illnesses are rare, which can affect subject enrollment; and critically ill children usually have multiple organ failure, necessitating careful selection of a study design. As a result, drug dosing in critically ill children is often based on extrapolations from adults or non-critically ill children. Dedicated clinical studies in critically ill children are urgently needed to identify optimal dosing of drugs in this population. This review will summarize the effect of critical illness on pediatric PK, the challenges associated with performing studies in this vulnerable subpopulation, and the clinical PK studies performed to date for commonly used drugs. PMID:27585904

  8. Pharmacological activities and pharmacokinetic study of hyperoside ...

    African Journals Online (AJOL)

    Studies on its pharmacokinetic (PK) properties revealed that it is a stable compound ... attention in drug discovery and food supplement research ... neurotrophic factor (BDNF) and cAMP response element ... antidepressant effect of hyperoside is mediated through .... Saposhnikovia divaricata by high performance counter-.

  9. Health, social, and economic consequences of narcolepsy

    DEFF Research Database (Denmark)

    Jennum, Poul; Ibsen, Rikke Falkner; Petersen, Eva Rosa

    2012-01-01

    Despite the fact that narcolepsy is a chronic disorder affecting younger people, there is insufficient information about its societal burden, time course, and familiar effect. We aimed to estimate the factual direct and indirect costs of narcolepsy patients and their families in a national sample...

  10. The incidence of narcolepsy in Europe

    DEFF Research Database (Denmark)

    Wijnans, Leonoor; Lecomte, Coralie; de Vries, Corinne

    2013-01-01

    In August 2010 reports of a possible association between exposure to AS03 adjuvanted pandemic A(H1N1)pdm09 vaccine and occurrence of narcolepsy in children and adolescents emerged in Sweden and Finland. In response to this signal, the background rates of narcolepsy in Europe were assessed to rapi...

  11. Cases of pediatric narcolepsy after misdiagnoses.

    Science.gov (United States)

    Kauta, Shilpa R; Marcus, Carole L

    2012-11-01

    Narcolepsy is characterized by recurrent brief attacks of irresistible sleepiness. Signs can begin during childhood. However, diagnoses are frequently delayed by 10-15 years because of unfamiliarity with pediatric narcolepsy and variable presentations of its associated features (cataplexy, hypnagogic/hypnopompic hallucinations, and sleep paralysis). Therefore, patients may remain untreated during their formative years. Three children with narcolepsy who were initially misdiagnosed are described. Each child's signs were initially related to depression, hypothyroidism, jaw dysfunction, or conversion disorder. However, after a multiple sleep latency test, the diagnosis of narcolepsy was established. All three patients were treated appropriately with stimulant medications, selective serotonin reuptake inhibitors, or sodium oxybate, and demonstrated positive responses. Although no definitive cure exists for narcolepsy, early recognition and appropriate symptomatic treatment with medications can allow affected children to improve quality of life and achieve normality, both academically and socially. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Imaging tools to study pharmacology: functional MRI on small rodents

    Directory of Open Access Journals (Sweden)

    Elisabeth eJonckers

    2015-10-01

    Full Text Available Functional Magnetic Resonance Imaging (fMRI is an excellent tool to study the effect of pharmacological modulations on brain function in a non-invasive and longitudinal manner. We introduce several blood oxygenation level dependent (BOLD fMRI techniques, including resting state (rsfMRI, stimulus-evoked (st-fMRI, and pharmacological MRI (phMRI. Respectively, these techniques permit the assessment of functional connectivity during rest as well as brain activation triggered by sensory stimulation and/or a pharmacological challenge. The first part of this review describes the physiological basis of BOLD fMRI and the hemodynamic response on which the MRI contrast is based. Specific emphasis goes to possible effects of anaesthesia and the animal’s physiological conditions on neural activity and the hemodynamic response. The second part of this review describes applications of the aforementioned techniques in pharmacologically-induced, as well as in traumatic and transgenic disease models and illustrates how multiple fMRI methods can be applied successfully to evaluate different aspects of a specific disorder. For example, fMRI techniques can be used to pinpoint the neural substrate of a disease beyond previously defined hypothesis-driven regions-of-interest (ROIs. In addition, fMRI techniques allow one to dissect how specific modifications (e.g. treatment, lesion etc. modulate the functioning of specific brain areas (st-fMRI, phMRI and how functional connectivity (rsfMRI between several brain regions is affected, both in acute and extended time frames. Furthermore, fMRI techniques can be used to assess/explore the efficacy of novel treatments in depth, both in fundamental research as well as in preclinical settings. In conclusion, by describing several exemplary studies, we aim to highlight the advantages of functional MRI in exploring the acute and long-term effects of pharmacological substances and/or pathology on brain functioning along with

  13. Clinical and Polysomnographic Comparison between Narcolepsy without Cataplexy and Idiopathic Hypersomnia

    Directory of Open Access Journals (Sweden)

    Tae Won Kim

    2012-10-01

    Full Text Available Background and Objective The aim of this study is to compare the clinical, electrophysiological (Polysomnography, PSG; Multiple Sleep Latency Test, MSLT and biological data (HLA DQB1*0602 typing in idiopathic hypersomnia with narcolepsy without cataplexy. Methods 80 patients with narcolepsy without cataplexy and 71 patients with idiopathic hypersomnia without a long sleep time were recruited at the Sleep Center of St. Vincent’s Hospital. MSLT data and PSG findings from the time of their diagnosis were reviewed. HLA typing was performed. Results Results indicated that the idiopathic hypersomnia group showed a significant longer mean sleep latency in MSLT compared with the narcolepsy without cataplexy group. But there was no significant difference in the Epworth Sleepiness Scale (ESS scores between the two groups. Although HLA positivity of both groups was not statistically significant (p = 0.065, HLA positivity tended to be higher in the narcolepsy without cataplexy group than the idiopathic hypersomnia group. The number of awakenings was slightly higher in the idiopathic hypersomnia group, but there was no statistical significance. The number of spontaneous arousal and total arousal indices was not significantly different between the groups. For the PSG, the idiopathic hypersomnia group showed a significantly longer sleep latency than the narcolepsy without cataplexy group (p = 0.009. REM sleep latency (REML was significantly shorter in the narcolepsy without cataplexy group compared to the idiopathic hypersomnia group. The percentage of REM (SREM was significantly higher in the narcolepsy without cataplexy group, and the percentage of the wake time during sleep period (SWT was significantly lower in the narcolepsy without cataplexy group. Conclusions There were no significant differences of subjective sleep measures such as ESS, disturbed nocturnal sleep, number of naps, age of onset of hypnagogic hallucination, and age of onset of sleep

  14. Narcolepsy/Cataplexy and Occult Neuroblastoma

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2013-11-01

    Full Text Available Investigators at the University of Chicago and Northwestern University, Chicago, IL; University Hospital Southampton, UK; and Kiev Paediatric Hospital, Ukraine, report three children with narcolepsy and cataplexy subsequently diagnosed with neuroblastoma.

  15. Anti-Tribbles homolog 2 (TRIB2) autoantibodies in narcolepsy are associated with recent onset of cataplexy

    DEFF Research Database (Denmark)

    Kawashima, Minae; Lin, Ling; Tanaka, Susumu

    2010-01-01

    Recent studies have found increased autoantibodies against Tribbles homolog 2 (anti-TRIB2) and anti-streptolysin O (ASO) in narcolepsy. In this study, we replicated this finding with a primary focus on recent onset cases....

  16. [Narcolepsy with cataplexy: an autoimmune disease?].

    Science.gov (United States)

    Jacob, Louis; Dauvilliers, Yves

    2014-12-01

    Narcolepsy type 1 (also named narcolepsy-cataplexy or hypocretin deficiency syndrome) is a rare sleep disorder characterized by excessive daytime sleepiness and cataplexy, plus frequently hypnagogic hallucinations, sleep paralysis and nocturnal sleep disturbances. Narcolepsy type 1 is an immune system-associated disease linked with the destruction of 70.000-90.000 hypocretin neurons notably involved in wakefulness. Among narcoleptic patients, 98% are positive for HLA-DQB1*06:02, a HLA class II allele, against 20-25% in general population. Individuals carrying HLA-DQB1*06:02 have an extraordinary risk to develop narcolepsy (odd ratio: 251). Other genes involved in CD4+ T cells and immune system activation as T-cell receptor α are also associated with narcolepsy. The development of the disease is linked with environmental factors such as influenza and streptococcal infections. Narcolepsy type 1 incidence also increased in Europe following the use of Pandemrix, a 2009 H1N1 AS03-adjuvanted vaccine manufactured by GlaxoSmithKline. Interestingly, such increase was not observed with Arepanrix, another vaccine developed by GSK very similar to Pandemrix. © 2014 médecine/sciences – Inserm.

  17. ApoE polymorphisms in narcolepsy

    Science.gov (United States)

    Gencik, Martin; Dahmen, Norbert; Wieczorek, Stefan; Kasten, Meike; Gencikova, Alexandra; Epplen, Jorg T

    2001-01-01

    Background Narcolepsy is a common neuropsychiatric disorder characterized by increased daytime sleepiness, cataplexy and hypnagogic hallucinations. Deficiency of the hypocretin neurotransmitter system was shown to be involved in the pathogenesis of narcolepsy in animals and men. There are several hints that neurodegeneration of hypocretin producing neurons in the hypothalamus is the pathological correlate of narcolepsy. The ApoE4 allele is a major contributing factor to early-onset neuronal degeneration in Alzheimer disease and other neurodegenerative diseases as well. Methods To clarify whether the ApoE4 phenotype predisposes to narcolepsy or associates with an earlier disease onset, we have genotyped the ApoE gene in 103 patients with narcolepsy and 101 healthy controls. Results The frequency of the E4 allele of the ApoE gene was 11% in the patient and 15% in the control groups. Furthermore, the mean age of onset did not differ between the ApoE4+ and ApoE4- patient groups. Conclusion Our results exclude the ApoE4 allele as a major risk factor for narcolepsy. PMID:11560764

  18. ApoE polymorphisms in narcolepsy

    Directory of Open Access Journals (Sweden)

    Kasten Meike

    2001-08-01

    Full Text Available Summary Background Narcolepsy is a common neuropsychiatric disorder characterized by increased daytime sleepiness, cataplexy and hypnagogic hallucinations. Deficiency of the hypocretin neurotransmitter system was shown to be involved in the pathogenesis of narcolepsy in animals and men. There are several hints that neurodegeneration of hypocretin producing neurons in the hypothalamus is the pathological correlate of narcolepsy. The ApoE4 allele is a major contributing factor to early-onset neuronal degeneration in Alzheimer disease and other neurodegenerative diseases as well. Methods To clarify whether the ApoE4 phenotype predisposes to narcolepsy or associates with an earlier disease onset, we have genotyped the ApoE gene in 103 patients with narcolepsy and 101 healthy controls. Results The frequency of the E4 allele of the ApoE gene was 11% in the patient and 15% in the control groups. Furthermore, the mean age of onset did not differ between the ApoE4+ and ApoE4- patient groups. Conclusion Our results exclude the ApoE4 allele as a major risk factor for narcolepsy.

  19. Psychotic symptoms in narcolepsy: phenomenology and a comparison with schizophrenia.

    NARCIS (Netherlands)

    Droogleever Fortuyn, H.A.; Lappenschaar, G.A.; Nienhuis, F.J.; Furer, J.W.; Hodiamont, P.P.G.; Rijnders, C.A.T.; Lammers, G.J.; Renier, W.O.; Buitelaar, J.K.; Overeem, S.

    2009-01-01

    OBJECTIVE: Patients with narcolepsy often experience pervasive hypnagogic hallucinations, sometimes even leading to confusion with schizophrenia. We aimed to provide a detailed qualitative description of hypnagogic hallucinations and other "psychotic" symptoms in patients with narcolepsy and

  20. Psychotic symptoms in narcolepsy : phenomenology and a comparison with schizophrenia

    NARCIS (Netherlands)

    Fortuyn, Hal A. Droogleever; Lappenschaar, G. A.; Nienhuis, Fokko J.; Furer, Joop W.; Hodiamont, Paul P.; Rijnders, Cees A.; Lammers, Gert Jan; Renier, Willy O.; Buitelaar, Jan K.; Overeem, Sebastlaan

    2009-01-01

    Objective: Patients with narcolepsy often experience pervasive hypnagogic hallucinations, sometimes even leading to confusion with schizophrenia. We aimed to provide a detailed qualitative description of hypnagogic hallucinations and other "psychotic" symptoms in patients with narcolepsy and

  1. Apomorphine and piribedil in rats: biochemical and pharmacologic studies.

    Science.gov (United States)

    Butterworth, R F; Poignant, J C; Barbeau, A

    1975-01-01

    We studied the biochemical and pharmacologic modes of action of piribedil and apomorphine in the rat. Although both drugs have many points in common, they are also different in many of their manifestations. Apomorphine causes high-intensity, short-duration stereotyped behavior; it is distributed within the brain in uneven fashion, the striatum being the area of lowest concentration as measured by fluorometry. Direct stereotactic injection within the dopaminergic mesolimbic system, and particularly the tuberculum olfactorium, produced constant intense responses. All effects of apomorphine can be blocked by pimozide, but propanolol, a beta blocker, only reduces aggression and ferocity, leaving stereotyped behaviors intact. Finally, L-5-HTP tends to reduce aggression, ferocity, and to a lesser extent stereotypy; MIF or piribedil, as well as reserpine, potentiates the stereotyped behaviors induced by apomorphine, whereas L-DOPA usually decreases them. Piribedil, on the other hand, causes low-intensity, long-duration stereotyped behavior. It is distributed within the brain almost uniformly. Most effects of piribedil can be blocked by pimozide, but propanolol blocks only aggression and ferocity, leaving stereotyped behaviors intact. On the other hand, clonidine, an alpha-receptor agonist, blocks stereotyped behaviors induced by piribedil but markedly increases aggression, ferocity, and motor activity. L-5-HTP and L-DOPA have little effect on piribedil-induced manifestations. Reserpine decreases piribedil stereotypy. The main metabolite of piribedil, S 584, had no clear-cut pharmacologic action in our hands at the dosage used. It is concluded that both apomorphine and piribedil produce stereotyped behavior by modifying the physiologic balance between mesolimbic and nigrostriatal dopaminergic systems. The other actions of apomorphine and piribedil upon aggression, ferocity, and motor activity are not always in parallel and depend probably on the fact that piribedil is less

  2. Reward-based behaviors and emotional processing in human with narcolepsy-cataplexy

    Directory of Open Access Journals (Sweden)

    Sophie eBayard

    2013-05-01

    Full Text Available ajor advances in the past decade have led a better understanding of the pathophysiology of narcolepsy with cataplexy caused by the early loss of hypothalamic hypocretin neurons. Although a role for hypocretin in the regulation of sleep/wakefulness state is widely recognized, other functions, not necessarily related to arousal, have been identified. Hence, the hypocretin system enhances signaling in the mesolimbic pathways regulating reward processing, emotion and mood regulation, and addiction. Although studies on hypocretin-deficient mice have shown that hypocretin plays an essential role in reward-seeking, depression-like behavior and addiction, results in human narcolepsy remained subject to debate. Most of studies revealed that hypocretin-deficient narcolepsy patients either drug-free or medicated with psychostimulant had preferences towards risky choices in a decision-making task under ambiguity together with higher frequency of depressive symptoms and binge eating disorder compared to controls. However, human studies mostly reported the lack of association with pathological impulsivity and gambling, and substance and alcohol abuse in the context of narcolepsy-cataplexy. Prospective larger studies are required to confirm these findings in drug-free and medicated patients with narcolepsy. Inclusion of patients with other central hypersomnias without hypocretin deficiency will provide answer to the major question of the role of the hypocretin system in reward-based behaviors and emotional processing in humans.

  3. Attenuated heart rate response is associated with hypocretin deficiency in patients with narcolepsy.

    Science.gov (United States)

    Sorensen, Gertrud Laura; Knudsen, Stine; Petersen, Eva Rosa; Kempfner, Jacob; Gammeltoft, Steen; Sorensen, Helge Bjarup Dissing; Jennum, Poul

    2013-01-01

    Several studies have suggested that hypocretin-1 may influence the cerebral control of the cardiovascular system. We analyzed whether hypocretin-1 deficiency in narcolepsy patients may result in a reduced heart rate response. We analyzed the heart rate response during various sleep stages from a 1-night polysomnography in patients with narcolepsy and healthy controls. The narcolepsy group was subdivided by the presence of +/- cataplexy and +/- hypocretin-1 deficiency. Sleep laboratory studies conducted from 2001-2011. In total 67 narcolepsy patients and 22 control subjects were included in the study. Cataplexy was present in 46 patients and hypocretin-1 deficiency in 38 patients. None. All patients with narcolepsy had a significantly reduced heart rate response associated with arousals and leg movements (P hypocretin-1 deficiency and cataplexy groups compared with patients with normal hypocretin-1 levels (P hypocretin-1 deficiency significantly predicted the heart rate response associated with arousals in both REM and non-REM in a multivariate linear regression. Our results show that autonomic dysfunction is part of the narcoleptic phenotype, and that hypocretin-1 deficiency is the primary predictor of this dysfunction. This finding suggests that the hypocretin system participates in the modulation of cardiovascular function at rest.

  4. Normal Morning MCH Levels and No Association with REM or NREM Sleep Parameters in Narcolepsy Type 1 and Type 2

    DEFF Research Database (Denmark)

    Schrölkamp, Maren; Jennum, Poul J; Gammeltoft, Steen

    2017-01-01

    in rapid eye movement (REM) and nonrapid eye movement (NREM) sleep regulation. Hypocretin neurons reciprocally interact with MCH neurons. We hypothesized that altered MCH secretion contributes to the symptoms and sleep abnormalities of narcolepsy and that this is reflected in morning cerebrospinal fluid...... MCH levels. CONCLUSION: Our study shows that MCH levels in CSF collected in the morning are normal in narcolepsy and not associated with the clinical symptoms, REM sleep abnormalities, nor number of muscle movements during REM or NREM sleep of the patients. We conclude that morning lumbar CSF MCH......STUDY OBJECTIVES: Other than hypocretin-1 (HCRT-1) deficiency in narcolepsy type 1 (NT1), the neurochemical imbalance of NT1 and narcolepsy type 2 (NT2) with normal HCRT-1 levels is largely unknown. The neuropeptide melanin-concentrating hormone (MCH) is mainly secreted during sleep and is involved...

  5. AS03 adjuvanted AH1N1 vaccine associated with an abrupt increase in the incidence of childhood narcolepsy in Finland.

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    Hanna Nohynek

    Full Text Available BACKGROUND: Narcolepsy is a chronic sleep disorder with strong genetic predisposition causing excessive daytime sleepiness and cataplexy. A sudden increase in childhood narcolepsy was observed in Finland soon after pandemic influenza epidemic and vaccination with ASO3-adjuvanted Pandemrix. No increase was observed in other age groups. METHODS: Retrospective cohort study. From January 1, 2009 to December 31, 2010 we retrospectively followed the cohort of all children living in Finland and born from January 1991 through December 2005. Vaccination data of the whole population was obtained from primary health care databases. All new cases with assigned ICD-10 code of narcolepsy were identified and the medical records reviewed by two experts to classify the diagnosis of narcolepsy according to the Brighton collaboration criteria. Onset of narcolepsy was defined as the first documented contact to health care because of excessive daytime sleepiness. The primary follow-up period was restricted to August 15, 2010, the day before media attention on post-vaccination narcolepsy started. FINDINGS: Vaccination coverage in the cohort was 75%. Of the 67 confirmed cases of narcolepsy, 46 vaccinated and 7 unvaccinated were included in the primary analysis. The incidence of narcolepsy was 9.0 in the vaccinated as compared to 0.7/100,000 person years in the unvaccinated individuals, the rate ratio being 12.7 (95% confidence interval 6.1-30.8. The vaccine-attributable risk of developing narcolepsy was 1:16,000 vaccinated 4 to 19-year-olds (95% confidence interval 1:13,000-1:21,000. CONCLUSIONS: Pandemrix vaccine contributed to the onset of narcolepsy among those 4 to 19 years old during the pandemic influenza in 2009-2010 in Finland. Further studies are needed to determine whether this observation exists in other populations and to elucidate potential underlying immunological mechanism. The role of the adjuvant in particular warrants further research before drawing

  6. The Humanistic and Economic Burden of Narcolepsy.

    Science.gov (United States)

    Flores, Natalia M; Villa, Kathleen F; Black, Jed; Chervin, Ronald D; Witt, Edward A

    2016-03-01

    To evaluate the burden of narcolepsy--with respect to psychiatric comorbidities, Health-Related Quality of Life (HRQoL), direct costs for healthcare resource utilization, and indirect costs for reported work loss-through comparison of patients to matched controls. This analysis was conducted on data from the 2011, 2012, and 2013 US National Health and Wellness Survey (NHWS; 2011 NHWS n = 75,000, 2012 NHWS n = 71,157, and 2013 NHWS n = 75,000). Patients who reported a narcolepsy diagnosis (n = 437) were matched 1:2 with controls (n = 874) on age, sex, race/ethnicity, marital status, education, household income, body mass index, smoking status, alcohol use, exercise, and physical comorbidity. Chi-square tests and one-way analyses of variance were used to assess whether the narcolepsy and control groups differed on psychiatric comorbidities, HRQoL, labor force participation, work productivity, and healthcare resource utilization. Patients with narcolepsy, in comparison to matched controls, reported substantially (two to four times) greater psychiatric comorbidity, HRQoL impairment, prevalence of long-term disability, absenteeism, and presenteeism, and greater resource use in the past 6 mo as indicated by higher mean number of hospitalizations, emergency department visits, traditional healthcare professional visits, neurologist visits, and psychiatrist visits (each p productivity through effective assessment and treatment of narcolepsy. © 2016 American Academy of Sleep Medicine.

  7. Narcolepsy: etiology, clinical features, diagnosis and treatment

    Directory of Open Access Journals (Sweden)

    Jolanta B. Zawilska

    2012-10-01

    Full Text Available [u][/u] Narcolepsy is a chronic hypersomnia characterized by excessive daytime sleepiness (EDS and manifestations of disrupted rapid eye movement sleep stage (cataplexy, sleep paralysis, and hypnagogic/hypnopompic hallucinations. Mechanisms underlying narcolepsy are not fully understood. Experimental data indicate that the disease is caused by a loss of hypocretin neurons in the hypothalamus, likely due to an autoimmune process triggered by environmental factors in susceptible individuals. Most patients with narcolepsy and cataplexy have very low hypocretin-1 levels in the cerebrospinal fluid. An appropriate clinical history, polysomnogram, and multiple sleep latency test are necessary for diagnosis of the disease. Additionally, two biological markers, i.e., cerebrospinal fluid hypocretin-1 levels and expression of the DQB1*0602 gene, are used. The treatment of narcolepsy is aimed at the different symptoms that the patient manifests. Excessive daytime sleepiness is treated with psychostimulants (amphetamine-like, modafinil and armodafinil. Cataplexy is treated with sodium oxybate (GHB, tricyclic antidepressants, or selective serotonin and noradrenaline reuptake inhibitors. Sleep paralysis, hallucinations, and fragmented sleep may be treated with sodium oxybate. Patients with narcolepsy should follow proper sleep hygiene and avoid strong emotions.

  8. Narcolepsy in Adolescence-A Missed Diagnosis: A Case Report.

    Science.gov (United States)

    Gupta, Anoop K; Sahoo, Swapnajeet; Grover, Sandeep

    2017-01-01

    Narcolepsy is an uncommon sleep cycle disorder with a usual onset in adolescence, but it is often misdiagnosed and underdiagnosed. Rarely is the tetrad of excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis seen in patients. The clinical characteristics of narcolepsy are often confused with many psychiatric and neurologic disorders. Lack of clinical awareness about narcolepsy leads to frequent prescriptions of antiepileptics and psychotropics, which can adversely affect the quality of life of children and adolescents. We report a case of an adolescent male who presented with all four cardinal symptoms of narcolepsy and had been misdiagnosed with epilepsy, psychosis, and depression. We discuss various issues regarding narcolepsy in children and adolescents.

  9. Narcolepsy and cataplexy: a pediatric case report.

    Science.gov (United States)

    Savaş, Tülin; Erol, Ilknur; Saygı, Semra; Habeşoğlu, Mehmet Ali

    2016-12-01

    Narcolepsy is characterized by excessive sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis during the rapid eye movement period of sleep. Herein, we present a boy aged eight years who was diagnosed as having narcolepsy and cataplexy about thirteen months after his first presentation. He was admitted with symptoms of daytime sleepiness. In the follow-up, cataplexy in the form of head dropping attacks developed seven months after the first admission. The patient was investigated for different prediagnoses and was eventually diagnosed as having narcolepsy and cataplexy through polysomnography and multiple sleep latency tests thirteen months after the first presentation. He is being followed up and is under drug therapy; his symptoms have improved substantially.

  10. [Workplace accomodations for two workers with narcolepsy].

    Science.gov (United States)

    Vico Garcerán, Belén; Monzó Salas, Monserrat; Cuenca Esteve, Francisco; Luis Domingo, José

    2013-01-01

    We describe the case of two workers evaluated in our occupational health unit. The first worker was a kitchen aide; the second was a primary care physician. Both had been diagnosed with narcolepsy and had obvious disability.We assessed occupational hazards related to their jobs, analysed their tasks, and performed medical examinations. Afterwards, we offered recommendations to the patients, consisting of avoidance of situations involving a risk of work accidents and improving their sleep habits. Narcolepsy is a rare disorder, but it has important social and occupational consequences. A better understanding of the disease and some work accommodations can help improve the quality of life of affected workers.

  11. Isotope effects: definitions and consequences for pharmacologic studies

    International Nuclear Information System (INIS)

    Van Langenhove, A.

    1986-01-01

    The use of stable isotope-labeled compounds for pharmacologic studies requires careful consideration of the nature of the stable isotope label (2H, 13C, 15N, 18O) and its position of incorporation in the molecule. When deuterium is used, improper positioning can lead to significant primary isotope effects. Primary isotope effects occur when the breaking of the bond to the heavy isotope is the rate-limiting step in a reaction (or metabolic transformation). A reaction will proceed slower for the molecule with the heavy isotope label because of the mass difference between the light and the heavy isotope. In addition to these primary isotope effects, smaller but nevertheless important secondary isotope effects, physicochemical isotope effects, active hydrogen/deuterium exchange, or isotope effects associated with either the enzyme-catalyzed biotransformation or the mass spectrometric ionization and fragmentation can be operative. In mechanistic studies, isotope effects are used to their advantage; however, in pharmacokinetic studies, the occurrence of isotope effects can lead to grossly misleading biologic and analytic results: the metabolism of the drug will differ when in vivo isotope effects are operative, and isotope effects occurring during the analysis procedure will obscure the true metabolic profile of the drug

  12. Absence of anti-hypocretin receptor 2 autoantibodies in post pandemrix narcolepsy cases.

    Directory of Open Access Journals (Sweden)

    Guo Luo

    Full Text Available A recent publication suggested molecular mimicry of a nucleoprotein (NP sequence from A/Puerto Rico/8/1934 (PR8 strain, the backbone used in the construction of the reassortant strain X-179A that was used in Pandemrix® vaccine, and reported on anti-hypocretin (HCRT receptor 2 (anti-HCRTR2 autoantibodies in narcolepsy, mostly in post Pandemrix® narcolepsy cases (17 of 20 sera. In this study, we re-examined this hypothesis through mass spectrometry (MS characterization of Pandemrix®, and two other pandemic H1N1 (pH1N1-2009 vaccines, Arepanrix® and Focetria®, and analyzed anti-HCRTR2 autoantibodies in narcolepsy patients and controls using three independent strategies.MS characterization of Pandemrix® (2 batches, Arepanrix® (4 batches and Focetria® (1 batch was conducted with mapping of NP 116I or 116M spectrogram. Two sets of narcolepsy cases and controls were used: 40 post Pandemrix® narcolepsy (PP-N cases and 18 age-matched post Pandemrix® controls (PP-C, and 48 recent (≤6 months early onset narcolepsy (EO-N cases and 70 age-matched other controls (O-C. Anti-HCRTR2 autoantibodies were detected using three strategies: (1 Human embryonic kidney (HEK 293T cells with transient expression of HCRTR2 were stained with human sera and then analyzed by flow cytometer; (2 In vitro translation of [35S]-radiolabelled HCRTR2 was incubated with human sera and immune complexes of autoantibody and [35S]-radiolabelled HCRTR2 were quantified using a radioligand-binding assay; (3 Optical density (OD at 450 nm (OD450 of human serum immunoglobulin G (IgG binding to HCRTR2 stably expressed in Chinese hamster ovary (CHO-K1 cell line was measured using an in-cell enzyme-linked immunosorbent assay (ELISA.NP 116M mutations were predominantly present in all batches of Pandemrix®, Arepanrix® and Focetria®. The wild-type NP109-123 (ILYDKEEIRRIWRQA, a mimic to HCRTR234-45 (YDDEEFLRYLWR, was not found to bind to DQ0602. Three or four subjects were found positive

  13. Pharmacological Studies of Artichoke Leaf Extract and Their Health Benefits.

    Science.gov (United States)

    Ben Salem, Maryem; Affes, Hanen; Ksouda, Kamilia; Dhouibi, Raouia; Sahnoun, Zouheir; Hammami, Serria; Zeghal, Khaled Mounir

    2015-12-01

    Artichoke (Cynara scolymus) leaf extract was one of the few herbal remedies which the clinical and experimental trials have complemented each other. Both experimental and clinical effects have been verified through extensive biomedical herbal remedy research. Specifically, antioxidant, choleretic, hepatoprotective, bile-enhancing and lipid-lowering effects have been demonstrated, which corresponded with its historical use. Ongoing research seems to indicate that artichoke indeed have medicinal qualities. Most significant appears to be its beneficial effect on the liver. In animal studies, liquid extracts of the roots and leaves of artichoke have demonstrated an ability to protect the liver, with possibly even to help liver cells regenerate. Although research is not yet conclusive, scientists were optimistic that its long-standing use in humans for digestive and bowel problems was indeed justified. It may also play a role in lowering cholesterol and thus help to prevent heart disease. Boiled wild artichoke reduced postprandial glycemic and insulinemic responses in normal subjects but has no effect on metabolic syndrome patients. This article intended to review the wide ranging pharmacological effects of artichoke leaf extract.

  14. Moebius syndrome and narcolepsy: A case dissertation

    Directory of Open Access Journals (Sweden)

    Lídia Sabaneeff

    2014-03-01

    Full Text Available Moebius syndrome (MS is a congenital syndrome characterized by unilateral or bilateral aplasia of the VI and VII cranial nerves, with consequent convergent strabismus and bilateral peripheral facial paralysis. This syndrome might be associated with diurnal excessive sleepiness and muscular hypotony, mimetizing in this manner, narcolepsy. The diagnostic criteria for narcolepsy depend on the presence of REM sleep during the day. As with patients with MS we do not have ocular movements due to the VI nerve paralysis, the absence of horizontal ocular movements might make it difficult to confirm narcolepsy in these patients. The common clinical characteristics of these patients are due to a possible impairment of the same structures that are affected in the central nervous system. However, the mechanism by which it occurs remains to be fully understood. Further electrophysiological researches are necessary to better clarify the association of these two diseases. The objective of this dissertation is to describe and discuss a case of Moebius syndrome with diurnal excessive sleepiness as a differential diagnosis for narcolepsy.

  15. [Pathogenesis of narcolepsy: from HLA association to hypocretin deficiency].

    Science.gov (United States)

    Klein, G; Burghaus, L; Diederich, N

    2012-11-01

    Narcolepsy is a rare and chronic sleep disorder, characterised by excessive daytime sleepiness. Frequently associated signs are cataplexy, sleep paralysis and hypnagogic or hypnopompic hallucinations. Advances in understanding the pathogenesis of the disease have essentially been elucidated during the last fifteen years. The most significant finding has been the discovery of hypocretin-1 and -2 in 1998. Hypocretin-containing cells have widespread projections throughout the entire CNS and play a crucial role in the regulation of the sleep-wake cycle. They also contribute to olefaction and to the regulation of food intake. Animal models and human studies concordantly show that the disturbed hypocretin system is the probable cause of narcolepsy. However, it remains unclear why there is neuronal death of hypocretin-producing cells in the lateral hypothalamus. As the HLA-allele DQB1*0602 is associated with narcolepsy and hypocretin deficiency, an autoimmune reaction against hypocretin-producing neurons has been vigorously discussed. Newly discovered gene polymorphisms as well as previously unknown pathogenetic mechanisms, linking the sleep-wake cycle with the immune system, may also contribute to the pathogenetic cascade. Worthy of mention in this context is, e.g., the "insulin-like growth factor"-binding protein 3 (IGFBP3), whose overexpression causes a down-regulation of the hypocretin production. Substitution of the deficient neuropeptides by hypocretin agonists may become the causal treatment strategy of the future, if an adequate administration route can be found. Presently, animal trials, including genetic therapy, cell transplantations or the administration of hypocretin receptor agonists, are underway. © Georg Thieme Verlag KG Stuttgart · New York.

  16. Sodium Oxybate treatment in pediatric type 1 narcolepsy.

    Science.gov (United States)

    Moresco, Monica; Pizza, Fabio; Antelmi, Elena; Plazzi, Giuseppe

    2018-03-05

    Narcolepsy type 1 (NT1) is a rare chronic neurologic disorder characterized by excessive daytime sleepiness, cataplexy, sleep paralysis, hallucinations and disrupted nocturnal sleep, usually with onset during childhood/adolescence. Pediatric NT1 is associated with limitations on children's activities and achievements, especially poor performance at school, difficulty with peers due to disease symptoms and comorbidities including depression, obesity, and precocious puberty. NT1 disease is caused by the selective loss of hypocretin-producing neurons in the lateral hypothalamus, most probably related to an autoimmune pathophysiology. Indeed a strong genetic predisposition including the HLA system and other associations in genes involved in immune responses has been found together with the triggering role of environmental agents such as H1N1 influenza infections and vaccinations. Sodium Oxybate (SO) is a sodium salt of γ-hydroxybutyric (GHB) acid that is synthetized by neurons in the brain and functions as neurotransmitter. GHB is a central nervous system depressant and produces dose-dependent sedation. SO is a first line medication for cataplexy and excessive daytime sleepiness in adults with NT1, but can be helpful also for sleep disruption, hypnagogic hallucination and sleep paralysis in these patients. Although in the majority of patients narcolepsy develops before 15 years of age, there are no approved treatments for pediatric NT1. However, SO has been widely used off-label to treat narcolepsy symptoms in children and adolescents with NT1 in non-controlled studies, showing a similar safety profile and therapeutic response to adult patients. Current therapy is based only on empirical data shared among expert sleep disorders clinicians. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Delayed Diagnosis, Range of Severity, and Multiple Sleep Comorbidities: A Clinical and Polysomnographic Analysis of 100 Patients of the Innsbruck Narcolepsy Cohort

    Science.gov (United States)

    Frauscher, Birgit; Ehrmann, Laura; Mitterling, Thomas; Gabelia, David; Gschliesser, Viola; Brandauer, Elisabeth; Poewe, Werner; Högl, Birgit

    2013-01-01

    Study Objectives: Narcolepsy is reported to affect 26-56/100,000 in the general population. We aimed to describe clinical and polysomnographic features of a large narcolepsy cohort in order to comprehensively characterize the narcoleptic spectrum. Methods: We performed a chart- and polysomnographybased review of all narcolepsy patients of the Innsbruck narcolepsy cohort. Results: A total of 100 consecutive narcolepsy patients (87 with cataplexy [NC], 13 without cataplexy [N]) were included in the analysis. All subjects had either excessive daytime sleepiness or cataplexy as their initial presenting clinical feature. Age at symptom onset was 20 (6-69) years. Diagnostic delay was 6.5 (0-39) years. The complete narcolepsy tetrad was present in 36/100 patients; 28/100 patients had three cardinal symptoms; 29/100 had two; and 7/100 had only excessive daytime sleepiness. Severity varied broadly with respect to excessive daytime sleepiness (median Epworth Sleepiness Scale score: 18, range 10-24), cataplexy (8-point Likert scale: median 4.5, range 1-8), hypnagogic hallucinations (median 4.5, range 1-7), and sleep paralysis (median 3, range 1-7). Sleep comorbidity was highly prevalent and ranged from sleeprelated movement disorders (n = 55/100), parasomnias (n = 34/100), and sleeprelated breathing disorders (n = 24/100), to insomnia (n = 28/100). REM sleep without atonia or a periodic limb movement in sleep index > 5/h were present in most patients (90/100 and 75/100). A high percentage of narcoleptic patients in the present study had high frequency leg movements (35%) and excessive fragmentary myoclonus (22%). Of the narcolepsy patients with clinical features of REM sleep behavior disorder (RBD), 76.5% had EMG evidence for RBD on the multiple sleep latency test (MSLT), based on a standard cutoff of a minimum of 18% of 3-sec miniepochs. Conclusion: This study is one of the largest monocentric polysomnographic studies to date of patients with narcolepsy and confirms the

  18. EIF3G is associated with narcolepsy across ethnicities

    DEFF Research Database (Denmark)

    Holm, Anja; Lin, Ling; Faraco, Juliette

    2015-01-01

    conserved in mammals and zebrafish containing PPAN, EIF3G and DNMT1 (DNA methyltransferase 1). As mutations in DNMT1 cause a rare dominant form of narcolepsy in association with deafness, cerebellar ataxia and dementia, we questioned whether the association with P2RY11 in sporadic narcolepsy could...... be secondary to linkage disequilibrium with DNMT1. Based on genome-wide association data from two cohorts of European and Chinese ancestry, we found that the narcolepsy association signal drops sharply between P2RY11/EIF3G and DNMT1, suggesting that the association with narcolepsy does not extend into the DNMT......1 gene region. Interestingly, using transethnic mapping, we identified a novel single-nucleotide polymorphism rs3826784 (c.596-260A>G) in the EIF3G gene also associated with narcolepsy. The disease-associated allele increases EIF3G mRNA expression. EIF3G is located in the narcolepsy risk locus...

  19. Narcolepsy in children: a diagnostic and management approach.

    Science.gov (United States)

    Babiker, Mohamed O E; Prasad, Manish

    2015-06-01

    To provide a diagnostic and management approach for narcolepsy in children. Narcolepsy is a chronic disabling disorder characterized by excessive daytime sleepiness, cataplexy, hypnogogic and/or hypnopompic hallucinations, and sleep paralysis. All four features are present in only half of the cases. Excessive daytime sleepiness is the essential feature of narcolepsy at any age and is usually the first symptom to manifest. A combination of excessive daytime sleepiness and definite cataplexy is considered pathognomonic of narcolepsy syndrome. New treatment options have become available over the past few years. Early diagnosis and management can significantly improve the quality of life of patients with narcolepsy with cataplexy. This review summarizes the pathophysiology, clinical features, and management options for children with narcolepsy. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Predictors of hypocretin (orexin) deficiency in narcolepsy without cataplexy.

    Science.gov (United States)

    Andlauer, Olivier; Moore, Hyatt; Hong, Seung-Chul; Dauvilliers, Yves; Kanbayashi, Takashi; Nishino, Seiji; Han, Fang; Silber, Michael H; Rico, Tom; Einen, Mali; Kornum, Birgitte R; Jennum, Poul; Knudsen, Stine; Nevsimalova, Sona; Poli, Francesca; Plazzi, Giuseppe; Mignot, Emmanuel

    2012-09-01

    concentration was normal. Almost all patients (87%) still complained of daytime sleepiness independent of hypocretin status. Objective (HLA typing, MSLT, and sleep studies) more than subjective (sleepiness and sleep paralysis) features predicted low concentration of CSF hypocretin-1 in patients with narcolepsy without cataplexy.

  1. [Clinical effect of atomoxetine hydrochloride in 66 children with narcolepsy].

    Science.gov (United States)

    Zhang, Shen; Ding, Changhong; Wu, Husheng; Fang, Fang; Wang, Xiaohui; Ren, Xiaotun

    2015-10-01

    To observe the efficacy and safety of atomoxetine hydrochloride in children with narcolepsy. Totally 66 patients with narcolepsy who were conformed international classification of sleep disturbances (ICSD-2) diagnostic criteria treated with atomoxetine hydrochloride seen from November 2010 to December 2014 were enrolled into this study, 42 of them were male and 24 female, mean age of onset was 7.5 years (3.75-13.00 years), mean duration before diagnosis was 1.75 years (0.25-5.00 years). Complete blood count, liver and kidney function, multiple sleep latency test (MSLT), polysomnography (PGS), neuroimaging and electroencephalography (EEG) were performed for each patient. For some of the children HLA-DR2 gene and serum markers of infection were tested. The 66 cases were followed up from 2 to 49 months (average 18 months) to observe the clinical efficacy and adverse reactions. In 62 cases excessive daytime sleepiness was improved, in 11 cases (16.7%) it was controlled (16.7%), in 29 cases (43.9%) the treatment was obviously effective and in 22 (33.3%) it was effective; cataplexy occurred in 54 cases, in 18 (33.3%) it was controlled, in 19 (35.2%) the treatment was obviously effective and in 10 (18.5%) effective; night sleep disorders existed in 55 cases, in 47 cases it was improved, in 14 (25.5%) it was controlled, in 20 (36.4%) the treatment was obviously effective and in 13 (23.6%) effective; hypnagogic or hypnopompic hallucination was present in 13 cases, in only 4 these symptoms were controlled. Sleep paralysis existed in 4 cases, it was controlled in only 1 case. In 18 cases attention and learning efficiency improved.Anorexia occurred in 18 cases, mood disorder in 5 cases, depression in 2 cases, nocturia, muscle tremors, involuntary tongue movement each occurred in 1 case. P-R interval prolongation and atrial premature contraction were found in 1 case. Atomoxetine hydrochloride showed good effects in patients with narcolepsy on excessive daytime sleepiness

  2. HYPOCRETIN/OREXIN AND NARCOLEPSY NEW BASIC AND CLINICAL INSIGHTS

    Science.gov (United States)

    NISHINO, Seiji; OKURO, Masashi; KOTORII, Nozomu; ANEGAWA, Emiko; ISHIMARU, Yuji; MATSUMURA, Mari; KANBAYASHI, Takashi

    2009-01-01

    Narcolepsy is a chronic sleep disorder, characterized by excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, and sleep paralysis. Both sporadic (95%) and familial (5%) forms of narcolepsy exist in humans. The major pathophysiology of human narcolepsy has been recently discovered based on the discovery of narcolepsy genes in animals; the genes involved in the pathology of the hypocretin/orexin ligand and its receptor. Mutations in hypocretin-related genes are rare in humans, but hypocretin-ligand deficiency is found in a large majority of narcolepsy with cataplexy. Hypocretin ligand deficiency in human narcolepsy is likely due to the postnatal cell death of hypocretin neurons. Although tight association between human leukocyte antigen (HLA) association and human narcolepsy with cataplexy suggests an involvement of autoimmune mechanisms, this has not yet been proven. Hypocretin deficiency is also found in symptomatic cases of narcolepsy and EDS with various neurological conditions, including immune-mediated neurological disorders, such as Guillain-Barre syndrome, MA2-positive paraneoplastic syndrome and neuromyelitis optica (NMO) related disorder. These findings likely have significant clinical relevance and for understanding the mechanisms of hypocretin cell death and choice of treatment option. These series of discoveries in humans lead to the establishment of the new diagnostic test of narcolepsy (i.e. low cerebrospinal fluid [CSF] hypocretin-1 levels for narcolepsy with cataplexy and narcolepsy due to medical condition). Since a large majority of human narcolepsy patients are ligand deficient, hypocretin replacement therapy may be a promising new therapeutic option, and animal experiments using gene therapy and cell transplantations are in progress. PMID:19555382

  3. Aberrant Food Choices after Satiation in Human Orexin-Deficient Narcolepsy Type 1

    NARCIS (Netherlands)

    van Holst, R.J.; van der Cruijsen, L.; van Mierlo, P.; Lammers, G.J.; Cools, R.; Overeem, S.; Aarts, E.

    2016-01-01

    STUDY OBJECTIVES: Besides influencing vigilance, orexin neurotransmission serves a variety of functions, including reward, motivation, and appetite regulation. As obesity is an important symptom in orexin-deficient narcolepsy, we explored the effects of satiety on food-related choices and

  4. Aberrant food choices after satiation in human orexin-deficient narcolepsy type 1

    NARCIS (Netherlands)

    van Holst, R.J.; van der Cruijsen, L.; van Mierlo, P.; Lammers, G.J.; Cools, R.; Overeem, S.; Aarts, E.

    2016-01-01

    STUDY OBJECTIVES: Besides influencing vigilance, orexin neurotransmission serves a variety of functions, including reward, motivation, and appetite regulation. As obesity is an important symptom in orexin-deficient narcolepsy, we explored the effects of satiety on food-related choices and

  5. DQB1*06:02 allele-specific expression varies by allelic dosage, not narcolepsy status

    DEFF Research Database (Denmark)

    Weiner Lachmi, Karin; Lin, Ling; Kornum, Birgitte Rahbek

    2012-01-01

    The association of narcolepsy-cataplexy, a sleep disorder caused by the loss of hypocretin/orexin neurons in the hypothalamus, with DQA1*01:02-DQB1*06:02 is one of the tightest known single-allele human leukocyte antigen (HLA) associations. In this study, we explored genome-wide expression...

  6. HLA DQB1*06:02 negative narcolepsy with hypocretin/orexin deficiency

    DEFF Research Database (Denmark)

    Han, Fang; Lin, Ling; Schormair, Barbara

    2014-01-01

    STUDY OBJECTIVES: To identify rare allelic variants and HLA alleles in narcolepsy patients with hypocretin (orexin, HCRT) deficiency but lacking DQB1*06:02. SETTINGS: China (Peking University People's Hospital), Czech Republic (Charles University), Denmark (Golstrup Hospital), Italy (University o...

  7. Noradrenergic augmentation strategies in the pharmacological treatment of depression and schizophrenia : An experimental study

    OpenAIRE

    Linnér, Love

    2002-01-01

    The pharmacological treatment of depression and schizophrenia, two major psychiatric disorders, is largely based on modulation of central monoaminergic neurotransmission. However, currently available pharmacological treatment alternatives possess a relatively modest clinical efficacy, making them less than optimal. The present series of studies, using in vivo electrophysiological, biochemical and behavioral techniques in rats, aim at the disclosure of mechanisms whereby an ...

  8. Psychotic symptoms in narcolepsy: phenomenology and a comparison with schizophrenia.

    Science.gov (United States)

    Fortuyn, Hal A Droogleever; Lappenschaar, G A; Nienhuis, Fokko J; Furer, Joop W; Hodiamont, Paul P; Rijnders, Cees A; Lammers, Gert Jan; Renier, Willy O; Buitelaar, Jan K; Overeem, Sebastiaan

    2009-01-01

    Patients with narcolepsy often experience pervasive hypnagogic hallucinations, sometimes even leading to confusion with schizophrenia. We aimed to provide a detailed qualitative description of hypnagogic hallucinations and other "psychotic" symptoms in patients with narcolepsy and contrast these with schizophrenia patients and healthy controls. We also compared the prevalence of formal psychotic disorders between narcolepsy patients and controls. We used SCAN 2.1 interviews to compare psychotic symptoms between 60 patients with narcolepsy, 102 with schizophrenia and 120 matched population controls. In addition, qualitative data was collected to enable a detailed description of hypnagogic hallucinations in narcolepsy. There were clear differences in the pattern of hallucinatory experiences in narcolepsy vs. schizophrenia patients. Narcoleptics reported multisensory "holistic" hallucinations rather than the predominantly verbal-auditory sensory mode of schizophrenia patients. Psychotic symptoms such as delusions were not more frequent in narcolepsy compared to population controls. In addition, the prevalence of formal psychotic disorders was not increased in patients with narcolepsy. Almost half of narcoleptics reported moderate interference with functioning due to hypnagogic hallucinations, mostly due to related anxiety. Hypnagogic hallucinations in narcolepsy can be differentiated on a phenomenological basis from hallucinations in schizophrenia which is useful in differential diagnostic dilemmas.

  9. CD4+ T-Cell Reactivity to Orexin/Hypocretin in Patients With Narcolepsy Type 1.

    Science.gov (United States)

    Ramberger, Melanie; Högl, Birgit; Stefani, Ambra; Mitterling, Thomas; Reindl, Markus; Lutterotti, Andreas

    2017-03-01

    Narcolepsy type 1 is accompanied by a selective loss of orexin/hypocretin (hcrt) neurons in the lateral hypothalamus caused by yet unknown mechanisms. Epidemiologic and genetic associations strongly suggest an immune-mediated pathogenesis of the disease. We compared specific T-cell reactivity to orexin/hcrt peptides in peripheral blood mononuclear cells of narcolepsy type 1 patients to healthy controls by a carboxyfluorescein succinimidyl ester proliferation assay. Orexin/hcrt-specific T-cell reactivity was also determined by cytokine (interferon gamma and granulocyte-macrophage colony-stimulating factor) analysis. Individuals were considered as responders if the cell division index of CD3+CD4+ T cells and both stimulation indices of cytokine secretion exceeded the cutoff 3. Additionally, T-cell reactivity to orexin/hcrt had to be confirmed by showing reactivity to single peptides present in different peptide pools. Using these criteria, 3/15 patients (20%) and 0/13 controls (0%) showed orexin/hcrt-specific CD4+ T-cell proliferation (p = .2262). The heterogeneous reactivity pattern did not allow the identification of a preferential target epitope. A significant role of orexin/hcrt-specific T cells in narcolepsy type 1 patients could not be confirmed in this study. Further studies are needed to assess the exact role of CD4+ T cells and possible target antigens in narcolepsy type 1 patients. © Sleep Research Society 2016. Published by Oxford University Press [on behalf of the Sleep Research Society].

  10. Subjective deficits of attention, cognition and depression in patients with narcolepsy.

    Science.gov (United States)

    Zamarian, Laura; Högl, Birgit; Delazer, Margarete; Hingerl, Katharina; Gabelia, David; Mitterling, Thomas; Brandauer, Elisabeth; Frauscher, Birgit

    2015-01-01

    Patients with narcolepsy often complain about attention deficits in everyday situations. In comparison with these subjective complaints, deficits in objective testing are subtler. The present study assessed the relationships between subjective complaints, objectively measured cognitive performance, disease-related variables, and mood. A total of 51 patients with narcolepsy and 35 healthy controls responded to questionnaires regarding subjectively perceived attention deficits, sleepiness, anxiety and depression. Moreover, they performed an extensive neuropsychological assessment tapping into attention, executive functions, and memory. Patients rated their level of attention in everyday situations to be relatively poor. In an objective assessment of cognitive functioning, they showed only slight attention and executive function deficits. The subjective ratings of attention deficits significantly correlated with ratings of momentary sleepiness, anxiety, and depression, but not with objectively measured cognitive performance. Momentary sleepiness and depression predicted almost 39% of the variance in the ratings of subjectively perceived attention deficits. The present study showed that sleepiness and depression, more than objective cognitive deficits, might play a role in the subjectively perceived attention deficits of patients with narcolepsy. The results suggested that when counselling and treating patients with narcolepsy, clinicians should pay attention to potential depression because subjective cognitive complaints may not relate to objective cognitive impairments. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Clinical effect of venlafaxine combined with methylphenidate hydrochloride on narcolepsy

    Directory of Open Access Journals (Sweden)

    YAN Bin

    2013-11-01

    Full Text Available This study aims to explore the clinical effect of venlafaxine sustained-release capsules combined with methylphenidate hydrochloride tablets on narcolepsy. Thirty-eight cases of narcoleptic patients were randomly divided into venlafaxine combined with methylphenidate hydrochloride treatment group (observation group, N = 19 and methylphenidate hydrochloride and clomipramine treatment group (control group, N = 19. After a total of 12-week treatment, clinical curative effect and adverse drug reactions were observed in 2 groups of patients. The results showed that effective rate of the treatment for excessive daytime sleepiness (EDS in observation group was higher than that of the control group (15/19 vs 8/19, P = 0.044, and effective rate of the treatment for cataplexy in observation group was higher than that of the control group (13/19 vs 6/19, P = 0.048. The rate of adverse drug reactions in observation group was lower than that in the control group (χ2 = 8.889, P = 0.003. It was indicated that venlafaxine combined with methylphenidate had good curative effect on narcolepsy with EDS and cataplexy symptoms.

  12. The effect of learning styles and study behavior on success of preclinical students in pharmacology.

    Science.gov (United States)

    Asci, Halil; Kulac, Esin; Sezik, Mekin; Cankara, F Nihan; Cicek, Ekrem

    2016-01-01

    To evaluate the effect of learning styles and study behaviors on preclinical medical students' pharmacology exam scores in a non-Western setting. Grasha-Reichmann Student Learning Study Scale and a modified Study Behavior Inventory were used to assess learning styles and study behaviors of preclinical medical students (n = 87). Logistic regression models were used to evaluate the independent effect of gender, age, learning style, and study behavior on pharmacology success. Collaborative (40%) and competitive (27%) dominant learning styles were frequent in the cohort. The most common study behavior subcategories were study reading (40%) and general study habits (38%). Adequate listening and note-taking skills were associated with pharmacology success, whereas students with adequate writing skills had lower exam scores. These effects were independent of gender. Preclinical medical students' study behaviors are independent predictive factors for short-term pharmacology success.

  13. Increased risk of narcolepsy in children and adults after pandemic H1N1 vaccination in France.

    Science.gov (United States)

    Dauvilliers, Yves; Arnulf, Isabelle; Lecendreux, Michel; Monaca Charley, Christelle; Franco, Patricia; Drouot, Xavier; d'Ortho, Marie-Pia; Launois, Sandrine; Lignot, Séverine; Bourgin, Patrice; Nogues, Béatrice; Rey, Marc; Bayard, Sophie; Scholz, Sabine; Lavault, Sophie; Tubert-Bitter, Pascale; Saussier, Cristel; Pariente, Antoine

    2013-08-01

    An increased incidence of narcolepsy in children was detected in Scandinavian countries where pandemic H1N1 influenza ASO3-adjuvanted vaccine was used. A campaign of vaccination against pandemic H1N1 influenza was implemented in France using both ASO3-adjuvanted and non-adjuvanted vaccines. As part of a study considering all-type narcolepsy, we investigated the association between H1N1 vaccination and narcolepsy with cataplexy in children and adults compared with matched controls; and compared the phenotype of narcolepsy with cataplexy according to exposure to the H1N1 vaccination. Patients with narcolepsy-cataplexy were included from 14 expert centres in France. Date of diagnosis constituted the index date. Validation of cases was performed by independent experts using the Brighton collaboration criteria. Up to four controls were individually matched to cases according to age, gender and geographic location. A structured telephone interview was performed to collect information on medical history, past infections and vaccinations. Eighty-five cases with narcolepsy-cataplexy were included; 23 being further excluded regarding eligibility criteria. Of the 62 eligible cases, 59 (64% males, 57.6% children) could be matched with 135 control subjects. H1N1 vaccination was associated with narcolepsy-cataplexy with an odds ratio of 6.5 (2.1-19.9) in subjects agedvaccine. Slight differences were found when comparing cases with narcolepsy-cataplexy exposed to H1N1 vaccination (n=32; mostly AS03-adjuvanted vaccine, n=28) to non-exposed cases (n=30), including shorter delay of diagnosis and a higher number of sleep onset rapid eye movement periods for exposed cases. No difference was found regarding history of infections. In this sub-analysis, H1N1 vaccination was strongly associated with an increased risk of narcolepsy-cataplexy in both children and adults in France. Even if, as in every observational study, the possibility that some biases participated in the association

  14. [Advances in the pharmacological study of Morus alba L].

    Science.gov (United States)

    Yang, Shuang; Wang, Bao-Lian; Li, Yan

    2014-06-01

    Morus alba L. (mulberry) is a well-known deciduous tree, belonging to the genus of Morus of Moraceae famlily. Its leaves, twigs, roots (bark) and fruits are widely used in the traditional Chinese medicine. The active constituents of mulberry contained flavonoids, alkaloids, steroids, coumarins, with the significant hypoglycemic, hypolipidemic, antihypertension, anti-oxidation, anti-inflammatory, anti-bacterial, anti-tumor and immunomodulatory activities. This review summarized the research progress of the major pharmacological activity, pharmacokinetics and drug-drug interaction based on CYPs and transporters of mulberry and its active constituents.

  15. The diagnosis and treatment of pediatric narcolepsy.

    Science.gov (United States)

    Nevsimalova, Sona

    2014-08-01

    Narcolepsy in children is a serious disorder marked by a chronic course and lifelong handicap in school performance and choice of employment, by free time activity limitation, and by behavior and personality changes, all of which constitute a major influence on the quality of life. Increased daytime sleepiness may be the only sign at the disease onset, with attacks of sleep becoming longer and lasting up to hours. Also present may be confusional arousals with features of sleep drunkenness. Paradoxically, preschool and young children may show inattentiveness, emotional lability, and hyperactive behavior. Cataplexy may develop after onset of sleepiness and affect mainly muscles of the face. Hypnagogic hallucinations and sleep paralysis are seldom present. Multiple Sleep Latency Test criteria are not available for children younger than 6 years. The haplotype (HLA-DQB1:0602) can be associated with the disorder; however, the best predictor of narcolepsy-cataplexy is hypocretin deficiency. The treatment generally used in adults is regarded as off-label in childhood, which is why the management of pediatric narcolepsy is difficult.

  16. Aberrant Food Choices after Satiation in Human Orexin-Deficient Narcolepsy Type 1.

    Science.gov (United States)

    van Holst, Ruth Janke; van der Cruijsen, Lisa; van Mierlo, Petra; Lammers, Gert Jan; Cools, Roshan; Overeem, Sebastiaan; Aarts, Esther

    2016-11-01

    Besides influencing vigilance, orexin neurotransmission serves a variety of functions, including reward, motivation, and appetite regulation. As obesity is an important symptom in orexin-deficient narcolepsy, we explored the effects of satiety on food-related choices and spontaneous snack intake in patients with narcolepsy type 1 (n = 24) compared with healthy matched controls (n = 19). In additional analyses, we also included patients with idiopathic hypersomnia (n = 14) to assess sleepiness-related influences. Participants were first trained on a choice task to earn salty and sweet snacks. Next, one of the snack outcomes was devalued by having participants consume it until satiation (i.e., sensory-specific satiety). We then measured the selective reduction in choices for the devalued snack outcome. Finally, we assessed the number of calories that participants consumed spontaneously from ad libitum available snacks afterwards. After satiety, all participants reported reduced hunger and less wanting for the devalued snack. However, while controls and idiopathic hypersomnia patients chose the devalued snack less often in the choice task, patients with narcolepsy still chose the devalued snack as often as before satiety. Subsequently, narcolepsy patients spontaneously consumed almost 4 times more calories during ad libitum snack intake. We show that the manipulation of food-specific satiety has reduced effects on food choices and caloric intake in narcolepsy type 1 patients. These mechanisms may contribute to their obesity, and suggest an important functional role for orexin in human eating behavior. Study registered at Netherlands Trial Register. URL: www.trialregister.nl. Trial ID: NTR4508. © 2016 Associated Professional Sleep Societies, LLC.

  17. Olfactory Dysfunction in Narcolepsy with and without Cataplexy

    Czech Academy of Sciences Publication Activity Database

    Bušková, J.; Klaschka, Jan; Šonka, K.; Nevšímalová, S.

    2010-01-01

    Roč. 11, č. 6 (2010), s. 558-561 ISSN 1389-9457 Institutional research plan: CEZ:AV0Z10300504 Keywords : narcolepsy * cataplexy * narcolepsy without cataplexy * RBD * olfactory dysfunction Subject RIV: FH - Neurology Impact factor: 3.430, year: 2010

  18. Narcolepsy induced by chronic heavy alcohol consumption: a case report

    Science.gov (United States)

    Wang, Xinyuan

    2012-01-01

    Summary Narcolepsy is a chronic neurological disorder, characterized by uncontrollable excessive daytime sleepiness, cataplectic episodes, sleep paralysis, hypnagogic hallucinations, and night time sleep disruption. The paper reviewed the related literature and reported a case of long-term drinking induced narcolepsy which was significantly improved after treatment with paroxetine and dexzopiclone. PMID:25328357

  19. Narcolepsy and Orexins: An Example of Progress in Sleep Research

    Science.gov (United States)

    De la Herrán-Arita, Alberto K.; Guerra-Crespo, Magdalena; Drucker-Colín, René

    2011-01-01

    Narcolepsy is a chronic neurodegenerative disease caused by a deficiency of orexin-producing neurons in the lateral hypothalamus. It is clinically characterized by excessive daytime sleepiness and by intrusions into wakefulness of physiological aspects of rapid eye movement sleep such as cataplexy, sleep paralysis, and hypnagogic hallucinations. The major pathophysiology of narcolepsy has been recently described on the bases of the discovery of the neuropeptides named orexins (hypocretins) in 1998; considerable evidence, summarized below, demonstrates that narcolepsy is the result of alterations in the genes involved in the pathology of the orexin ligand or its receptor. Deficient orexin transmission is sufficient to produce narcolepsy, as we describe here, animal models with dysregulated orexin signaling exhibit a narcolepsy-like phenotype. Remarkably, these narcoleptic models have different alterations of the orexinergic circuit, this diversity provide us with the means for making comparison, and have a better understanding of orexin-cell physiology. It is of particular interest that the most remarkable findings regarding this sleep disorder were fortuitous and due to keen observations. Sleep is a highly intricate and regulated state, and narcolepsy is a disorder that still remains as one of the unsolved mysteries in science. Nevertheless, advances and development of technology in neuroscience will provide us with the necessary tools to unravel the narcolepsy puzzle in the near future. Through an evaluation of the scientific literature we traced an updated picture of narcolepsy and orexins in order to provide insight into the means by which neurobiological knowledge is constructed. PMID:21541306

  20. Narcolepsy and Psychiatric Disorders: Comorbidities or Shared Pathophysiology?

    Directory of Open Access Journals (Sweden)

    Anne Marie Morse

    2018-02-01

    Full Text Available Narcolepsy and psychiatric disorders have a significant but unrecognized relationship, which is an area of evolving interest, but unfortunately, the association is poorly understood. It is not uncommon for the two to occur co-morbidly. However, narcolepsy is frequently misdiagnosed initially as a psychiatric condition, contributing to the protracted time to accurate diagnosis and treatment. Narcolepsy is a disabling neurodegenerative condition that carries a high risk for development of social and occupational dysfunction. Deterioration in function may lead to the secondary development of psychiatric symptoms. Inversely, the development of psychiatric symptoms can lead to the deterioration in function and quality of life. The overlap in pharmaceutical intervention may further enhance the difficulty to distinguish between diagnoses. Comprehensive care for patients with narcolepsy should include surveillance for psychiatric illness and appropriate treatment when necessary. Further research is necessary to better understand the underlying pathophysiology between psychiatric disease and narcolepsy.

  1. Narcolepsy in Adolescence—A Missed Diagnosis: A Case Report

    Science.gov (United States)

    Gupta, Anoop K.; Sahoo, Swapnajeet

    2017-01-01

    ABSTRACT: Narcolepsy is an uncommon sleep cycle disorder with a usual onset in adolescence, but it is often misdiagnosed and underdiagnosed. Rarely is the tetrad of excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis seen in patients. The clinical characteristics of narcolepsy are often confused with many psychiatric and neurologic disorders. Lack of clinical awareness about narcolepsy leads to frequent prescriptions of antiepileptics and psychotropics, which can adversely affect the quality of life of children and adolescents. We report a case of an adolescent male who presented with all four cardinal symptoms of narcolepsy and had been misdiagnosed with epilepsy, psychosis, and depression. We discuss various issues regarding narcolepsy in children and adolescents. PMID:29616151

  2. Status Cataplecticus as Initial Presentation of Late Onset Narcolepsy

    Science.gov (United States)

    Panda, Samhita

    2014-01-01

    Narcolepsy, one of the important causes of hypersomnia, is an under diagnosed sleep disorder. It has a bimodal age of onset around 15 and 35 years. It is characterized by the tetrad of excessive daytime sleepiness, cataplexy, hypnagogic/ hypnopompic hallucinations, and sleep paralysis. Cataplexy is by far the most predictive feature of narcolepsy. Status cataplecticus is the occurrence of cataplexy repeatedly for hours or days, a rare presentation of narcolepsy. This report describes an elderly gentleman with late onset narcolepsy in the sixth decade of life presenting with initial and chief symptom of status cataplecticus. Citation: Panda S. Status cataplecticus as initial presentation of late onset narcolepsy. J Clin Sleep Med 2014;10(2):207-209. PMID:24533005

  3. Pharmacologic studies in vulnerable populations: Using the pediatric experience.

    Science.gov (United States)

    Zimmerman, Kanecia; Gonzalez, Daniel; Swamy, Geeta K; Cohen-Wolkowiez, Michael

    2015-11-01

    Historically, few data exist to guide dosing in children and pregnant women. Multiple barriers to inclusion of these vulnerable populations in clinical trials have led to this paucity of data. However, federal legislation targeted at pediatric therapeutics, innovative clinical trial design, use of quantitative clinical pharmacology methods, pediatric thought leadership, and collaboration have successfully overcome many existing barriers. This success has resulted in improved knowledge on pharmacokinetics, safety, and efficacy of therapeutics in children. To date, research in pregnant women has not been characterized by similar success. Wide gaps in knowledge remain despite the common use of therapeutics in pregnancy. Given the similar barriers to drug research and development in pediatric and pregnant populations, the route toward success in children may serve as a model for the advancement of drug development and appropriate drug administration in pregnant women. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Validation of the ICSD-2 criteria for CSF hypocretin-1 measurements in the diagnosis of narcolepsy in the Danish population

    DEFF Research Database (Denmark)

    Knudsen, Stine; Jennum, Poul J; Alving, Jørgen

    2010-01-01

    STUDY OBJECTIVES: The International Classification of Sleep Disorders (ICSD-2) criteria for low CSF hypocretin-1 levels (CSF hcrt-1) still need validation as a diagnostic tool for narcolepsy in different populations because inter-assay variability and different definitions of hypocretin deficiency...... complicate direct comparisons of study results. DESIGN AND PARTICIPANTS: Interviews, polysomnography, multiple sleep latency test, HLA-typing, and CSF hcrt-1 measurements in Danish patients with narcolepsy with cataplexy (NC) and narcolepsy without cataplexy (NwC), CSF hcrt-1 measurements in other......). MEASUREMENTS AND RESULTS: In Danes, low CSF hcrt-1 was present in 40/46 NC, 3/14 NwC and 0/106 controls (P sleep latency, more sleep...

  5. Facial expression recognition and emotional regulation in narcolepsy with cataplexy.

    Science.gov (United States)

    Bayard, Sophie; Croisier Langenier, Muriel; Dauvilliers, Yves

    2013-04-01

    Cataplexy is pathognomonic of narcolepsy with cataplexy, and defined by a transient loss of muscle tone triggered by strong emotions. Recent researches suggest abnormal amygdala function in narcolepsy with cataplexy. Emotion treatment and emotional regulation strategies are complex functions involving cortical and limbic structures, like the amygdala. As the amygdala has been shown to play a role in facial emotion recognition, we tested the hypothesis that patients with narcolepsy with cataplexy would have impaired recognition of facial emotional expressions compared with patients affected with central hypersomnia without cataplexy and healthy controls. We also aimed to determine whether cataplexy modulates emotional regulation strategies. Emotional intensity, arousal and valence ratings on Ekman faces displaying happiness, surprise, fear, anger, disgust, sadness and neutral expressions of 21 drug-free patients with narcolepsy with cataplexy were compared with 23 drug-free sex-, age- and intellectual level-matched adult patients with hypersomnia without cataplexy and 21 healthy controls. All participants underwent polysomnography recording and multiple sleep latency tests, and completed depression, anxiety and emotional regulation questionnaires. Performance of patients with narcolepsy with cataplexy did not differ from patients with hypersomnia without cataplexy or healthy controls on both intensity rating of each emotion on its prototypical label and mean ratings for valence and arousal. Moreover, patients with narcolepsy with cataplexy did not use different emotional regulation strategies. The level of depressive and anxious symptoms in narcolepsy with cataplexy did not differ from the other groups. Our results demonstrate that narcolepsy with cataplexy accurately perceives and discriminates facial emotions, and regulates emotions normally. The absence of alteration of perceived affective valence remains a major clinical interest in narcolepsy with cataplexy

  6. The cost-utility of sodium oxybate as narcolepsy treatment

    DEFF Research Database (Denmark)

    Bolin, K; Berling, P; Wasling, P

    2017-01-01

    cost per additional QALY for the sodium oxybate treatment alternative compared with standard treatment was estimated above the informal Swedish willingness-to-pay threshold (SEK 500,000). The estimated cost per additional QALY obtained here is likely to overestimate the true cost-effectiveness ratio......AIMS AND OBJECTIVES: Based on class-I studies, sodium oxybate is regarded as a first-line treatment for both EDS and cataplexy. The cost-effectiveness of sodium oxybate is largely unknown, though. In this study, we estimate the cost-effectiveness of sodium oxybate as treatment for patients...... with narcolepsy as compared to standard treatment, by calculating incremental cost-effectiveness ratios (cost per quality-adjusted life year, QALY) for patients in a Swedish setting. MATERIALS AND METHODS: Calculations were performed using a Markov model with a 10-year time horizon. The study population consisted...

  7. Mechanism of action of narcolepsy medications.

    Science.gov (United States)

    Gowda, Chandan R; Lundt, Leslie P

    2014-12-01

    The medications used to treat narcolepsy are targeted toward alleviating symptoms such as excessive sleepiness and cataplexy. The cause of this neurological sleep disorder is still not completely clear, though a destruction of hypocretin/orexin neurons has been implicated. The destruction of these neurons is linked to inactivity of neurotransmitters including histamine, norepinephrine, acetylcholine, and serotonin, causing a disturbance in the sleep/wake cycles of narcoleptic patients. Stimulants and MAOIs have traditionally been used to counteract excessive daytime sleepiness and sleep attacks by inhibiting the breakdown of catecholamines. Newer drugs, called wake-promoting agents, have recently become first-line agents due to their better side-effect profile, efficacy, and lesser potential for abuse. These agents similarly inhibit reuptake of dopamine, but have a novel mechanism of action, as they have been found to increase neuronal activity in the tuberomamillary nucleus and in orexin neurons. Sodium oxybate, a sodium salt of gamma-hydroxybutyrate (GHB), is another class that is used to treat many symptoms of narcolepsy, and is the only U.S. Food and Drug Administration (FDA)-approved medication for cataplexy. It has a different mechanism of action than either stimulants or wake-promoting agents, as it binds to its own unique receptor. Antidepressants, like selective serotonin re-uptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs), have also been used, as similar to stimulants, they inhibit reuptake of specific catecholamines. In this article, we seek to review the mechanisms behind these classes of drugs in relation to the proposed pathophysiology of narcolepsy. Appropriate clinical strategies will be discussed, including specific combinations of medications that have been shown to be effective.

  8. Sleep Transitions in Hypocretin-Deficient Narcolepsy

    DEFF Research Database (Denmark)

    Sorensen, Gertrud Laura; Knudsen, Stine; Jennum, Poul

    2013-01-01

    Narcolepsy is characterized by instability of sleep-wake, tonus, and rapid eye movement (REM) sleep regulation. It is associated with severe hypothalamic hypocretin deficiency, especially in patients with cataplexy (loss of tonus). As the hypocretin neurons coordinate and stabilize the brain......'s sleep-wake pattern, tonus, and REM flip-flop neuronal centers in animal models, we set out to determine whether hypocretin deficiency and/or cataplexy predicts the unstable sleep-wake and REM sleep pattern of the human phenotype....

  9. Improving recruitment to pharmacological trials for illicit opioid use: findings from a qualitative focus group study.

    Science.gov (United States)

    Neale, Joanne; Tompkins, Charlotte N E; McDonald, Rebecca; Strang, John

    2018-06-01

    To explore potential study participants' views on willingness to join clinical trials of pharmacological interventions for illicit opioid use to inform and improve future recruitment strategies. Qualitative focus group study [six groups: oral methadone (two groups); buprenorphine tablets (two groups); injectable opioid agonist treatment (one group); and former opioid agonist treatment (one group)]. Drug and alcohol services and a peer support recovery service (London, UK). Forty people with experience of opioid agonist treatment for heroin dependence (26 males, 14 females; aged 33-66 years). Data collection was facilitated by a topic guide that explored willingness to enrol in clinical pharmacological trials. Groups were audio-recorded and transcribed. Transcribed data were analysed inductively via Iterative Categorization. Participants' willingness to join pharmacological trials of medications for opioid dependence was affected by factors relating to study burden, study drug, study design, study population and study relationships. Participants worried that the trial drug might be worse than, or interfere with, their current treatment. They also misunderstood aspects of trial design despite the researchers' explanations. Recruitment of participants for clinical trials of pharmacological interventions for illicit opioid use could be improved if researchers became better at explaining clinical trials to potential participants, dispelling misconceptions about trials and increasing trust in the research process and research establishment. A checklist of issues to consider when designing pharmacological trials for illicit opioid use is proposed. © 2018 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

  10. Degenerative pontine lesions in patients with familial narcolepsy.

    Science.gov (United States)

    Stepień, Adam; Staszewski, Jacek; Domzał, Teofan M; Tomczykiewicz, Kazimierz; Skrobowska, Ewa; Durka-Kesy, Marta

    2010-01-01

    Narcolepsy is characterized by chronic excessive daytime sleepiness with episodic sleep attacks. There are several associated symptoms of narcolepsy: cataplexy (bilateral muscle weakness without loss of consciousness provoked by an emotional trigger, e.g. laughter), sleep paralysis and hypnagogic-hypnopompic hallucinations. Most cases are sporadic; familial narcolepsy contributes to only 1-5% of all cases. While most cases of narcolepsy are idiopathic and are not associated with clinical or radiographic evidence of brain pathology, symptomatic or secondary narcolepsy may occur occasionally in association with lesions caused by tumours, demyelination or strokes of the diencephalon, midbrain, and pons. There are some examples of non-specific brainstem lesions found in magnetic resonance imaging (MRI) in patients with idiopathic narcolepsy. The authors present eleven patients from a five-generation family with many members who suffer from episodic excessive daytime sleepiness. Narcolepsy was diagnosed in 9 patients. Sleepiness was frequently associated with cataplexy, hypnagogic-hypnopompic hallucinations and sleep paralysis. Improvement in their clinical state was observed during the treatment with modafinil. All probands had MRI of the brain, routine blood tests, EEG, polysomnography, examination of the level of hypocretin in cerebrospinal fluid and evaluation by means of Epworth and Stanford Sleepiness Scales. In 9 patients with narcolepsy, decreased thickness of the substantia nigra was found and in six of them degenerative lesions in the pontine substantia nigra were also noticed. The significance of these changes remains unclear. No data have been published until now concerning the presence of any brain lesions in patients with familial narcolepsy.

  11. Treatment cost of narcolepsy with cataplexy in Central Europe

    Directory of Open Access Journals (Sweden)

    Maresova P

    2016-11-01

    Full Text Available Petra Maresova,1 Michal Novotny,2,3 Blanka Klímová,4 Kamil Kuča3,51Department of Economics, Faculty of Informatics and Management, 2Department of Chemistry, Faculty of Science, University of Hradec Králové, 3Biomedical Research Center, University Hospital Hradec Králové, 4Department of Applied Linguistics, Faculty of Informatics and Management, 5Faculty of Informatics and Management, University of Hradec Králové, Hradec Králové, Czech Republic Background: Narcolepsy is a lifelong, rare neurological sleep disorder characterized by chronic, excessive attacks of daytime sleepiness. This disease is often extremely incapacitating, interfering with every aspect of life, in work and social settings.Objective: The purpose of this study is to specify the treatment costs of patients in the Central Europe (Czech Republic, while the attention is mainly paid to the drugs that were fully or partially covered by public health insurance. Furthermore, concomitant therapy is also evaluated, since it incurs a certain financial burden for patients and their family members. On the basis of the calculated costs, impact on the public budget is evaluated.Patients and methods: This study monitors the direct costs of the drugs for 13 patients, who represent ~1.3% of the total number of diagnosed patients in the Czech Republic, and evaluates the costs associated with their treatment during the period from January 9, 2011 to April 23, 2013.Results: Most of the treatment costs (~80% were covered by publicly available sources. This finding is also true for the concomitant therapy of comorbidities. Additional payments for the drugs constitute about 20% of the total costs. Keywords: cataplexy, cost, narcolepsy, orphan drug, rare disease, sodium oxybate

  12. Novel method for evaluation of eye movements in patients with narcolepsy

    DEFF Research Database (Denmark)

    Christensen, Julie A E; Kempfner, Lykke; Leonthin, Helle L

    2017-01-01

    BACKGROUND: Narcolepsy causes abnormalities in the control of wake-sleep, non-rapid-eye-movement (non-REM) sleep and REM sleep, which includes specific eye movements (EMs). In this study, we aim to evaluate EM characteristics in narcolepsy as compared to controls using an automated detector....... RESULTS: NT1 patients had significantly less EMs during wake, N1, and N2 sleep and more EMs during REM sleep compared to clinical controls, and significantly less EMs during wake and N1 sleep compared to NT2 patients. Furthermore, NT1 patients showed less EMs during NREM sleep in the first sleep cycle....... METHODS: We developed a data-driven method to detect EMs during sleep based on two EOG signals recorded as part of a polysomnography (PSG). The method was optimized using the manually scored hypnograms from 36 control subjects. The detector was applied on a clinical sample with subjects suspected...

  13. Cerebrospinal fluid cytokine levels in type 1 narcolepsy patients very close to onset

    DEFF Research Database (Denmark)

    Kornum, Birgitte Rahbek; Pizza, Fabio; Knudsen, Stine

    2015-01-01

    Type 1 narcolepsy is caused by a loss of hypocretin (orexin) signaling in the brain. Genetic data suggests the disorder is caused by an autoimmune attack on hypocretin producing neurons in hypothalamus. This hypothesis has however not yet been confirmed by consistent findings of autoreactive....... In this study, we tested whether an active immune process in the brain could be detected in these patients, as reflected by increased cytokine levels in the cerebrospinal fluid (CSF). Using multiplex analysis, we measured the levels of 51 cytokines and chemokines in the CSF of 40 type 1 narcolepsy patients...... having varying disease duration. For comparison, we used samples from 9 healthy controls and 9 patients with other central hypersomnia. Cytokine levels did not differ significantly between controls and patients, even in 5 patients with disease onset less than a month prior to CSF sampling....

  14. Predictors of hypocretin (orexin) deficiency in narcolepsy without cataplexy

    DEFF Research Database (Denmark)

    Andlauer, Olivier; Moore, Hyatt; Hong, Seung-Chul

    2012-01-01

    To compare clinical, electrophysiologic, and biologic data in narcolepsy without cataplexy with low (≤ 110 pg/ml), intermediate (110-200 pg/ml), and normal (> 200 pg/ml) concentrations of cerebrospinal fluid (CSF) hypocretin-1.......To compare clinical, electrophysiologic, and biologic data in narcolepsy without cataplexy with low (≤ 110 pg/ml), intermediate (110-200 pg/ml), and normal (> 200 pg/ml) concentrations of cerebrospinal fluid (CSF) hypocretin-1....

  15. Narcolepsy and Orexins: An Example of Progress in Sleep Research

    Directory of Open Access Journals (Sweden)

    Alberto K De La Herrán-Arita

    2011-04-01

    Full Text Available Narcolepsy is a chronic neurodegenerative disease caused by a deficiency of orexin-producing neurons in the lateral hypothalamus (LH. It is clinically characterized by excessive daytime sleepiness and by intrusions into wakefulness of physiological aspects of rapid eye movement (REM sleep such as cataplexy, sleep paralysis and hypnagogic hallucinations. The major pathophysiology of narcolepsy has been recently described on the bases of the discovery of the neuropeptides named orexins (hypocretins in 1998; considerable evidence, summarized below, demonstrates that narcolepsy is the result of alterations in the genes involved in the pathology of the orexin ligand or its receptor. Deficient orexin transmission is sufficient to produce narcolepsy, as we describe here, animal models with dysregulated orexin signaling exhibit a narcolepsy-like phenotype. Remarkably, these narcoleptic models have different alterations of the orexinergic circuit, this diversity provide us with the means for making comparison, and have a better understanding of orexin cell physiology.It is of particular interest that the most remarkable findings regarding this sleep disorder were fortuitous and due to keen observations. Sleep is a highly intricate and regulated state, and narcolepsy is a disorder that still remains as one of the unsolved mysteries in science. Nevertheless, advances and development of technology in neuroscience will provide us with the necessary tools to unravel the narcolepsy puzzle in the near future.Through an evaluation of the scientific literature we traced an updated picture of narcolepsy and orexins in order to provide insight into the means by which neurobiological knowledge is constructed.

  16. A review on indole alkaloids isolated from Uncaria rhynchophylla and their pharmacological studies.

    Science.gov (United States)

    Ndagijimana, Andre; Wang, Xiaoming; Pan, Guixiang; Zhang, Fan; Feng, Hong; Olaleye, Olajide

    2013-04-01

    Uncaria rhynchophylla (Miq.) Jacks, Rubiaceae, is one of the original plants of the important Chinese crude drug, Gou-teng, mainly used for the treatment of convulsion, hypertension, epilepsy, eclampsia, and cerebral diseases. The pharmacological activities of this plant are related to the presence of active compounds predominantly indole alkaloids. In this article, we have reviewed some reports about the pharmacological activities of the main indole alkaloids isolated from U. rhynchophylla. This review paper will contribute to the studies on the chemistry, safety and quality control of medicinal preparations containing Uncaria species. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Continuous intrathecal orexin delivery inhibits cataplexy in a murine model of narcolepsy.

    Science.gov (United States)

    Kaushik, Mahesh K; Aritake, Kosuke; Imanishi, Aya; Kanbayashi, Takashi; Ichikawa, Tadashi; Shimizu, Tetsuo; Urade, Yoshihiro; Yanagisawa, Masashi

    2018-06-05

    Narcolepsy-cataplexy is a chronic neurological disorder caused by loss of orexin (hypocretin)-producing neurons, associated with excessive daytime sleepiness, sleep attacks, cataplexy, sleep paralysis, hypnagogic hallucinations, and fragmentation of nighttime sleep. Currently, human narcolepsy is treated by providing symptomatic therapies, which can be associated with an array of side effects. Although peripherally administered orexin does not efficiently penetrate the blood-brain barrier, centrally delivered orexin can effectively alleviate narcoleptic symptoms in animal models. Chronic intrathecal drug infusion through an implantable pump is a clinically available strategy to treat a number of neurological diseases. Here we demonstrate that the narcoleptic symptoms of orexin knockout mice can be reversed by lumbar-level intrathecal orexin delivery. Orexin was delivered via a chronically implanted intrathecal catheter at the upper lumbar level. The computed tomographic scan confirmed that intrathecally administered contrast agent rapidly moved from the spinal cord to the brain. Intrathecally delivered orexin was detected in the brain by radioimmunoassay at levels comparable to endogenous orexin levels. Cataplexy and sleep-onset REM sleep were significantly decreased in orexin knockout mice during and long after slow infusion of orexin (1 nmol/1 µL/h). Sleep/wake states remained unchanged both quantitatively as well as qualitatively. Intrathecal orexin failed to induce any changes in double orexin receptor-1 and -2 knockout mice. This study supports the concept of intrathecal orexin delivery as a potential therapy for narcolepsy-cataplexy to improve the well-being of patients.

  18. Pharmacological and toxicity studies of the crude extracts and ...

    African Journals Online (AJOL)

    Revd Dr Femi Olaleye

    This study assessed the anti-nociceptive and anti-inflammatory potency of the ... rats and acetic acid-induced writhing in mice. The effect of the ... Experimental animals: Sprague ... by kinetic method; creatinine (picrate method) and glucose ...

  19. Phytochemical and Pharmacological Studies of the Genus Tacca : A ...

    African Journals Online (AJOL)

    Tacca is an important genus comprising of approximately 15 species of the medicinal plants (Taccaceae). The plants are used in traditional medicine to relieve pains of the body and stomach, as an antidote for food poisoning as well as for their analgesic, antipyretic and anti-inflammatory activities. Chemical studies have ...

  20. Pharmacological study on traditional Chinese medicine and natural product in China

    Institute of Scientific and Technical Information of China (English)

    Yong-xiang ZHANG

    2017-01-01

    China is abundant in natural medicinal resources. Natural medicine (NP), especially traditional Chinese medicine (TCM), have been widely employed in prevention and treatment of diseases in China for thousands of years, which make a great contribution to health care of Chinese people and the prosperity of the Chinese nation. TCM is the excellence culture inheritance of China and a medicine system with long history, tradition and unique theory and technique. Prescriptions or formula are the main form of TCM and the compatibility and composition of them are made up following the theory of TCM among which the theory of compatibility is the essential part. Clinical application and modern pharmacological study both demonstrated that TCM prescription possesses unique effect in comparison with chemical drugs. However, the pharmacological study of TCM prescription is very difficult due to multiple herbs which contain complicated chemical components in the prescription. So, the key point for the pharmacological study of TCM prescription is to elucidate its integrative effect and the mechanism of action. In recent years, great advances have been achieved in the research on TCM prescription and modern study of TCM prescription, including pharmacological and chemical studies, has becoming a hot research field in China. The pharmacological studies of TCM and NP are conducted with different ways and methods including holistic approaches in various experimental model animals and in vitro experiments in tissue, organ and cell models. In addition, a lot of new technics and methods such as″ omics″ technologies were employed in the molecular level studies, for example, researches on the mechanism of action of TCM and NP. In addition, a lot of new drugs have been developed from TCM prescriptions in China. The classical preparations of TCM, including decoction, pill, powder, ointment and pellet, etc, are prepared with traditional methods. While, the new preparations are similar to

  1. Cultured neurons as model systems for biochemical and pharmacological studies on receptors for neurotransmitter amino acids

    DEFF Research Database (Denmark)

    Schousboe, A; Drejer, J; Hansen, Gert Helge

    1985-01-01

    By the use of primary cultures of neurons consisting of cerebral cortex interneurons or cerebellar granule cells it is possible to study biochemical and pharmacological aspects of receptors for GABA and glutamate. Cerebellar granule cells have been shown to express both high- and low-affinity GAB...

  2. Pharmacological Studies of p, N-(3, 4-Methylenedioxy phenyl Benzoic Acid (RRL-1364 - Part-I

    Directory of Open Access Journals (Sweden)

    Dahanukar Sharadini

    1978-01-01

    Full Text Available Detailed pharmacological investigations of p-N-(3, 4-methylene dioxy phenyl benzoic acid revealed marked hypotensive action which was dose dependent and most marked in cats; it was absent in rats. Atropine could block this hypotensive action, thus suggest-ing cholinomimetic mechanism. Further studies indicated that the hypotension produced was central and possibly medullary in origin.

  3. Non-clinical models: validation, study design and statistical consideration in safety pharmacology.

    Science.gov (United States)

    Pugsley, M K; Towart, R; Authier, S; Gallacher, D J; Curtis, M J

    2010-01-01

    The current issue of the Journal of Pharmacological and Toxicological Methods (JPTM) focuses exclusively on safety pharmacology methods. This is the 7th year the Journal has published on this topic. Methods and models that specifically relate to methods relating to the assessment of the safety profile of a new chemical entity (NCE) prior to first in human (FIH) studies are described. Since the Journal started publishing on this topic there has been a major effort by safety pharmacologists, toxicologists and regulatory scientists within Industry (both large and small Pharma as well as Biotechnology companies) and also from Contract Research Organizations (CRO) to publish the surgical details of the non-clinical methods utilized but also provide important details related to standard and non-standard (or integrated) study models and designs. These details from core battery and secondary (or ancillary) drug safety assessment methods used in drug development programs have been the focus of these special issues and have been an attempt to provide validation of methods. Similarly, the safety pharmacology issues of the Journal provide the most relevant forum for scientists to present novel and modified methods with direct applicability to determination of drug safety-directly to the safety pharmacology scientific community. The content of the manuscripts in this issue includes the introduction of additional important surgical methods, novel data capture and data analysis methods, improved study design and effects of positive control compounds with known activity in the model. Copyright 2010 Elsevier Inc. All rights reserved.

  4. On the pedagogy of pharmacological communication: a study of final semester health science students.

    Science.gov (United States)

    Zetterqvist, Ann; Aronsson, Patrik; Hägg, Staffan; Kjellgren, Karin; Reis, Margareta; Tobin, Gunnar; Booth, Shirley

    2015-10-26

    There is a need to improve design in educational programmes for the health sciences in general and in pharmacology specifically. The objective of this study was to investigate and problematize pharmacological communication in educational programmes for the health sciences. An interview study was carried out where final semester students from programmes for the medical, nursing and specialist nursing in primary health care professions were asked to discuss the pharmacological aspects of two written case descriptions of the kind they would meet in their everyday work. The study focused on the communication they envisaged taking place on the concerns the patients were voicing, in terms of two features: how communication would take place and what would be the content of the communication. A phenomenographic research approach was used. The results are presented as outcome spaces, sets of categories that describe the variation of ways in which the students voiced their understanding of communication in the two case descriptions and showed the qualitatively distinct ways in which the features of communication were experienced. The results offer a base of understanding the students' perspectives on communication that they will take with them into their professional lives. We indicate that there is room for strengthening communication skills in the field of pharmacology, integrating them into programmes of education, by more widely implementing a problem-based, a case-oriented or role-playing pedagogy where final year students work across specialisations and there is a deliberate effort to evoke and assess advanced conceptions and skills.

  5. Patient-Reported Measures of Narcolepsy: The Need for Better Assessment.

    Science.gov (United States)

    Kallweit, Ulf; Schmidt, Markus; Bassetti, Claudio L

    2017-05-15

    Narcolepsy, a chronic disorder of the central nervous system, is clinically characterized by a symptom pentad that includes excessive daytime sleepiness, cataplexy, sleep paralysis, hypnopompic/hypnagogic hallucinations, and disrupted nighttime sleep. Ideally, screening and diagnosis instruments that assist physicians in evaluating a patient for type 1 or type 2 narcolepsy would be brief, easy for patients to understand and physicians to score, and would identify or rule out the need for electrophysiological testing. A search of the literature was conducted to review patient-reported measures used for the assessment of narcolepsy, mainly in clinical trials, with the goal of summarizing existing scales and identifying areas that may require additional screening questions and clinical practice scales. Of the seven scales reviewed, the Epworth Sleepiness Scale continues to be an important outcome measure to screen adults for excessive daytime sleepiness, which may be associated with narcolepsy. Several narcolepsy-specific scales have demonstrated utility, such as the Ullanlinna Narcolepsy Scale, Swiss Narcolepsy Scale, and Narcolepsy Symptom Assessment Questionnaire, but further validation is required. Although the narcolepsy-specific scales currently in use may identify type 1 narcolepsy, there are no validated questionnaires to identify type 2 narcolepsy. Thus, there remains a need for short, easily understood, and well-validated instruments that can be readily used in clinical practice to distinguish narcolepsy subtypes, as well as other hypersomnias, and for assessing symptoms of these conditions during treatment. © 2017 American Academy of Sleep Medicine

  6. Normal Morning Melanin-Concentrating Hormone Levels and No Association with Rapid Eye Movement or Non-Rapid Eye Movement Sleep Parameters in Narcolepsy Type 1 and Type 2

    DEFF Research Database (Denmark)

    Schrölkamp, Maren; Jennum, Poul J; Gammeltoft, Steen

    2017-01-01

    in rapid eye movement (REM) and non-rapid eye movement (NREM) sleep regulation. Hypocretin neurons reciprocally interact with MCH neurons. We hypothesized that altered MCH secretion contributes to the symptoms and sleep abnormalities of narcolepsy and that this is reflected in morning cerebrospinal fluid...... MCH levels. CONCLUSIONS: Our study shows that MCH levels in CSF collected in the morning are normal in narcolepsy and not associated with the clinical symptoms, REM sleep abnormalities, nor number of muscle movements during REM or NREM sleep of the patients. We conclude that morning lumbar CSF MCH......STUDY OBJECTIVES: Other than hypocretin-1 (HCRT-1) deficiency in narcolepsy type 1 (NT1), the neurochemical imbalance of NT1 and narcolepsy type 2 (NT2) with normal HCRT-1 levels is largely unknown. The neuropeptide melanin-concentrating hormone (MCH) is mainly secreted during sleep and is involved...

  7. Narcolepsy in childhood and adolescence

    Directory of Open Access Journals (Sweden)

    Rubens Reimão

    1991-09-01

    Full Text Available The objective of this study was to evaluate clinical, polysomnography and the multiple sleep latency test (MSLT features in young narcoleptics. We evaluated 14 patients with mean age of 13.6 years old (ranging from 6 to 18 years ; 11 were males and 3 females. Daytime sleepiness was the main complaint in all cases and started at the ages of 6 to 17 years. Cataplexy was described in 10 cases and it was considered mild to moderate in all but one case. Sleep paralysis was present in 6 cases and hypnagogic hallucinations in 7 cases. The main polysomnography characteristics were the short sleep latency in 9 cases and the sudden onset of REM periods in 7 cases. The MSLT showed short or borderline sleep latencies in 13 cases, with a mean of 4.9 min; 2 or more REM periods were present in 13 cases. Clinical, polysomnographic and MSLT characteristics in the age bracket focused were remarkably similar to those of adult narcoleptics suggesting the stability of these psysiopa-thological markers.

  8. An observational study of clozapine induced sedation and its pharmacological management.

    Science.gov (United States)

    Ramos Perdigués, Sònia; Sauras Quecuti, Rosa; Mané, Anna; Mann, Louisa; Mundell, Clare; Fernandez-Egea, Emilio

    2016-01-01

    Clozapine induced sedation is common but its management is unclear. We analyzed the factors associated with clozapine-induced sedation and the efficacy of common pharmacological strategies. We conducted a naturalistic observational study using two years electronic records of a cohort patients and three analyses: a cross sectional analysis of factors associated with total number of hours slept (as an objective proxy of sedation), and two prospective analyses of which factors were associated with changes in hours slept and the efficacy of two pharmacological strategies. 133 patients were included, of which 64.7% slept at least 9h daily. Among monotherapy patients (n=30), only norclozapine levels (r=.367, p=.03) correlated with hours slept. Using the prospective cohort (n=107), 42 patients decreased the number of hours slept, due to decreasing clozapine (40%) or augmenting with aripiprazole (36%). These two strategies were recommended to 22 (20.6%) and 23 (21.5%) subjects respectively but the majority (81.8% and 73.9%) did not reduce number of hours slept. Thus, pharmacological and non-pharmacological factors are involved in sedation. Norclozapine plasma levels correlated with total sleeping hours. Reducing clozapine and aripiprazole augmentation were associated to amelioration of sedation, although both strategies were effective only in a limited numbers of subjects. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  9. Clinical utility of the Chinese version of the Pediatric Daytime Sleepiness Scale in children with obstructive sleep apnea syndrome and narcolepsy.

    Science.gov (United States)

    Yang, Chien-Ming; Huang, Yu-Shu; Song, Yu-Chen

    2010-04-01

    The present study examined the psychometric properties of the Chinese version of the Pediatric Daytime Sleepiness Scale (PDSS) and the utility of the PDSS as a screening tool for pathological daytime sleepiness in teenagers with obstructive sleep apnea (OSA) and narcolepsy. The PDSS was first administered to 238 middle and high school students to assess the reliability of the scale, and then administered to 28 teenagers with OSA, 31 teenagers with narcolepsy, and 34 normal controls to evaluate its clinical utility. Test-retest reliability and internal consistency were acceptable. The PDSS scores were significantly higher in narcoleptic subjects than in subjects with OSA, and higher in OSA syndrome (OSAS) subjects than normal controls. Furthermore, the scores decreased in narcoleptic subjects after medical treatment. Both reliability and validity were proven to be good. As a screening tool for narcolepsy, receiver operator characteristic (ROC) curve analysis showed that the PDSS, with a cut-off score of 16/17, had good sensitivity (87.1%) and fair specificity (74.3%) for identifying individuals with narcolepsy. When used for screening OSA, however, the differentiating power was not as good. The PDSS is a reliable and valid tool for the measurement of sleepiness in clinical youth populations. When used as a screening tool, it is useful for sleep disorders involving more severe pathological sleepiness, as in narcolepsy.

  10. The spectrum of REM sleep-related episodes in children with type 1 narcolepsy.

    Science.gov (United States)

    Antelmi, Elena; Pizza, Fabio; Vandi, Stefano; Neccia, Giulia; Ferri, Raffaele; Bruni, Oliviero; Filardi, Marco; Cantalupo, Gaetano; Liguori, Rocco; Plazzi, Giuseppe

    2017-06-01

    .e. status cataplecticus) and more complaints of disrupted nocturnal sleep and of excessive daytime sleepiness. The neurophysiological hallmark of this severe motor dyscontrol during REM sleep was a decreased atonia index. The present study reports for the first time the occurrence of a severe and peculiar motor disorder during REM sleep in paediatric type 1 narcolepsy and confirms the presence of a severe motor dyscontrol in these patients, emerging not only from wakefulness (i.e. status cataplecticus), but also from sleep (i.e. complex behaviours during REM sleep). This is probably related to the acute imbalance of the hypocretinergic system, which physiologically acts by promoting movements during wakefulness and suppressing them during sleep. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Narcolepsy following yellow fever vaccination: A case report

    Directory of Open Access Journals (Sweden)

    Richard Ewald Rosch

    2016-08-01

    Full Text Available Narcolepsy with cataplexy is a rare, but important differential diagnosis for daytime sleepiness and atonic paroxysms in an adolescent. A recent increase in incidence in the paediatric age-group probably linked to the use of the Pandremix influenza vaccine in 2009, has increased awareness that different environmental factors can ‘trigger’ narcolepsy with cataplexy in a genetically susceptible population.Here we describe the case of a 13 year-old boy with narcolepsy following yellow-fever vaccination. He carries the HLA DQB1*0602 haplotype strongly associated with narcolepsy and cataplexy. Polysomnography showed rapid sleep onset with rapid eye movement (REM latency of 47 minutes, significant sleep fragmentation and a mean sleep latency of 1.6 minutes with sleep onset REM in 4 out of 4 nap periods. Together with the clinical history, these findings are diagnostic of narcolepsy type 1. The envelope protein E of the yellow fever vaccine strain 17D has significant amino acid sequence overlap with both hypocretin and the hypocretin receptor 2 receptors in protein regions that are predicted to act as epitopes for antibody production. These findings raise the question whether the yellow fever vaccine strain may, through a potential molecular mimicry mechanism, be another infectious trigger for this neuro-immunological disorder.

  12. Social housing of non-rodents during cardiovascular recordings in safety pharmacology and toxicology studies.

    Science.gov (United States)

    Prior, Helen; Bottomley, Anna; Champéroux, Pascal; Cordes, Jason; Delpy, Eric; Dybdal, Noel; Edmunds, Nick; Engwall, Mike; Foley, Mike; Hoffmann, Michael; Kaiser, Robert; Meecham, Ken; Milano, Stéphane; Milne, Aileen; Nelson, Rick; Roche, Brian; Valentin, Jean-Pierre; Ward, Gemma; Chapman, Kathryn

    2016-01-01

    The Safety Pharmacology Society (SPS) and National Centre for the Replacement, Refinement & Reduction of Animals in Research (NC3Rs) conducted a survey and workshop in 2015 to define current industry practices relating to housing of non-rodents during telemetry recordings in safety pharmacology and toxicology studies. The aim was to share experiences, canvas opinion on the study procedures/designs that could be used and explore the barriers to social housing. Thirty-nine sites, either running studies (Sponsors or Contract Research Organisations, CROs) and/or outsourcing work responded to the survey (51% from Europe; 41% from USA). During safety pharmacology studies, 84, 67 and 100% of respondents socially house dogs, minipigs and non-human primates (NHPs) respectively on non-recording days. However, on recording days 20, 20 and 33% of respondents socially house the animals, respectively. The main barriers for social housing were limitations in the recording equipment used, study design and animal temperament/activity. During toxicology studies, 94, 100 and 100% of respondents socially house dogs, minipigs and NHPs respectively on non-recording days. However, on recording days 31, 25 and 50% of respondents socially house the animals, respectively. The main barriers for social housing were risk of damage to and limitations in the recording equipment used, food consumption recording and temperament/activity of the animals. Although the majority of the industry does not yet socially house animals during telemetry recordings in safety pharmacology and toxicology studies, there is support to implement this refinement. Continued discussions, sharing of best practice and data from companies already socially housing, combined with technology improvements and investments in infrastructure are required to maintain the forward momentum of this refinement across the industry. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Pharmacological treatment of sleep disorders and its relationship with neuroplasticity.

    Science.gov (United States)

    Abad, Vivien C; Guilleminault, Christian

    2015-01-01

    Sleep and wakefulness are regulated by complex brain circuits located in the brain stem, thalamus, subthalamus, hypothalamus, basal forebrain, and cerebral cortex. Wakefulness and NREM and REM sleep are modulated by the interactions between neurotransmitters that promote arousal and neurotransmitters that promote sleep. Various lines of evidence suggest that sleep disorders may negatively affect neuronal plasticity and cognitive function. Pharmacological treatments may alleviate these effects but may also have adverse side effects by themselves. This chapter discusses the relationship between sleep disorders, pharmacological treatments, and brain plasticity, including the treatment of insomnia, hypersomnias such as narcolepsy, restless legs syndrome (RLS), obstructive sleep apnea (OSA), and parasomnias.

  14. Traditional biomarkers in narcolepsy: experience of a Brazilian sleep centre

    Directory of Open Access Journals (Sweden)

    Fernando Morgadinho Santos Coelho

    2010-10-01

    Full Text Available This study was thought to characterized clinical and laboratory findings of a narcoleptic patients in an out patients unit at São Paulo, Brazil. METHOD: 28 patients underwent polysomnographic recordings (PSG and Multiple Sleep Latency Test (MSLT were analyzed according to standard criteria. The analysis of HLADQB1*0602 allele was performed by PCR. The Hypocretin-1 in cerebral spinal fluid (CSF was measured using radioimmunoassay. Patients were divided in two groups according Hypocretin-1 level: Normal (N - Hypocretin-1 higher than 110pg/ml and Lower (L Hypocretin-1 lower than 110 pg/ml. RESULTS: Only 4 patients of the N group had cataplexy when compared with 14 members of the L group (p=0.0002. DISCUSSION: This results were comparable with other authors, confirming the utility of using specific biomarkers (HLA-DQB1*0602 allele and Hypocretin-1 CSF level in narcolepsy with cataplexy. However, the HLADQB1*0602 allele and Hypocretin-1 level are insufficient to diagnose of narcolepsy without cataplexy.Este estudo foi idealizado para avaliar as características clinicas e laboratoriais de uma população de narcolépticos atendidos num centro de referência na cidade de São Paulo (Brasil. MÉTODO: 28 pacientes realizaram polissonografia e teste de múltiplas latências do sono segundo critérios internacionais. O alelo HLADQB1*0602 foi identificado por PCR. A Hipocretina-1 no líquido cefalorradiano (LCR foi mensurada por radioimunoensaio. Os pacientes foram divididos em 2 grupos conforme o nível de Hipocretina-1. Normal (N - Hypocretin-1 >110pg/ml e baixa (B - Hypocretina-1 <110pg/ml. RESULTADOS: Somente 4 pacientes do grupo N tinham cataplexia quando comparados com 14 pacientes do grupo B (p=0,0002. DISCUSSÃO: Estes resultados foram comparáveis com outros autores, confirmando a utilidade do uso de biomarcadores específicos (HLA-DQB1*0602 e nível da hipocretina-1 no LCR em narcolepsia com cataplexia. Porém, o alelo HLADQB1*0602 e a dosagem

  15. Effects of oral L-carnitine administration in narcolepsy patients: a randomized, double-blind, cross-over and placebo-controlled trial.

    Directory of Open Access Journals (Sweden)

    Taku Miyagawa

    Full Text Available UNLABELLED: Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness, cataplexy, and rapid eye movement (REM sleep abnormalities. A genome-wide association study (GWAS identified a novel narcolepsy-related single nucleotide polymorphism (SNP, which is located adjacent to the carnitine palmitoyltransferase 1B (CPT1B gene encoding an enzyme involved in β-oxidation of long-chain fatty acids. The mRNA expression levels of CPT1B were associated with this SNP. In addition, we recently reported that acylcarnitine levels were abnormally low in narcolepsy patients. To assess the efficacy of oral L-carnitine for the treatment of narcolepsy, we performed a clinical trial administering L-carnitine (510 mg/day to patients with the disease. The study design was a randomized, double-blind, cross-over and placebo-controlled trial. Thirty narcolepsy patients were enrolled in our study. Two patients were withdrawn and 28 patients were included in the statistical analysis (15 males and 13 females, all with HLA-DQB1*06:02. L-carnitine treatment significantly improved the total time for dozing off during the daytime, calculated from the sleep logs, compared with that of placebo-treated periods. L-carnitine efficiently increased serum acylcarnitine levels, and reduced serum triglycerides concentration. Differences in the Japanese version of the Epworth Sleepiness Scale (ESS and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36 vitality and mental health subscales did not reach statistical significance between L-carnitine and placebo. This study suggests that oral L-carnitine can be effective in reducing excessive daytime sleepiness in narcolepsy patients. TRIAL REGISTRATION: University hospital Medical Information Network (UMIN UMIN000003760.

  16. Pharmacological toxicological studies on certain drugs subjected to radiation or used radioprotective agents

    Energy Technology Data Exchange (ETDEWEB)

    Hassan, S H.M. [Durng Research Dept., National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, (Egypt)

    1995-10-01

    The present study represents two main subjects. The first encounters the effect of radiosterilization of certain pharmaceretical preparations such as antihistaminics (cimetidine), anticonvulsants (diazepam), beta and calcium channel blacker (propranolol and verapamil) on their pharmacological activity. Results of this study revealed that the previously mentioned drugs can be effectively and safely sterilized by gamma irradiation without deleterious effect on their pharmacological activity. The other subject presented in this study is essentially a pharmacological subject encountering toxicological problems. Data of this study demonstrated that chemical radiation protection has been successfully reported using single drug administration has been successfully reported using single drug administration such as imidazole, and Sh-bearing compounds. In the present work, the radioprotective effect of imidazole was demonstrated on the cardiovascular and respiratory systems. Furthermore, combined drug administration was found to exert more protective action with less toxicity and therefore minimize the side effects of the radioprotective drugs. Thus, combination of imidazole and serotonin showed potential protective effect on blood gases was also reported. In addition, combination of cysteine and vitamin E afforded a better protection on adrenocortical function in rats than either agent alone. 4 figs., 1 tab.

  17. Pharmacological toxicological studies on certain drugs subjected to radiation or used radioprotective agents

    International Nuclear Information System (INIS)

    Hassan, S.H.M.

    1995-01-01

    The present study represents two main subjects. The first encounters the effect of radiosterilization of certain pharmaceretical preparations such as antihistaminics (cimetidine), anticonvulsants (diazepam), beta and calcium channel blacker (propranolol and verapamil) on their pharmacological activity. Results of this study revealed that the previously mentioned drugs can be effectively and safely sterilized by gamma irradiation without deleterious effect on their pharmacological activity. The other subject presented in this study is essentially a pharmacological subject encountering toxicological problems. Data of this study demonstrated that chemical radiation protection has been successfully reported using single drug administration has been successfully reported using single drug administration such as imidazole, and Sh-bearing compounds. In the present work, the radioprotective effect of imidazole was demonstrated on the cardiovascular and respiratory systems. Furthermore, combined drug administration was found to exert more protective action with less toxicity and therefore minimize the side effects of the radioprotective drugs. Thus, combination of imidazole and serotonin showed potential protective effect on blood gases was also reported. In addition, combination of cysteine and vitamin E afforded a better protection on adrenocortical function in rats than either agent alone. 4 figs., 1 tab

  18. Nursing students learning the pharmacology of diabetes mellitus with complexity-based computerized models: A quasi-experimental study.

    Science.gov (United States)

    Dubovi, Ilana; Dagan, Efrat; Sader Mazbar, Ola; Nassar, Laila; Levy, Sharona T

    2018-02-01

    Pharmacology is a crucial component of medications administration in nursing, yet nursing students generally find it difficult and self-rate their pharmacology skills as low. To evaluate nursing students learning pharmacology with the Pharmacology Inter-Leaved Learning-Cells environment, a novel approach to modeling biochemical interactions using a multiscale, computer-based model with a complexity perspective based on a small set of entities and simple rules. This environment represents molecules, organelles and cells to enhance the understanding of cellular processes, and combines these cells at a higher scale to obtain whole-body interactions. Sophomore nursing students who learned the pharmacology of diabetes mellitus with the Pharmacology Inter-Leaved Learning-Cells environment (experimental group; n=94) or via a lecture-based curriculum (comparison group; n=54). A quasi-experimental pre- and post-test design was conducted. The Pharmacology-Diabetes-Mellitus questionnaire and the course's final exam were used to evaluate students' knowledge of the pharmacology of diabetes mellitus. Conceptual learning was significantly higher for the experimental than for the comparison group for the course final exam scores (unpaired t=-3.8, pLearning with complexity-based computerized models is highly effective and enhances the understanding of moving between micro and macro levels of the biochemical phenomena, this is then related to better understanding of medication actions. Moreover, the Pharmacology Inter-Leaved Learning-Cells approach provides a more general reasoning scheme for biochemical processes, which enhances pharmacology learning beyond the specific topic learned. The present study implies that deeper understanding of pharmacology will support nursing students' clinical decisions and empower their proficiency in medications administration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Post-Traumatic Narcolepsy Associated with Thalamic/Hypothalamic Injury

    Directory of Open Access Journals (Sweden)

    Kikyoung Yi

    2015-12-01

    Full Text Available The hypothalamus is an important structure that regulates sleep via hypocretin neurotransmission. Central nervous system disorders such as tumors and vascular legions involving the hypothalamus can cause secondary narcolepsy. In addition, brain trauma can contribute to post-traumatic narcolepsy despite lack of any definite brain lesion. Here, we present a case of a 37-year-old man suffering from a hypothalamus-to-thalamus hemorrhage after a traffic accident. After this trauma, he suffered from excessive daytime sleepiness and was diagnosed with post-traumatic narcolepsy by polysomnography and multiple sleep latency tests. He was positive for human leukocyte antigen (HLA-DQB1*03:01 and HLA-DQB1*06:01 antigens.

  20. Comorbidity of narcolepsy and schizophrenia in an adolescent patient

    Directory of Open Access Journals (Sweden)

    Mu-Hong Chen

    2014-11-01

    Full Text Available A 13-year-old boy suffered from hypersomnia, fragmented nighttime sleep, and cataplexy since age 10 years, and then developed prominent psychotic symptoms (i.e., auditory and visual hallucination, hallucinatory behavior, delusions of reference, and misidentification that occurred persistently during the wakeful and consciously clear period when he was aged 12 years. The child underwent additional medical evaluation and testing, and comorbidity of narcolepsy and schizophrenia was diagnosed. The child's psychotic symptoms and narcolepsy improved significantly upon treatment with methylphenidate 30 mg, olanzapine 25 mg, and haloperidol 10 mg. In this case, the child's symptomology of narcolepsy and schizophrenia and the dilemma of the use of antipsychotics and psychostimulants are representative examples of the diagnostic and therapeutic challenges in adolescent psychiatry.

  1. Characteristics of rapid eye movement sleep behavior disorder in narcolepsy

    DEFF Research Database (Denmark)

    Jennum, Poul Jørgen; Frandsen, Rune Asger Vestergaard; Knudsen, Stine

    2013-01-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by dream-enacting behavior and impaired motor inhibition during REM sleep (REM sleep without atonia, RSWA). RBD is commonly associated with Parkinsonian disorders, but is also reported in narcolepsy. Most patients...... of hypocretin deficiency. Thus, hypocretin deficiency is linked to the two major disturbances of REM sleep motor regulation in narcolepsy: RBD and cataplexy. Moreover, it is likely that hypocretin deficiency independently predicts periodic limb movements in REM and NREM sleep, probably via involvement...... of the dopaminergic system. This supports the hypothesis that an impaired hypocretin system causes general instability of motor regulation during wakefulness, REM and NREM sleep in human narcolepsy. We propose that hypocretin neurons are centrally involved in motor tone control during wakefulness and sleep in humans...

  2. The European Narcolepsy Network (EU-NN) database

    DEFF Research Database (Denmark)

    Khatami, Ramin; Luca, Gianina; Baumann, Christian R

    2016-01-01

    Narcolepsy with cataplexy is a rare disease with an estimated prevalence of 0.02% in European populations. Narcolepsy shares many features of rare disorders, in particular the lack of awareness of the disease with serious consequences for healthcare supply. Similar to other rare diseases, only a ......, identification of post-marketing medication side-effects, and will contribute to improve clinical trial designs and provide facilities to further develop phase III trials....... Narcolepsy Network is introduced. The database structure, standardization of data acquisition and quality control procedures are described, and an overview provided of the first 1079 patients from 18 European specialized centres. Due to its standardization this continuously increasing data pool is most...

  3. Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies.

    Science.gov (United States)

    Braff, D L; Geyer, M A; Swerdlow, N R

    2001-07-01

    Since the mid-1970s, cross-species translational studies of prepulse inhibition (PPI) have increased at an astounding pace as the value of this neurobiologically informative measure has been optimized. PPI occurs when a relatively weak sensory event (the prepulse) is presented 30-500 ms before a strong startle-inducing stimulus, and reduces the magnitude of the startle response. In humans, PPI occurs in a robust, predictable manner when the prepulse and startling stimuli occur in either the same or different modalities (acoustic, visual, or cutaneous). This review covers three areas of interest in human PPI studies. First, we review the normal influences on PPI related to the underlying construct of sensori- (prepulse) motor (startle reflex) gating. Second, we review PPI studies in psychopathological disorders that form a family of gating disorders. Third, we review the relatively limited but interesting and rapidly expanding literature on pharmacological influences on PPI in humans. All studies identified by a computerized literature search that addressed the three topics of this review were compiled and evaluated. The principal studies were summarized in appropriate tables. The major influences on PPI as a measure of sensorimotor gating can be grouped into 11 domains. Most of these domains are similar across species, supporting the value of PPI studies in translational comparisons across species. The most prominent literature describing deficits in PPI in psychiatrically defined groups features schizophrenia-spectrum patients and their clinically unaffected relatives. These findings support the use of PPI as an endophenotype in genetic studies. Additional groups of psychopathologically disordered patients with neuropathology involving cortico-striato-pallido-pontine circuits exhibit poor gating of motor, sensory, or cognitive information and corresponding PPI deficits. These groups include patients with obsessive compulsive disorder, Tourette's syndrome

  4. [Application progress of proteomic in pharmacological study of Chinese medicinal formulae].

    Science.gov (United States)

    Liu, Yu-Qian; Zhan, Shu-Yu; Ruan, Yu-Er; Zuo, Zhi-Yan; Ji, Xiao-Ming; Wang, Shuai-Jie; Ding, Bao-Yue

    2017-10-01

    Chinese medicinal formulae are the important means of clinical treatment in traditional Chinese medicine. It is urgent to use modern advanced scientific and technological means to reveal the complicated mechanism of Chinese medicinal formulae because they have the function characteristics of multiple components, multiple targets and integrated regulation. The systematic and comprehensive research model of proteomic is in line with the function characteristics of Chinese medicinal formulae, and proteomic has been widely used in the study of pharmacological mechanism of Chinese medicinal formulae. The recent applications of proteomic in pharmacological study of Chinese medicinal formulae in anti-cardiovascular and cerebrovascular diseases, anti-liver disease, antidiabetic, anticancer, anti-rheumatoid arthritis and other diseases were reviewed in this paper, and then the future development direction of proteomic in pharmacological study of Chinese medicinal formulae was put forward. This review is to provide the ideas and method for proteomic research on function mechanism of Chinese medicinal formulae. Copyright© by the Chinese Pharmaceutical Association.

  5. A review on phytochemical, ethnomedical and pharmacological studies on genus Sophora, Fabaceae

    Directory of Open Access Journals (Sweden)

    Panthati Murali Krishna

    2012-10-01

    Full Text Available Sophora is a genus of the Fabaceae family, contains about 52 species, nineteen varieties, and seven forms that are widely distributed in Asia, Oceanica, and the Pacific islands, in the family Fabaceae of herbaceous (Sophora flavescens Aiton to trees (Sophora japonica L.. More than fifteen species in this genus have a long history of use in traditional Chinese medicines. In the last decades the use of this genus in traditional Chinese drugs has led to rapid increase in the information available on active components and reported to posses various pharmacological/therapeutic properties. The paper reviews the ethnopharmacology, the biological activities and the correlated chemical compounds of genus Sophora, Fabaceae. More than 300 compounds has been isolated, among them major are quinolizidine alkaloids particularly matrine and oxymatrine and flavonoids particularly prenylated and isoprenylated flavonoids. Modern pharmacological studies and clinical studies demonstrated that these chemical constituens possess wide reaching pharmacological actions like anti oxidant, anticancer, anti-asthamatic, anti-neoplastic, antimicrobial, antiviral, antidote, anti pyretic, cardiotonic, antinflammatory, diuretic and in the treatment of skin diseases like eczema, colitis and psoriasis.

  6. A review on phytochemical, ethnomedical and pharmacological studies on genus Sophora, Fabaceae

    Directory of Open Access Journals (Sweden)

    Panthati Murali Krishna

    2012-04-01

    Full Text Available Sophora is a genus of the Fabaceae family, contains about 52 species, nineteen varieties, and seven forms that are widely distributed in Asia, Oceanica, and the Pacific islands, in the family Fabaceae of herbaceous (Sophora flavescens Aiton to trees (Sophora japonica L.. More than fifteen species in this genus have a long history of use in traditional Chinese medicines. In the last decades the use of this genus in traditional Chinese drugs has led to rapid increase in the information available on active components and reported to posses various pharmacological/therapeutic properties. The paper reviews the ethnopharmacology, the biological activities and the correlated chemical compounds of genus Sophora, Fabaceae. More than 300 compounds has been isolated, among them major are quinolizidine alkaloids particularly matrine and oxymatrine and flavonoids particularly prenylated and isoprenylated flavonoids. Modern pharmacological studies and clinical studies demonstrated that these chemical constituens possess wide reaching pharmacological actions like anti oxidant, anticancer, anti-asthamatic, anti-neoplastic, antimicrobial, antiviral, antidote, anti pyretic, cardiotonic, antinflammatory, diuretic and in the treatment of skin diseases like eczema, colitis and psoriasis.

  7. Molecular catchers for pharmacologically active substances in wastewaters, a theoretical study

    International Nuclear Information System (INIS)

    Salazar Valencia, P J; Pérez Merchancano, S T; Bolívar Marinez, L E; Paredes, H

    2016-01-01

    A basic and pressing need in the treatment of residual waste waters for urban and rural centers is the removal of pharmacological active residues from them, these resides are originated in a wide array of domestic, agricultural and industrial sources and can't be removed in the residual waters treatment plants by conventional methods, the result is the incorporation of them into the ecosystem altering the physiology and behavior of living organisms. Among the most active pharmacological substances found in very high concentration in residual waters is paracetamol, an analgesic of very wide excessive use due to its ease of access and low cost [1]. No pharmacological substance is entirely absorbed by the human organism and therefore a wide family of molecular residues is excreted by the urinary tract. In this work we have used the AM1 (Austin Model 1), PM3 (Parametric Method 3) and ZINDO/CI semiempirical methods, from the NDO (Neglect Differential Overlap) family [2] to study and observe the structural, electronic and optical characteristics of paracetamol while immersed in different basic and acidic aqueous environments, either alone or interacting with lignosulphonates. We have previously found that lignosulphonates, a lignin derivatives of wide industrial applications, can be engineered as a binding and flocculant agent and acts as molecular catchers therefore showing the potential to be used as a mean to filter and eliminate molecular residues from the residual waters [3]. (paper)

  8. Sex differences in the pharmacological treatment of hypertension : a review of population-based studies

    NARCIS (Netherlands)

    Klungel, O.H.; de Boer, A; Paes, A.H.P.; Seidell, J C; Bakker, A

    OBJECTIVE: To summarize all available literature on sex differences in the pharmacological treatment of hypertension with respect to the percentage of hypertensive patients treated pharmacologically and the selection of antihypertensive drugs. The influences of the calendar period, age, definition

  9. Use of PCR with Sequence-specific Primers for High-Resolution Human Leukocyte Antigen Typing of Patients with Narcolepsy

    Science.gov (United States)

    Woo, Hye In; Joo, Eun Yeon; Lee, Kyung Wha

    2012-01-01

    Background Narcolepsy is a neurologic disorder characterized by excessive daytime sleepiness, symptoms of abnormal rapid eye movement (REM) sleep, and a strong association with HLA-DRB1*1501, -DQA1*0102, and -DQB1*0602. Here, we investigated the clinico-physical characteristics of Korean patients with narcolepsy, their HLA types, and the clinical utility of high-resolution PCR with sequence-specific primers (PCR-SSP) as a simple typing method for identifying DRB1*15/16, DQA1, and DQB1 alleles. Methods The study population consisted of 67 consecutively enrolled patients having unexplained daytime sleepiness and diagnosed narcolepsy based on clinical and neurological findings. Clinical data and the results of the multiple sleep latency test and polysomnography were reviewed, and HLA typing was performed using both high-resolution PCR-SSP and sequence-based typing (SBT). Results The 44 narcolepsy patients with cataplexy displayed significantly higher frequencies of DRB1*1501 (Pc= 0.003), DQA1*0102 (Pc=0.001), and DQB1*0602 (Pc=0.014) than the patients without cataplexy. Among patients carrying DRB1*1501-DQB1*0602 or DQA1*0102, the frequencies of a mean REM sleep latency of less than 20 min in nocturnal polysomnography and clinical findings, including sleep paralysis and hypnagogic hallucination were significantly higher. SBT and PCR-SSP showed 100% concordance for high-resolution typing of DRB1*15/16 alleles and DQA1 and DQB1 loci. Conclusions The clinical characteristics and somnographic findings of narcolepsy patients were associated with specific HLA alleles, including DRB1*1501, DQA1*0102, and DQB1*0602. Application of high-resolution PCR-SSP, a reliable and simple method, for both allele- and locus-specific HLA typing of DRB1*15/16, DQA1, and DQB1 would be useful for characterizing clinical status among subjects with narcolepsy. PMID:22259780

  10. Core Body and Skin Temperature in Type 1 Narcolepsy in Daily Life; Effects of Sodium Oxybate and Prediction of Sleep Attacks

    NARCIS (Netherlands)

    van der Heide, Astrid; Werth, Esther; Donjacour, Claire E H M; Reijntjes, Robert H A M; Lammers, Gert Jan; Van Someren, Eus J W; Baumann, Christian R; Fronczek, Rolf

    2016-01-01

    STUDY OBJECTIVES: Previous laboratory studies in narcolepsy patients showed altered core body and skin temperatures, which are hypothesised to be related to a disturbed sleep wake regulation. In this ambulatory study we assessed temperature profiles in normal daily life, and whether sleep attacks

  11. Modafinil alters intrinsic functional connectivity of the right posterior insula: a pharmacological resting state fMRI study.

    Directory of Open Access Journals (Sweden)

    Nicoletta Cera

    Full Text Available Modafinil is employed for the treatment of narcolepsy and has also been, off-label, used to treat cognitive dysfunction in neuropsychiatric disorders. In a previous study, we have reported that single dose administration of modafinil in healthy young subjects enhances fluid reasoning and affects resting state activity in the Fronto Parietal Control (FPC and Dorsal Attention (DAN networks. No changes were found in the Salience Network (SN, a surprising result as the network is involved in the modulation of emotional and fluid reasoning. The insula is crucial hub of the SN and functionally divided in anterior and posterior subregions.Using a seed-based approach, we have now analyzed effects of modafinil on the functional connectivity (FC of insular subregions.Analysis of FC with resting state fMRI (rs-FMRI revealed increased FC between the right posterior insula and the putamen, the superior frontal gyrus and the anterior cingulate cortex in the modafinil-treated group.Modafinil is considered a putative cognitive enhancer. The rs-fMRI modifications that we have found are consistent with the drug cognitive enhancing properties and indicate subregional targets of action.ClinicalTrials.gov NCT01684306.

  12. Hypocretin (orexin) biology and the pathophysiology of narcolepsy with cataplexy.

    Science.gov (United States)

    Liblau, Roland S; Vassalli, Anne; Seifinejad, Ali; Tafti, Mehdi

    2015-03-01

    The discovery of hypocretins (orexins) and their causal implication in narcolepsy is the most important advance in sleep research and sleep medicine since the discovery of rapid eye movement sleep. Narcolepsy with cataplexy is caused by hypocretin deficiency owing to destruction of most of the hypocretin-producing neurons in the hypothalamus. Ablation of hypocretin or hypocretin receptors also leads to narcolepsy phenotypes in animal models. Although the exact mechanism of hypocretin deficiency is unknown, evidence from the past 20 years strongly favours an immune-mediated or autoimmune attack, targeting specifically hypocretin neurons in genetically predisposed individuals. These neurons form an extensive network of projections throughout the brain and show activity linked to motivational behaviours. The hypothesis that a targeted immune-mediated or autoimmune attack causes the specific degeneration of hypocretin neurons arose mainly through the discovery of genetic associations, first with the HLA-DQB1*06:02 allele and then with the T-cell receptor α locus. Guided by these genetic findings and now awaiting experimental testing are models of the possible immune mechanisms by which a specific and localised brain cell population could become targeted by T-cell subsets. Great hopes for the identification of new targets for therapeutic intervention in narcolepsy also reside in the development of patient-derived induced pluripotent stem cell systems. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Positive effects of massage therapy on a patient with narcolepsy.

    Science.gov (United States)

    Hill, Robyn; Baskwill, Amanda

    2013-01-01

    The purpose of this case report was to investigate the effects of massage therapy on the sleep patterns of a woman with narcolepsy. The 23-year-old woman's primary symptoms included excessive daytime sleepiness and periodic leg movements (PLM), which were associated with her diagnoses of both narcolepsy and cataplexy. Five 45-minute massage therapy treatments were administered over a five-week period. The patient's sleep patterns were recorded each week before the treatment. A final measurement was recorded in the sixth week. The sleep patterns were monitored using the Leeds Sleep Evaluation Questionnaire, which included ten visual analogue scales. The results of this case report included an improvement in getting to sleep by 148%, an improvement in quality of sleep by 1100%, an improvement in awake following sleep by 121%, and an improvement in behaviour following wakening by 28% using the Leeds Sleep Evaluation Questionnaire. This case report suggests that massage therapy had a positive effect on this patient with narcolepsy. Further research is needed to investigate the effects of massage therapy on narcolepsy and sleep patterns.

  14. Unravelling narcolepsy : from pathophysiology to measuring treatment effects

    NARCIS (Netherlands)

    Heide, van der A.

    2017-01-01

    Narcolepsy is a disorder of the regulation of sleep and wakefulness, with as its major features excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, sleep paralysis and disturbed nocturnal sleep. The first part of this thesis concernes an overview of the pathophysiology,

  15. The study of chemical composition and pharmacological action of the alkaloid from plants of Lycoris Herb

    Science.gov (United States)

    Ji, Y. B.; Wei, C.; Xin, G. S.

    2017-12-01

    Recently, studies on Lycoris type alkaloids received the attention of scholars home and abroad. Lycoris type contains lots of alkaloids, it can be divided into seven types according to its molecular structure, including Lycorine, Crinine, Galanthamine, Tazettine, Narciclasine, Lycorenine, Homolycorine and Montanine. Researches have shown that Lycoris type possess multiple phamocology activity, such as strong anti-tumor activity of human breast cancer cell (MCF-7), human leukemia cell(HL-60); and strong inhibition effect of flu virus, measles virus, polio virus and SARS virus; Besides, Lycorine type has strong anti-Acetylcholinesterase effect. In a word, Lycorine type, Lycoris type alkaloids carries multiple pharmacology effect and is a promising substance.

  16. Serotonergic modulation of reward and punishment: evidence from pharmacological fMRI studies.

    Science.gov (United States)

    Macoveanu, Julian

    2014-03-27

    Until recently, the bulk of research on the human reward system was focused on studying the dopaminergic and opioid neurotransmitter systems. However, extending the initial data from animal studies on reward, recent pharmacological brain imaging studies on human participants bring a new line of evidence on the key role serotonin plays in reward processing. The reviewed research has revealed how central serotonin availability and receptor specific transmission modulates the neural response to both appetitive (rewarding) and aversive (punishing) stimuli in putative reward-related brain regions. Thus, serotonin is suggested to be involved in behavioral control when there is a prospect of reward or punishment. The new findings may have implications in understanding psychiatric disorders such as major depression which is characterized by abnormal serotonergic function and reward-related processing and may also provide a neural correlated for the emotional blunting observed in the clinical treatment of psychiatric disorders with selective serotonin reuptake inhibitors. Given the unique profile of action of each serotonergic receptor subtype, future pharmacological studies may favor receptor specific investigations to complement present research mainly focused on global serotonergic manipulations. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Complex Diagnostic and Treatment Issues in Psychotic Symptoms Associated with Narcolepsy

    Science.gov (United States)

    Ivanenko, Anna

    2009-01-01

    Narcolepsy is an uncommon chronic, neurological disorder characterized by abnormal manifestations of rapid eye movement sleep and perturbations in the sleep-wake cycle. Accurate diagnosis of psychotic symptoms in a person with narcolepsy could be difficult due to side effects of stimulant treatment (e.g., hallucinations) as well as primary symptoms of narcolepsy (e.g., sleep paralysis and hypnagogic and/or hypnapompic hallucinations). Pertinent articles from peer-reviewed journals were identified to help understand the complex phenomenology of psychotic symptoms in patients with narcolepsy. In this ensuing review and discussion, we present an overview of narcolepsy and outline diagnostic and management approaches for psychotic symptoms in patients with narcolepsy. PMID:19724760

  18. Development of a Bifunctional Andrographolide-Based Chemical Probe for Pharmacological Study.

    Science.gov (United States)

    Hsu, Ya-Hsin; Hsu, Yu-Ling; Liu, Sheng-Hung; Liao, Hsin-Chia; Lee, Po-Xuan; Lin, Chao-Hsiung; Lo, Lee-Chiang; Fu, Shu-Ling

    2016-01-01

    Andrographolide (ANDRO) is a lactone diterpenoid compound present in the medicinal plant Andrographis paniculata which is clinically applied for multiple human diseases in Asia and Europe. The pharmacological activities of andrographolide have been widely demonstrated, including anti-inflammation, anti-cancer and hepatoprotection. However, the pharmacological mechanism of andrographolide remains unclear. Therefore, further characterization on the kinetics and molecular targets of andrographolide is essential. In this study, we described the synthesis and characterization of a novel fluorescent andrographolide derivative (ANDRO-NBD). ANDRO-NBD exhibited a comparable anti-cancer spectrum to andrographolide: ANDRO-NBD was cytotoxic to various types of cancer cells and suppressed the migration activity of melanoma cells; ANDRO-NBD treatment induced the cleavage of heat shock protein 90 (Hsp90) and the downregulation of its client oncoproteins, v-Src and Bcr-abl. Notably, ANDRO-NBD showed superior inhibitory effects to andrographolide in all anticancer assays we have performed. In addition, ANDRO-NBD was further used as a fluorescent probe to investigate the uptake kinetics, cellular distribution and molecular targets of andrographolide. Our data revealed that ANDRO-NBD entered cells rapidly and its fluorescent signal could be detected in nucleus, cytoplasm, mitochondria, and lysosome. Moreover, we demonstrated that ANDRO-NBD was covalently bound to several putative target proteins of andrographolide, including NF-κB and hnRNPK. In summary, we developed a fluorescent andrographolide probe with comparable bioactivity to andrographolide, which serves as a powerful tool to explore the pharmacological mechanism of andrographolide.

  19. Development of a Bifunctional Andrographolide-Based Chemical Probe for Pharmacological Study.

    Directory of Open Access Journals (Sweden)

    Ya-Hsin Hsu

    Full Text Available Andrographolide (ANDRO is a lactone diterpenoid compound present in the medicinal plant Andrographis paniculata which is clinically applied for multiple human diseases in Asia and Europe. The pharmacological activities of andrographolide have been widely demonstrated, including anti-inflammation, anti-cancer and hepatoprotection. However, the pharmacological mechanism of andrographolide remains unclear. Therefore, further characterization on the kinetics and molecular targets of andrographolide is essential. In this study, we described the synthesis and characterization of a novel fluorescent andrographolide derivative (ANDRO-NBD. ANDRO-NBD exhibited a comparable anti-cancer spectrum to andrographolide: ANDRO-NBD was cytotoxic to various types of cancer cells and suppressed the migration activity of melanoma cells; ANDRO-NBD treatment induced the cleavage of heat shock protein 90 (Hsp90 and the downregulation of its client oncoproteins, v-Src and Bcr-abl. Notably, ANDRO-NBD showed superior inhibitory effects to andrographolide in all anticancer assays we have performed. In addition, ANDRO-NBD was further used as a fluorescent probe to investigate the uptake kinetics, cellular distribution and molecular targets of andrographolide. Our data revealed that ANDRO-NBD entered cells rapidly and its fluorescent signal could be detected in nucleus, cytoplasm, mitochondria, and lysosome. Moreover, we demonstrated that ANDRO-NBD was covalently bound to several putative target proteins of andrographolide, including NF-κB and hnRNPK. In summary, we developed a fluorescent andrographolide probe with comparable bioactivity to andrographolide, which serves as a powerful tool to explore the pharmacological mechanism of andrographolide.

  20. The feasibility of implementing recovery, psychosocial and pharmacological interventions for psychosis: comparison study.

    Science.gov (United States)

    van der Krieke, Lian; Bird, Victoria; Leamy, Mary; Bacon, Faye; Dunn, Rebecca; Pesola, Francesca; Janosik, Monika; Le Boutillier, Clair; Williams, Julie; Slade, Mike

    2015-05-23

    Clinical guidelines for the treatment of people experiencing psychosis have existed for over a decade, but implementation of recommended interventions is limited. Identifying influences on implementation may help to reduce this translational gap. The Structured Assessment of Feasibility (SAFE) measure is a standardised assessment of implementation blocks and enablers. The aim of this study was to characterise and compare the implementation blocks and enablers for recommended psychosis interventions. SAFE was used to evaluate and compare three groups of interventions recommended in the 2014 NICE psychosis guideline: pharmacological (43 trials testing 5 interventions), psychosocial (65 trials testing 5 interventions), and recovery (19 trials testing 5 interventions). The 127 trial reports rated with SAFE were supplemented by published intervention manuals, research protocols, trial registrations and design papers. Differences in the number of blocks and enablers across the three interventions were tested statistically, and feasibility profiles were generated. There was no difference between psychosocial and recovery interventions in the number of blocks or enablers to implementation. Pharmacological interventions (a) had fewer blocks than both psychosocial interventions (χ (2)(3) = 133.77, p Feasibility profiles show that pharmacological interventions are relatively easy to implement but can sometimes involve risks. Psychosocial and recovery interventions are relatively complex but tend to be more flexible and more often manualised. SAFE ratings can contribute to tackling the current implementation challenges in mental health services, by providing a reporting guideline structure for researchers to maximise the potential for implementation and by informing prioritisation decisions by clinical guideline developers and service managers.

  1. The power of using functional fMRI on small rodents to study brain pharmacology and disease

    OpenAIRE

    Jonckers, Elisabeth; Shah, Disha; Hamaide, Julie; Verhoye, Marleen; Van der Linden, Annemie

    2015-01-01

    Abstract: Functional magnetic resonance imaging (fMRI) is an excellent tool to study the effect of pharmacological modulations on brain function in a non-invasive and longitudinal manner. We introduce several blood oxygenation level dependent (BOLD) fMRI techniques, including resting state (rsfMRI), stimulus-evoked (st-fMRI), and pharmacological MRI (phMRI). Respectively, these techniques permit the assessment of functional connectivity during rest as well as brain activation triggered by sen...

  2. miRNA profiles in plasma from patients with sleep disorders reveal dysregulation of miRNAs in narcolepsy and other central hypersomnias

    DEFF Research Database (Denmark)

    Holm, Anja; Bang-Berthelsen, Claus Heiner; Knudsen, Stine

    2014-01-01

    STUDY OBJECTIVES: MicroRNAs (miRNAs) have been implicated in the pathogenesis of human diseases including neurological disorders. The aim is to address the involvement of miRNAs in the pathophysiology of central hypersomnias including autoimmune narcolepsy with cataplexy and hypocretin deficiency...

  3. Pharmacological and Toxicological Studies of Essential Oil of Lavandula stoechas subsp. luisieri.

    Science.gov (United States)

    Arantes, Sílvia; Candeias, Fátima; Lopes, Orlando; Lima, Mónica; Pereira, Marízia; Tinoco, Teresa; Cruz-Morais, J; Martins, M Rosário

    2016-09-01

    The present study was carried out to evaluate the chemical and pharmacological properties of the essential oil of Lavandula stoechas subsp. luisieri, which is a spontaneous shrub widespread in Alentejo (Portugal). Oxygenated monoterpenes, such as 1,8-cineole, lavandulol, and necrodane derivatives, are the main components of essential oil. It revealed important antioxidant activity with a high ability to inhibit lipid peroxidation and showed an outstanding effect against a wide spectrum of microorganisms, such as gram-positive and gram-negative bacteria and pathogenic yeasts. The analgesic effect studied in rats was dose dependent, reaching a maximum of 67 % at 60 min with the dose of 200 mg/kg and the anti-inflammatory activity with this dose caused an inhibition in carrageenan-induced rat paw oedema (83 %) that is higher than dexamethasone 1 mg/Kg (69 %). Besides, animals exhibited normal behaviour after essential oil administration, revealing low toxicity. The essential oil of L. luisieri from Alentejo presents important pharmacological properties and low toxicity, and is a promised candidate to be used as a food supplement or in pharmaceutical applications. Georg Thieme Verlag KG Stuttgart · New York.

  4. Knowledge and pharmacological management of Alzheimer's disease by managing community pharmacists: a nationwide study.

    Science.gov (United States)

    Zerafa, Natalie; Scerri, Charles

    2016-12-01

    Background Managing community pharmacists can play a leading role in supporting community dwelling individuals with Alzheimer's disease and their caregivers. Objective The main purpose of this study was to assess knowledge of managing community pharmacists towards Alzheimer's disease and its pharmacological management. Setting Community pharmacies in the Maltese islands. Method A nationwide survey was conducted with full-time managing community pharmacists in possession of a tertiary education degree in pharmacy studies. The level of knowledge was investigated using the Alzheimer's Disease Knowledge Scale and the Alzheimer's Disease Pharmacotherapy Measure. Participants were also asked to rate a number of statements related to disease management. Results Maltese managing community pharmacists (57 % response rate) had inadequate knowledge on risk factors, caregiving issues and pharmacological management of Alzheimer's disease. Age and number of years working in a community pharmacy setting were found to be negatively correlated with increased knowledge. Conclusion The findings highlight the need of providing training and continued educational support to managing community pharmacists in order to provide quality advice to individuals with dementia and their caregivers in the community.

  5. Evaluation of regional metabolic abnormality and treatment effect in patients with narcolepsy

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yu Kyeong; Yoon, In Young; Shin, Youn Kyung; Eo, Jae Sean; Won, Oh So; Lee, Won Woo; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2005-07-01

    The aim of the present study was to evaluated regional metabolic abnormalities in untreated narcoleptic patients and the changes in regional cerebral metabolism after treatment with modafinil. Eight drug free narcoleptic patients (mean age of 17{+-}1 yr) participated in this study. Two [{sup 18}F]fluorodeoxyglucose positron emission tomography (FDG-PET) scans before and after a 2-week titrated modafinil treatment (target dose = 100{approx}400 mg/day). The PET data were analyzed by using statistical parametric mapping methods to identify the regional cerebral abnormalities compared with those of healthy young controls. In addition, treatment effect was evaluated by comparison between before and after treatment scan. In narcolepsy patients, a significant reduction of regional metabolism was demonstrated in the brain stem, bilateral hypothalamus, posterior thalamus, hippocampus, parahippocampal gyrus, and adjacent perihinal area on pretreatment scans compared with those of healthy subjects. The decrease glucose metabolism was also found in the occipital cortex and cerebellum. The patients could control daytime sleepiness after treatment. Posttreatment scan showed a significant increase in regional metabolism in the left hippocampus. This study demonstrated the metabolic abnormalities and the effect of modafinil treatment in narcoleptic patients in the sleep associated regions. This results could be helpful to understand the pathophysiology of the narcolepsy and treatment mechanism.

  6. Sleep-wake stability in narcolepsy patients with normal, low and unmeasurable hypocretin levels.

    Science.gov (United States)

    Hansen, Mathias Hvidtfelt; Kornum, Birgitte Rahbek; Jennum, Poul

    2017-06-01

    To compare diurnal and nocturnal electrophysiological data from narcolepsy patients with undetectable (110 pg/mL) cerebrospinal fluid (CSF) hypocretin-1 levels. A total of 109 narcolepsy patients and 37 controls were studied; all had available CSF hypocretin-1 measurements. The sleep laboratory studies were conducted between 2008 and 2014. The study retrospectively examined measurements of sleep stage transitions in diurnal and nocturnal continuous polysomnography. The percentage distribution of time awake and rapid eye movement (REM) sleep, and the occurrence of sleep onset REM (SOREM) in the nocturnal polysomnography were also measured. Participants with undetectable hypocretin-1 levels had significantly higher frequencies of transitions than controls and those with normal hypocretin-1 levels. Participants with low hypocretin-1 levels showed more transitions than controls and, in some cases, also more than those with normal hypocretin-1. Participants with normal hypocretin-1 failed to show any significant difference from the controls, except in the overall diurnal transitions. Undetectable hypocretin-1 levels in particular, but also low hypocretin-1 levels, were associated with a less stable phenotype featuring more sleep state transitions and SOREM episodes. In addition, there was a distinction between nocturnal and diurnal REM sleep in hypocretin-deficient participants, expressed as increased diurnal REM sleep, which was not reflected in nocturnal sleep. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Human hypocretin-deficient narcolepsy - aberrant food choice due to impaired taste?

    Directory of Open Access Journals (Sweden)

    Giselle de Martin Truzzi

    Full Text Available Authors demonstrate that patients with narcolepsy type 1 (N1 have more tendency of eat salty snacks after satiety than health volunteers. A few mechanisms to explain the weight gain have been discussed in narcolepsy. The hypocretin-1 deficiency can influence the olfactory system. The olfactory system should be modulated through hypocretin-1 via connections from the hypothalamic to other brain regions. Likewise, hypocretin-1 can be synthesized locally in our olfactory mucosa with possible private role modulating the olfactory. In experimental studies, different kinds of smell influence the preference for type of diet. Olfactory and taste sensations help control of appetite and regulate the quantity and quality of foods that will be chosen. N1 patients have lower levels of hypocretin-1 and consequent inferior olfactory threshold, less olfactory discrimination, and these findings improved after nasal hypocretin-1 administration. It is possible that the hyposmia influenced the quality and quantity of food by narcoleptic patients. We suggest that a complementary analysis of olfactory function should be done concomitant with food preferences to compare narcoleptic patients with and without hypocretin-1 deficiency.

  8. Narcolepsy with cataplexy and hyperthyroidism sudden appeared after H1N1 vaccination

    Directory of Open Access Journals (Sweden)

    Silvia Leiva

    Full Text Available Narcolepsy type 1 (NT1 is a chronic sleep disorder, characterized by excessive daytime sleepiness, cataplexy and fragmented nocturnal sleep. It is caused by a hypocretin deficiency due to a significant reduction of the neurons producing it. In the last years, it has been postulated that an autoimmune mechanism would be responsible for the destruction of these neurons in those genetically predisposed patients. The increased incidence of narcolepsy after the pandemic H1N1 influenza vaccination campaign in 2009-2010 is known. We present below the case of an adult patient who, 10 days after receiving H1N1 vaccination, suffers a traffic accident after falling asleep. Subsequent studies revealed hyperthyroidism due to Graves disease. In spite of the treatment, the patient persisted with daily and disabling daytime sleepiness, sleep attacks and episodes of generalized muscle atony with preservation of consciousness. A nocturnal polysomnography and multiple sleep latency test (MSLT were performed with a diagnosis of NT1. The particularity of this case is the presentation of 2 autoimmune diseases triggered by an H1N1 vaccine without adjuvant, so far there is only evidence of NT1 associated with vaccines with adjuvant and viral infection. The association of both entities has made us reflect on the autoimmune mechanism, reinforcing the theory of its role in the onset of the disease.

  9. Anesthetic pharmacology

    National Research Council Canada - National Science Library

    Evers, Alex S; Maze, M; Kharasch, Evan D

    2011-01-01

    ...: Section 1 introduces the principles of drug action, Section 2 presents the molecular, cellular and integrated physiology of the target organ/functional system and Section 3 reviews the pharmacology...

  10. Four-year follow-up study of pharmacological treatment in pathological gamblers.

    Science.gov (United States)

    Rosenberg, Oded; Dinur, Limor Klein; Dannon, Pinhas N

    2013-01-01

    In the past decade, we have witnessed the emergence of pharmacological treatments for pathological gambling with some success but many question marks. We aimed to explore pharmacological treatments that have been previously explored with some success, with the intent of comparing their efficacy and pave the way to larger placebo-controlled trials. In this study, we allocated 78 patients to 4 different types of psychotropic medications: naltrexone, topiramate, bupropion, and escitalopram. We treated patients for more than 2 years, with additional 2-year follow-ups without medication. The sample was evaluated using the 21-item Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, the Global Assessment of Functioning, and the Visual Analog Scale to measure general well-being before enrollment as well as at 1 month, 6 months, 24 months, and 48 months after beginning medication treatment. During the first 2 years of treatment, 34 patients dropped out, with one more dropping out during the additional 2 years of follow-up. Significant improvement on all rating scales was seen in all groups after 2 years, except HAMD in the group that received topiramate. We found the naltrexone-treated group of patients to have a statistically significant lower dropout rate compared with other groups, statistically significant lower HAMD scores in comparison to the group treated with bupropion, statistically significant lower Hamilton Anxiety Rating Scale score compared to the groups treated with escitalopram and topiramate, and significantly higher Visual Analog Scale scores compared to the groups treated with bupropion and topiramate. Pathological gambling is essentially a biopsychological disorder that may be attenuated provided that patients adhere to medication. In our study, among 4 medications with different mechanisms of action, naltrexone was found to be the most effective. Placebo-controlled studies involving large numbers of subjects are required before

  11. [Pharmacological study on hemostasis, analgesic and anti inflammation effects of the alcohol extract of Hibiscus tiliaceus].

    Science.gov (United States)

    Qiu, Fen; Tian, Hui; Zhang, Zhi; Yuan, Xian-Ling; Tan, Yuan-Feng; Ning, Xiao-Qing

    2013-10-01

    To study the effects of hemostasis, analgesic and anti inflammation of the alcohol extract of Hibiscus tiliaceus and offer pharmacological and experimental basis for its safe and effective use in clinic. The effects of hemostasist were observed with tail breaking method, capillary tube method and slide method; Hot board and body distortion induced by acetic acid methods were applied in mice analgesia experiment, the mice model of acute auricle swelling induced by dmi ethylbenzene and capillary permeability induced by acetic acid were applied to observe the anti inflammatory effects. The alcohol extract of Hibiscus tiliaceus could significantly reduce the bleeding time and the clotting time, delay the plant reaction time and reduce the writhing times of the mice, and it also had effect on inhibiting swelling of mice ear and the permeability of the capillary. These results suggest that the alcohol extract of Hibiscus tiliaceus has the effects of hemostasis, analgesic and anti inflammation.

  12. Preparation and preclinical pharmacological study on a novel bone imaging agent 99mTc-EMIDP

    International Nuclear Information System (INIS)

    Lin Jianguo; Luo Shineng; Chen Chuanqing; Qiu Ling; Wang Yan; Cheng Wen; Ye Wanzhong; Xia Yongmei

    2010-01-01

    A novel zoledronic acid (ZL) derivative, 1-hydroxy-2-(2-ethyl-4-methyl-1H-imidazol-1-yl)ethane-1,1-diyldiphosphonic acid (EMIDP), was prepared and labeled with 99m Tc successfully in a high labeling yield and good stability in vitro. The preclinical pharmacological properties of 99m Tc-EMIDP were investigated and compared with 99m Tc-MDP and 99m Tc-ZL. The studies of biodistribution in mice and SPECT bone imaging of the rabbit suggest that 99m Tc-EMIDP has highly selective uptake in the skeletal system and rapid clearance in the soft tissues. The present findings indicate that 99m Tc-EMIDP holds great potential for bone scintigraphy.

  13. Ventilatory function assessment in safety pharmacology: Optimization of rodent studies using normocapnic or hypercapnic conditions

    International Nuclear Information System (INIS)

    Goineau, Sonia; Rompion, Sonia; Guillaume, Philippe; Picard, Sandra

    2010-01-01

    Although the whole body plethysmography for unrestrained animals is the most widely used method to assess the respiratory risk of new drugs in safety pharmacology, non-appropriate experimental conditions may mask deleterious side effects of some substances. If stimulant or bronchodilatory effects can be easily evidenced in rodents under standard experimental conditions, i.e. normal air breathing and diurnal phase, drug-induced respiratory depression remains more difficult to detect. This study was aimed at comparing the responsiveness of Wistar rats, Duncan Hartley guinea-pigs or BALB/c mice to the respiratory properties of theophylline (50 or 100 mg/kg p.o.) or morphine (30 mg/kg i.p.) under varying conditions (100% air versus 5% CO 2 -enriched air, light versus dark day phase), in order to select the most appropriate experimental conditions to each species for safety airway investigations. Our results showed that under normocapnia the ventilatory depressant effects of morphine can be easily evidenced in mice, slightly observed in guinea-pigs and not detected in rats in any day phase. Slight hypercapnic conditions enhanced the responsiveness of rats to morphine but not that of guinea-pigs and importantly they did not blunt the airway responsiveness of rats to the stimulation and bronchodilation evoked by theophylline, the most widely used reference agent in safety pharmacology studies. In conclusion, hypercapnic conditions associated with the non-invasive whole body plethysmography should be considered for optimizing the assessment of both the ventilatory depressant potential of morphine-like substances or the respiratory stimulant effects of new drugs in the rat, the most extensively used species in rodent safety and toxicological investigations.

  14. Approaches in studying the pharmacology of Chinese Medicine formulas: bottom-up, top-down-and meeting in the middle.

    Science.gov (United States)

    Huang, Tao; Zhong, Linda L D; Lin, Chen-Yuan; Zhao, Ling; Ning, Zi-Wan; Hu, Dong-Dong; Zhang, Man; Tian, Ke; Cheng, Chung-Wah; Bian, Zhao-Xiang

    2018-01-01

    Investigating the pharmacology is key to the modernization of Chinese Medicine (CM) formulas. However, identifying which are the active compound(s) of CM formulas, which biological entities they target, and through which signaling pathway(s) they act to modify disease symptoms, are still difficult tasks for researchers, even when equipped with an arsenal of advanced modern technologies. Multiple approaches, including network pharmacology, pharmaco-genomics, -proteomics, and -metabolomics, have been developed to study the pharmacology of CM formulas. They fall into two general categories in terms of how they tackle a problem: bottom-up and top-down. In this article, we compared these two different approaches in several dimensions by using the case of MaZiRenWan (MZRW, also known as Hemp Seed Pill), a CM herbal formula for functional constipation. Multiple hypotheses are easy to be proposed in the bottom-up approach (e.g. network pharmacology); but these hypotheses are usually false positives and hard to be tested. In contrast, it is hard to suggest hypotheses in the top-down approach (e.g. pharmacometabolomics); however, once a hypothesis is proposed, it is much easier to be tested. Merging of these two approaches could results in a powerful approach, which could be the new paradigm for the pharmacological study of CM formulas.

  15. Rare missense mutations in P2RY11 in narcolepsy with cataplexy

    DEFF Research Database (Denmark)

    Degn, Matilda; Dauvilliers, Yves; Dreisig, Karin

    2017-01-01

    these are single nucleotide polymorphisms in the P2RY11-EIF3G locus. It is unknown how these genetic variants affect narcolepsy pathogenesis and whether the effect is directly related to P2Y11 signalling or EIF3G function. Exome sequencing in 18 families with at least two affected narcolepsy with cataplexy...

  16. Cerebrospinal fluid biomarkers of neurodegeneration are decreased or normal in narcolepsy

    DEFF Research Database (Denmark)

    Jennum, Poul Jørgen; Pedersen, Lars Østergaard; Bahl, Justyna Maria Czarna

    2017-01-01

    OBJECTIVES: To investigate whether cerebrospinal fluid (CSF) biomarkers of neurodegeneration are altered in narcolepsy in order to evaluate whether the hypocretin deficiency and abnormal sleep-wake pattern in narcolepsy leads to neurodegeneration. METHODS: Twenty-one patients with central...... that hypocretin deficiency and an abnormal sleep-wake pattern alter the turnover of these proteins in CNS....

  17. Narcolepsy with hypocretin/orexin deficiency, infections and autoimmunity of the brain

    DEFF Research Database (Denmark)

    Kornum, Birgitte Rahbek; Faraco, Juliette; Mignot, Emmanuel

    2011-01-01

    The loss of hypothalamic hypocretin/orexin (hcrt) producing neurons causes narcolepsy with cataplexy. An autoimmune basis for the disease has long been suspected and recent results have greatly strengthened this hypothesis. Narcolepsy with hcrt deficiency is now known to be associated with a Huma...

  18. Common variants in P2RY11 are associated with narcolepsy

    DEFF Research Database (Denmark)

    Kornum, Birgitte R; Kawashima, Minae; Faraco, Juliette

    2011-01-01

    Growing evidence supports the hypothesis that narcolepsy with cataplexy is an autoimmune disease. We here report genome-wide association analyses for narcolepsy with replication and fine mapping across three ethnic groups (3,406 individuals of European ancestry, 2,414 Asians and 302 African Ameri...

  19. Psychosis in patients with narcolepsy as an adverse effect of sodium oxybate

    Directory of Open Access Journals (Sweden)

    Tomi eSarkanen

    2014-08-01

    Full Text Available Aim: Hypnagogic and hypnopompic hallucinations are characteristic symptoms of narcolepsy, as are excessive daytime sleepiness, cataplexy and sleep paralysis. Narcolepsy patients may also experience daytime hallucinations unrelated to sleep-wake transitions. The effect of medication on hallucinations is of interest since treatment of narcolepsy may provoke psychotic symptoms. We aim to analyze the relation between sodium oxybate (SXB treatment and psychotic symptoms in narcolepsy patients. Furthermore, we analyze the characteristics of hallucinations to determine their nature as mainly psychotic or hypnagogic and raise a discussion about whether SXB causes psychosis or if psychosis occurs as an endogenous complication in narcolepsy.Method: We present altogether four patients with narcolepsy who experienced psychotic symptoms during treatment with SXB. In addition, we searched the literature for descriptions of hallucinations in narcolepsy and similarities and differences with psychotic symptoms in schizophrenia.Results: Three out of four patients had hallucinations typical for psychosis and one had symptoms that resembled aggravated hypnagogic hallucinations. Two patients also had delusional symptoms primarily associated with mental disorders. Tapering down SXB was tried and helped in two out of four cases. Adding antipsychotic treatment (risperidone alleviated psychotic symptoms in two cases. Conclusion: Psychotic symptoms in narcolepsy may appear during SXB treatment. Hallucinations resemble those seen in schizophrenia however the insight that symptoms are delusional is usually preserved. In case of SXB-induced psychotic symptoms or hallucinations, reducing SXB dose or adding antipsychotic medication can be tried.

  20. Complex Movement Disorders at Disease Onset in Childhood Narcolepsy with Cataplexy

    Science.gov (United States)

    Plazzi, Giuseppe; Pizza, Fabio; Palaia, Vincenzo; Franceschini, Christian; Poli, Francesca; Moghadam, Keivan K.; Cortelli, Pietro; Nobili, Lino; Bruni, Oliviero; Dauvilliers, Yves; Lin, Ling; Edwards, Mark J.; Mignot, Emmanuel; Bhatia, Kailash P.

    2011-01-01

    Narcolepsy with cataplexy is characterized by daytime sleepiness, cataplexy (sudden loss of bilateral muscle tone triggered by emotions), sleep paralysis, hypnagogic hallucinations and disturbed nocturnal sleep. Narcolepsy with cataplexy is most often associated with human leucocyte antigen-DQB1*0602 and is caused by the loss of…

  1. Psychosis in patients with narcolepsy as an adverse effect of sodium oxybate.

    Science.gov (United States)

    Sarkanen, Tomi; Niemelä, Valter; Landtblom, Anne-Marie; Partinen, Markku

    2014-01-01

    Hypnagogic and hypnopompic hallucinations are characteristic symptoms of narcolepsy, as are excessive daytime sleepiness, cataplexy, and sleep paralysis. Narcolepsy patients may also experience daytime hallucinations unrelated to sleep-wake transitions. The effect of medication on hallucinations is of interest since treatment of narcolepsy may provoke psychotic symptoms. We aim to analyze the relation between sodium oxybate (SXB) treatment and psychotic symptoms in narcolepsy patients. Furthermore, we analyze the characteristics of hallucinations to determine their nature as mainly psychotic or hypnagogic and raise a discussion about whether SXB causes psychosis or if psychosis occurs as an endogenous complication in narcolepsy. We present altogether four patients with narcolepsy who experienced psychotic symptoms during treatment with SXB. In addition, we searched the literature for descriptions of hallucinations in narcolepsy and similarities and differences with psychotic symptoms in schizophrenia. Three out of four patients had hallucinations typical for psychosis and one had symptoms that resembled aggravated hypnagogic hallucinations. Two patients also had delusional symptoms primarily associated with mental disorders. Tapering down SXB was tried and helped in two out of four cases. Adding antipsychotic treatment (risperidone) alleviated psychotic symptoms in two cases. Psychotic symptoms in narcolepsy may appear during SXB treatment. Hallucinations resemble those seen in schizophrenia; however, the insight that symptoms are delusional is usually preserved. In case of SXB-induced psychotic symptoms or hallucinations, reducing SXB dose or adding antipsychotic medication can be tried.

  2. [Study on characteristics of pharmacological effects of traditional Chinese medicines distributing along lung meridian based on medicinal property combination].

    Science.gov (United States)

    Gu, Hao; Zhang, Yan-Ling; Wang, Yun; Qiao, Yan-Jiang

    2014-07-01

    Medicinal properties are the basic attribute of traditional Chinese medicines (TCM), while the medicinal property theory is the core theoretical foundation of TCM formula combination. In this particle, authors studied the characteristics of pharmacological effects of property combination of traditional Chinese medicines distributing along meridians, with the aim to introduce the medicinal property combination regularity into the design and optimization process of compound TCMs, and bring the medicinal property theory into full play in guiding the formula combination. In this paper, TCMs distributing along "the lung meridian" was taken for example. The medicinal property combinations of TCMs distributing along "the lung meridian" recorded in Pharmacopeia (2010) was collected and processed. Besides, Chinese journal full-text database (CNKI) was used to collect all of pharmacological study literatures concerning the above TCMs that have been published since 1980. The pharmacological information was also supplemented by reference to Science of Chinese Materia Medica and Clinical Science of Chinese Materia Medica. TCMs distributing along the lung meridian with different properties and tastes showed significant differences in pharmacological effects. For example, mild-sweet-lung medicines could lower blood sugar levels, decrease anoxia and enhance immunity; Mild-bitter-lung medicines showed anti-bacterial, anti-hypertension, anti-oxidation effects; Hot-sweet-lung medicines showed antibechic and anti-bacterial effects. And Hot-bitter-lung medicines showed phlegm eliminating and anti-inflammatory effects. Meanwhile, TCMs distributing along the lung meridian had similar pharmacological characteristics, such as anti-bacterial and anti-inflammatory effects, which is consistent with lung's feature in susceptibility to exogenous pathogenic factors. In this study, authors discovered pharmacological characteristics of different TCMs distributing along the lung meridian, which

  3. Rapid eye movement sleep behavior disorder and rapid eye movement sleep without atonia in narcolepsy

    DEFF Research Database (Denmark)

    Dauvilliers, Yves; Jennum, Poul; Plazzi, Giuseppe

    2013-01-01

    Narcolepsy is a rare disabling hypersomnia disorder that may include cataplexy, sleep paralysis, hypnagogic hallucinations, and sleep-onset rapid eye movement (REM) periods, but also disrupted nighttime sleep by nocturnal awakenings, and REM sleep behavior disorder (RBD). RBD is characterized...... by dream-enacting behavior and impaired motor inhibition during REM sleep (REM sleep without atonia, RSWA). RBD is commonly associated with neurodegenerative disorders including Parkinsonisms, but is also reported in narcolepsy in up to 60% of patients. RBD in patients with narcolepsy is, however...... with narcolepsy often present dissociated sleep features including RSWA, increased density of phasic chin EMG and frequent shift from REM to NREM sleep, with or without associated clinical RBD. Most patients with narcolepsy with cataplexy lack the hypocretin neurons in the lateral hypothalamus. Tonic and phasic...

  4. Effective treatment of narcolepsy-like symptoms with high-frequency repetitive transcranial magnetic stimulation

    Science.gov (United States)

    Lai, Jian-bo; Han, Mao-mao; Xu, Yi; Hu, Shao-hua

    2017-01-01

    Abstract Rationale: Narcolepsy is a rare sleep disorder with disrupted sleep-architecture. Clinical management of narcolepsy lies dominantly on symptom-driven pharmacotherapy. The treatment role of repetitive transcranial magnetic stimulation (rTMS) for narcolepsy remains unexplored. Patient concerns: In this paper, we present a case of a 14-year-old young girl with excessive daytime sleepiness (EDS), cataplexy and hypnagogic hallucinations. Diagnoses: After excluding other possible medical conditions, this patient was primarily diagnosed with narcolepsy. Interventions: The patient received 25 sessions of high-frequency rTMS over the left dorsolateral prefrontal cortex (DLPFC). Outcomes: The symptoms of EDS and cataplexy significantly improved after rTMS treatment. Meanwhile, her score in the Epworth sleep scale (ESS) also remarkably decreased. Lessons: This case indicates that rTMS may be selected as a safe and effective alternative strategy for treating narcolepsy-like symptoms. Well-designed researches are warranted in future investigations on this topic. PMID:29145290

  5. Aralia elata var. mandshurica (Rupr. & Maxim.) J.Wen: An overview of pharmacological studies.

    Science.gov (United States)

    Shikov, Alexander N; Pozharitskaya, Olga N; Makarov, Valery G

    2016-11-15

    Aralia elata var. mandshurica (Rupr. & Maxim.) J.Wen syn. A. mandshurica Rupr. & Maxim is evaluated for its medicinal application. The aim of this study is to analyze pharmacological studies on A. elata var. mandshurica published until December 2015. The information regarding the chemistry, safety, effectiveness, and pharmacological and clinical effects of A. elata was systematically collected from the scientific literature through library catalogs; online services such as E-library.ru, Medline/PubMed, Scopus, Web of Science, and Google Scholar. A. elata is often considered an example of a medicinal plant used in Chinese, Korean, and Japanese traditional medicine. However, the contemporary applications of Aralia in officinal medicine result primarily from a large number of pharmacological and clinical investigations carried out in the former USSR in the mid-20th century. Since the 1950s, medicinal preparations from radices of A. elata and radices of A. mandshurica have secured an established position within Russian/USSR medicine as evidenced by the inclusion of the drug in recent editions of the National Pharmacopoeia of the USSR and in the Register of Medicinal Preparations of Russia. Pharmacological studies on animals have shown that Aralia increases physical working capacity and affords a stress-protective effect against a broad spectrum of harmful factors including cold stress, immobilization, UV irradiation, and low air pressure. The phytoadaptogen exerts an effect on the central nervous, reproductive, immune, respiratory, and gastrointestinal systems; the metabolic syndrome including hypolipidemic and antidiabetic effects; and blood coagulation. Together with general properties of adaptogens, Aralia has its own specificity, which manifests in cardioprotective and antiarrhythmic activities. Studies on isolated organs, cells, and enzymes have revealed that Aralia preparations exhibit antioxidant activities and enhance sarcoplasmic reticulum Ca 2+ -ATPase

  6. Use of Learning Media by Undergraduate Medical Students in Pharmacology: A Prospective Cohort Study

    Science.gov (United States)

    Gutmann, Joanna; Kühbeck, Felizian; Berberat, Pascal O.; Fischer, Martin R.; Engelhardt, Stefan; Sarikas, Antonio

    2015-01-01

    The ubiquity of the internet and computer-based technologies has an increasing impact on higher education and the way students access information for learning. Moreover, there is a paucity of information about the quantitative and qualitative use of learning media by the current student generation. In this study we systematically analyzed the use of digital and non-digital learning resources by undergraduate medical students. Daily online surveys and semi-structured interviews were conducted with a cohort of 338 third year medical students enrolled in a general pharmacology course. Our data demonstrate a predominant use of digital over non-digital learning resources (69 ± 7% vs. 31 ± 7%; p students. Most used media for learning were lecture slides (26.8 ± 3.0%), apps (22.0 ± 3.7%) and personal notes (15.5 ± 2.7%), followed by textbooks (> 300 pages) (10.6 ± 3.3%), internet search (7.9 ± 1.6%) and e-learning cases (7.6 ± 3.0%). When comparing learning media use of teaching vs. pre-exam self-study periods, textbooks were used significantly less during self-study (-55%; p learning cases (+176%; p learning resources by undergraduate medical students, in particular mobile applications. PMID:25849565

  7. Comparative Study of Multimodal and Pharmacological Therapy in Treating School Aged Children with ADHD

    Directory of Open Access Journals (Sweden)

    Susana Bogdana MILEA

    2012-09-01

    Full Text Available The attention deficit hyperactivity disorder (ADHD, one of the most commonly diagnosed psychiatric disorders among school aged children, continues to create disputes between specialists, upon the best treatment to be used. The herby study aims to bring forward some differences that may exist between the efficacy of the multimodal treatment compared to the drug treatment of ADHD. The novelty component of this study, unfolded February 2010-July 2012, is that the children, their parents and also their teachers were included in the multimodality treatment. The children included in this research (n=63, aged 6-14 and ADHD diagnosed, were randomly assigned in two groups. In the medication (Med group (n=32 the children only received the specific pharmacological treatment (Atomoxetine or Methylphenidate, and for the multimodality (MM group (n=31 the therapy included psychosocial interventions besides the drug therapy. All children were evaluated, both pre and post intervention, with the Achenbach System of Empirically Based Assessment – ASEBA, for the 6-18 aged category. We have compared the influence of therapy on the core symptoms, on the adaptive functionality and academic performance and on the competences and social functioning of the children in the two groups. The multimodal intervention proved to be more effective (p<0.05 than medication alone, firstly in ameliorating the child’s social behavior in both family and school environment, than in what concerns the main ADHD symptoms. The children’s academic performance was little impacted by either of the two therapies.

  8. Impact of cytokine in type 1 narcolepsy: Role of pandemic H1N1 vaccination ?

    Science.gov (United States)

    Lecendreux, Michel; Libri, Valentina; Jaussent, Isabelle; Mottez, Estelle; Lopez, Régis; Lavault, Sophie; Regnault, Armelle; Arnulf, Isabelle; Dauvilliers, Yves

    2015-06-01

    Recent advances in the identification of susceptibility genes and environmental exposures (pandemic influenza 2009 vaccination) provide strong support that narcolepsy type 1 is an immune-mediated disease. Considering the limited knowledge regarding the immune mechanisms involved in narcolepsy whether related to flu vaccination or not and the recent progresses in cytokine measurement technology, we assessed 30 cytokines, chemokines and growth factors using the Luminex technology in either peripheral (serum) or central (CSF) compartments in a large population of 90 children and adult patients with narcolepsy type 1 in comparison to 58 non-hypocretin deficient hypersomniacs and 41 healthy controls. Furthermore, we compared their levels in patients with narcolepsy whether exposed to pandemic flu vaccine or not, and analyzed the effect of age, duration of disease and symptom severity. Comparison for sera biomarkers between narcolepsy (n = 84, 54 males, median age: 15.5 years old) and healthy controls (n = 41, 13 males, median age: 20 years old) revealed an increased stimulation of the immune system with high release of several pro- and anti-inflammatory serum cytokines and growth factors with interferon-γ, CCL11, epidermal growth factor, and interleukin-2 receptor being independently associated with narcolepsy. Increased levels of interferon-γ, CCL11, and interleukin-12 were found when close to narcolepsy onset. After several adjustments, only one CSF biomarker differed between narcolepsy (n = 44, 26 males, median age: 15 years old) and non-hypocretin deficient hypersomnias (n = 57, 24 males, median age: 36 years old) with higher CCL 3 levels found in narcolepsy. Comparison for sera biomarkers between patients with narcolepsy who developed the disease post-pandemic flu vaccination (n = 36) to those without vaccination (n = 48) revealed an increased stimulation of the immune system with high release of three cytokines, regulated upon activation normal T-cell expressed

  9. Comparative study of native and irradiated crotoxin. Biochemical and pharmacological effects

    International Nuclear Information System (INIS)

    Nascimento, N. do.

    1991-01-01

    Ionizing radiation is able to detoxify several venoms, including snake venom, without affecting significantly their antigenic and immunogenic properties. In order to elucidate this phenomena, we conceived a comparative biochemical and pharmacological study between native and gamma irradiated (2000Gy) crotoxin, main toxin of south american rattlesnake Crotalus durissus terrificus. Crotoxin was isolated and purified from crude venom by molecular exclusion chromatography, pI precipitation and then irradiated. Immunodiffusion, electrophoresis and gel filtration showed that the molecular integrity was preserved after irradiation with some higher molecular weight aggregate formation and maintenance of its antigenic capacity. The antibodies induced by irradiated toxin had a similar titer to the antibodies induced by native crotoxin; however with higher protective effects in mice. Crotoxin toxicity became 15 times lower after irradiation, as determined by LD sub(50) in mice. Native and irradiated crotoxin biodistribution occurred with a similar general pattern, with renal elimination. In contrast to irradiated crotoxin, the native crotoxin is initially retained in kidneys. A later concentration (2-3hs) occurs in phagocyticmononuclear cells rich organs (liver and spleen) and neural junctions rich organs (muscle and brain). (author)

  10. Highlights from the 15th International Congress of Twin Studies/Twin Research: Differentiating MZ Co-twins Via SNPs; Mistaken Infant Twin-Singleton Hospital Registration; Narcolepsy With Cataplexy; Hearing Loss and Language Learning/Media Mentions: Broadway Musical Recalls Conjoined Hilton Twins; High Fashion Pair; Twins Turn 102; Insights From a Conjoined Twin Survivor.

    Science.gov (United States)

    Segal, Nancy L

    2015-02-01

    Highlights from the 15th International Congress of Twin Studies are presented. The congress was held November 16-19, 2014 in Budapest, Hungary. This report is followed by summaries of research addressing the differentiation of MZ co-twins by single nucleotide polymorphisms (SNPs), an unusual error in infant twin-singleton hospital registration, twins with childhood-onset narcolepsy with cataplexy, and the parenting effects of hearing loss in one co-twin. Media interest in twins covers a new Broadway musical based on the conjoined twins Violet and Daisy Hilton, male twins becoming famous in fashion, twins who turned 102 and unique insights from a conjoined twin survivor. This article is dedicated to the memory of Elizabeth (Liz) Hamel, DZA twin who met her co-twin for the first time at age seventy-eight years. Liz and her co-twin, Ann Hunt, are listed in the 2015 Guinness Book of Records as the longest separated twins in the world.

  11. CSF Hypocretin-1 Levels and Clinical Profiles in Narcolepsy and Idiopathic CNS Hypersomnia in Norway

    Science.gov (United States)

    Heier, Mona Skard; Evsiukova, Tatiana; Vilming, Steinar; Gjerstad, Michaela D.; Schrader, Harald; Gautvik, Kaare

    2007-01-01

    Objective: To evaluate the relationship between CSF hypocretin-1 levels and clinical profiles in narcolepsy and CNS hypersomnia in Norwegian patients. Method: CSF hypocretin-1 was measured by a sensitive radioimmunoassay in 47 patients with narcolepsy with cataplexy, 7 with narcolepsy without cataplexy, 10 with idiopathic CNS hypersomnia, and a control group. Results: Low hypocretin-1 values were found in 72% of the HLA DQB1*0602 positive patients with narcolepsy and cataplexy. Patients with low CSF hypocretin-1 levels reported more extensive muscular involvement during cataplectic attacks than patients with normal levels. Hypnagogic hallucinations and sleep paralysis occurred more frequently in patients with cataplexy than in the other patient groups, but with no correlation to hypocretin-1 levels. Conclusion: About three quarters of the HLA DQB1*0602 positive patients with narcolepsy and cataplexy had low CSF hypocretin-1 values, and appear to form a distinct clinical entity. Narcolepsy without cataplexy could not be distinguished from idiopathic CNS hypersomnia by clinical symptoms or biochemical findings. Citation: Heier MS; Evsiukova T; Vilming S; Gjerstad MD; Schrader H; Gautvik K. CSF hypocretin-1 levels and clinical profiles in narcolepsy and idiopathic CNS hypersomnia in norway. SLEEP 2007;30(8):969-973. PMID:17702265

  12. Diretrizes brasileiras para o tratamento da narcolepsia Brazilian guidelines for the treatment of narcolepsy

    Directory of Open Access Journals (Sweden)

    Flávio Alóe

    2010-09-01

    -controlled trials and to issue consensus opinions on the use of other available medications as well as to inform about safety and adverse effects of these medications. Management of narcolepsy relies on several classes of drugs, namely, stimulants for excessive sleepiness, antidepressants for cataplexy and hypnotics for disturbed nocturnal sleep. Behavioral measures are likewise valuable and universally recommended. All therapeutic trials were analyzed according to their class of evidence. Recommendations concerning the treatment of each single symptom of narcolepsy as well as general recommendations were made. Modafinil is the first-line pharmacological treatment of excessive sleepiness. Second-line choices for the treatment of excessive sleepiness are slow-release metylphenidate followed by mazindol. The first-line treatments of cataplexy are the antidepressants, reboxetine, clomipramine, venlafaxine, desvenlafaxine or high doses of selective serotonin reuptake inibitors antidepressants. As for disturbed nocturnal sleep the best option is still hypnotics. Antidepressants and hypnotics are used to treat hypnagogic hallucinations and sleep paralysis.

  13. Narcolepsy-cataplexy and loss of sphincter control.

    Science.gov (United States)

    Vgontzas, A. N.; Sollenberger, S. E.; Kales, A.; Bixler, E. O.; Vela-Bueno, A.

    1996-01-01

    We describe the case of a 34-year-old man who presented intermittent faecal incontinence as a manifestation of cataplexy. The patient's sleep history was positive for the full narcoleptic tetrad (sleep attacks, cataplexy, sleep paralysis and hypnagogic hallucinations) while extensive neuropsychiatric work up was negative for any neurologic or psychiatric illness. Repeat polysomnograms (including a polysomnogram with a full seizure montage) were positive for pathologic sleepiness, but there was no evidence of a seizure disorder. The course of the patient's symptomatology and the favourable response of his symptoms to stimulants and imipramine support the theory that his intermittent loss of sphincter control is part of his narcolepsy-cataplexy. PMID:8796217

  14. Renal studies in safety pharmacology and toxicology: A survey conducted in the top 15 pharmaceutical companies.

    Science.gov (United States)

    Benjamin, Amanda; Gallacher, David J; Greiter-Wilke, Andrea; Guillon, Jean-Michel; Kasai, Cheiko; Ledieu, David; Levesque, Paul; Prelle, Katja; Ratcliffe, Sian; Sannajust, Frederick; Valentin, Jean-Pierre

    2015-01-01

    With the recent development of more sensitive biomarkers to assess kidney injury preclinically, a survey was designed i) to investigate what strategies are used to investigate renal toxicity in both ICH S7A compliant Safety Pharmacology (SP) studies after a single dose of a compound and within repeat-dose toxicity studies by large pharmaceutical companies today; ii) to understand whether renal SP studies have impact or utility in drug development and/or if it may be more appropriate to assess renal effects after multiple doses of compounds; iii) to ascertain how much mechanistic work is performed by the top 15 largest pharmaceutical companies (as determined by R&D revenue size); iv) to gain an insight into the impact of the validation of DIKI biomarkers and their introduction in the safety evaluation paradigm; and v) to understand the impact of renal/urinary safety study data on progression of projects. Two short anonymous surveys were submitted to SP leaders of the top 15 pharmaceutical companies, as defined by 2012 R&D portfolio size. Fourteen multiple choice questions were designed to explore the strategies used to investigate renal effects in both ICH S7A compliant SP studies and within toxicology studies. A 67% and 60% response rate was obtained in the first and second surveys, respectively. Nine out of ten respondent companies conduct renal excretory measurements (eg. urine analysis) in toxicology studies whereas only five out of ten conduct specific renal SP studies; and all of those 5 also conduct the renal excretory measurements in toxicology studies. These companies measure and/or calculate a variety of parameters as part of these studies, and also on a case by case basis include regulatory qualified and non-qualified DIKI biomarkers. Finally, only one company has used renal/urinary functional data alone to stop a project, whereas the majority of respondents combine renal data with other target organ assessments to form an integrated decision-making set

  15. Oral sodium phenylbutyrate in patients with recurrent malignant gliomas: a dose escalation and pharmacologic study.

    Science.gov (United States)

    Phuphanich, Surasak; Baker, Sharyn D; Grossman, Stuart A; Carson, Kathryn A; Gilbert, Mark R; Fisher, Joy D; Carducci, Michael A

    2005-04-01

    We determined the maximum tolerated dose (MTD), toxicity profile, pharmacokinetic parameters, and preliminary efficacy data of oral sodium phenylbutyrate (PB) in patients with recurrent malignant gliomas. Twenty-three patients with supratentorial recurrent malignant gliomas were enrolled on this dose escalation trial. Four dose levels of PB were studied: 9, 18, 27, and 36 g/day. Data were collected to assess toxicity, response, survival, and pharmacokinetics. All PB doses of 9, 18, and 27 g/day were well tolerated. At 36 g/day, two of four patients developed dose-limiting grade 3 fatigue and somnolence. At the MTD of 27 g/day, one of seven patients developed reversible grade 3 somnolence. Median survival from time of study entry was 5.4 months. One patient had a complete response for five years, and no partial responses were noted, which yielded an overall response rate of 5%. Plasma concentrations of 706, 818, 1225, and 1605 muM were achieved with doses of 9, 18, 27, and 36 g/day, respectively. The mean value for PB clearance in this patient population was 22 liters/h, which is significantly higher than the 16 liters/h reported in patients with other malignancies who were not receiving P450 enzyme-inducing anticonvulsant drugs (P = 0.038). This study defines the MTD and recommended phase 2 dose of PB at 27 g/day for heavily pretreated patients with recurrent gliomas. The pharmacology of PB appears to be affected by concomitant administration of P450-inducing anticonvulsants.

  16. Oral sodium phenylbutyrate in patients with recurrent malignant gliomas: A dose escalation and pharmacologic study1

    Science.gov (United States)

    Phuphanich, Surasak; Baker, Sharyn D.; Grossman, Stuart A.; Carson, Kathryn A.; Gilbert, Mark R.; Fisher, Joy D.; Carducci, Michael A.

    2005-01-01

    We determined the maximum tolerated dose (MTD), toxicity profile, pharmacokinetic parameters, and preliminary efficacy data of oral sodium phenylbutyrate (PB) in patients with recurrent malignant gliomas. Twenty-three patients with supratentorial recurrent malignant gliomas were enrolled on this dose escalation trial. Four dose levels of PB were studied: 9, 18, 27, and 36 g/day. Data were collected to assess toxicity, response, survival, and pharmacokinetics. All PB doses of 9, 18, and 27 g/day were well tolerated. At 36 g/day, two of four patients developed dose-limiting grade 3 fatigue and somnolence. At the MTD of 27 g/day, one of seven patients developed reversible grade 3 somnolence. Median survival from time of study entry was 5.4 months. One patient had a complete response for five years, and no partial responses were noted, which yielded an overall response rate of 5%. Plasma concentrations of 706, 818, 1225, and 1605 μM were achieved with doses of 9, 18, 27, and 36 g/day, respectively. The mean value for PB clearance in this patient population was 22 liters/h, which is significantly higher than the 16 liters/h reported in patients with other malignancies who were not receiving P450 enzyme–inducing anticonvulsant drugs (P = 0.038). This study defines the MTD and recommended phase 2 dose of PB at 27 g/day for heavily pretreated patients with recurrent gliomas. The pharmacology of PB appears to be affected by concomitant administration of P450-inducing anticonvulsants. PMID:15831235

  17. Preclinical pharmacological studies of 99Tcm-TRODAT-1 as a dopamine transporter imaging agent

    International Nuclear Information System (INIS)

    Fang Ping; Wan Weixing; Liu Zhenguo; Wu Chunying; Chen Shengdi; Chen Zhengping; Zhou Xiang; Ji Shuren

    2001-01-01

    Objective: To develop a 99 Tc m labelled dopamine transporter (DAT) imaging agent, 99 Tc m -TRODAT-1 [TRODAT-1: 2β-([N,N'-bis(2-mercaptoethyl) ethylene diamino] methyl), 3β-(4-chlorophenyl) tropane], for evaluating the variation of DAT in patients with Parkinson's disease. Methods: 99 Tc m -TRODAT-1 was successfully prepared on a kit basis. Preclinical pharmacological studies were performed in rats, mice, rabbits, monkeys and a volunteer with diagnosed Parkinson disease (PD). Results: Radiochemical purity of 99 Tc m -TRODAT-1 was over 90%, and remained stable for 6 hours. The specific uptake in striatum was significantly diminished, from 3.45 to 0.12 at 2 h by pretreating rats with a dose of DAT competing ligand, β-CIT [1 mg/kg, 2β-carbomethoxy-3β-(4-iodophenyl) tropane]. Blood clearance kinetics was studied in rabbits, and the initial half-life was of 1.2 min, the elimination half-life was of 368 min. Images of normal monkey's brain exhibited an excellent accumulation in basal ganglia region, where dopamine neurons were concentrated. In hemi parkinsonism model monkeys, the ratio of normal ST/CB and lesioned ST/CB were 1.56 and 0.94, respectively. Brain imaging studies in volunteer indicated that uptake and retention in the basal ganglia, the ratio of normal striatal uptake to lesioned one's was 1.15 measured by SPECT imaging at 2 h. The result of imaging was conformable with his clinical symptoms. Conclusions: The stable, neutral and lipophilic complex, 99 Tc m -TRODAT-1, can be accumulated in the striatal area, where DAT is concentrated, high quality images can be obtained. It suggests that 99 Tc m -TRODAT-1 might be a safe and effective tracer for monitoring the variation in DAT which is associated with various neurodegenerative diseases

  18. Acute Pharmacological Effects of 2C-B in Humans: An Observational Study

    Directory of Open Access Journals (Sweden)

    Esther Papaseit

    2018-03-01

    Full Text Available 2,5-dimethoxy-4-bromophenethylamine (2C-B is a psychedelic phenylethylamine derivative, structurally similar to mescaline. It is a serotonin 5-hydroxytryptamine-2A (5-HT2A, 5-hydroxytryptamine-2B (5-HT2B, and 5-hydroxytryptamine-2C (5-HT2C receptor partial agonist used recreationally as a new psychoactive substance. It has been reported that 2C-B induces mild psychedelic effects, although its acute pharmacological effects and pharmacokinetics have not yet been fully studied in humans. An observational study was conducted to assess the acute subjective and physiological effects, as well as pharmacokinetics of 2C-B. Sixteen healthy, experienced drug users self-administered an oral dose of 2C-B (10, 15, or 20 mg. Vital signs (blood pressure and heart rate were measured at baseline 1, 2, 3, 4, and 6 hours (h. Each participant completed subjective effects using three rating scales: the visual analog scale (VAS, the Addiction Research Centre Inventory (ARCI, and the Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE at baseline, 2–3 and 6 h after self-administration (maximum effects along 6 h, and the Hallucinogenic Rating Scale (maximum effects along 6 h. Oral fluid (saliva was collected to assess 2C-B and cortisol concentrations during 24 h. Acute administration of 2C-B increased blood pressure and heart rate. Scores of scales related to euphoria increased (high, liking, and stimulated, and changes in perceptions (distances, colors, shapes, and lights and different body feelings/surrounding were produced. Mild hallucinating effects were described in five subjects. Maximum concentrations of 2C-B and cortisol were reached at 1 and 3 h after self-administration, respectively. Oral 2C-B at recreational doses induces a constellation of psychedelic/psychostimulant-like effects similar to those associated with serotonin-acting drugs.

  19. Biochemical and pharmacological studies of native and irradiated crotamine with gamma radiation of Co60

    International Nuclear Information System (INIS)

    Mitake, M.B.

    2000-01-01

    Ionizing radiation can change the molecular structure and affect the biological properties of biomolecules. This has been employed to attenuate animal toxins. Crotamine is a strongly basic polypeptide from South American rattlesnake venom, composed of 42 amino acid residues. It induces skeletal muscle spasms, leading to a spastic paralysis of hind limbs in mice. The objective was to carry out biochemical and pharmacological studies of native and irradiated crotamine with Co. Crotamine was purified from Crotalus durissus terrificus venom by Sephadex G-100 gel filtration followed by ion exchange chromatography, using a Fast performance Liquid Chromatography (FPLC) system. It was irradiated at 2 mg/ml in 0.15 m NaCl with 2.0 kGy gamma radiation emitted by a Co source. Native and irradiated crotamine were evaluated by biochemical characterization, toxic activity (LD50), and biodistribution. The native and irradiated crotamine were labeled with 29.6 MBq of I using chloramine T method and separated in a Sephadex G-50 column. Male Swiss mice (35 @ 5 g) were injected IP with 0.1 mL (2.4x10 cpm/mouse) of I native crotamine or with 0.4 mL (1.3 x 10 cpm/mouse) of I irradiated crotamine. The animals were sacrificed by ether inhalation at 0.08, 0.25, 0.5,1, 2, 3, 4, 8, 12, and 24 hours. Blood, spleen, liver, kidneys, brain, lungs, heart, and skeletal muscle were collected in order to determine radioactivity content. The results showed that gamma radiation did not change protein concentration, electrophoretic profile, or protein primary structure, although differences could be seen by spectroscopic techniques. Gamma radiation reduced crotamine toxicity, but did not eliminate bioactivity. Biodistribution studies showed that native and irradiated crotamine have hepatic metabolism and renal elimination. Native and irradiated crotamine have an affinity to skeletal muscle and did not cross the blood-brain barrier. (author)

  20. An ethno-pharmacological study of plants used for traditional medication in Tangail district, Bangladesh.

    Science.gov (United States)

    Mahmudur Rahman, A H M; Rafieian-Kopaei, Mahmoud

    2017-07-01

    In Bangladesh, folk medicinal practitioners are called "Kaviraj" and are consulted for treatment of various ailments by a large part of the rural and urban population. There are some previous studies conducted in the Tangail district of Bangladesh about medicinal plants, but there is no relevant information about this aspect in some parts of this district. To conduct an ethno-pharmacological survey among the "Kaviraj" of two upazilas (regions) in Tangail district, namely Tangail Sadar Upazila and Nagarpur Upazila, to identify the trouble-free formulations of medicinal plants for various diseases used by the folk medicine practitioners on or after other forms of medical practices. A guided field-walk survey was carried out employing a local guide and asking local people about practicing "Kaviraj"; four of the "Kaviraj" convened and after receiving permission from the "Kaviraj", interviews were conducted through focused group discussion. It was observed that the "Kaviraj" of the two upazilas used a total of 25 plants distributed into 20 families for healing of various diseases. In most of the cases, leaves were the key part of most of the plants used for treatment. Plants were mainly used for treating gastrointestinal tract disorders, fever, constipation, and diarrhea, and indigestion, loss of appetite, pain and skin disorders. "Kaviraj" also treat complicated diseases such as tuberculosis, hypertension, sexual disorders, infections, urinary problems, hepatic disorders, pneumonia, stomach stones, diabetes, swellings, debility, kidney problems, tumor, vitamin C deficiency and poisoning by using medicinal plants. For a country such as Bangladesh, and particularly the district studied, medicinal plants are essential assets and have a major role in people's health care structure. Also, appropriate research should be conducted for using these medicinal plants in possible new drug designs as well as many other pharmaceutical benefits.

  1. Increased β-haemolytic group A streptococcal M6 serotype and streptodornase B-specific cellular immune responses in Swedish narcolepsy cases.

    Science.gov (United States)

    Ambati, A; Poiret, T; Svahn, B-M; Valentini, D; Khademi, M; Kockum, I; Lima, I; Arnheim-Dahlström, L; Lamb, F; Fink, K; Meng, Q; Kumar, A; Rane, L; Olsson, T; Maeurer, M

    2015-09-01

    Type 1 narcolepsy is a neurological disorder characterized by excessive daytime sleepiness and cataplexy associated with the HLA allele DQB1*06:02. Genetic predisposition along with external triggering factors may drive autoimmune responses, ultimately leading to the selective loss of hypocretin-positive neurons. The aim of this study was to investigate potential aetiological factors in Swedish cases of postvaccination (Pandemrix) narcolepsy defined by interferon-gamma (IFNγ) production from immune cells in response to molecularly defined targets. Cellular reactivity defined by IFNγ production was examined in blood from 38 (HLA-DQB1*06:02(+) ) Pandemrix-vaccinated narcolepsy cases and 76 (23 HLA-DQB1*06:02(+) and 53 HLA-DQB1*06:02(-) ) control subjects, matched for age, sex and exposure, using a variety of different antigens: β-haemolytic group A streptococcal (GAS) antigens (M5, M6 and streptodornase B), influenza (the pandemic A/H1N1/California/7/09 NYMC X-179A and A/H1N1/California/7/09 NYMC X-181 vaccine antigens, previous Flu-A and -B vaccine targets, A/H1N1/Brisbane/59/2007, A/H1N1/Solomon Islands/3/2006, A/H3N2/Uruguay/716/2007, A/H3N2/Wisconsin/67/2005, A/H5N1/Vietnam/1203/2004 and B/Malaysia/2506/2004), noninfluenza viral targets (CMVpp65, EBNA-1 and EBNA-3) and auto-antigens (hypocretin peptide, Tribbles homolog 2 peptide cocktail and extract from rat hypothalamus tissue). IFN-γ production was significantly increased in whole blood from narcolepsy cases in response to streptococcus serotype M6 (P = 0.0065) and streptodornase B protein (P = 0.0050). T-cell recognition of M6 and streptodornase B was confirmed at the single-cell level by intracellular cytokine (IL-2, IFNγ, tumour necrosis factor-alpha and IL-17) production after stimulation with synthetic M6 or streptodornase B peptides. Significantly, higher (P = 0.02) titres of serum antistreptolysin O were observed in narcolepsy cases, compared to vaccinated controls. β-haemolytic GAS may be

  2. Narcolepsy in pediatric age – Experience of a tertiary pediatric hospital

    Directory of Open Access Journals (Sweden)

    Filipa Dias Costa

    2014-03-01

    Full Text Available Narcolepsy, a chronic disorder of the sleep–wake cycle of multifactorial etiology, is characterized by excessive daytime sleepiness, often associated with cataplexy, hypnagogic/hypnopompic hallucinations and sleep paralysis. Both early clinical suspicion and therapeutic approach are essential for promotion of cognitive development and social integration of these children. The authors present a descriptive retrospective study of a series of eight children in whom symptoms first started between 6.8 and 10.5 years of age. Diagnostic delay ranged from 4 months to 2 years. One child had H1N1 flu vaccination eight months before the clinical onset. The first multiple sleep latency test was positive in 6 of 8 cases. All cases were treated with methylphenidate, and venlafaxine was associated in 4 of them. In one case the initial therapy was exclusively behavioral. In all cases, symptomatic improvement, better school performance and social integration were achieved after therapeutic adjustment.

  3. Narcolepsy in pediatric age – Experience of a tertiary pediatric hospital

    Science.gov (United States)

    Dias Costa, Filipa; Barreto, Maria Inês; Clemente, Vanda; Vasconcelos, Mónica; Estêvão, Maria Helena; Madureira, Núria

    2014-01-01

    Narcolepsy, a chronic disorder of the sleep–wake cycle of multifactorial etiology, is characterized by excessive daytime sleepiness, often associated with cataplexy, hypnagogic/hypnopompic hallucinations and sleep paralysis. Both early clinical suspicion and therapeutic approach are essential for promotion of cognitive development and social integration of these children. The authors present a descriptive retrospective study of a series of eight children in whom symptoms first started between 6.8 and 10.5 years of age. Diagnostic delay ranged from 4 months to 2 years. One child had H1N1 flu vaccination eight months before the clinical onset. The first multiple sleep latency test was positive in 6 of 8 cases. All cases were treated with methylphenidate, and venlafaxine was associated in 4 of them. In one case the initial therapy was exclusively behavioral. In all cases, symptomatic improvement, better school performance and social integration were achieved after therapeutic adjustment. PMID:26483902

  4. Studying of the standardization principles of pharmacological activity of recombinant erythropoietin preparations

    OpenAIRE

    A. K. Yakovlev; L. A. Gayderova; N. A. Alpatova; T. N. Lobanova; E. L. Postnova; E. I. Yurchikova; T. A. Batuashvili; R. A. Volkova; V. N. Podkuiko; Yu. V. Olefir

    2016-01-01

    Analysis of the publications devoted to the structure, functions, mechanism of action of erythropoietin is given in the article. Erythropoietin preparations derived from recombinant DNA technology are a mixture of isoforms with different biological activity, which determine the biological properties pharmacological activity, pharmacokinetics, efficacy and safety of medicinal product. Erythropoietin preparations derived by using recombinant DNA technology are a mixture of isoforms with differe...

  5. Pharmacological modulation of the BOLD response: a study of acetazolamide and glyceryl trinitrate in humans

    DEFF Research Database (Denmark)

    Asghar, Mohammed Sohail; Hansen, Adam E; Pedersen, Simon

    2011-01-01

    To examine the effect of acetazolamide, known to increase cerebral blood flow (CBF) and glyceryl trinitrate (GTN), known to increase cerebral blood volume (CBV) on the blood oxygenation level-dependent (BOLD) response in humans using 3 T magnetic resonance imaging (MRI), and to evaluate how...... pharmacological agents may modulate cerebral hemodynamic and thereby possibly the BOLD signal....

  6. Synthesis, Pharmacological Profile and Docking Studies of New Sulfonamides Designed as Phosphodiesterase-4 Inhibitors.

    Directory of Open Access Journals (Sweden)

    Isabelle Karine da Costa Nunes

    Full Text Available Prior investigations showed that increased levels of cyclic AMP down-regulate lung inflammatory changes, stimulating the interest in phosphodiesterase (PDE4 as therapeutic target. Here, we described the synthesis, pharmacological profile and docking properties of a novel sulfonamide series (5 and 6a-k designed as PDE4 inhibitors. Compounds were screened for their selectivity against the four isoforms of human PDE4 using an IMAP fluorescence polarized protocol. The effect on allergen- or LPS-induced lung inflammation and airway hyper-reactivity (AHR was studied in A/J mice, while the xylazine/ketamine-induced anesthesia test was employed as a behavioral correlate of emesis in rodents. As compared to rolipram, the most promising screened compound, 6a (LASSBio-448 presented a better inhibitory index concerning PDE4D/PDE4A or PDE4D/PDE4B. Accordingly, docking analyses of the putative interactions of LASSBio-448 revealed similar poses in the active site of PDE4A and PDE4C, but slight unlike orientations in PDE4B and PDE4D. LASSBio-448 (100 mg/kg, oral, 1 h before provocation, inhibited allergen-induced eosinophil accumulation in BAL fluid and lung tissue samples. Under an interventional approach, LASSBio-448 reversed ongoing lung eosinophilic infiltration, mucus exacerbation, peribronchiolar fibrosis and AHR by allergen provocation, in a mechanism clearly associated with blockade of pro-inflammatory mediators such as IL-4, IL-5, IL-13 and eotaxin-2. LASSBio-448 (2.5 and 10 mg/kg also prevented inflammation and AHR induced by LPS. Finally, the sulfonamide derivative was shown to be less pro-emetic than rolipram and cilomilast in the assay employed. These findings suggest that LASSBio-448 is a new PDE4 inhibitor with marked potential to prevent and reverse pivotal pathological features of diseases characterized by lung inflammation, such as asthma.

  7. Pharmacologic studies on ET-26 hydrochloride in a rat model of lipopolysaccharide-induced sepsis.

    Science.gov (United States)

    Wang, Bin; Jiang, Junli; Yang, Jun; Chen, Jun; Zhu, Zhaoqiong; Liu, Jin; Zhang, Wensheng

    2017-11-15

    ET-26 hydrochloride (ET-26 HCl) is a promising sedation-hypnotic compound with stable hemodynamic features that elicits virtually no adrenocortical suppression. However, whether it preserves better pharmacologic characteristics in a rat model of sepsis is not known. This study compared the survival rate, levels of corticosterone and pro-inflammatory cytokines, and histologic injury in the lungs and kidneys of rats suffering from sepsis treated with ET-26 HCl, etomidate, or normal saline (NS). Rats were given lipopolysaccharide (1mg/kg body weight, i.v.) to establish a sepsis model. Thirty minutes after lipopolysaccharide administration, ET-26 HCl, etomidate or NS were given as a bolus injection at equivalent doses. Plasma levels of corticosterone, interleukin-1β, interleukin-6, interleukin-10, and tumor necrosis factor-α were measured 1, 2, 4, 6 and 24h after administration. Histologic injury was observed at the time of death or 24h after drug administration. The survival rate for rats in the etomidate, ET-26 HCl and NS groups was 40%, 90% and 90%, respectively. Corticosterone concentrations in the etomidate group were lower than those in the other groups 1h after administration of hypnotic compounds. Concentrations of pro-inflammatory cytokines in the ET-26 HCl group and NS group were not significantly different, but were significantly lower than those in the etomidate group. The injury scores of kidneys and lungs in the etomidate group were higher than those in ET-26 HCl and NS groups. ET-26 HCl showed virtually no suppression of corticosterone synthesis, lower concentrations of pro-inflammatory cytokines, higher survival rate, and less organ injury in rats suffering from sepsis compared with the etomidate group. It may be safer to induce anesthesia using ET-26 HCl, rather than etomidate, in patients suffering from sepsis. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Pharmacological studies of dopamine transporter imaging agent 125/131I-β-CIT

    International Nuclear Information System (INIS)

    Ding Shiyu; Zhou Xiang; Chen Zhengping; Wu Chunying; Lin Yansong; Ji Shuren; Lu Chunxiong; Fang Ping; Tang Jun; Wang Feng

    2001-01-01

    To prepare 125/131 I-β-CIT (2β-carbomethoxy-3β-(4-iodophenyl) tropane) as an imaging agent for dopamine transporter (DAT), the labelling method from tributylstannyl precursor with peracetic acid has been reported. The radiochemical purity (RCP) of the labelled compound was over 95% determined by HPLC and TLC. The stability, partition coefficients were also determined. The pharmacological studies of the imaging agent were performed in rats, mice, rabbits and normal monkey. The ligand showed preferable uptake in brain (1.9% ID/organ in rats and 4.5% ID/organ in mice at 5 min). The ratios of striatum/cerebellum, hippocampus/cerebellum and cortex/cerebellum were 28.9, 3.97 and 4.75 at 6 h in rats, and 8.52, 2.99 and 3.06 at 6 h in mice, respectively. In monkey brain imaging the ratios of striatum/frontal cortex (ST/FC) and striatum/occipital cortex (ST/OC) were 5.14 and 5.97 at 4h, respectively. All of above showed the high affinity of the ligand to DAT. The compound was primarily metabolized in liver because the hepatic uptake was much higher than other organs (75.4% ID/organ at 18h). The half-life of blood elimination was 5 min. The dose received by mice was 2500 times as high as that received by human in the test of undue toxicity, which evaluated the safety of the agent. All the results suggest that β-CIT can be used as a potential DAT imaging agent

  9. Obtaining of labelled 'Co-101' preparation and study of its pharmacological kinetics

    International Nuclear Information System (INIS)

    Khujaev, S.; Sultanov, A.; Ganiev, D.A.; Tashmetov, M.; Shermatova, L.; Aliev, Kh.U.; Nazarov, E.A.

    2004-01-01

    Full text: One of the most actual problems for the last years is the problem of studying physiological role of microelements in animate nature and their use in biological and medical practice. For some time coordination compounds of microelements are used more bots as less toxic and biologically active medical products. Among numerous microelements favorably influencing a number of physiological processes in an organism, special place takes Cobalt. This element differs from others in that it is part of vitamin B 12 (4,5%). Microorganisms for biosynthesis of B 12 in an organism use Cobalt. At lack of vitamin B 12 in an organism, preparations and concentrates of the vitamin B 12 may be used. One of such preparations is the new preparation 'Co-101', synthesized in Tashkent Pharmaceutical Institute. The given preparation is coordination compound of Cobalt with Inozin. In research of the new preparation Co-101', the most modern method - radio indication (a method of labeled compounds) is used. For labeling of the preparation 57 Co and 58 Co radioisotopes are used. Radioisotopes are obtaining in a nuclear reactor ( 58 Co) and on cyclotron ( 57 Co). From the point of radioactive safety, the more favorable appeared to be 57 Co. Two variants of introduction of radioactive Cobalt in chemical structure of a preparation are of considered: 1-by exchange of an isotope, 2- by introduce of radioisotopes Cobalt into asparagine Cobalt at stage of it synthesis, which is an intermediate product during synthesis of preparation 'Co-101'. The second method had been yield with output compound of up 80% and higher. Received labeling preparation has been used for investigation of his own pharmacological kinetics

  10. Environmental toxins and risk of narcolepsy among people with HLA DQB1*0602

    Science.gov (United States)

    Ton, Thanh G.N.; Longstreth, WT; Koepsell, Thomas D.

    2010-01-01

    One etiologic model for narcolepsy suggests that some environmental toxin selectively and irreversibly destroys hypocretin-producing cells in individuals with human leukocyte antigen (HLA) DQB1*0602. Between 2001-2005, the authors conducted a population-based case-control study in King County, Washington to examine narcolepsy risk in relation to toxins found in jobs, hobbies and other non-vocational activities. Sixty-seven cases and 95 controls were enrolled; all were between ages 18-50 and positive for HLA DQB1*0602. All were administered in-person interviews about jobs, hobbies or other non-vocational activities before age 21. All analyses were adjusted for African American race and income. Risk increased significantly for jobs involving heavy metals (odds ratio [OR]=4.7; 95% confidence interval [CI]: 1.5, 14.5) and for highest levels of exposure to woodwork (OR: 3.0; 95% CI: 1.0, 8.9), fertilizer (OR=3.1; 95% CI: 1.1, 9.1), and bug or weed killer (OR=4.5; 95% CI: 1.5, 13.4). Associations were of borderline significance for activities involving ceramics, pesticides, and painting projects. Significant dose-response relationships were evident for jobs involving metals (p<0.03), paints (p<0.03), and bug or weed killer (p<0.02). Additional studies are needed to replicate these findings and continue the search for specific toxins that could damage hypocretin neurons in genetically susceptible people. PMID:20519130

  11. Medicinal plants in Brazil: Pharmacological studies, drug discovery, challenges and perspectives.

    Science.gov (United States)

    Dutra, Rafael C; Campos, Maria M; Santos, Adair R S; Calixto, João B

    2016-10-01

    This review article focuses on pre-clinical and clinical studies with some selected Brazilian medicinal plants in different areas of interest, conducted by research groups in Brazil and abroad. It also highlights the Brazilian market of herbal products and the efforts of Brazilian scientists to develop new phytomedicines. This review is divided into three sections. The section I describes the Brazilian large biodiversity and some attempts of Brazilian scientists to assess the pharmacological profile of most plant extracts or isolated active principles. Of note, Brazilian scientists have made a great effort to study the Brazilian biodiversity, especially among the higher plants. In fact, more than 10,000 papers were published on plants in international scientific journals between 2011 and 2013. This first part also discussed the main efforts to develop new medicines from plants, highlighting the Brazilian phytomedicines market. Despite the large Brazilian biodiversity, notably with the higher plants, which comprise over 45,000 species (20-22% of the total worldwide), and the substantial number of scientific publications on medicinal plants, only one phytomedicine is found in the top 20 market products. Indeed, this market is still only worth about 261 million American dollars. This represents less than 5% of the global Brazilian medicine market. The section II of this review focus on the use of Brazilian plant extract and/or active principles for some selected diseases, namely: central nervous systems disorders, pain, immune response and inflammation, respiratory diseases, gastrointestinal tract and metabolic diseases. Finally, section III discusses in more details some selected Brazilian medicinal plants including: Cordia verbenacea, Euphorbia tirucalli, Mandevilla velutina, Phyllanthus spp., Euterpe oleracea, Vitis labrusca, Hypericum caprifoliatum and Hypericum polyanthemum, Maytenus ilicifolia, Protium kleinii and Protium heptaphylium and Trichilia catigua. Most

  12. Prevalence of eating disorders and eating attacks in narcolepsy

    Directory of Open Access Journals (Sweden)

    Norbert Dahmen

    2008-03-01

    Full Text Available Norbert Dahmen, Julia Becht, Alice Engel, Monika Thommes, Peter TonnPsychiatry Department, University of Mainz, GermanyAbstract: Narcoleptic patients suffer frequently from obesity and type II diabetes. Most patients show a deficit in the energy balance regulating orexinergic system. Nevertheless, it is not known, why narcoleptic patients tend to be obese. We examined 116 narcoleptic patients and 80 controls with the structured interview for anorectic and bulimic eating disorders (SIAB to test the hypothesis that typical or atypical eating attacks or eating disorders may be more frequent in narcoleptic patients. No difference in the current prevalence of eating disorders bulimia nervosa, binge eating disorder, or anorexia nervosa was found, nor was the frequency of eating attacks higher in the narcolepsy group. We conclude that present eating disorders and eating attacks as defined in DSM IV are not the reason for the observed differences in body composition. Additional factors, such as basal metabolic rates and lifestyle factors need to be considered.Keywords: narcolepsy, eating disorder, SIAB, bulimia, anorexia, eating attack

  13. Facing emotions in narcolepsy with cataplexy: haemodynamic and behavioural responses during emotional stimulation.

    Science.gov (United States)

    de Zambotti, Massimiliano; Pizza, Fabio; Covassin, Naima; Vandi, Stefano; Cellini, Nicola; Stegagno, Luciano; Plazzi, Giuseppe

    2014-08-01

    Narcolepsy with cataplexy is a complex sleep disorder that affects the modulation of emotions: cataplexy, the key symptom of narcolepsy, is indeed strongly linked with emotions that usually trigger the episodes. Our study aimed to investigate haemodynamic and behavioural responses during emotional stimulation in narco-cataplexy. Twelve adult drug-naive narcoleptic patients (five males; age: 33.3 ± 9.4 years) and 12 healthy controls (five males; age: 30.9 ± 9.5 years) were exposed to emotional stimuli (pleasant, unpleasant and neutral pictures). Heart rate, arterial blood pressure and mean cerebral blood flow velocity of the middle cerebral arteries were continuously recorded using photoplethysmography and Doppler ultrasound. Ratings of valence and arousal and coping strategies were scored by the Self-Assessment Manikin and by questionnaires, respectively. Narcoleptic patients' haemodynamic responses to pictures overlapped with the data obtained from controls: decrease of heart rate and increase of mean cerebral blood flow velocity regardless of pictures' content, increase of systolic blood pressure during the pleasant condition, and relative reduction of heart rate during pleasant and unpleasant conditions. However, when compared with controls, narcoleptic patients reported lower arousal scores during the pleasant and neutral stimulation, and lower valence scores during the pleasant condition, respectively, and also a lower score at the 'focus on and venting of emotions' dimensions of coping. Our results suggested that adult narcoleptic patients, compared with healthy controls, inhibited their emotion-expressive behaviour to emotional stimulation, and that may be related to the development of adaptive cognitive strategies to face emotions avoiding cataplexy. © 2014 European Sleep Research Society.

  14. [Pharmacological treatment].

    Science.gov (United States)

    Arriola Manchola, Enrique; Álaba Trueba, Javier

    2016-06-01

    Alzheimer's disease (AD) is a chronic degenerative and inflammatory process leading to synapticdysfunction and neuronal death. A review about the pharmacological treatment alternatives is made: acetylcholinesterase inhibitors (AChEI), a nutritional supplement (Souvenaid) and Ginkgo biloba. A special emphasis on Ginkgo biloba due to the controversy about its use and the approval by the European Medicines Agency is made. Copyright © 2016 Sociedad Española de Geriatría y Gerontología. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Thromboprophylaxis using combined intermittent pneumatic compression and pharmacologic prophylaxis versus pharmacologic prophylaxis alone in critically ill patients: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Arabi, Yaseen M; Alsolamy, Sami; Al-Dawood, Abdulaziz; Al-Omari, Awad; Al-Hameed, Fahad; Burns, Karen E A; Almaani, Mohammed; Lababidi, Hani; Al Bshabshe, Ali; Mehta, Sangeeta; Al-Aithan, Abdulsalam M; Mandourah, Yasser; Almekhlafi, Ghaleb; Finfer, Simon; Abdukahil, Sheryl Ann I; Afesh, Lara Y; Dbsawy, Maamoun; Sadat, Musharaf

    2016-08-03

    Venous thromboembolism (VTE) remains a common problem in critically ill patients. Pharmacologic prophylaxis is currently the standard of care based on high-level evidence from randomized controlled trials. However, limited evidence exists regarding the effectiveness of intermittent pneumatic compression (IPC) devices. The Pneumatic compREssion for preventing VENous Thromboembolism (PREVENT trial) aims to determine whether the adjunct use of IPC with pharmacologic prophylaxis compared to pharmacologic prophylaxis alone in critically ill patients reduces the risk of VTE. The PREVENT trial is a multicenter randomized controlled trial, which will recruit 2000 critically ill patients from over 20 hospitals in three countries. The primary outcome is the incidence of proximal lower extremity deep vein thrombosis (DVT) within 28 days after randomization. Radiologists interpreting the scans are blinded to intervention allocation, whereas the patients and caregivers are unblinded. The trial has 80 % power to detect a 3 % absolute risk reduction in proximal DVT from 7 to 4 %. The first patient was enrolled in July 2014. As of May 2015, a total of 650 patients have been enrolled from 13 centers in Saudi Arabia, Canada and Australia. The first interim analysis is anticipated in July 2016. We expect to complete recruitment by 2018. Clinicaltrials.gov: NCT02040103 (registered on 3 November 2013). Current controlled trials: ISRCTN44653506 (registered on 30 October 2013).

  16. Systems Pharmacology-Based Approach of Connecting Disease Genes in Genome-Wide Association Studies with Traditional Chinese Medicine.

    Science.gov (United States)

    Kim, Jihye; Yoo, Minjae; Shin, Jimin; Kim, Hyunmin; Kang, Jaewoo; Tan, Aik Choon

    2018-01-01

    Traditional Chinese medicine (TCM) originated in ancient China has been practiced over thousands of years for treating various symptoms and diseases. However, the molecular mechanisms of TCM in treating these diseases remain unknown. In this study, we employ a systems pharmacology-based approach for connecting GWAS diseases with TCM for potential drug repurposing and repositioning. We studied 102 TCM components and their target genes by analyzing microarray gene expression experiments. We constructed disease-gene networks from 2558 GWAS studies. We applied a systems pharmacology approach to prioritize disease-target genes. Using this bioinformatics approach, we analyzed 14,713 GWAS disease-TCM-target gene pairs and identified 115 disease-gene pairs with q value < 0.2. We validated several of these GWAS disease-TCM-target gene pairs with literature evidence, demonstrating that this computational approach could reveal novel indications for TCM. We also develop TCM-Disease web application to facilitate the traditional Chinese medicine drug repurposing efforts. Systems pharmacology is a promising approach for connecting GWAS diseases with TCM for potential drug repurposing and repositioning. The computational approaches described in this study could be easily expandable to other disease-gene network analysis.

  17. Studies of the biotransformation and pharmacology of ketamine and its metabolites

    International Nuclear Information System (INIS)

    Leung, Y.

    1986-01-01

    The first part of the research is concerned with the synthesis, resolution and metabolism of norketamine, the primary metabolite of ketamine. Incubations of racemic norketamine, individual enantiomers of norketamine and the pseudoracemates in rat liver microsomes revealed stereoselectivity and enantiomeric interactions during the metabolism of norketamine. The second part of the research describes the synthesis of 6-OH-norketamine, the major secondary metabolite of ketamine, and reports on its pharmacological activity and cerebral distribution in the rat. Primary deuterium isotope effects associated with the metabolism and pharmacological activity of ketamine-N-CD 3 were examined in the third part of this research. The last part of the research deals with the effect of diazepam on the metabolic transformation of ketamine to norketamine in the rat. The fractions of ketamine metabolized to norketamine were found not to be different in the presence or the absence of diazepam

  18. Pharmacologic study of calcium influx pathways in rabbit aortic smooth muscle

    International Nuclear Information System (INIS)

    Lukeman, D.S.

    1987-01-01

    Functional characteristics and pharmacologic domains of receptor-operated and potential-sensitive calcium (Ca 2+ ) channels (ROCs and PSCs, respectively) were derived via measurements of 45 Ca 2+ influx (M/sup Ca/) during activation by the neurotransmitters norepinephrine (NE), histamine (HS), and serotonin (5-HT) and by elevated extracellular potassium (K + ) in the individual or combined presence of organic Ca 2+ channel antagonists (CAts), calmodulin antagonists (Calm-ants), lanthanum (La 3+ ), and agents that increase intracellular levels of cyclic AMP

  19. 12. Narcolepsy in a Pre-teen Girl a Case Report

    African Journals Online (AJOL)

    user

    best of our knowledge, this is the first documented case of ... Objective: To familiarize the health workers about narcolepsy and ... microscopy, HIV test, all came out normal. She .... detailed subjective and collateral history, the diagnosis of ...

  20. Levothyroxine Improves Subjective Sleepiness in a Euthyroid Patient with Narcolepsy without Cataplexy

    Science.gov (United States)

    Sobol, Danielle L.; Spector, Andrew R.

    2014-01-01

    Objective: We discuss the use of levothyroxine for excessive daytime sleepiness (EDS) and prolonged nocturnal sleep time in a euthyroid patient with narcolepsy. Methods: After failure of first-line narcolepsy treatments, a 48-year-old female began levothyroxine (25 mcg/day). After 12 weeks of treatment, the patient was evaluated for improvement in total sleep time and subjective daytime sleepiness assessed by Epworth Sleepiness Scale (ESS). Results: At baseline, ESS score was 16 and total sleep time averaged 16 h/day. After 12 weeks, ESS was 13 and reported total sleep time was 13 h/day. Conclusions: Levothyroxine improved EDS and total sleep time in a euthyroid patient with narcolepsy without cataplexy after 12 weeks without side effects. Citation: Sobol DL, Spector AR. Levothyroxine improves subjective sleepiness in a euthyroid patient with narcolepsy without cataplexy. J Clin Sleep Med 2014;10(11):1231-1232. PMID:25325591

  1. Narcolepsy Patient Presenting as Drop Attack without Emotional Triggering and Subjective Sleepiness

    Directory of Open Access Journals (Sweden)

    Joon Hyun Baek

    2016-12-01

    Full Text Available Narcolepsy type I is characterized by excessive daytime sleepiness (EDS, cataplexy, sleep paralysis, hypnagogic hallucination, and fragmented night-time sleep. Although diagnosis is based on clinical history, it needs to be confirmed by nocturnal polysomnography, followed by a daytime multiple sleep latency test (MSLT. However, EDS, which is the central symptom of the narcolepsy, is unspecific and there could be a disparity between subjective daytime sleepiness and objective daytime sleepiness measured by MSLT. Also, cataplexy, which is the exclusive symptom of narcolepsy, has a wide phenotypical variability and is triggered by a range of stimuli, even without definite identifiable emotional trigger. We report an unusual narcolepsy patient with spontaneous cataplexy, without an identifiable trigger and subjective daytime sleepiness.

  2. Case report of narcolepsy in a six-year-old child initially misdiagnosed as atypical epilepsy.

    Science.gov (United States)

    Zhou, Jinquan; Zhang, Xi; Dong, Zaiwen

    2014-08-01

    This report describes a case of first-onset narcolepsy in a six-year-old female that was misdiagnosed as atypical epilepsy and other diagnoses at eight different hospitals over a period of 10 months before the correct diagnosis was made. The diagnosis of narcolepsy is more difficult in children because very few of them experience all four cardinal symptoms of narcolepsy - paroxysmal sleep, cataplexy, hypnagogic hallucination, and sleep paralysis - and they often have a more prolonged onset and diverse symptoms. To decrease the time lag between initial presentation and accurate diagnosis, we recommend that in all cases in which children report excessive sleep of unknown etiology - regardless of the associated symptoms - that sleep monitoring and sleep latency tests be conducted to rule out the possibility of narcolepsy. The case highlights the wide variety of presentations of uncommon psychiatric conditions, particularly in children, and the need for clinicians to be aware of the atypical presentations of these conditions when collecting medical histories.

  3. The preclinical pharmacological study of dopamine transporter imaging agnet (99mTc)trodat-1

    International Nuclear Information System (INIS)

    Fang, P.; Wan, W.; Wu, C.; Liu, Z.; Wang, T.; Chen, S.; Chen, Z.; Zhou, X.

    2000-01-01

    To develop 99m Tc labeled dopamine transporter (DAT) imaging agent 99m Tc-TRODAT-1 (TRODAT-1:2 β-[[N,N'-bis(2-mercaptoethyl)ethylenediamino]methl], 3 β-(4-chlorophenyl)tropane], used in SPECT, for evaluating changes of DAT in patients with Parkinson's disease(PD). Using Stannous as reducing agent, and the present of Na-glucoheptonate, 99m Tc-TRODAT-1 was successfully prepared. Preclinical pharmacological studies have been performed in rats. C57BL mice, normal and PD model monkeys and volunteers. Radiochemical purity of 99m Tc-TRODAT-1 was over 90%, and stable for 6 hours. The specific uptake in striatum was significantly diminished from 3.45 to 0.12 at 3 h by pretreated rats with a dose of competing DAT ligand β-CIT (1 mg/kg). Autoradiographic images in C57BL mice shows that the specific uptake has a good linear relationship with the quantity of neural-toxin (MPTP) which was given to the animals (r=0.9792). Images of normal monkey's brain exhibited excellent localization in basal ganglia region, where dopamine neurons were concentrated, and the ratios of ST/CB were 1.56-2.0. In hemiparkinsonian model monkeys, the ratio of normal ST/CB and lesioned ST/CB were 1.56 and 0.94, respectively. Brain image studies in volunteers indicated that uptake and retention in the basal ganglia, the ratio of normal striatal to lesioned one was 1.15 measured by SPECT imaging at 2 h. The result of images was consistent with the clinical symptoms. Above-mentioned results showed that 99m Tc-TRODAT-1 can be accumulated in the striatal area, where DAT are concentrated, high quality images were obtained. It is suggested that 99m Tc-TRODAT-1 might turn to be a safe and effective tracer for monitoring the change in DAT associated with various neurodegenerative diseases

  4. Biochemical and pharmacological studies of native and irradiated crotamine with gamma radiation of 60Co

    International Nuclear Information System (INIS)

    Mitake, Malvina Boni

    2000-01-01

    Ionizing radiation can change the molecular structure and affect the biological properties of biomolecules. This has been employed to attenuate animal toxins. Crotamine is a strongly basic polypeptide from the South American rattlesnake venom, composed of 42 amino acid residues. It induces skeletal muscle spasms leading to a spastic paralysis of hind limbs in mice. The objective of this thesis was carry out biochemical and pharmacological studies of native and irradiated crotamine with 60 Co. Crotamine was purified from Crotalus durissus terrificus venom by Sephadex G-100 gel filtration followed by ion exchange chromatography, using a Fast Performance Liquid Chromatography (FPLC) system. It was irradiated at 2 mg/ml in 0.15 M Na Cl with 2.0 kGy gamma radiation emitted by a 60 Co source. The native and irradiated crotamine were evaluated by biochemical characterization, toxic activity (LD 50 and biodistribution. The native and irradiated crotamine were labelled with 29.6 MBq of 125 I using chloramine T method, and separated in a Sephadex G-50 column. Male Swiss mice (35± 5 g), were injected i.p. with o.1 mL (2.4 x 10 6 cpm/mouse) of 125 I native crotamine or with 0.4 mL (1.3 x 10 6 cpm/mouse) of 125 I irradiated crotamine. At 0.08; 0.25; 0.5; 1; 2; 4; 8; 12 and 24 hours the animal were killed by ether inhalation. Blood, spleen, liver, kidneys, brain, lungs, heart, and skeletal muscle were collected in order to determine radioactivity content. The results showed that gamma radiation did not change the protein concentration, the electroforetic profile or the primary structure of the protein, although differences were shown by spectroscopic techniques. The gamma radiation diminished the toxicity of crotamine, but it did not abolish bioactivity. Biodistribution studies showed that native and irradiated crotamine have hepatic metabolism and renal elimination. The native and irradiated crotamine have affinity by skeletal muscle and they did not pass the blood - brain

  5. Pain experiences and non-pharmacological strategies for pain management after tonsillectomy: a qualitative interview study of children and parents.

    Science.gov (United States)

    Idvall, Ewa; Holm, Charlotta; Runeson, Ingrid

    2005-09-01

    Tonsillectomy is one of the most common paediatric surgical procedures. This study aimed to investigate children's experience of pain and the nonpharmacological strategies that they used to manage pain after tonsillectomy. A further aim was to investigate parental views on these same phenomena. Six children (aged seven to 18 years) and their parents (four mothers and two fathers) were interviewed separately on the day after tonsillectomy. The data were analysed using a qualitative approach. Pain experiences were divided into the categories of physiological pain and psychological pain. Children rated their 'worst pain' during the past 24 hours between 6 and 10 (visual analogue scale, 0-10). The non-pharmacological strategies used most frequently to manage pain were thermal regulation (physical method) and distraction (cognitive-behavioural method) according to the framework used. Specific non-pharmacological strategies for pain management relative to different surgical procedures need to be considered.

  6. Risk of narcolepsy associated with inactivated adjuvanted (AS03 A/H1N1 (2009 pandemic influenza vaccine in Quebec.

    Directory of Open Access Journals (Sweden)

    Jacques Montplaisir

    Full Text Available An association between an adjuvanted (AS03 A/H1N1 pandemic vaccine and narcolepsy has been reported in Europe.To assess narcolepsy risk following administration of a similar vaccine in Quebec.Retrospective population-based study.Neurologists and lung specialists in the province were invited to report narcolepsy cases to a single reference centre.Patients were interviewed by two sleep experts and standard diagnostic tests were performed. Immunization status was verified in the provincial pandemic influenza vaccination registry.Confirmed narcolepsy with or without cataplexy with onset of excessive daytime sleepiness between January 1st, 2009, and December 31st, 2010. Relative risks (RRs were calculated using a Poisson model in a cohort analysis, by a self-controlled case series (SCCS and a case-control method.A total of 24 cases were included and overall incidence rate was 1.5 per million person-years. A cluster of 7 cases was observed among vaccinated persons in the winter 2009-2010. In the primary cohort analysis, 16-week post-vaccination RR was 4.32 (95% CI: 1.50-11.12. RR was 2.07 (0.70-6.17 in the SCCS, and 1.48 (0.37-7.03 using the case-control method. Estimates were lower when observation was restricted to the period of pandemic influenza circulation, and tended to be higher in persons <20 years old and for cataplexy cases.Results are compatible with an excess risk of approximately one case per million vaccine doses, mainly in persons less than 20 years of age. However, a confounding effect of the influenza infection cannot be ruled out.

  7. A Network-Based Pharmacology Study of the Herb-Induced Liver Injury Potential of Traditional Hepatoprotective Chinese Herbal Medicines.

    Science.gov (United States)

    Hong, Ming; Li, Sha; Tan, Hor Yue; Cheung, Fan; Wang, Ning; Huang, Jihan; Feng, Yibin

    2017-04-14

    Herbal medicines are widely used for treating liver diseases and generally regarded as safe due to their extensive use in Traditional Chinese Medicine practice for thousands of years. However, in recent years, there have been increased concerns regarding the long-term risk of Herb-Induced Liver Injury (HILI) in patients with liver dysfunction. Herein, two representative Chinese herbal medicines: one-Xiao-Chai-Hu-Tang (XCHT)-a composite formula, and the other- Radix Polygoni Multiflori (Heshouwu) -a single herb, were analyzed by network pharmacology study. Based on the network pharmacology framework, we exploited the potential HILI effects of XCHT and Heshouwu by predicting the molecular mechanisms of HILI and identified the potential hepatotoxic ingredients in XCHT and Heshouwu . According to our network results, kaempferol and thymol in XCHT and rhein in Heshouwu exhibit the largest number of liver injury target connections, whereby CASP3, PPARG and MCL1 may be potential liver injury targets for these herbal medicines. This network pharmacology assay might serve as a useful tool to explore the underlying molecular mechanism of HILI. Based on the theoretical predictions, further experimental verification should be performed to validate the accuracy of the predicted interactions between herbal ingredients and protein targets in the future.

  8. Biostructural and pharmacological studies of bicyclic analogues of the 3-isoxazolol glutamate receptor agonist ibotenic acid

    DEFF Research Database (Denmark)

    Frydenvang, Karla Andrea; Pickering, Darryl S; Greenwood, Jeremy R

    2010-01-01

    We describe an improved synthesis and detailed pharmacological characterization of the conformationally restricted analogue of the naturally occurring nonselective glutamate receptor agonist ibotenic acid (RS)-3-hydroxy-4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine-7-carboxylic acid (7-HPCA, 5......) at AMPA receptor subtypes. Compound 5 was shown to be a subtype-discriminating agonist at AMPA receptors with higher binding affinity and functional potency at GluA1/2 compared to GluA3/4, unlike the isomeric analogue (RS)-3-hydroxy-4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine-5-carboxylic acid (5-HPCA, 4...

  9. Pseudotumor cerebri syndrome in a patient with narcolepsy type 1.

    Science.gov (United States)

    Rossor, Thomas; Lim, Ming; VanDenEshof, Kirandeep; Gringras, Paul

    2018-01-01

    Type 1 narcolepsy (NT1) is a chronic primary disorder of hypersomnolence characterized by excessive daytime sleepiness, cataplexy, sleep paralysis, hypnagogic hallucinations and disrupted nocturnal sleep. NT1 is linked to hypothalamic hypocretin deficiency, strongly associated with Human Leukocyte Antigen (HLA) marker DQB1*06:02 and of probable autoimmune origin. NT1 is usually associated with increased rates of overweight and obesity, and sometimes with increases in overnight blood pressure and increased rates of hypoventilation with raised CO 2 levels overnight. Many of these are predisposing factors for pseudotumor cerebri syndrome (PTCS). We present a case of a young girl with both NT1 and PTCS that responded well to treatment with acetazolamide after early identification, with improvement of headache and resolution of hypoventilation. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  10. Pharmacological analysis of paregoric elixir and its constituents: in vitro and in vivo studies.

    Science.gov (United States)

    Andrade, Edinéia Lemos; Ferreira, Juliano; Santos, Adair R S; Calixto, João B

    2007-11-01

    Paregoric elixir is a phytomedicinal product which is used widely as an analgesic, antispasmodic and antidiarrheal agent. Here, we investigated the pharmacological actions and some of the mechanisms of action of paregoric elixir and compared its action with some of its components, the alkaloids morphine and papaverine. The paregoric elixir given orally to mice did not present relevant toxic effects, even when administered in doses up to 2000-fold higher than those used clinically. However, it showed an antinociceptive action that was more potent, but less efficacious, than morphine. In contrast to morphine, its effect was not dose-dependent and not reversed by the non-selective opioid antagonist naloxone. Moreover, paregoric elixir produced tolerance, but did not cause cross-tolerance, with the antinociceptive actions of morphine. When assessed in the gastrointestinal motility in vivo, paregoric elixir elicited graduated reduction of gastrointestinal transit. Finally, like morphine and papaverine, paregoric elixir concentration-dependently inhibited electrically-induced contraction of the guinea pig isolated ileum. In vivo and in vitro gastrointestinal actions of paregoric elixir were not reversed by naloxone. Collectively, the present findings lead us to suggest that the pharmacological actions produced by paregoric elixir are probably due to a synergic action of its constituents.

  11. Pharmacological/dynamic rehabilitative behavioural therapy for premature ejaculation: Results of a pilot study

    Directory of Open Access Journals (Sweden)

    Franco Mantovani

    2017-06-01

    Full Text Available Objectives: Premature ejaculation (PE is a sexual disorder characterised by excessive rapidity of orgasm. It is defined as either primary (60%, present since the onset of sexual activity, or secondary (40%, manifesting later in life. To date, dapoxetine is the only preparation approved for the on-demand treatment of PE. However, side effects, costs associated with the treatment of chronic PE, drug dependence and its variable effectiveness leads to a not insignificant drop-out rate. Dynamic rehabilitative/behavioural therapy may be a viable therapeutic option, working alongside pharmacological treatment, as long as the participation and involvement of both the individual and the couple is optimal. Materials and methods: 18 patients were enrolled, aged between 25 and 55 (mean: 40, all with primary PE, free of comorbidities and with their partners involved. Six patients were prescribed 30 mg dapoxetine two hours before sexual relations for 3 months (group A; 6 patients began the dynamic rehabilitative treatment (group B; 6 other couples were assigned to pharmacological treatment in association with dynamic rehabilitative behavioural treatment for 3 months (group C. Division of subjects was carried out by simple randomisation, excluding patients with a short frenulum, phimosis, ED, chronic prostatitis or experiencing results from previous treatment. Results: Outcomes of treatment were evaluated at the end of the 3 months of treatment and 3 months after discontinuing treatment. In Group A 75% of patients were cured at 3 months and 25% at 6 months. In Group B 25% patients were cured at 3 months and 25% at 6 months. In Group C 75% of patients were cured 3 months and 50% at 6 months. "Cured" means a Premature Ejaculation Diagnostic Tool (PEDT score reduced from an average of 12 to an average of 6 and Intravaginal Ejaculation Latency Time (IELT values from < 1 to > 6 minutes. Conclusions: the integration of pharmacological treatment with dynamic

  12. Thermodynamic study of three pharmacologically significant drugs: Density, viscosity, and refractive index measurements at different temperatures

    International Nuclear Information System (INIS)

    Iqbal, Muhammad Javed; Chaudhry, Mansoora Ahmed

    2009-01-01

    Measurements of density, viscosity, and refractive index of three pharmacologically significant drugs, i.e. diclofenac sodium, cetrizine, and doxycycline have been carried in aqueous medium at T = (293.15 to 313.15) K. An automated vibrating-tube densimeter, viscometer, and refractometer are used in a concentration range from (7.5) . 10 -3 to 25 . 10 -3 ) mol . kg -1 . The precise density results are used to evaluate the apparent molar volume, partial molar volume, thermal expansion coefficient, partial molar expansivity, and the Hepler's constant. Viscosity results are used to calculate the Jones-Dole viscosity B-coefficient, free energy of activation of the solute and solvent, activation enthalpy, and activation entropy. The molar refractive indices of the drug solutions can be employed to calculate molar refraction. It is inferred from these results that the above mentioned drugs act as structure-making compounds due to hydrophobic hydration of the molecules in the drugs

  13. Studies on the pharmacological action of cactus: identification of its anti-inflammatory effect.

    Science.gov (United States)

    Park, E H; Kahng, J H; Paek, E A

    1998-02-01

    The ethanol extracts of Opuntia ficus-indica fructus (EEOF) and Opuntia ficus-indica stem (EEOS) were prepared and used to evaluate the pharmacological effects of cactus. Both the extracts inhibited the writhing syndrome induced by acetic acid, indicating that they contains analgesic effect. The oral administrations of EEOF and EEOS suppressed carrageenan-induced rat paw edema and also showed potent inhibition in the leukocyte migration of CMC-pouch model in rats. Moreover, the extracts suppressed the release of beta-glucuronidase, a lysosomal enzyme in rat neutrophils. It was also noted that the extracts showed the protective effect on gastric mucosal layers. From the results it is suggested that the cactus extracts contain anti-inflammatory action having protective effect against gastric lesions.

  14. Neuronal Antibodies in Children with or without Narcolepsy following H1N1-AS03 Vaccination.

    Directory of Open Access Journals (Sweden)

    Simon Thebault

    Full Text Available Type 1 narcolepsy is caused by deficiency of hypothalamic orexin/hypocretin. An autoimmune basis is suspected, but no specific antibodies, either causative or as biomarkers, have been identified. However, the AS03 adjuvanted split virion H1N1 (H1N1-AS03 vaccine, created to protect against the 2009 Pandemic, has been implicated as a trigger of narcolepsy particularly in children. Sera and CSFs from 13 H1N1-AS03-vaccinated patients (12 children, 1 young adult with type 1 narcolepsy were tested for autoantibodies to known neuronal antigens including the N-methyl-D-aspartate receptor (NMDAR and contactin-associated protein 2 (CASPR2, both associated with encephalopathies that include disordered sleep, to rodent brain tissue including the lateral hypothalamus, and to live hippocampal neurons in culture. When sufficient sample was available, CSF levels of melanin-concentrating hormone (MCH were measured. Sera from 44 H1N1-ASO3-vaccinated children without narcolepsy were also examined. None of these patients' CSFs or sera was positive for NMDAR or CASPR2 antibodies or binding to neurons; 4/13 sera bound to orexin-neurons in rat brain tissue, but also to other neurons. MCH levels were a marginally raised (n = 8; p = 0.054 in orexin-deficient narcolepsy patients compared with orexin-normal children (n = 6. In the 44 H1N1-AS03-vaccinated healthy children, there was no rise in total IgG levels or in CASPR2 or NMDAR antibodies three weeks following vaccination. In conclusion, there were no narcolepsy-specific autoantibodies identified in type 1 narcolepsy sera or CSFs, and no evidence for a general increase in immune reactivity following H1N1-AS03 vaccination in the healthy children. Antibodies to other neuronal specific membrane targets, with their potential for directing use of immunotherapies, are still an important goal for future research.

  15. Neuronal Antibodies in Children with or without Narcolepsy following H1N1-AS03 Vaccination.

    Science.gov (United States)

    Thebault, Simon; Waters, Patrick; Snape, Matthew D; Cottrell, Dominic; Darin, Niklas; Hallböök, Tove; Huutoniemi, Anne; Partinen, Markku; Pollard, Andrew J; Vincent, Angela

    2015-01-01

    Type 1 narcolepsy is caused by deficiency of hypothalamic orexin/hypocretin. An autoimmune basis is suspected, but no specific antibodies, either causative or as biomarkers, have been identified. However, the AS03 adjuvanted split virion H1N1 (H1N1-AS03) vaccine, created to protect against the 2009 Pandemic, has been implicated as a trigger of narcolepsy particularly in children. Sera and CSFs from 13 H1N1-AS03-vaccinated patients (12 children, 1 young adult) with type 1 narcolepsy were tested for autoantibodies to known neuronal antigens including the N-methyl-D-aspartate receptor (NMDAR) and contactin-associated protein 2 (CASPR2), both associated with encephalopathies that include disordered sleep, to rodent brain tissue including the lateral hypothalamus, and to live hippocampal neurons in culture. When sufficient sample was available, CSF levels of melanin-concentrating hormone (MCH) were measured. Sera from 44 H1N1-ASO3-vaccinated children without narcolepsy were also examined. None of these patients' CSFs or sera was positive for NMDAR or CASPR2 antibodies or binding to neurons; 4/13 sera bound to orexin-neurons in rat brain tissue, but also to other neurons. MCH levels were a marginally raised (n = 8; p = 0.054) in orexin-deficient narcolepsy patients compared with orexin-normal children (n = 6). In the 44 H1N1-AS03-vaccinated healthy children, there was no rise in total IgG levels or in CASPR2 or NMDAR antibodies three weeks following vaccination. In conclusion, there were no narcolepsy-specific autoantibodies identified in type 1 narcolepsy sera or CSFs, and no evidence for a general increase in immune reactivity following H1N1-AS03 vaccination in the healthy children. Antibodies to other neuronal specific membrane targets, with their potential for directing use of immunotherapies, are still an important goal for future research.

  16. Predictive Value of Parkinsonian Primates in Pharmacologic Studies: A Comparison between the Macaque, Marmoset, and Squirrel Monkey.

    Science.gov (United States)

    Veyres, Nicolas; Hamadjida, Adjia; Huot, Philippe

    2018-05-01

    The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned primate is the gold-standard animal model of Parkinson disease (PD) and has been used to assess the effectiveness of experimental drugs on dyskinesia, parkinsonism, and psychosis. Three species have been used in most studies-the macaque, marmoset, and squirrel monkey-the last much less so than the first two species; however, the predictive value of each species at forecasting clinical efficacy, or lack thereof, is poorly documented. Here, we have reviewed all the published literature detailing pharmacologic studies that assessed the effects of experimental drugs on dyskinesia, parkinsonism, and psychosis in each of these species and have calculated their predictive value of success and failure at the clinical level. We found that, for dyskinesia, the macaque has a positive predictive value of 87.5% and a false-positive rate of 38.1%, whereas the marmoset has a positive predictive value of 76.9% and a false-positive rate of 15.6%. For parkinsonism, the macaque has a positive predictive value of 68.2% and a false-positive rate of 44.4%, whereas the marmoset has a positive predictive value of 86.9% and a false-positive rate of 41.7%. No drug that alleviates psychosis in the clinic has shown efficacy at doing so in the macaque, whereas the marmoset has 100% positive predictive value. The small number of studies conducted in the squirrel monkey precluded us from calculating its predictive efficacy. We hope our results will help in the design of pharmacologic experiments and will facilitate the drug discovery and development process in PD. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

  17. A yeast expression system for functional and pharmacological studies of the malaria parasite Ca2+/H+ antiporter

    Directory of Open Access Journals (Sweden)

    Salcedo-Sora J

    2012-08-01

    Full Text Available Abstract Background Calcium (Ca2+ signalling is fundamental for host cell invasion, motility, in vivo synchronicity and sexual differentiation of the malaria parasite. Consequently, cytoplasmic free Ca2+ is tightly regulated through the co-ordinated action of primary and secondary Ca2+ transporters. Identifying selective inhibitors of Ca2+ transporters is key towards understanding their physiological role as well as having therapeutic potential, therefore screening systems to facilitate the search for potential inhibitors are a priority. Here, the methodology for the expression of a Calcium membrane transporter that can be scaled to high throughputs in yeast is presented. Methods The Plasmodium falciparum Ca2+/H+ antiporter (PfCHA was expressed in the yeast Saccharomyces cerevisiae and its activity monitored by the bioluminescence from apoaequorin triggered by divalent cations, such as calcium, magnesium and manganese. Results Bioluminescence assays demonstrated that PfCHA effectively suppressed induced cytoplasmic peaks of Ca2+, Mg2+ and Mn2+ in yeast mutants lacking the homologue yeast antiporter Vcx1p. In the scalable format of 96-well culture plates pharmacological assays with a cation antiporter inhibitor allowed the measurement of inhibition of the Ca2+ transport activity of PfCHA conveniently translated to the familiar concept of fractional inhibitory concentrations. Furthermore, the cytolocalization of this antiporter in the yeast cells showed that whilst PfCHA seems to locate to the mitochondrion of P. falciparum, in yeast PfCHA is sorted to the vacuole. This facilitates the real-time Ca2+-loading assays for further functional and pharmacological studies. Discussion The functional expression of PfCHA in S. cerevisiae and luminescence-based detection of cytoplasmic cations as presented here offer a tractable system that facilitates functional and pharmacological studies in a high-throughput format. PfCHA is shown to behave as a divalent

  18. Nursing workload and adherence to non-pharmacological measures in the prevention of ventilator-associated pneumonia. A pilot study.

    Science.gov (United States)

    Jam, R; Hernández, O; Mesquida, J; Turégano, C; Carrillo, E; Pedragosa, R; Gómez, V; Martí, L; Vallés, J; Delgado-Hito, P

    To analyse whether adherence to non-pharmacological measures in the prevention of ventilator-associated pneumonia (VAP) is associated with nursing workload. A prospective observational study performed in a single medical-surgical ICU. Nurses in charge of patients under ventilator support were assessed. knowledge questionnaire, application of non-pharmacological VAP prevention measures, and workload (Nine Equivalents of Nursing Manpower Use Score). Phases: 1) the nurses carried out a educational programme, consisting of 60-minute lectures on non-pharmacological measures for VAP prevention, and at the end completed a questionnaire knowledge; 2) observation period; 3) knowledge questionnaire. Among 67 ICU-staff nurses, 54 completed the educational programme and were observed. A total of 160 observations of 49 nurses were made. Adequate knowledge was confirmed in both the initial and final questionnaires. Application of preventive measures ranged from 11% for hand washing pre-aspiration to 97% for the use of a sterile aspiration probe. The Nine Equivalents of Nursing Manpower Use Score was 50±13. No significant differences were observed between the association of the nurses' knowledge and the application of preventive measures or between workload and the application of preventive measures. Nurses' knowledge of VAP prevention measures is not necessarily applied in daily practice. Failure to follow these measures is not subject to lack of knowledge or to increased workload, but presumably to contextual factors. Copyright © 2017 Sociedad Española de Enfermería Intensiva y Unidades Coronarias (SEEIUC). Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Cataplexy in anxious patients: is subclinical narcolepsy underrecognized in anxiety disorders?

    Science.gov (United States)

    Flosnik, Dawn L; Cortese, Bernadette M; Uhde, Thomas W

    2009-06-01

    Excessive daytime sleepiness, hypnagogic-hypnopompic hallucinations, sleep paralysis, and cataplexy are symptoms associated with narcolepsy. Recent findings indicate that anxiety disorders also are associated with excessive daytime sleepiness, hypnagogic-hypnopompic hallucinations, and sleep paralysis. These observations suggest a possible relationship between anxiety disorders and narcolepsy. Cataplexy is considered the most specific symptom of narcolepsy, but its association with anxiety disorders is unknown. This preliminary investigation examined the prevalence and types of cataplexy in patients with primary anxiety disorders. Sex- and age-matched patients with anxiety disorders (N = 33) and healthy volunteers (N = 33) were assessed on standardized and validated measures of subjective sleep quality (Pittsburgh Sleep Quality Index) and subclinical narcoleptic events in the form of cataplexy (Stanford Center for Narcolepsy Revised Sleep Inventory). Patients were recruited from October 2006 to January 2007 from 2 programs of the Penn State Behavioral Health Clinic. Anxiety disorder patients as a group reported poorer sleep quality and endorsed a larger number of different types of situations (e.g., surprise, embarrassment) associated with cataplectic events. Among anxious patients, 33.3% (11 of 33) endorsed events specific for classic cataplexy, as opposed to 9.1% (3 of 33) of healthy volunteers (chi(2) = 5.80, p = .016). Our preliminary findings suggest that anxiety disorders are associated with increased rates of cataplexy. Future research is indicated to elucidate the relationship between anxiety and narcolepsy, with a particular focus on panic and generalized anxiety disorders. Copyright 2009 Physicians Postgraduate Press, Inc.

  20. Effective treatment of narcolepsy-like symptoms with high-frequency repetitive transcranial magnetic stimulation: A case report.

    Science.gov (United States)

    Lai, Jian-Bo; Han, Mao-Mao; Xu, Yi; Hu, Shao-Hua

    2017-11-01

    Narcolepsy is a rare sleep disorder with disrupted sleep-architecture. Clinical management of narcolepsy lies dominantly on symptom-driven pharmacotherapy. The treatment role of repetitive transcranial magnetic stimulation (rTMS) for narcolepsy remains unexplored. In this paper, we present a case of a 14-year-old young girl with excessive daytime sleepiness (EDS), cataplexy and hypnagogic hallucinations. After excluding other possible medical conditions, this patient was primarily diagnosed with narcolepsy. The patient received 25 sessions of high-frequency rTMS over the left dorsolateral prefrontal cortex (DLPFC). The symptoms of EDS and cataplexy significantly improved after rTMS treatment. Meanwhile, her score in the Epworth sleep scale (ESS) also remarkably decreased. This case indicates that rTMS may be selected as a safe and effective alternative strategy for treating narcolepsy-like symptoms. Well-designed researches are warranted in future investigations on this topic.

  1. The potential effects of Ocimum basilicum on health: a review of pharmacological and toxicological studies.

    Science.gov (United States)

    Sestili, Piero; Ismail, Tariq; Calcabrini, Cinzia; Guescini, Michele; Catanzaro, Elena; Turrini, Eleonora; Layla, Anam; Akhtar, Saeed; Fimognari, Carmela

    2018-06-11

    Basil (Ocimum basilicum L., OB) is a plant world widely used as a spice and a typical ingredient of the healthy Mediterranean diet. In traditional medicine, OB is indicated for many maladies and conditions; OB-containing nutritional supplements are increasingly sold. Conversely, safety concerns have been raised about the promutagens and procarcinogens alkenylbenzenes contained in OB. Areas covered: A critical review of the current status of OB as a nutraceutical, the pharmacology of its bioactive components, the rationale for its indications, and its safety. Expert opinion: Due to the polyphenolic and flavonoidic content, OB can be considered as an important ingredient in healthy diets; OB preparations may be effective as chemopreventive agents or adjunctive therapy in the treatment of different clinical conditions. From a toxicological perspective, since the tumorigenic potential of alkenylbenzenes is counteracted by other OB constituents such as nevadensin, it can be concluded that OB consumption in food and preparations is safe. The only concern relates to OB essential oils: in this case, a concentration limit for alkenylbenzenes should be precautionary defined, and the use of plant chemotypes with no or low levels of these alkylbenzenes for the preparation of essential oils should be made compulsory.

  2. Thermodynamic study of three pharmacologically significant drugs: Density, viscosity, and refractive index measurements at different temperatures

    Energy Technology Data Exchange (ETDEWEB)

    Iqbal, Muhammad Javed [Department of Chemistry, Quaid-i-Azam University, Islamabad 45320 (Pakistan)], E-mail: mjiqauchem@yahoo.com; Chaudhry, Mansoora Ahmed [Department of Chemistry, Quaid-i-Azam University, Islamabad 45320 (Pakistan)

    2009-02-15

    Measurements of density, viscosity, and refractive index of three pharmacologically significant drugs, i.e. diclofenac sodium, cetrizine, and doxycycline have been carried in aqueous medium at T = (293.15 to 313.15) K. An automated vibrating-tube densimeter, viscometer, and refractometer are used in a concentration range from (7.5) . 10{sup -3} to 25 . 10{sup -3}) mol . kg{sup -1}. The precise density results are used to evaluate the apparent molar volume, partial molar volume, thermal expansion coefficient, partial molar expansivity, and the Hepler's constant. Viscosity results are used to calculate the Jones-Dole viscosity B-coefficient, free energy of activation of the solute and solvent, activation enthalpy, and activation entropy. The molar refractive indices of the drug solutions can be employed to calculate molar refraction. It is inferred from these results that the above mentioned drugs act as structure-making compounds due to hydrophobic hydration of the molecules in the drugs.

  3. Neurochemical, pharmacological, and developmental studies on cerebellar receptors for dicarboxylic amino acids

    International Nuclear Information System (INIS)

    Sharif, N.A.; Roberts, P.J.

    1984-01-01

    Specific binding of L-[ 3 H]glutamate ([ 3 H]Glu) and L[ 3 H]Asp) to cerebellar membranes represented a time-, temperature-, pH- and protein-dependent interaction which was both saturable and reversible. Binding sites for both radioligands appeared maximally enriched in synaptosomal fractions isolated by gradient centrifugation. Kinetically derived dissociation constant (K/sub off//K/sub on/ . K/sub d/) for [ 3 H]Glu binding to this fraction indicated high-affinity (433 nM). Competition experiments employing analogs of excitatory amino acids, including new antagonists, helped identify binding sites for [ 3 H]Glu and [ 3 H]Asp as receptors with differential pharmacological specificities. Membrane freezing reduced numbers of both receptor types, but binding activity could be recovered partially by incubation at 37 degrees C. Glu receptors exhibited a pronounced deleterious sensitivity to thiol modifying reagents and L-Glu (50-1000 microM) provided protection against these compounds during co-incubation with cerebellar membranes. It is suggested that cold storage may induce partially reversible receptor inactivation by promoting sulfhydryl group/bond modification. Rat cerebellar glutamatergic function (endogenous Glu content, Glu uptake and receptor sites) exhibited an apparent ontogenetic peak between days 8-12 postpartum with a plateauing profile from day 30 to adulthood. The accelerated development (days 8-12) coincides with the first demonstrable Glu release and kainic acid neurotoxicity, as described previously

  4. Narcolepsy and depression Narcolepsia e depressão

    Directory of Open Access Journals (Sweden)

    Carla Adda

    1997-09-01

    Full Text Available Narcolepsy main symptoms include excessive daytime sleepiness and cataplexy. Its chronic course is accompanied by psychosocial impairment added to the difficulties and side effects of stimulants and tricyclics long term use. Depressive complaints are occasionally reported. The aim of this paper was to evaluate objectively the possibility of depression in a sample of 12 narcoleptics (7F;5 M, with mean age of 53 years (12 years SD, using the Beck Depression Inventory (BDI and the Hamilton Rating Scale for Depression (HAM-D. The results showed absence of depressive disorder in 75.0% of the cases according to BDI (or 58.3% according to HAM-D. The remaining patients had mild depression (only one patient presented major depression. The findings showed no correlation between narcolepsy and major depression.Narcolepsia é um distúrbio do sono caracterizado por sonolência diurna excessiva e ataques de cataplexia. Sendo crônico, traz uma série de dificuldades psicossociais às quais se aliam aquelas geradas pelos efeitos colaterais dos estimulantes e tricíclicos utilizados. Queixas depressivas são encontradas ocasionalmente. Esta pesquisa buscou verificar objetivamente a ocorrência de depressão em narcolépticos. Foi avaliado um grupo de 12 pacientes narcolépticos (7F; 5M com média de idade de 53 anos (DP 12 usando-se como instrumentos o Inventário de Beck para Depressão (BDI e a Escala Hamilton de Depressão (HAM-D. Os resultados demonstraram ausência de distúrbio depressivo em 75.0% dos pacientes avaliados pelo BDI e em 58.3% pela HAM-D. Os demais escores evidenciaram depressão leve ou disforia; depressão maior foi encontrada em apenas um caso. Tais achados não sugerem correlação entre narcolepsia e depressão.

  5. Evaluation of a filmed clinical scenario as a teaching resource for an introductory pharmacology unit for undergraduate health students: A pilot study.

    Science.gov (United States)

    East, Leah; Hutchinson, Marie

    2015-12-01

    Simulation is frequently being used as a learning and teaching resource for both undergraduate and postgraduate students, however reporting of the effectiveness of simulation particularly within the pharmacology context is scant. The aim of this pilot study was to evaluate a filmed simulated pharmacological clinical scenario as a teaching resource in an undergraduate pharmacological unit. Pilot cross-sectional quantitative survey. An Australian university. 32 undergraduate students completing a healthcare degree including nursing, midwifery, clinical science, health science, naturopathy, and osteopathy. As a part of an undergraduate online pharmacology unit, students were required to watch a filmed simulated pharmacological clinical scenario. To evaluate student learning, a measurement instrument developed from Bloom's cognitive domains (knowledge, comprehension, application, analysis, synthesis and evaluation) was employed to assess pharmacological knowledge conceptualisation and knowledge application within the following fields: medication errors; medication adverse effects; medication interactions; and, general pharmacology. The majority of participants were enrolled in an undergraduate nursing or midwifery programme (72%). Results demonstrated that the majority of nursing and midwifery students (56.52%) found the teaching resource complementary or more useful compared to a lecture although less so compared to a tutorial. Students' self-assessment of learning according to Bloom's cognitive domains indicated that the filmed scenario was a valuable learning tool. Analysis of variance indicated that health science students reported higher levels of learning compared to midwifery and nursing. Students' self-report of the learning benefits of a filmed simulated clinical scenario as a teaching resource suggest enhanced critical thinking skills and knowledge conceptualisation regarding pharmacology, in addition to being useful and complementary to other teaching and

  6. Brain Imaging Studies on the Cognitive, Pharmacological and Neurobiological Effects of Cannabis in Humans: Evidence from Studies of Adult Users.

    Science.gov (United States)

    Weinstein, Aviv; Livny, Abigail; Weizman, Abraham

    2016-01-01

    Cannabis is the most widely used illicit drug worldwide. Regular cannabis use has been associated with a range of acute and chronic mental health problems, such as anxiety, depression, psychotic symptoms and neurocognitive impairments and their neural mechanisms need to be examined. This review summarizes and critically evaluates brain-imaging studies of cannabis in recreational and regular cannabis users between January 2000 and January 2016. The search has yielded eligible 103 structural and functional studies. Regular use of cannabis results in volumetric, gray matter and white matter structural changes in the brain, in particular in the hippocampus and the amygdala. Regular use of cannabis affects cognitive processes such as attention, memory, inhibitory control, decision-making, emotional processing, social cognition and their associated brain areas. There is evidence that regular cannabis use leads to altered neural function during attention and working memory and that recruitment of activity in additional brain regions can compensate for it. Similar to other drugs of abuse, cannabis cues activated areas in the reward pathway. Pharmacological studies showed a modest increase in human striatal dopamine transmission after administration of THC in healthy volunteers. Regular cannabis use resulted in reduced dopamine transporter occupancy and reduced dopamine synthesis but not in reduced striatal D2/D3 receptor occupancy compared with healthy control participants. Studies also showed different effects of Δ-9 tetrahydrocannabinol (THC) and cannabidiol (CBD) on emotion, cognition and associated brain regions in healthy volunteers, whereby CBD protects against the psychoactive effects of THC. Brain imaging studies using selective high-affinity radioligands for the imaging of cannabinoid CB1 receptor availability in Positron Emission Tomography (PET) showed downregulation of CB1 in regular users of cannabis. In conclusion, regular use of the cannabinoids exerts

  7. Rapid eye movement sleep behaviour disorder in patients with narcolepsy is associated with hypocretin-1 deficiency

    DEFF Research Database (Denmark)

    Knudsen, Stine; Gammeltoft, Steen; Jennum, Poul J

    2010-01-01

    variables were analysed in relation to cataplexy and hypocretin deficiency with uni- and multivariate logistic/linear regression models, controlling for possible rapid eye movement sleep behaviour disorder biasing factors (age, gender, disease duration, previous anti-cataplexy medication). Only hypocretin......Rapid eye movement sleep behaviour disorder is characterized by dream-enacting behaviour and impaired motor inhibition during rapid eye movement sleep. Rapid eye movement sleep behaviour disorder is commonly associated with neurodegenerative disorders, but also reported in narcolepsy with cataplexy....... Most narcolepsy with cataplexy patients lack the sleep-wake, and rapid eye movement sleep, motor-regulating hypocretin neurons in the lateral hypothalamus. In contrast, rapid eye movement sleep behaviour disorder and hypocretin deficiency are rare in narcolepsy without cataplexy. We hypothesized...

  8. Cisplatin and radiation in the treatment of tumors of the central nervous system: Pharmacological considerations and results of early studies

    International Nuclear Information System (INIS)

    Stewart, D.J.; Molepo, J.M.; Eapen, L.; Montpetit, V.A.J.; Goel, R.; Wong, P.T.T.; Popovic, P.; Taylor, K.D.; Raaphorst, G.P.

    1994-01-01

    The purpose of this study was to review the human central nervous system pharmacology of cisplatin, factors that affect cisplatin uptake in tumors, and use alone and with radiation for the treatment of primary brain tumors. The authors review their own prior published and unpublished experience and data published by other groups on the above issues. Cisplatin is one of the most active chemotherapy drugs available for the treatment of solid tumors. It is synergistic with several other agents, including radiation. While it attains only low concentrations in the normal central nervous system, concentrations and plasma-tissue transfer constants for human intracerebral tumors are comparable to those in extracerebral tumors. Tumor type appears to be a more important determinant of platinum concentration than is tumor location, and gliomas do achieve lower concentrations than do other intracerebral or extracerebral tumors. Several other factors have also been identified that correlate with concentrations of cisplatin achieved in human tumors. While cisplatin alone and in combination with other drugs does have some degree of efficacy against primary brain tumors, combining it with cranial irradiation has generally not resulted in any substantial improvement in outcome to date, although some individual studies have been somewhat encouraging. New approaches are currently under investigation. Human pharmacology studies provide a rationale for use of cisplatin in the treatment of human brain tumors, and human and in vitro studies suggest some manipulations that might potentially further augment tumor platinum concentrations. While clinical studies suggest that cisplatin combinations may be of some value vs. human primary brain tumors and brain metastases, and while in vitro studies suggest that cisplatin potentiates radiation efficacy, no combination of cisplatin plus radiation yet tested has appeared to be superior to radiation alone. 123 refs., 5 tabs

  9. Comparison Study of Airway Reactivity Outcomes due to a Pharmacologic Challenge Test: Impulse Oscillometry versus Least Mean Squared Analysis Techniques

    Directory of Open Access Journals (Sweden)

    Elena Rodriguez

    2013-01-01

    Full Text Available The technique of measuring transpulmonary pressure and respiratory airflow with manometry and pneumotachography using the least mean squared analysis (LMS has been used broadly in both preclinical and clinical settings for the evaluation of neonatal respiratory function during tidal volume breathing for lung tissue and airway frictional mechanical properties measurements. Whereas the technique of measuring respiratory function using the impulse oscillation technique (IOS involves the assessment of the relationship between pressure and flow using an impulse signal with a range of frequencies, requires less cooperation and provides more information on total respiratory system resistance (chest wall, lung tissue, and airways. The present study represents a preclinical animal study to determine whether these respiratory function techniques (LMS and IOS are comparable in detecting changes in respiratory resistance derived from a direct pharmacological challenge.

  10. Mutations in DNMT1 cause autosomal dominant cerebellar ataxia, deafness and narcolepsy

    DEFF Research Database (Denmark)

    Winkelmann, Juliane; Lin, Ling; Schormair, Barbara

    2012-01-01

    to HDAC2. It is also highly expressed in immune cells and required for the differentiation of CD4+ into T regulatory cells. Mutations in exon 20 of this gene were recently reported to cause hereditary sensory neuropathy with dementia and hearing loss (HSAN1). Our mutations are all located in exon 21......Autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN) is characterized by late onset (30-40 years old) cerebellar ataxia, sensory neuronal deafness, narcolepsy-cataplexy and dementia. We performed exome sequencing in five individuals from three ADCA-DN kindreds and identified DNMT...

  11. Psychosocial intervention for children with narcolepsy: Parents' expectations and perceived support.

    Science.gov (United States)

    Kippola-Pääkkönen, Anu; Härkäpää, Kristiina; Valkonen, Jukka; Tuulio-Henriksson, Annamari; Autti-Rämö, Ilona

    2016-04-18

    The study focuses on the parents of children who were affected by narcolepsy after a pandemic influenza and vaccination campaign in Finland. The main aim of the study was to clarify parents' expectations and perceived support from the intervention and to assess their need for additional support. The data were gathered using questionnaires. Fifty-eight parents answered the baseline questionnaire and 40 parents the final questionnaire. Parents' expectations of and perceived support from the intervention mainly related to peer support. The intervention offered an arena for sharing information and experiences and provided encouragement for coping in everyday life. Many expectations were not met, especially those concerning information about needed services, financial benefits and availability of local support. The results highlight that for persons with rare disorders and their families, an inpatient psychosocial intervention can offer an important arena to receive both informal and professionally led peer support. Comprehensive psychosocial and other support services are also needed in the community. Listening to parents' perspectives on the intervention and perceived support can help to establish multiform family-centred support for families with children affected by a rare chronic disabling condition. © The Author(s) 2016.

  12. Pattern of Frequent But Nontargeted Pharmacologic Thromboprophylaxis for Hospitalized Patients With Cancer at Academic Medical Centers: A Prospective, Cross-Sectional, Multicenter Study

    Science.gov (United States)

    Zwicker, Jeffrey I.; Rojan, Adam; Campigotto, Federico; Rehman, Nadia; Funches, Renee; Connolly, Gregory; Webster, Jonathan; Aggarwal, Anita; Mobarek, Dalia; Faselis, Charles; Neuberg, Donna; Rickles, Frederick R.; Wun, Ted; Streiff, Michael B.; Khorana, Alok A.

    2014-01-01

    Purpose Hospitalized patients with cancer are considered to be at high risk for venous thromboembolism (VTE). Despite strong recommendations in numerous clinical practice guidelines, retrospective studies have shown that pharmacologic thromboprophylaxis is underutilized in hospitalized patients with cancer. Patients and Methods We conducted a prospective, cross-sectional study of hospitalized patients with cancer at five academic hospitals to determine prescription rates of thromboprophylaxis and factors influencing its use during hospitalization. Results A total of 775 patients with cancer were enrolled across five academic medical centers. Two hundred forty-seven patients (31.9%) had relative contraindications to pharmacologic prophylaxis. Accounting for contraindications to anticoagulation, the overall rate of pharmacologic thromboprophylaxis was 74.2% (95% CI, 70.4% to 78.0%; 392 of 528 patients). Among the patients with cancer without contraindications for anticoagulation, individuals hospitalized with nonhematologic malignancies were significantly more likely to receive pharmacologic thromboprophylaxis than those with hematologic malignancies (odds ratio [OR], 2.34; 95% CI, 1.43 to 3.82; P = .007). Patients with cancer admitted for cancer therapy were significantly less likely to receive pharmacologic thromboprophylaxis than those admitted for other reasons (OR, 0.37; 95% CI, 0.22 to 0.61; P < .001). Sixty-three percent of patients with cancer classified as low risk, as determined by the Padua Scoring System, received anticoagulant thromboprophylaxis. Among the 136 patients who did not receive anticoagulation, 58.8% were considered to be high risk by the Padua Scoring System. Conclusion We conclude that pharmacologic thromboprophylaxis is frequently administered to hospitalized patients with cancer but that nearly one third of patients are considered to have relative contraindications for prophylactic anticoagulation. Pharmacologic thromboprophylaxis in

  13. Predicting new indications of compounds with a network pharmacology approach: Liuwei Dihuang Wan as a case study.

    Science.gov (United States)

    Wang, Yin-Ying; Bai, Hong; Zhang, Run-Zhi; Yan, Hong; Ning, Kang; Zhao, Xing-Ming

    2017-11-07

    With the ever increasing cost and time required for drug development, new strategies for drug development are highly demanded, whereas repurposing old drugs has attracted much attention in drug discovery. In this paper, we introduce a new network pharmacology approach, namely PINA, to predict potential novel indications of old drugs based on the molecular networks affected by drugs and associated with diseases. Benchmark results on FDA approved drugs have shown the superiority of PINA over traditional computational approaches in identifying new indications of old drugs. We further extend PINA to predict the novel indications of Traditional Chinese Medicines (TCMs) with Liuwei Dihuang Wan (LDW) as a case study. The predicted indications, including immune system disorders and tumor, are validated by expert knowledge and evidences from literature, demonstrating the effectiveness of our proposed computational approach.

  14. Schizophrenia-like symptoms in narcolepsy type 1: shared and distinctive clinical characteristics.

    Science.gov (United States)

    Plazzi, Giuseppe; Fabbri, Chiara; Pizza, Fabio; Serretti, Alessandro

    2015-01-01

    The occurrence of psychotic symptoms in narcolepsy type 1 (NT1) has been reported as responsible for delayed diagnosis due to the misdiagnosis of schizophrenia. This study aimed to identify shared and distinctive clinical characteristics between NT1 and schizophrenia, with the focus on psychotic symptoms. A total of 28 NT1 and 21 schizophrenia patients were included. Hallucination characteristics and PANSS (Positive and Negative Syndrome Scale), HRSD (Hamilton Rating Scale for Depression), DES (Dissociative Experiences Scale), and STAI (State-Trait Anxiety Inventory) scores were collected. Symptom overlap was investigated by χ(2), Fisher's or t tests and multiple logistic regression models. Hallucinations and illusions frequently occurred in both diseases. Unimodal hallucinations were more common in schizophrenia (p = 6.30e-07) and multimodal hallucinations in NT1, but no clear difference was identified in their sensory modality. Hypnagogic/hypnopompic hallucinations were typical of NT1 (p = 5.22e-07), and 25% of NT1 patients exhibited some degree of insight deficit. Hypnagogic/hypnopompic hallucinations, unimodal hallucinations and PANSS score were the most distinctive clinical characteristics. Clinical overlap was found in the dissociative and anxiety domains, while higher depressive scores were observed in schizophrenia. The overlap between NT1 and schizophrenia should be further investigated under a clinical and pathogenetic point of view to improve diagnostic and therapeutic approaches. © 2015 S. Karger AG, Basel.

  15. Study of specific pharmacological activity of standardized composition of bee product substances for treatment of urogenital system

    Directory of Open Access Journals (Sweden)

    V. M. Koval

    2017-10-01

    Full Text Available Introduction. The work presents review of the data literature, which indicate the prospects of creation new highly efficient drugs for the treatment of chronic prostatitis and prostate gland adenoma based bioactive standardized substances of bee products, including powdered honey (PH, propolis phenolic hydrophobic drug (PPHD and bee pollen (BP. Materials and methods. Results of discussion of preclinical pharmacological studies of standardized substances of bee products composition – PH, PPHD and BP for the treatment of specified pathology is given in the experimental part. Results. It was found that the most pronounced anti-inflammatory effect on the level 40 % the mixture of APIs (PH, PPHD and BP detects at a dose of 100 mg/kg in relation to the reference drug – trianom capsules in doses of 100 and 130 mg/kg. Conclusions. Usage of bee products is grounded in creation of the new drug on their basis in the form of standardized substances of bee products composition –PH, PPHD and BP for chronic prostatitis and prostate gland adenoma. It was found that the most pronounced anti-inflammatory effect on 40 % the mixture of APIs (PH, PPHD and BP detects at a dose of 100 mg/kg. It was established that the composition of standard substances of bee products – PH, PPHD and BP at a dose of 100 mg/kg shows a more pronounced specific pharmacological effect in comparison to the reference product – trianom capsules at doses of 100 and 130 mg/kg, which positively affect the course of the pilot prostatitis in male rats caused by dichloroethyl.

  16. Amphetamine, past and present--a pharmacological and clinical perspective.

    Science.gov (United States)

    Heal, David J; Smith, Sharon L; Gosden, Jane; Nutt, David J

    2013-06-01

    Amphetamine was discovered over 100 years ago. Since then, it has transformed from a drug that was freely available without prescription as a panacea for a broad range of disorders into a highly restricted Controlled Drug with therapeutic applications restricted to attention deficit hyperactivity disorder (ADHD) and narcolepsy. This review describes the relationship between chemical structure and pharmacology of amphetamine and its congeners. Amphetamine's diverse pharmacological actions translate not only into therapeutic efficacy, but also into the production of adverse events and liability for recreational abuse. Accordingly, the balance of benefit/risk is the key challenge for its clinical use. The review charts advances in pharmaceutical development from the introduction of once-daily formulations of amphetamine through to lisdexamfetamine, which is the first d-amphetamine prodrug approved for the management of ADHD in children, adolescents and adults. The unusual metabolic route for lisdexamfetamine to deliver d-amphetamine makes an important contribution to its pharmacology. How lisdexamfetamine's distinctive pharmacokinetic/pharmacodynamic profile translates into sustained efficacy as a treatment for ADHD and its reduced potential for recreational abuse is also discussed.

  17. Amphetamine, past and present – a pharmacological and clinical perspective

    Science.gov (United States)

    Smith, Sharon L; Gosden, Jane; Nutt, David J

    2013-01-01

    Amphetamine was discovered over 100 years ago. Since then, it has transformed from a drug that was freely available without prescription as a panacea for a broad range of disorders into a highly restricted Controlled Drug with therapeutic applications restricted to attention deficit hyperactivity disorder (ADHD) and narcolepsy. This review describes the relationship between chemical structure and pharmacology of amphetamine and its congeners. Amphetamine’s diverse pharmacological actions translate not only into therapeutic efficacy, but also into the production of adverse events and liability for recreational abuse. Accordingly, the balance of benefit/risk is the key challenge for its clinical use. The review charts advances in pharmaceutical development from the introduction of once-daily formulations of amphetamine through to lisdexamfetamine, which is the first d-amphetamine prodrug approved for the management of ADHD in children, adolescents and adults. The unusual metabolic route for lisdexamfetamine to deliver d-amphetamine makes an important contribution to its pharmacology. How lisdexamfetamine’s distinctive pharmacokinetic/pharmacodynamic profile translates into sustained efficacy as a treatment for ADHD and its reduced potential for recreational abuse is also discussed. PMID:23539642

  18. Aberrant Food Choices after Satiation in Human Orexin-Deficient Narcolepsy Type 1

    NARCIS (Netherlands)

    van Holst, Ruth Janke; van der Cruijsen, Lisa; van Mierlo, Petra; Lammers, Gert Jan; Cools, Roshan; Overeem, Sebastiaan; Aarts, Esther

    2016-01-01

    Besides influencing vigilance, orexin neurotransmission serves a variety of functions, including reward, motivation, and appetite regulation. As obesity is an important symptom in orexin-deficient narcolepsy, we explored the effects of satiety on food-related choices and spontaneous snack intake in

  19. Sleep–Wake Transition in Narcolepsy and Healthy Controls Using a Support Vector Machine

    DEFF Research Database (Denmark)

    Jensen, Julie B; Sorensen, Helge B D; Kempfner, Jacob

    2014-01-01

    .0199) and healthy subjects (P = 0.0265). In addition, the sleep-wake transitions were elevated in hypocretin-deficient patients. It is concluded that the classifier shows high validity for identifying the sleep-wake transition. Narcolepsy with cataplexy patients have more sleep-wake transitions during night...

  20. Cataplectic facies: clinical marker in the diagnosis of childhood narcolepsy-report of two cases.

    Science.gov (United States)

    Prasad, Manish; Setty, Gururaj; Ponnusamy, Athi; Hussain, Nahin; Desurkar, Archana

    2014-05-01

    Narcolepsy is a chronic disease and is commonly diagnosed in adulthood. However, more than half of the patients have onset of symptoms in childhood and/or adolescence. The full spectrum of clinical manifestations, namely excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis, is usually not present at disease onset, delaying diagnosis during childhood. Mean delay in diagnosis since symptom onset is known to be several years. Initial manifestations can sometimes be as subtle as only partial drooping of eyelids leading to confusion with a myasthenic condition. We present two children who presented with "cataplectic facies," an unusual facial feature only recently described in children with narcolepsy with cataplexy. The diagnosis of narcolepsy was confirmed by multiple sleep latency test along with human leukocyte antigen typing and cerebrospinal fluid hypocretin assay. The diagnosis of narcolepsy with cataplexy at onset can be challenging in young children. With more awareness of subtle signs such as cataplectic facies, earlier diagnosis is possible. To date, only 11 children between 6 and 18 years of age presenting with typical cataplectic facies have been reported in the literature. We present two patients, one of whom is the youngest individual (4 years old) yet described with the typical cataplectic facies. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. The Psychosocial Problems of Children with Narcolepsy and Those with Excessive Daytime Sleepiness of Uncertain Origin

    Science.gov (United States)

    Stores, Gregory; Montgomery, Paul; Wiggs, Luci

    2007-01-01

    Background: Narcolepsy is a predominantly rapid eye movement sleep disorder with onset usually in the second decade but often in earlier childhood. Classically it is characterized by combinations of excessive sleepiness especially sleep attacks, cataplexy, hypnagogic hallucinations, and sleep paralysis. The psychosocial effects of this lifelong…

  2. The role of dopamine in inhibitory control in smokers and non-smokers: a pharmacological fMRI study

    NARCIS (Netherlands)

    Luijten, Maartje; Veltman, Dick J.; Hester, Robert; Smits, Marion; Nijs, Ilse M. T.; Pepplinkhuizen, Lolke; Franken, Ingmar H. A.

    2013-01-01

    Contemporary theoretical models of substance dependence posit that deficits in inhibitory control play an important role in substance dependence. The neural network underlying inhibitory control and its association with substance dependence have been widely investigated. However, the pharmacology of

  3. The role of dopamine in inhibitory control in smokers and non-smokers: A pharmacological fMRI study

    NARCIS (Netherlands)

    Luijten, M.; Veltman, D.J.; Hester, R.; Smits, M.; Nijs, I.M.T.; Pepplinkhuizen, L.; Franken, I.H.A.

    2013-01-01

    Contemporary theoretical models of substance dependence posit that deficits in inhibitory control play an important role in substance dependence. The neural network underlying inhibitory control and its association with substance dependence have been widely investigated. However, the pharmacology of

  4. Airway pathology in COPD : smoking cessation and pharmacological treatment intervention. Results from the GLUCOLD study

    NARCIS (Netherlands)

    Lapperre, Thérèse Sophie

    2010-01-01

    This thesis comprises data from the GLUCOLD study (Groningen Leiden Universities and Corticosteroids in Obstructive Lung Disease), a prospective study in COPD. In chapter 2 is shown that airflow limitation, asthma-like components, exhaled nitric oxide and sputum inflammatory cell counts offer

  5. Narcolepsy susceptibility gene CCR3 modulates sleep-wake patterns in mice.

    Directory of Open Access Journals (Sweden)

    Hiromi Toyoda

    Full Text Available Narcolepsy is caused by the loss of hypocretin (Hcrt neurons and is associated with multiple genetic and environmental factors. Although abnormalities in immunity are suggested to be involved in the etiology of narcolepsy, no decisive mechanism has been established. We previously reported chemokine (C-C motif receptor 3 (CCR3 as a novel susceptibility gene for narcolepsy. To understand the role of CCR3 in the development of narcolepsy, we investigated sleep-wake patterns of Ccr3 knockout (KO mice. Ccr3 KO mice exhibited fragmented sleep patterns in the light phase, whereas the overall sleep structure in the dark phase did not differ between Ccr3 KO mice and wild-type (WT littermates. Intraperitoneal injection of lipopolysaccharide (LPS promoted wakefulness and suppressed both REM and NREM sleep in the light phase in both Ccr3 KO and WT mice. Conversely, LPS suppressed wakefulness and promoted NREM sleep in the dark phase in both genotypes. After LPS administration, the proportion of time spent in wakefulness was higher, and the proportion of time spent in NREM sleep was lower in Ccr3 KO compared to WT mice only in the light phase. LPS-induced changes in sleep patterns were larger in Ccr3 KO compared to WT mice. Furthermore, we quantified the number of Hcrt neurons and found that Ccr3 KO mice had fewer Hcrt neurons in the lateral hypothalamus compared to WT mice. We found abnormalities in sleep patterns in the resting phase and in the number of Hcrt neurons in Ccr3 KO mice. These observations suggest a role for CCR3 in sleep-wake regulation in narcolepsy patients.

  6. Two cases of childhood narcolepsy mimicking epileptic seizures in video-EEG/EMG.

    Science.gov (United States)

    Yanagishita, Tomoe; Ito, Susumu; Ohtani, Yui; Eto, Kaoru; Kanbayashi, Takashi; Oguni, Hirokazu; Nagata, Satoru

    2018-06-06

    Narcolepsy is characterized by excessive sleepiness, hypnagogic hallucinations, and sleep paralysis, and can occur with or without cataplexy. Here, we report two children with narcolepsy presenting with cataplexy mimicking epileptic seizures as determined by long-term video-electroencephalography (EEG) and electromyography (EMG) monitoring. Case 1 was a 15-year-old girl presenting with recurrent episodes of "convulsions" and loss of consciousness, who was referred to our hospital with a diagnosis of epilepsy showing "convulsions" and "complex partial seizures". The long-term video-polygraph showed a clonic attack lasting for 15 s, which corresponded to 1-2 Hz with interruption of mentalis EMG discharges lasting for 70-300 ms without any EEG changes. Narcolepsy was suspected due to the attack induced by hearty laughs and the presence of sleep attacks, and confirmed by low orexin levels in cerebrospinal fluid (CSF). Case 2 was an 11-year-old girl presenting with recurrent episodes of myoclonic attacks simultaneously with dropping objects immediately after hearty laughs, in addition to sleep attacks, hypnagogic hallucinations, and sleep paralysis. The long-term video-polygraph showed a subtle attack, characterized by dropping chopsticks from her hand, which corresponded to an interruption of ongoing deltoid EMG discharges lasting 140 ms without any EEG changes. A diagnosis of narcolepsy was confirmed by the low orexin levels in CSF. These cases demonstrate that children with narcolepsy may have attacks of cataplexy that resemble clonic or myoclonic seizures. Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  7. The ICSD-3 and DSM-5 guidelines for diagnosing narcolepsy: clinical relevance and practicality.

    Science.gov (United States)

    Ruoff, Chad; Rye, David

    2016-07-20

    Narcolepsy is a chronic neurological disease manifesting as difficulty with maintaining continuous wake and sleep. Clinical presentation varies but requires excessive daytime sleepiness (EDS) occurring alone or together with features of rapid-eye movement (REM) sleep dissociation (e.g., cataplexy, hypnagogic/hypnopompic hallucinations, sleep paralysis), and disrupted nighttime sleep. Narcolepsy with cataplexy is associated with reductions of cerebrospinal fluid (CSF) hypocretin due to destruction of hypocretin peptide-producing neurons in the hypothalamus in individuals with a specific genetic predisposition. Updated diagnostic criteria include the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) and International Classification of Sleep Disorders Third Edition (ICSD-3). DSM-5 criteria require EDS in association with any one of the following: (1) cataplexy; (2) CSF hypocretin deficiency; (3) REM sleep latency ≤15 minutes on nocturnal polysomnography (PSG); or (4) mean sleep latency ≤8 minutes on multiple sleep latency testing (MSLT) with ≥2 sleep-onset REM-sleep periods (SOREMPs). ICSD-3 relies more upon objective data in addition to EDS, somewhat complicating the diagnostic criteria: 1) cataplexy and either positive MSLT/PSG findings or CSF hypocretin deficiency; (2) MSLT criteria similar to DSM-5 except that a SOREMP on PSG may count as one of the SOREMPs required on MSLT; and (3) distinct division of narcolepsy into type 1, which requires the presence of cataplexy or documented CSF hypocretin deficiency, and type 2, where cataplexy is absent, and CSF hypocretin levels are either normal or undocumented. We discuss limitations of these criteria such as variability in clinical presentation of cataplexy, particularly when cataplexy may be ambiguous, as well as by age; multiple and/or invasive CSF diagnostic test requirements; and lack of normative diagnostic test data (e.g., MSLT) in certain populations. While ICSD-3 criteria

  8. Studies of Mechanisms of Pharmacological Enhancement of Functional Recovery After Cortical Contusion

    Science.gov (United States)

    1993-01-29

    ablation, as described in detail elsewhere (4,8,9). In other projects, SMCx injury was induced via contusion of the cortex through a craniotomy site...in vivo microdialysis study in the awake rat. J. Neurochem. 76. Steindler D.A. (1981) Locus coeruleus neurons have axons that branch to the forebrain...microdialysis study in the awake rat. J. Neurochem. Weisend, M.P. and Feeney, D.M. (Submitted) Brain temperature before and after traumatic brain injury is

  9. The revised dopamine hypothesis of schizophrenia: evidence from pharmacological MRI studies with atypical antipsychotic medication

    NARCIS (Netherlands)

    da Silva Alves, Fabiana; Figee, Martijn; van Amelsvoort, Thérèse; Veltman, Dick; de Haan, Lieuwe

    2008-01-01

    The revised dopamine (DA) hypothesis states that clinical symptoms of schizophrenia are caused by an imbalance of the DA system. In this article, we aim to review evidence for this hypothesis by evaluating functional magnetic resonance imaging studies in schizophrenia. Because atypical drugs are

  10. PHARMACOLOGICAL VALIDATION OF Musa paradisiaca BHASMA FOR ANTIULCER ACTIVITY IN ALBINO RATS - A PRELIMINARY STUDY.

    Science.gov (United States)

    Vadivelan, R; Elango, K; Suresh, B; Ramesh, B R

    2006-01-01

    Siddha system of medicine is one of the ancient systems of medicine in India. According to Siddhars, peptic ulcer is known as Valigunmam with its signs and symptoms as detailed in Siddha literature matching modern terminology of peptic ulcer. Bhasma refers to calcinated metals and minerals. During this study the Bhasma of Musa paradisiaca Linn, is prepared and evaluated for its antiulcer effect in albino wistar rats which could not be attempted by researchers earlier.

  11. PHARMACOLOGICAL VALIDATION OF Musa paradisiaca BHASMA FOR ANTIULCER ACTIVITY IN ALBINO RATS – A PRELIMINARY STUDY

    Science.gov (United States)

    Vadivelan, R.; Elango, K.; Suresh, B.; Ramesh, B. R.

    2006-01-01

    Siddha system of medicine is one of the ancient systems of medicine in India. According to Siddhars, peptic ulcer is known as Valigunmam with its signs and symptoms as detailed in Siddha literature matching modern terminology of peptic ulcer. Bhasma refers to calcinated metals and minerals. During this study the Bhasma of Musa paradisiaca Linn, is prepared and evaluated for its antiulcer effect in albino wistar rats which could not be attempted by researchers earlier. PMID:22557209

  12. Synthesis, pharmacological evaluation and molecular docking studies of pyrimidinedione based DPP-4 inhibitors as antidiabetic agents

    Science.gov (United States)

    Jha, Vibhu; Bhadoriya, Kamlendra Singh

    2018-04-01

    Dipeptidyl peptidase-4 (DPP-4) inhibitors are a class of newly developed antidiabetic drugs that bock DPP-4. DPP-4 is responsible for degradation of incretins harmones such as GLP-1 (Glucagon like Peptide) and GIP (Gastric inhibitory polypeptide) that maintain blood-glucose level. Pyrimidinedione based compounds were designed and synthesized for DPP-4 inhibitory activity. These heterocycles were designed by taking Alogliptin as a reference DPP-4 inhibitors and synthesized as N-methylated and N-benzylated pyrimidinediones. These compounds were subjected to DPP-4 assay, five out of nine synthesized compounds have shown in vitro DPP-4 inhibitory activity in significant range. Further, molecular docking studies of these compounds were performed on DPP-4 subunit and compared with natural DPP-4 inhibitors like Flavone, Resveratrol, Quercetin, Diprotin A. Docking studies have led to the conclusion that there are some identical amino acid interactions as Tyr 666 and Tyr 662, seen in both synthesized compounds and natural DPP-4 inhibitors. This study completely gives a good scope for further derivatisation and optimization of synthesized compounds to get clinical candidate as DPP-4 inhibitor for antidiabetic activity.

  13. Chronic Stress Improves NO- and Ca2+ Flux-Dependent Vascular Function: A Pharmacological Study

    Energy Technology Data Exchange (ETDEWEB)

    Bruder-Nascimento, Thiago, E-mail: bruderthiago@usp.br [Departamento de Farmacologia - Instituto de Biociências de Botucatu - Universidade do Estado de São Paulo (UNESP), Botucatu, São Paulo (Brazil); Departamento de Clínica Médica - Faculdade de Medicina de Botucatu - Universidade do Estado de São Paulo (UNESP), Botucatu, São Paulo (Brazil); Campos, Dijon Henrique Salome [Departamento de Clínica Médica - Faculdade de Medicina de Botucatu - Universidade do Estado de São Paulo (UNESP), Botucatu, São Paulo (Brazil)

    2015-03-15

    Stress is associated with cardiovascular diseases. This study aimed at assessing whether chronic stress induces vascular alterations, and whether these modulations are nitric oxide (NO) and Ca2+ dependent. Wistar rats, 30 days of age, were separated into 2 groups: control (C) and Stress (St). Chronic stress consisted of immobilization for 1 hour/day, 5 days/week, 15 weeks. Systolic blood pressure was assessed. Vascular studies on aortic rings were performed. Concentration-effect curves were built for noradrenaline, in the presence of L-NAME or prazosin, acetylcholine, sodium nitroprusside and KCl. In addition, Ca{sup 2+} flux was also evaluated. Chronic stress induced hypertension, decreased the vascular response to KCl and to noradrenaline, and increased the vascular response to acetylcholine. L-NAME blunted the difference observed in noradrenaline curves. Furthermore, contractile response to Ca{sup 2+} was decreased in the aorta of stressed rats. Our data suggest that the vascular response to chronic stress is an adaptation to its deleterious effects, such as hypertension. In addition, this adaptation is NO- and Ca{sup 2+}-dependent. These data help to clarify the contribution of stress to cardiovascular abnormalities. However, further studies are necessary to better elucidate the mechanisms involved in the cardiovascular dysfunction associated with stressors. (Arq Bras Cardiol. 2014; [online].ahead print, PP.0-0)

  14. Narcolepsy with cataplexy after A/H1N1 vaccination – A case reported from Cuba

    Directory of Open Access Journals (Sweden)

    Yaimi Rosales Mesa

    2014-03-01

    Full Text Available Narcolepsy with cataplexy is a rare sleep disorder with a neurological basis which has been recently linked to H1N1 vaccination either in children or adults. Cases from Europe, United States and Brasil were registered. Authors describe a case report of a 15 years old boy who developed narcolepsy with cataplexy after H1N1 vaccination in Havana. As far as it is concerned this is the first case reported from Cuba.

  15. Pharmacology podcasts: a qualitative study of non-medical prescribing students' use, perceptions and impact on learning.

    Science.gov (United States)

    Meade, Oonagh; Bowskill, Dianne; Lymn, Joanne S

    2011-01-11

    There is growing research on student use of podcasts in academic settings. However, there is little in-depth research focusing on student experience of podcasts, in particular in terms of barriers to, and facilitators of, podcast use and students' perceptions of the usefulness of podcasts as learning tools. This study aimed to explore the experiences of non-medical prescribing students who had access to podcasts of key pharmacology lectures as supplementary learning tools to their existing course materials. Semi-structured interviews were carried out with seven non-medical prescribing students (average age = 43 years), all of whom were nurses, who had access to seven podcasts of key pharmacology lectures. These podcasts took the form of downloadable audio lecture recordings available through the virtual learning environment WebCT. Low, medium and high users of the podcasts took part in the interviews in order to access a variety of student experiences. Interview data was analysed using thematic template analysis to identify key themes surrounding student experience of podcast availability, particularly in relation to barriers to and facilitators of podcast use, and students' experiences of podcasts as a learning tool. Students used podcasts for a variety of reasons such as revisiting lectures, preparing for exams, to clarify or revise specific topics and, to a lesser extent, to catch up on a missed lecture. Barriers to podcast use centred mainly around technological issues. Lack of experience of the technology required to access podcasts proved a barrier for some students. A lack of access to suitable technology was also a reported barrier. Family assistance and I.T. assistance from the university helped facilitate students' use of the podcasts. Students found that using podcasts allowed them to have greater control over their learning and to gauge their learning needs, as well as helping them build their understanding of a complex topic. Students used podcasts for

  16. Abnormal GABAergic function and face processing in schizophrenia: A pharmacologic-fMRI study.

    Science.gov (United States)

    Tso, Ivy F; Fang, Yu; Phan, K Luan; Welsh, Robert C; Taylor, Stephan F

    2015-10-01

    The involvement of the gamma-aminobutyric acid (GABA) system in schizophrenia is suggested by postmortem studies and the common use of GABA receptor-potentiating agents in treatment. In a recent study, we used a benzodiazepine challenge to demonstrate abnormal GABAergic function during processing of negative visual stimuli in schizophrenia. This study extended this investigation by mapping GABAergic mechanisms associated with face processing and social appraisal in schizophrenia using a benzodiazepine challenge. Fourteen stable, medicated schizophrenia/schizoaffective patients (SZ) and 13 healthy controls (HC) underwent functional MRI using the blood oxygenation level-dependent (BOLD) technique while they performed the Socio-emotional Preference Task (SePT) on emotional face stimuli ("Do you like this face?"). Participants received single-blinded intravenous saline and lorazepam (LRZ) in two separate sessions separated by 1-3weeks. Both SZ and HC recruited medial prefrontal cortex/anterior cingulate during the SePT, relative to gender identification. A significant drug by group interaction was observed in the medial occipital cortex, such that SZ showed increased BOLD signal to LRZ challenge, while HC showed an expected decrease of signal; the interaction did not vary by task. The altered BOLD response to LRZ challenge in SZ was significantly correlated with increased negative affect across multiple measures. The altered response to LRZ challenge suggests that abnormal face processing and negative affect in SZ are associated with altered GABAergic function in the visual cortex, underscoring the role of impaired visual processing in socio-emotional deficits in schizophrenia. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Kinetics of Iodine 131 labelled fibrinogen in cancerous patients. Pharmacological study

    International Nuclear Information System (INIS)

    Boneu-Valmalette, Andree; Bugat, Roland; David, J.-F.; Combes, P.-F.

    1977-01-01

    The results obtained in a previous study using 131 I fibrinogen in cancerous patients suggested a local intravascular clotting process. In order to elucidate the mechanism of fibrinogen kinetic abnormalities different drugs including heparin, prednisone, ticlopidin, aspirin and indomethacin were administred in 68 patients and their effects evaluated by change in the 131 I fibrinogen disappearance rate. The results suggest that these drugs may counteract with the early stages of coagulation (kinin-forming system, factor XII) and that abnormal 131 I fibrinogen kinetic in cancer would be a non specific phenomenon [fr

  18. Carbamazepine reduces memory induced activation of mesial temporal lobe structures: a pharmacological fMRI-study

    Directory of Open Access Journals (Sweden)

    Okujava Michael

    2001-11-01

    Full Text Available Abstract Background and Purpose It is not known whether carbamazepine (CBZ; a drug widely used in neurology and psychiatry influences the blood oxygenation level dependent (BOLD contrast changes induced by neuronal activation and measured by functional MRI (fMRI. We aimed to investigate the influence of CBZ on memory induced activation of the mesial temporal lobes in patients with symptomatic temporal lobe epilepsy (TLE. Material and Methods Twenty-one individual patients with refractory symptomatic TLE with different CBZ serum levels and 20 healthy controls were studied using BOLD fMRI. Mesial temporal lobe (MTL activation was induced by a task that is based on the retrieval of individually familiar visuo-spatial knowledge. The extent of significant MTL fMRI activation was measured and correlated with the CBZ serum level. Results In TLE patients, the extent of significant fMRI activation over both MTL was negatively correlated to the CBZ serum level (Spearman r = -0.654, P Conclusions In TLE patients, carbamazepine reduces the fMRI-detectable changes within the mesial temporal lobes as induced by effortful memory retrieval. FMRI appears to be suitable to study the effects of chronic drug treatment in patients with epilepsy.

  19. A comparative study of five centrally acting drugs on the pharmacological treatment of obesity.

    Science.gov (United States)

    Suplicy, H; Boguszewski, C L; dos Santos, C M C; do Desterro de Figueiredo, M; Cunha, D R; Radominski, R

    2014-08-01

    No long-term studies have compared centrally acting drugs for treating obesity. To compare the efficacy and safety of diethylpropion (DEP), fenproporex (FEN), mazindol (MZD), fluoxetine (FXT) and sibutramine (SIB) in promoting weight loss. A prospective, randomized, placebo (PCB)-controlled study conducted at a single academic institution. A total of 174 obese premenopausal women. Participants randomly received DEP 75 mg (n=28), FEN 25 mg (n=29), MZD 2 mg (n=29), SIB 15 mg (n=30), FXT 20 mg (n=29) or PCB (n=29) daily over 52 weeks. Diet and physical activity were encouraged. The primary endpoints were changes in body weight and the proportion of women who achieved at least 5% weight loss by week 52 in the intent-to-treat population. Other measurements included anthropometry, safety, metabolic and cardiovascular parameters. Weight loss was greater than PCB (-3.1±4.3 kg) with DEP (-10.0±6.4 kg; Pobese premenopausal women, with a satisfactory benefit-risk profile.

  20. Pharmacologic and radioimmunologic studies on some endocrine functions in experimental hypothyreosis

    International Nuclear Information System (INIS)

    Boyadzhieva, N.; Visheva, N.; Milanov, S.; Krysteva, S.

    1990-01-01

    The study was performed on two groups of rats: 1) sexually mature males with experimental hypothyreosis produced with methisol 2) progeny of female rats with hypothyreosis. Prolactin and growth hormone levels were determined by radioimmunoassay. Changes were found in rats with experimental hypothyreosis. In the progeny there were changes only in prolactin level. The content of dopamine and serotonine in the brain of the progeny were also determined. Changes were found in the dopamine content, which correlated with the elevated prolactin level. The hypothesis is advanced that disturbances exist in the central neuro-mediatory mechanisms during the pre-and postnatal life, controlling the functions of the pituitary-thyroid axis and the production and release of prolactin and growth hormone. 3 tabs., 7 refs

  1. Pharmacological evaluation and preliminary pharmacokinetics studies of a new diclofenac prodrug without gastric ulceration effect.

    Science.gov (United States)

    Santos, Jean Leandro Dos; Moreira, Vanessa; Campos, Michel Leandro; Chelucci, Rafael Consolin; Barbieri, Karina Pereira; de Castro Souto, Pollyana Cristina Maggio; Matsubara, Márcio Hideki; Teixeira, Catarina; Bosquesi, Priscila Longhin; Peccinini, Rosângela Gonçalves; Chin, Chung Man

    2012-11-19

    Long-term nonsteroidal anti-inflammatory drugs (NSAIDs) therapy has been associated with several adverse effects such as gastric ulceration and cardiovascular events. Among the molecular modifications strategies, the prodrug approach is a useful tool to discover new safe NSAIDs. The 1-(2,6-dichlorophenyl)indolin-2-one is a diclofenac prodrug which demonstrated relevant anti-inflammatory properties without gastro ulceration effect. In addition, the prodrug decreases PGE(2) levels, COX-2 expression and cellular influx into peritoneal cavity induced by carrageenan treatment. Preliminary pharmacokinetic studies have shown in vivo bioconversion of prodrug to diclofenac. This prodrug is a new nonulcerogenic NSAID useful to treat inflammatory events by long-term therapy.

  2. Pharmacological Evaluation and Preliminary Pharmacokinetics Studies of a New Diclofenac Prodrug without Gastric Ulceration Effect

    Directory of Open Access Journals (Sweden)

    Chung Man Chin

    2012-11-01

    Full Text Available Long-term nonsteroidal anti-inflammatory drugs (NSAIDs therapy has been associated with several adverse effects such as gastric ulceration and cardiovascular events. Among the molecular modifications strategies, the prodrug approach is a useful tool to discover new safe NSAIDs. The 1-(2,6-dichlorophenylindolin-2-one is a diclofenac prodrug which demonstrated relevant anti-inflammatory properties without gastro ulceration effect. In addition, the prodrug decreases PGE2 levels, COX-2 expression and cellular influx into peritoneal cavity induced by carrageenan treatment. Preliminary pharmacokinetic studies have shown in vivo bioconversion of prodrug to diclofenac. This prodrug is a new nonulcerogenic NSAID useful to treat inflammatory events by long-term therapy.

  3. Enhancement of carer skills and patient function in the non-pharmacological management of frontotemporal dementia (FTD): A call for randomised controlled studies

    Science.gov (United States)

    O'Connor, Claire M.; Clemson, Lindy; da Silva, Thaís Bento Lima; Piguet, Olivier; Hodges, John R.; Mioshi, Eneida

    2013-01-01

    FTD is a unique condition which manifests with a range of behavioural symptoms, marked dysfunction in activities of daily living (ADL) and increased levels of carer burden as compared to carers of other dementias. No efficacious pharmacological interventions to treat FTD currently exist, and research on pharmacological symptom management is variable. The few studies on non-pharmacological interventions in FTD focus on either the carer or the patients' symptoms, and lack methodological rigour. This paper reviews and discusses current studies utilising non-pharmacological approaches, exposing the clear need for more rigorous methodologies to be applied in this field. Finally, a successful randomised controlled trial helped reduce behaviours of concern in dementia, and through implementing participation in tailored activities, the FTD-specific Tailored Activities Program (TAP) is presented. Crucially, this protocol has scope to target both the person with FTD and their carer. This paper highlights that studies in this area would help to elucidate the potential for using activities to reduce characteristic behaviours in FTD, improving quality of life and the caregiving experience in FTD. PMID:29213832

  4. Phase I and pharmacologic study of 72-hour infused 5-fluorouracil and hyperfractionated cyclical radiation

    Energy Technology Data Exchange (ETDEWEB)

    Byfield, J.E.; Frankel, S.S.; Sharp, T.R.; Hornbeck, C.L.; Callipari, F.B.

    1985-04-01

    The authors have studied 21 patients infused for 72 hours with 5- Fluorouracil (5-FU) at progressive doses combined with hyperfractionated radiation. The schedule was chosen as being one capable of inducing 5-FU radiosensitization (RS). All patients were started at a daily 5-FU dose of 40 mg/kg/24 hours; doses were then escalated with each subsequent treatment cycle to limiting toxicity or until taken off study. Patients received between one and six infusion cycles. Every treatment cycle included coincident hyperfractionated radiation to various body areas including the abdomen, chest, and head and neck region. Radiation fractionation was invariant; 1,000 rad were delivered in four equal fractions. Two fractions of 250 rad each were given on days 1 and 2 of each three day 5-FU cycle, i.e. at approximately 0, 8, 24, and 32 hours into the drug infusion. Patients were followed for toxicity; serum 5-FU concentrations were determined using a high pressure liquid chromatographic assay. 5-FU clearances were calculated from the mean serum drug levels and the infused drug dose. The toxicity spectrum was not found to be significantly different from infused drug alone in this dose range except when the head and neck region received coincident irradiation. In that region the two anticipated toxicities combined in what appears to be a synergistic fashion to enhance mucositis. Most toxicities including gastrointestinal and bone marrow appeared dependent on the mean serum 5-FU level as did mucositis itself. 5-FU clearance was found to be non-linear in this dose region but did not appear influenced by radiation to any part of the body.

  5. Evaluation the ethno-pharmacological studies in Iran during 2004-2016: A systematic review.

    Science.gov (United States)

    Sadeghi, Zahra; Akaberi, Maryam; Sobhkhizi, Alireza; Sahebkar, Amirhossein; Emami, Seyed Ahmad

    2018-02-01

    Although Iran has a deep history in herbal medicine and great heritage of ancient medical scholars, few efforts have been made to evaluate ethnopharmacological aspects of medicinal plants in this country. In the present study, the authors have reviewed all important literature about the ethnopharmacological investigations on medicinal plants used in the last decade in Iran. All provinces of Iran were categorized according to a phytogeographical division. Information was collected through bibliographic investigations from scientific journals and books. Afterward, the data were analyzed through the construction of specific ecological regions of the country. Fifty-five references reporting medicinal plants in five ecological zones were retrieved. The Irano-Turanian subregion has produced the greatest number of publications in this field among others (47%). Results illustrate that the most reported botanical families were Lamiaceae and Asteraceae (28.57% and 27.73%, respectively). Among various illnesses reported for these plants, gastrointestinal (30.15%), respiratory problems (14.28%), diabetes (11.11%), and cold/flu (11.11%) were the most cited. The most frequently cited medicinal uses were attributed to decoction and infusion preparations. Iran has a rich history of knowledge about phytotherapy and has also a diverse geographical regions, and a plant flora that is a good candidate for drug discovery. Documentation of indigenous knowledge about herbal medicine used by Iranian tribes is vital for the future development of herbal drugs. Ethnopharmacological studies of Iranian folk medicine with quantitative analytical techniques are warranted to find drug candidates, and also to preserve the precious knowledge of the Iranian folk medicine. © 2017 Wiley Periodicals, Inc.

  6. Preclinical pharmacological study on I-ADAM as a serotonin transporter ligand

    International Nuclear Information System (INIS)

    Wu Chunying; Lu Chunxiong; Jiang Quanfu; Zou Meifen; Chen Zhengping; Wang Songpei; Li Xiaomin; Zhang Tongxing; Zhu Junqing; Lin Xiangtong

    2004-01-01

    Objective: To evaluate the new ligand: I-2-( (22( (dimethylamino) methyl) phenyl) thio)-5- iodophenylamine (ADAM) as a serotonin imaging agent. Methods: Biological evaluations were performed in rats and mice. Results: Biodistribution studies in rats showed that the initial uptake of 131 I-ADAM in the brain was high (1.087%ID/organ at 2 min postinjection), and consistently displayed the highest binding (between 60-240 min postinjection) in hypothalamus, a region with the highest density of serotonin transporter (SERT). The specific binding [(TPCB)-1] of 131 I-ADAM in hypothalamus was 2.94, 3.03 and 3.09 at 60, 120 and 240 min postinjection, respectively. The (TPCB)-1 was significantly blocked by pretreatment with Paroxetine, which is known as a serotonin site reuptake inhibitor, while another nonselective competing drug, Ketanserin, showed no blocking effect. The rat brain autoradiography and analysis showed that there was high 131 I-ADAM uptake in hypothalamus, the ratio of hypothalamus/cerebellum was significantly reduced from 7.94 ± 0.39 to 1.30 ± 0.56 by pretreatment with Paroxetine at 60 min postinjection. Blood clearance kinetics was studied in rats, and the initial half-life of 13.79 min and late half-life of 357.14 min were obtained. The kinetic equation was: C=3.6147·e -0.0725t + 1.0413 e -0.0028t . The thyroid uptake was 0.009 and 1.421% ID/organ at 2 min and 120 min postinjection, respectively, suggesting that in vivo deiodination maybe the major route of metabolism. Toxicity trial showed that the dose per kilogram administered to mice was 1000 times greater than that to human beings, assuming a body-weight of 50 kg. Conclusion: These data suggest that 131 I-ADAM may be useful for SPECT imaging of SERT binding sits in the brain. (authors)

  7. Phase I and pharmacologic study of 72-hour infused 5-fluorouracil and hyperfractionated cyclical radiation

    International Nuclear Information System (INIS)

    Byfield, J.E.; Frankel, S.S.; Sharp, T.R.; Hornbeck, C.L.; Callipari, F.B.

    1985-01-01

    The authors have studied 21 patients infused for 72 hours with 5- Fluorouracil (5-FU) at progressive doses combined with hyperfractionated radiation. The schedule was chosen as being one capable of inducing 5-FU radiosensitization (RS). All patients were started at a daily 5-FU dose of 40 mg/kg/24 hours; doses were then escalated with each subsequent treatment cycle to limiting toxicity or until taken off study. Patients received between one and six infusion cycles. Every treatment cycle included coincident hyperfractionated radiation to various body areas including the abdomen, chest, and head and neck region. Radiation fractionation was invariant; 1,000 rad were delivered in four equal fractions. Two fractions of 250 rad each were given on days 1 and 2 of each three day 5-FU cycle, i.e. at approximately 0, 8, 24, and 32 hours into the drug infusion. Patients were followed for toxicity; serum 5-FU concentrations were determined using a high pressure liquid chromatographic assay. 5-FU clearances were calculated from the mean serum drug levels and the infused drug dose. The toxicity spectrum was not found to be significantly different from infused drug alone in this dose range except when the head and neck region received coincident irradiation. In that region the two anticipated toxicities combined in what appears to be a synergistic fashion to enhance mucositis. Most toxicities including gastrointestinal and bone marrow appeared dependent on the mean serum 5-FU level as did mucositis itself. 5-FU clearance was found to be non-linear in this dose region but did not appear influenced by radiation to any part of the body

  8. [Study on pharmacologic action characteristics of traditional Chinese medicines distributed along liver meridian based on medicinal properties combinations].

    Science.gov (United States)

    Guo, Hong-Ling; Gu, Hao; Wang, Yun; Qiao, Yan-Jiang

    2014-07-01

    To establish a characterization system of traditional Chinese medicinal properties in line with modern scientific cognition regularity, in order to reveal properties of traditional Chinese medicines distributed along liver meridian and relations of effects of medicinal properties. By collecting data about traditional Chinese medicinal properties recorded in the Pharmacopoeia of the People's Republic of China (2005 Edition), literature and data about pharmacological effects of traditional Chinese medicines recorded in the Chinese Materia Medica, by using the method of association rules, the authors dug pharmacological effect rules corresponds to relevant medicinal property combinations, with the medicinal property combination of traditional Chinese medicines distributed along liver meridian as the target. It was found that either obvious different pharmacological effects or identical pharmacological characteristics existed in traditional Chinese medicines distributed along liver meridian. With the aim to explore the correlations between traditional Chinese medicine medicinal properties and pharmacological effects, the authors linked the traditional Chinese medicine theory with modern research achievements, in order to provide the ideas and methods for interpreting mechanisms of medicinal properties.

  9. Pharmacological study of radioactive-gold colloid transport by blood and by serous exudate

    International Nuclear Information System (INIS)

    Rousselet, J.

    1966-06-01

    After giving the essential physico-chemical properties of the colloids, the author considers the biological role of these substances and, in connection with their transport by the blood, their capture by elements of the reticula-endothelial system. A summary is given of present knowledge concerning the role of serous proteins in the transport of substances, particularly that of radio-active colloidal gold. The blood fractions which can take part in colloidal gold transport are the red blood corpuscles, the leukocytes and histiocytic elements as well as the plasma. The radioactive distribution in these various fractions is obtained by autoradiography of blood sediments. After showing the importance of the role of the plasma in radioactive particle transport, the author, describes the attempts made to detect a possible of colloidal gold 198 on the various serous proteins using various methods of separation. The ''in vitro'' and ''in vivo'' bonds between colloidal gold-198 particles and either the serous proteins or healthy specimens or the effusion liquids of pathological origin in man, or due to an experimental inflammation with carregenin in the rat, have been studied. The bonding appears to be effective because of the protective macromolecular layer formed by the gelatine. The different positions of the colloidal grains on the electrophoregram can only be explained by their different physico-chemical characteristics. Gold in the ionic form, on the other hand, is combined only with the albumen is the amount metal present does not exceed a certain value. (author) [fr

  10. In vivo pharmacological study on the effectiveness of available polyclonal antivenom against Hemiscorpius lepturus venom

    Directory of Open Access Journals (Sweden)

    A Jalali

    2011-01-01

    Full Text Available The available Razi Institute antivenom is still, empirically, used by intramuscular (IM administration for the treatment of scorpion stings in humans by six medically dangerous species including Hemiscorpius lepturus (H. lepturus. The aim of this study was to assess the neutralizing ability and effectiveness of the antivenom in inhibiting hemoglobinuria, biochemical changes, increased microalbuminuria and urinary lactate dehydrogenase (LDH following H. lepturus sting. Simultaneous intramuscular administration of 10 μL and 100 μL of antivenom, after 24 hours, had no significant preventive effect on the extent and degree of hemoglobinuria or proteinuria produced in venom-treated rats. After IM administration of antivenom, no significant changes in decreased red blood cell (RBC count and hemoglobin were observed. Immediate intramuscular administration of 10 μL of antivenom had no significant effects on both LDH and microalbuminuria. The present findings did not present correlation with clinical signs. Therefore, to fully assess the efficacy of the available antivenom and make appropriate recommendations, more in vivo or in vitro investigations including antigen-antibody interaction, enzymatic analysis and route-dependent administration are required.

  11. Pharmacologic study of C-terminal fragments of frog skin calcitonin gene-related peptide.

    Science.gov (United States)

    Ladram, Ali; Besné, Isabelle; Breton, Lionel; de Lacharrière, Olivier; Nicolas, Pierre; Amiche, Mohamed

    2008-07-01

    The calcitonin gene-related peptide from the skin of the frog Phyllomedusa bicolor (pbCGRP) is a 37-residue neuropeptide that differs from human alpha CGRP (halphaCGRP) at 16 positions. The affinities of the C-terminal fragments of pbCGRP and halphaCGRP were evaluated in SK-N-MC cells: pbCGRP(8-37) (K(i)=0.2nM) and pbCGRP(27-37) (K(i)=95nM) were, respectively, 3 times and 20 times more potent than the human fragments halphaCGRP(8-37) and halphaCGRP(27-37). Their antagonistic potencies were measured in SK-N-MC and Col 29 cells, and the rat vas deferens. pbCGRP(8-37) inhibited the halphaCGRP-stimulated production of cAMP by SK-N-MC and Col 29 cells 3 to 4 times more strongly than halphaCGRP(8-37). Thus pbCGRP(8-37) is the most potent CGRP-1 competitive antagonist of all the natural sequences reported to date. pbCGRP(27-37) was also as potent as [D(31), A(34), F(35)] halphaCGRP(27-37), a prototypic antagonist analog derived from structure-activity relationship studies of halphaCGRP(8-37).

  12. Studies on functional roles of the histaminergic neuron system by using pharmacological agents, knockout mice and positron emission tomography

    International Nuclear Information System (INIS)

    Watanabe, Takehiko; Yanai, Kazuhiko

    2001-01-01

    Since one of us, Takehiko Watanabe (TW), elucidated the location and distribution of the histaminergic neuron system in the brain with antibody raised against L-histidine decarboxylase (a histamine-forming enzyme, HDC) as a marker in 1984 and came to Tohoku University School of Medicine in Sendai, we have been collaborating on the functions of this neuron system by using pharmacological agents, knockout mice of the histamine-related genes, and, in some cases, positron emission tomography (PET). Many of our graduate students and colleagues have been actively involved in histamine research since 1985. Our extensive studies have clarified some of the functions of histamine neurons using methods from molecular techniques to non-invasive human PET imaging. Histamine neurons are involved in many brain functions, such as spontaneous locomotion, arousal in wake-sleep cycle, appetite control, seizures, learning and memory, aggressive behavior and emotion. Particularly, the histaminergic neuron system is one of the most important neuron systems to maintain and stimulate wakefulness. Histamine also functions as a biprotection system against various noxious and unfavorable stimuli (for examples, convulsion, nociception, drug sensitization, ischemic lesions, and stress). Although activators of histamine neurons have not been clinically available until now, we would like to point out that the activation of the histaminergic neuron system is important to maintain mental health. Here, we summarize the newly-discovered functions of histamine neurons mainly on the basis of results from our research groups. (author)

  13. [Study on the separation process of pharmacological active total alkaloids from Chelidonium majus L. growing in Georgia].

    Science.gov (United States)

    Bozhadze, A D; Vachnadze, V Iu; Dzhokhadze, M S; Berashvili, D T; Bakuridze, A Dzh

    2013-04-01

    In present article was studied the separation process of pharmacological active total alkaloids from Chelidonium majus L. growing in Georgia. Alkaloids were extracted from medicinal herbal material and separated by liquid extraction, diluents gas and a microfiltration through membrane equipment. The obtained A1, A2, A3 fractions were analyzed by GC/MS method; in all cases separation proceeds by the principle of extraction of the target alkaloids. It was concluded that the A1 is enriched with α and β cryptopins, and protopin, but homochelidonine and chelidonine are in low contents. As accompanying alkaloid is identified dihydrosanguinarine as an artifact; the A2 is enriched with the maximum contents of stylopine and protopin, but the poor contents of chelidonine and homochelidonine; the A3 is enriched with α and β cryptopins and maximum content of chelidonine. Extraction of alkaloids from Chelidonium majus L. proceeds selectively, but depending on a way of separation of the total alkaloids allows varying qualitative and quantitative consistence of the final product.

  14. In question: the scientific value of preclinical safety pharmacology and toxicology studies with cell-based therapies

    Directory of Open Access Journals (Sweden)

    Christiane Broichhausen

    2014-01-01

    Full Text Available A new cell-based medicinal product containing human regulatory macrophages, known as Mreg_UKR, has been developed and conforms to expectations of a therapeutic drug. Here, Mreg_UKR was subjected to pharmacokinetic, safety pharmacology, and toxicological testing, which identified no adverse reactions. These results would normally be interpreted as evidence of the probable clinical safety of Mreg_UKR; however, we contend that, owing to their uncertain biological relevance, our data do not fully support this conclusion. This leads us to question whether there is adequate scientific justification for preclinical safety testing of similar novel cell-based medicinal products using animal models. In earlier work, two patients were treated with regulatory macrophages prior to kidney transplantation. In our opinion, the absence of acute or chronic adverse effects in these cases is the most convincing available evidence of the likely safety of Mreg_UKR in future recipients. On this basis, we consider that safety information from previous clinical investigations of related cell products should carry greater weight than preclinical data when evaluating the safety profile of novel cell-based medicinal products. By extension, we argue that omitting extensive preclinical safety studies before conducting small-scale exploratory clinical investigations of novel cell-based medicinal products data may be justifiable in some instances.

  15. Studies on functional roles of the histaminergic neuron system by using pharmacological agents, knockout mice and positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Takehiko; Yanai, Kazuhiko [Tohoku Univ., Sendai (Japan). Graduate School of Medicine

    2001-12-01

    Since one of us, Takehiko Watanabe (TW), elucidated the location and distribution of the histaminergic neuron system in the brain with antibody raised against L-histidine decarboxylase (a histamine-forming enzyme, HDC) as a marker in 1984 and came to Tohoku University School of Medicine in Sendai, we have been collaborating on the functions of this neuron system by using pharmacological agents, knockout mice of the histamine-related genes, and, in some cases, positron emission tomography (PET). Many of our graduate students and colleagues have been actively involved in histamine research since 1985. Our extensive studies have clarified some of the functions of histamine neurons using methods from molecular techniques to non-invasive human PET imaging. Histamine neurons are involved in many brain functions, such as spontaneous locomotion, arousal in wake-sleep cycle, appetite control, seizures, learning and memory, aggressive behavior and emotion. Particularly, the histaminergic neuron system is one of the most important neuron systems to maintain and stimulate wakefulness. Histamine also functions as a biprotection system against various noxious and unfavorable stimuli (for examples, convulsion, nociception, drug sensitization, ischemic lesions, and stress). Although activators of histamine neurons have not been clinically available until now, we would like to point out that the activation of the histaminergic neuron system is important to maintain mental health. Here, we summarize the newly-discovered functions of histamine neurons mainly on the basis of results from our research groups. (author)

  16. Phytochemical and pharmacological variability in Golden Thistle functional parts: comparative study of roots, stems, leaves and flowers.

    Science.gov (United States)

    Marmouzi, Ilias; El Karbane, Miloud; El Hamdani, Maha; Kharbach, Mourad; Naceiri Mrabti, Hanae; Alami, Rachid; Dahraoui, Souhail; El Jemli, Meryem; Ouzzif, Zhor; Cherrah, Yahia; Derraji, Soufiane; Faouzi, My El Abbes

    2017-11-01

    Scolymus hispanicus or the Golden Thistle, locally known as 'Guernina' or 'Taghediwt', is one of the most appreciated wild vegetables in Morocco. This study aims to characterise the functional chemical and pharmacological variability of Scolymus hispanicus parts (roots, stems, leaves and flowers). The chemical analysis revealed higher content of α-tocopherol in the flowers (2.79 ± 0.07 mg/100 g) and lead to the identification of 3 flavonoids and 13 phenolic acids, with high content of gallic acid in leaves (187.01 ± 10.19 mg/kg); chlorogenic (936.18 ± 92.66 mg/kg) and caffeic (4400.14 ± 191.43 mg/kg) acids in flowers, roots were much more higher in sinapic acid (0.25 ± 0.03 mg/kg) compared to the other parts. Moreover, Scolymus hispanicus ethanolic extracts exhibited interesting antioxidant and antimicrobial properties, promising anti-amylase and anti-glucosidase activities and relevant diuretic effect that confirms its traditional uses.

  17. Mucuna pruriens in Parkinson's disease: a double blind clinical and pharmacological study

    Science.gov (United States)

    Katzenschlager, R; Evans, A; Manson, A; Patsalos, P; Ratnaraj, N; Watt, H; Timmermann, L; Van der Giessen, R; Lees, A

    2004-01-01

    Background: The seed powder of the leguminous plant, Mucuna pruriens has long been used in traditional Ayurvedic Indian medicine for diseases including parkinsonism. We have assessed the clinical effects and levodopa (L-dopa) pharmacokinetics following two different doses of mucuna preparation and compared them with standard L-dopa/carbidopa (LD/CD). Methods: Eight Parkinson's disease patients with a short duration L-dopa response and on period dyskinesias completed a randomised, controlled, double blind crossover trial. Patients were challenged with single doses of 200/50 mg LD/CD, and 15 and 30 g of mucuna preparation in randomised order at weekly intervals. L-Dopa pharmacokinetics were determined, and Unified Parkinson's Disease Rating Scale and tapping speed were obtained at baseline and repeatedly during the 4 h following drug ingestion. Dyskinesias were assessed using modified AIMS and Goetz scales. Results: Compared with standard LD/CD, the 30 g mucuna preparation led to a considerably faster onset of effect (34.6 v 68.5 min; p = 0.021), reflected in shorter latencies to peak L-dopa plasma concentrations. Mean on time was 21.9% (37 min) longer with 30 g mucuna than with LD/CD (p = 0.021); peak L-dopa plasma concentrations were 110% higher and the area under the plasma concentration v time curve (area under curve) was 165.3% larger (p = 0.012). No significant differences in dyskinesias or tolerability occurred. Conclusions: The rapid onset of action and longer on time without concomitant increase in dyskinesias on mucuna seed powder formulation suggest that this natural source of L-dopa might possess advantages over conventional L-dopa preparations in the long term management of PD. Assessment of long term efficacy and tolerability in a randomised, controlled study is warranted. PMID:15548480

  18. Pharmacological evaluation of an [(123)I] labelled imidazopyridine-3-acetamide for the study of benzodiazepine receptors.

    Science.gov (United States)

    Mattner, Filomena; Mardon, Karine; Loc'h, Christian; Katsifis, Andrew

    2006-06-13

    In vitro binding of the iodinated imidazopyridine, N',N'-dimethyl-6-methyl-(4'-[(123)I]iodophenyl)imidazo[1,2-a]pyridine-3-acetamide [(123)I]IZOL to benzodiazepine binding sites on brain cortex, adrenal and kidney membranes is reported. Saturation experiments showed that [(123)I]IZOL, bound to a single class of binding site (n(H)=0.99) on adrenal and kidney mitochondrial membranes with a moderate affinity (K(d)=30 nM). The density of binding sites was 22+/-6 and 1.2+/-0.4 pmol/mg protein on adrenal and kidney membranes, respectively. No specific binding was observed in mitochondrial-synaptosomal membranes of brain cortex. In biodistribution studies in rats, the highest uptake of [(123)I]IZOL was found 30 min post injection in adrenals (7.5% ID/g), followed by heart, kidney, lung (1% ID/g) and brain (0.12% ID/g), consistent with the distribution of peripheral benzodiazepine binding sites. Pre-administration of unlabelled IZOL and the specific PBBS drugs, PK 11195 and Ro 5-4864 significantly reduced the uptake of [(123)I]IZOL by 30% (p<0.05) in olfactory bulbs and by 51-86% (p<0.01) in kidney, lungs, heart and adrenals, while it increased by 30% to 50% (p<0.01) in the rest of the brain and the blood. Diazepam, a mixed CBR-PBBS drug, inhibited the uptake in kidney, lungs, heart, adrenals and olfactory bulbs by 32% to 44% (p<0.01) but with no effect on brain uptake and in blood concentration. Flumazenil, a central benzodiazepine drug and haloperidol (dopamine antagonist/sigma receptor drug) displayed no effect in [(123)I]IZOL in peripheral organs and in the brain. [(123)I]IZOL may deserve further development for imaging selectively peripheral benzodiazepine binding sites.

  19. A Novel Pharmacological Method to Study the Chinese Medicinal Formula Hua-Zheng-Hui-Sheng-Dan

    Directory of Open Access Journals (Sweden)

    Rui Cao

    2015-01-01

    Full Text Available Objectives. Hua-Zheng-Hui-Sheng-Dan (HZHSD was used as an experimental model to explore research methods of large formulae in traditional Chinese medicine (TCM using current molecular biology approaches. Materials and Methods. The trypan blue exclusion assay was used to determine cell viability and cell numbers. Flow cytometry was used to assess cell cycle distribution and apoptosis. The concentration of cyclin D1 was analyzed by enzyme-linked immunosorbent assay. The median effect principle was used in drug combination studies. An orthogonal experimental design was used to estimate the effects of each herb at different concentrations. The HeLa xenograft mouse model was used to compare the antitumor activity of drugs in vivo. Results. Among the 35 herbs that comprise HZHSD, Radix Rehmanniae Preparata (RRP, Caesalpinia sappan (CS, Evodia rutaecarpa (ER, Folium Artemisiae Argyi (FAA, Leonurus japonicus Houtt (LJH, Tumeric (Tu, Radix Paeoniae Alba (RPA, and Trogopterus Dung (TD effectively inhibited the proliferation of HeLa and SKOV3 cells. Only RRR had an effect on HeLa and SKOV3 cell viability. According to the median effect principle, Angelica sinensis (Oliv. (AS, Tabanus (Ta, and Pollen Typhae (PT, which were proven to have a significant synergistic inhibitory effect on the proliferation of HeLa cells, were added to the original eight positive herbs. The combination of RPA and AS had a synergistic effect on inducing cell cycle S phase arrest and decreasing intracellular cyclin D1 in HeLa cells. By orthogonal experimental design, LJH and Tu were considered unnecessary herbs. The small formula (SHZHSD consisted of RPA, AS, RRR, Ta., TD, PT, ER, CS, and FAA and was able to inhibit cell proliferation and induce cell apoptosis. The antitumor effects of HZHSD and SHZHSD were also compared in vivo. Conclusions. Through molecular biology approaches both in vitro and in vivo, research into single drugs, and analysis using the median effect principle

  20. Effect of pharmacological interventions on the fronto-cingulo-parietal cognitive control network in psychiatric disorders: a transdiagnostic systematic review of fMRI studies

    Directory of Open Access Journals (Sweden)

    Therese eVan Amelsvoort

    2016-05-01

    Full Text Available Executive function deficits such as working memory, decision-making, and attention problems are a common feature of several psychiatric disorders for which no satisfactory treatment exists. Here, we transdiagnostically investigate the effects of pharmacological interventions (other than methylphenidate on the fronto-cingulo-parietal cognitive control network, in order to identify functional brain markers for future pro-cognitive pharmacological interventions. 29 manuscripts investigated the effect of pharmacological treatment on executive function-related brain correlates in psychotic disorders (n=11, depression (n=4, bipolar disorder (n=4, ADHD (n=4, OCD (n=2, smoking dependence (n=2, alcohol dependence (n=1 and pathological gambling (n=1. In terms of impact on the fronto-cingulo-parietal networks, the preliminary evidence for catechol-o-methyl-transferase inhibitors, nicotinic receptor agonists and atomoxetine suggested was relatively consistent, the data for atypical antipsychotics and anticonvulsants moderate, and interpretation of the data for antidepressants was hampered by the employed study designs. Increased activity in task-relevant areas and decreased activity in task-irrelevant areas were the most common transdiagnostic effects of pharmacological treatment. These markers showed good positive and moderate negative predictive value. It is concluded that fronto-cingulo-parietal activity changes can serve as a marker for future pro-cognitive interventions. Future recommendations include the use of randomized double-blind designs and selective cholinergic and glutamatergic compounds.

  1. Assessment of Safety, Tolerability, Pharmacokinetics, and Pharmacological Effect of Orally Administered CORT125134: An Adaptive, Double-Blind, Randomized, Placebo-Controlled Phase 1 Clinical Study.

    Science.gov (United States)

    Hunt, Hazel; Donaldson, Kirsteen; Strem, Mark; Zann, Vanessa; Leung, Pui; Sweet, Suzanne; Connor, Alyson; Combs, Dan; Belanoff, Joseph

    2018-05-01

    CORT125134 is an orally active, high-affinity, selective antagonist of the glucocorticoid receptor that is being developed for indications that may benefit from the modulation of cortisol activity. This first-in-human study was conducted to evaluate the dose-related safety, tolerability, pharmacokinetics and pharmacological effects of CORT125134 and its active metabolite CORT125201. Eighty-one healthy male or female subjects received a single dose of 5 to 500 mg CORT125134 or matching placebo across 9 cohorts; 1 cohort received 150 mg CORT125134 after a high-fat breakfast; and 46 subjects received 50 to 500 mg CORT125134 or matching placebo once daily for up to 14 days across 4 cohorts. CORT125134 was well tolerated at doses up to 250 mg per day for 14 days. CORT125134 was absorbed rapidly and eliminated with a mean half-life ranging from 11 to 19 hours. Steady state was achieved by day 7. Exposure increased in a greater than proportional manner, particularly at lower doses. Exposure to CORT125201 at steady state was less than 5% that of parent CORT125134. Evidence for the desired pharmacological effect (glucocorticoid receptor antagonism) was demonstrated by the ability of CORT125134 to prevent several effects of the glucocorticoid receptor agonist prednisone. © 2018 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

  2. Pharmacological repositioning of Achyranthes aspera as an antidepressant using pharmacoinformatic tools PASS and PharmaExpert: a case study with wet lab validation.

    Science.gov (United States)

    Goel, R K; Gawande, D Y; Lagunin, A A; Poroikov, V V

    2018-01-01

    Traditional knowledge guides the use of plants for restricted therapeutic indications, but their pharmacological actions may be found beyond their ethnic therapeutic indications employing emerging computational tools. In this context, the present study was envisaged to explore the novel pharmacological effect of Achyranthes aspera (A. aspera) using PASS and PharmaExpert software tools. Based on the predicted mechanisms of the antidepressant effect for all analysed phytoconstituents of A. aspera, one may suggest its significant antidepressant action. The possible mechanism of this novel pharmacological effect is the enhancement of serotonin release, in particular caused by hexatriacontane. Therefore, pharmacological validation of the methanolic extract, hexatriacontane rich (HRF) and hexatriacontane lacking fraction (HLF) of A. aspera was carried out using the Forced Swimming Test and Tail suspension test in mice. The cortical and hippocampal monoamine and their metabolite levels were measured using high performance liquid chromatography (HPLC). A. aspera methanolic extract, HRF treatments showed a significant antidepressant effect comparable to imipramine. Further, the corresponding surge in cortical and hippocampal monoamine and their metabolite levels was also observed with these treatments. In conclusion, A. aspera has shown a significant antidepressant effect, possibly due to hexatriacontane, by raising monoamine levels.

  3. Hypocretin and brain β-amyloid peptide interactions in cognitive disorders and narcolepsy

    Directory of Open Access Journals (Sweden)

    Yves A Dauvilliers

    2014-06-01

    Full Text Available Objective: To examine relationships between cerebrospinal fluid (CSF Alzheimer’ disease (AD biomarkers and hypocretin-1 levels in patients with cognitive abnormalities and hypocretin-deficient narcolepsy-cataplexy (NC, estimate diagnostic accuracy, and determine correlations with sleep disturbances. Background: Sleep disturbances are frequent in AD. Interactions between brain β-amyloid (Aβ aggregation and a wake-related neurotransmitter hypocretin have been reported in a mouse model of AD. Methods: Ninety-one cognitive patients (37 AD, 16 mild cognitive impairment – MCI that converts to AD, 38 other dementias and 15 elderly patients with NC were recruited. Patients were diagnosed blind to CSF results. CSF A42, total tau, ptau181, and hypocretin-1 were measured. Sleep disturbances were assessed with questionnaires in 32 cognitive patients. Results: Lower CSF Aβ42 but higher tau and P-tau levels were found in AD and MCI compared to other dementias. CSF hypocretin-1 levels were higher in patients with MCI due to AD compared to other dementias, with a similar tendency for patients with advanced AD. CSF hypocretin-1 was significantly and independently associated with AD/MCI due to AD, with an OR of 2.70 after full adjustment, exceeding that for Aβ42. Aβ42 correlated positively with hypocretin-1 levels in advanced stage AD. No association was found between sleep disturbances and CSF biomarkers. No patients with NC achieved pathological cutoffs for Aβ42, with respectively one and four patients with NC above tau and P-tau cutoffs and no correlations between hypocretin-1 and other biomarkers. Conclusions: Our results suggest a pathophysiological relationship between Aβ42 and hypocretin-1 in the AD process, with higher CSF hypocretin-1 levels in early disease stages. Further longitudinal studies are needed to validate these biomarker interactions and to determine the cause-effect relationship and the role of wake/sleep behavior in amyloid

  4. Effects of haloperidol and aripiprazole on the human mesolimbic motivational system: A pharmacological fMRI study.

    Science.gov (United States)

    Bolstad, Ingeborg; Andreassen, Ole A; Groote, Inge; Server, Andres; Sjaastad, Ivar; Kapur, Shitij; Jensen, Jimmy

    2015-12-01

    The atypical antipsychotic drug aripiprazole is a partial dopamine (DA) D2 receptor agonist, which differentiates it from most other antipsychotics. This study compares the brain activation characteristic produced by aripiprazole with that of haloperidol, a typical D2 receptor antagonist. Healthy participants received an acute oral dose of haloperidol, aripiprazole or placebo, and then performed an active aversive conditioning task with aversive and neutral events presented as sounds, while blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) was carried out. The fMRI task, targeting the mesolimbic motivational system that is thought to be disturbed in psychosis, was based on the conditioned avoidance response (CAR) animal model - a widely used test of therapeutic potential of antipsychotic drugs. In line with the CAR animal model, the present results show that subjects given haloperidol were not able to avoid more aversive than neutral task trials, even though the response times were shorter during aversive events. In the aripiprazole and placebo groups more aversive than neutral events were avoided. Accordingly, the task-related BOLD-fMRI response in the mesolimbic motivational system was diminished in the haloperidol group compared to the placebo group, particularly in the ventral striatum, whereas the aripiprazole group showed task-related activations intermediate of the placebo and haloperidol groups. The current results show differential effects on brain function by aripiprazole and haloperidol, probably related to altered DA transmission. This supports the use of pharmacological fMRI to study antipsychotic properties in humans. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  5. ADME studies and preliminary safety pharmacology of LDT5, a lead compound for the treatment of benign prostatic hyperplasia

    Directory of Open Access Journals (Sweden)

    F. Noël

    Full Text Available This study aimed to estimate the absorption, distribution, metabolism and excretion (ADME properties and safety of LDT5, a lead compound for oral treatment of benign prostatic hyperplasia that has previously been characterized as a multi-target antagonist of α1A-, α1D-adrenoceptors and 5-HT1A receptors. The preclinical characterization of this compound comprised the evaluation of its in vitro properties, including plasma, microsomal and hepatocytes stability, cytochrome P450 metabolism and inhibition, plasma protein binding, and permeability using MDCK-MDR1 cells. De-risking and preliminary safety pharmacology assays were performed through screening of 44 off-target receptors and in vivo tests in mice (rota-rod and single dose toxicity. LDT5 is stable in rat and human plasma, human liver microsomes and hepatocytes, but unstable in rat liver microsomes and hepatocytes (half-life of 11 min. LDT5 is highly permeable across the MDCK-MDR1 monolayer (Papp ∼32×10-6 cm/s, indicating good intestinal absorption and putative brain penetration. LDT5 is not extensively protein-bound and is a substrate of human CYP2D6 and CYP2C19 but not of CYP3A4 (half-life >60 min, and did not significantly influence the activities of any of the human cytochrome P450 isoforms screened. LDT5 was considered safe albeit new studies are necessary to rule out putative central adverse effects through D2, 5-HT1A and 5-HT2B receptors, after chronic use. This work highlights the drug-likeness properties of LDT5 and supports its further preclinical development.

  6. Spatial heterogeneity of the relation between resting-state connectivity and blood flow: an important consideration for pharmacological studies.

    Science.gov (United States)

    Khalili-Mahani, Najmeh; van Osch, Matthias J; de Rooij, Mark; Beckmann, Christian F; van Buchem, Mark A; Dahan, Albert; van Gerven, Johannes M; Rombouts, Serge A R B

    2014-03-01

    Resting state fMRI (RSfMRI) and arterial spin labeling (ASL) provide the field of pharmacological Neuroimaging tool for investigating states of brain activity in terms of functional connectivity or cerebral blood flow (CBF). Functional connectivity reflects the degree of synchrony or correlation of spontaneous fluctuations--mostly in the blood oxygen level dependent (BOLD) signal--across brain networks; but CBF reflects mean delivery of arterial blood to the brain tissue over time. The BOLD and CBF signals are linked to common neurovascular and hemodynamic mechanisms that necessitate increased oxygen transportation to the site of neuronal activation; however, the scale and the sources of variation in static CBF and spatiotemporal BOLD correlations are likely different. We tested this hypothesis by examining the relation between CBF and resting-state-network consistency (RSNC)--representing average intranetwork connectivity, determined from dual regression analysis with eight standard networks of interest (NOIs)--in a crossover placebo-controlled study of morphine and alcohol. Overall, we observed spatially heterogeneous relations between RSNC and CBF, and between the experimental factors (drug-by-time, time, drug and physiological rates) and each of these metrics. The drug-by-time effects on CBF were significant in all networks, but significant RSNC changes were limited to the sensorimotor, the executive/salience and the working memory networks. The post-hoc voxel-wise statistics revealed similar dissociations, perhaps suggesting differential sensitivity of RSNC and CBF to neuronal and vascular endpoints of drug actions. The spatial heterogeneity of RSNC/CBF relations encourages further investigation into the role of neuroreceptor distribution and cerebrovascular anatomy in predicting spontaneous fluctuations under drugs. Copyright © 2012 Wiley Periodicals, Inc.

  7. Increased serum brain-derived neurotrophic factor (BDNF) levels in patients with narcolepsy

    DEFF Research Database (Denmark)

    Klein, Anders B; Jennum, Poul; Knudsen, Stine

    2013-01-01

    in hypocretin neurons in hypothalamus in post-mortem tissue. Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are important for activity-dependent neuronal function and synaptic modulation and it is considered that these mechanisms are important in sleep regulation. We hypothesised......Narcolepsy is a lifelong sleep disorder characterized by excessive daytime sleepiness, sudden loss of muscle tone (cataplexy), fragmentation of nocturnal sleep and sleep paralysis. The symptoms of the disease strongly correlate with a reduction in hypocretin levels in CSF and a reduction...... that serum levels of these factors are altered in patients with narcolepsy compared to healthy controls without sleep disturbances. Polysomnography data was obtained and serum BDNF and NGF levels measured using ELISA, while hypocretin was measured using RIA. Serum BDNF levels were significantly higher...

  8. Pharmacological therapy for amblyopia

    Directory of Open Access Journals (Sweden)

    Anupam Singh

    2017-01-01

    Full Text Available Amblyopia is the most common cause of preventable blindness in children and young adults. Most of the amblyopic visual loss is reversible if detected and treated at appropriate time. It affects 1.0 to 5.0% of the general population. Various treatment modalities have been tried like refractive correction, patching (both full time and part time, penalization and pharmacological therapy. Refractive correction alone improves visual acuity in one third of patients with anisometropic amblyopia. Various drugs have also been tried of which carbidopa & levodopa have been popular. Most of these agents are still in experimental stage, though levodopa-carbidopa combination therapy has been widely studied in human amblyopes with good outcomes. Levodopa therapy may be considered in cases with residual amblyopia, although occlusion therapy remains the initial treatment choice. Regression of effect after stoppage of therapy remains a concern. Further studies are therefore needed to evaluate the full efficacy and side effect profile of these agents.

  9. Pharmacological therapy for amblyopia

    Science.gov (United States)

    Singh, Anupam; Nagpal, Ritu; Mittal, Sanjeev Kumar; Bahuguna, Chirag; Kumar, Prashant

    2017-01-01

    Amblyopia is the most common cause of preventable blindness in children and young adults. Most of the amblyopic visual loss is reversible if detected and treated at appropriate time. It affects 1.0 to 5.0% of the general population. Various treatment modalities have been tried like refractive correction, patching (both full time and part time), penalization and pharmacological therapy. Refractive correction alone improves visual acuity in one third of patients with anisometropic amblyopia. Various drugs have also been tried of which carbidopa & levodopa have been popular. Most of these agents are still in experimental stage, though levodopa-carbidopa combination therapy has been widely studied in human amblyopes with good outcomes. Levodopa therapy may be considered in cases with residual amblyopia, although occlusion therapy remains the initial treatment choice. Regression of effect after stoppage of therapy remains a concern. Further studies are therefore needed to evaluate the full efficacy and side effect profile of these agents. PMID:29018759

  10. Attenuated Heart Rate Response is Associated with Hypocretin Deficiency in Patients with Narcolepsy

    DEFF Research Database (Denmark)

    Sørensen, Gertrud Laura; Knudsen, Stine; Petersen, Eva Rosa

    2013-01-01

    Our results show that autonomic dysfunction is part of the narcoleptic phenotype, and that hypocretin-1 deficiency is the primary predictor of this dysfunction. This finding suggests that the hypocretin system participates in the modulation of cardiovascular function at rest. CITATION: Sorensen GL......; Knudsen S; Petersen ER; Kempfner J; Gammeltoft S; Sorensen HBD; Jennum P. Attenuated heart rate response is associated with hypocretin deficiency in patients with narcolepsy. SLEEP 2013;36(1):91-98....

  11. A patient with coexisting narcolepsy and morbid jealousy showing favourable response to fluoxetine.

    Science.gov (United States)

    Wing, Y. K.; Lee, S.; Chiu, H. F.; Ho, C. K.; Chen, C. N.

    1994-01-01

    A 37 year old Chinese man suffered from coexisting narcolepsy and morbid jealousy which were precipitated by head injury 5 years previously. Fluoxetine 20 mg/day reduced his narcoleptic symptoms and morbid jealousy but not his sleepiness. On defaulting treatment, the patient's symptoms and marital problem recurred. A common central serotonin disturbance might be involved in mediating the sleep disorder and associated psychopathology. PMID:8140016

  12. Treatment with venlafaxine in six cases of children with narcolepsy and with cataplexy and hypnagogic hallucinations.

    Science.gov (United States)

    Møller, Lene Ruge; Østergaard, John R

    2009-04-01

    Narcolepsy with cataplexy is a chronic neuropsychiatric disorder associated with inappropriate control of rapid eye movement (REM) sleep. The main symptoms are excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and disturbed nocturnal sleep. Cataplexy is marked by episodes of muscular weakness and may cause the patient to collapse to the ground. So far, pharmacotherapy of cataplexy and hypnagogic hallucinations has been predominantly based on tricyclic antidepressants. Recently, new drugs that block the reuptake of norepineprine and serotonin (e.g., venlafaxine) have been suggested as first-line treatment. These drugs have become our choice in treating children with cataplexy and nightmares as a symptom in narcolepsy. We describe clinical case reports of venlafaxine treatment in 6 children aged 7-12 years old when diagnosed with narcolepsy-cataplexy. In 2 cases with up to 50 daily cataplectic attacks, an initial effect of 37.5 mg of venlafaxine was initially observed. However, during the first year, the dose had to be increased to 112.5 mg daily to avoid cataplexy. A third patient with partial cataplexy was treated with 75 mg of venlafaxine daily. In 2 cases, hypnagogic hallucinations, described by the patients as nightmares, were the most troubling symptom and were successfully treated with only 37.5 mg of venlafaxine daily. Side effects included an increase of disturbed nocturnal sleep when venlafaxine was taken after 2:00 p.m. No major aggressive or suicidal thoughts and no raised blood pressure were recorded. Venlafaxine has proven to be an effective treatment of cataplexy and hypnagogic hallucinations in 6 children with narcolepsy. No severe side effects were observed.

  13. Study of gamma radiation from 60Co effects on Apis mellifera venom: biochemical, pharmacological and immunological aspects

    International Nuclear Information System (INIS)

    Costa, Helena

    2001-01-01

    Africanized honeybees are very common insects in Brazil and frequently cause accidents followed by important immunological reactions and even deaths. Their venoms are composed of a complex mixture of substances of general biological actions. Ionizing radiation is able to modify molecular structures affecting the biological properties of proteins. It decreases toxic and enzymatic activities and so, it appears promising as a venom detoxification tool. The main objective of this work was to study the effects of gamma radiation on bee venom, regarding biochemical, pharmacological and immunological aspects. Africanized Apis mellifera whole venom (2 mg/ml) in 0.15 M NaCl solution was irradiated with 2 kGy in a 60 Co source. Native and irradiated bee venoms were submitted to high performance size exclusion chromatography (Tosohaas G2000SW column), high performance reversed phase chromatography in a C-18 column under water/acetonitrile gradient, SDS-PAGE. For both venoms studies have been carried out in UV absorption spectrum, protein concentration, hemolytic activity, and PLA 2 activity analysis, lethality assay (LD 50 ). Biodistribution studies was carried out after labelling native and irradiated bee venom with 99m Tc. The results showed that gamma radiation did not change the protein concentration nor its immunogenicity, although it could be observed that irradiated bee venom UV spectrum and SDS-PAGE profile presented differences when compared to native bee venom. This suggests that some structural alterations in bee venom components could have occurred after irradiation. HPLC-RP profiles showed that gamma radiation could have caused conformational changes, such as unfolding of molecule chains, changing their hydrophobic groups exposuring. The hemolytic and the PLA 2 activities of irradiated bee venom were smaller than the native ones. The gamma radiation diminished the toxicity of bee venom, but did not abolish its bioactivity, like hemolysis. Biodistribution studies

  14. Hypocretin-1 Levels Associate with Fragmented Sleep in Patients with Narcolepsy Type 1.

    Science.gov (United States)

    Alakuijala, Anniina; Sarkanen, Tomi; Partinen, Markku

    2016-05-01

    We aimed to analyze nocturnal sleep characteristics of patients with narcolepsy type 1 (narcolepsy with cataplexy) measured by actigraphy in respect to cerebrospinal fluid hypocretin-1 levels of the same patients. Actigraphy recording of 1-2 w and hypocretin-1 concentration analysis were done to thirty-six unmedicated patients, aged 7 to 63 y, 50% female. Twenty-six of them had hypocretin-1 levels under 30 pg/mL and the rest had levels of 31-79 pg/mL. According to actigraphy, patients with very low hypocretin levels had statistically significantly longer sleep latency (P = 0.033) and more fragmented sleep, indicated by both the number of immobile phases of 1 min (P = 0.020) and movement + fragmentation index (P = 0.049). There were no statistically significant differences in the actual sleep time or circadian rhythm parameters measured by actigraphy. Actigraphy gives additional information about the stabilization of sleep in patients with narcolepsy type 1. Very low hypocretin levels associate with more wake intruding into sleep. © 2016 Associated Professional Sleep Societies, LLC.

  15. Bioactive non-sterol triterpenoid from Streblus asper: microwave-assisted extraction, HPTLC profiling, computational studies and neuro-pharmacological evaluation in BALB/c mice.

    Science.gov (United States)

    Verma, Vandana; Tripathi, Avinash C; Saraf, Shailendra K

    2016-11-01

    In folk medicine, the stem bark of Streblus asper Lour. (Moraceae) has been reported to possess anticonvulsant activity. However, no systematic/scientific validation is available. Objective This study explores the constituents in the stem bark, their biosassy-guided isolation and their efficacy in neuro-pharmacological disorders, for validating the traditional claims. Microwave-assisted extraction (MAE) technique was employed to obtain the crude extract. The n-hexane, dichloromethane and aqueous fractions were prepared and phytoconstituents were ascertained by phytochemical tests. The isolated compound, betulin, was characterized by different physicochemical and spectral methods, including HPTLC. Finally, neuro-pharmacological evaluations were conducted at 100, 200, 400 mg/kg b.w., p.o. (25, 50, 100 mg/kg b.w. for betulin) doses in BALB/c mice. The n-hexane fraction (400 mg/kg), and isolated compound betulin (100 mg/kg), showed maximum anticonvulsant activity in maximal electroshock (87.84% and 85.14% seizure inhibition), and isoniazid induced convulsion models (88.85% and 83.18% seizure inhibition), respectively. A dose-dependent attenuation of epileptic seizures was observed, probably through GABArgic mechanism of anticonvulsant action. Moreover, the antidepressant study was also conducted using behavioural models and the results expound that n-hexane and dichloromethane fractions (400 mg/kg) significantly reduced the duration of immobility, as compared to the control. This study reports some novel aspects like applying an environmentally benign/green approach of MAE, neuro-pharmacological screening and use of docking studies, for the first time, on the plant S. asper. The findings present a rational explanation for its use in traditional medicine, for the management of neuro-pharmacological disorders.

  16. The role of GABAB(1) receptor isoforms in anxiety and depression : genetic and pharmacological studies in the mouse

    OpenAIRE

    Jacobson, Laura Helen

    2007-01-01

    Anxiety and depression disorders represent common, serious and growing health problems world-wide. The neurobiological basis of anxiety and depression, however, remains poorly understood. Further, there is a clear need for the development of better treatments for these disorders. Emerging data with genetic and pharmacological tools supports a role for GABAB receptors in both anxiety and depression. GABAB receptors are metabotropic GABA receptors that are comprised of two subunits, GABAB1 and ...

  17. Narcolepsy: Autoimmunity, Effector T Cell Activation Due to Infection, or T Cell Independent, Major Histocompatibility Complex Class II Induced Neuronal Loss?

    Science.gov (United States)

    Fontana, Adriano; Gast, Heidemarie; Reith, Walter; Recher, Mike; Birchler, Thomas; Bassetti, Claudio L.

    2010-01-01

    Human narcolepsy with cataplexy is a neurological disorder, which develops due to a deficiency in hypocretin producing neurons in the hypothalamus. There is a strong association with human leucocyte antigens HLA-DR2 and HLA-DQB1*0602. The disease typically starts in adolescence. Recent developments in narcolepsy research support the hypothesis of…

  18. Biological and Pharmacological properties

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Biological and Pharmacological properties. NOEA inhibits Ceramidase. Anandamide inhibits gap junction conductance and reduces sperm fertilizing capacity. Endogenous ligands for Cannabinoid receptors (anandamide and NPEA). Antibacterial and antiviral ...

  19. A multi-site comparison of in vivo safety pharmacology studies conducted to support ICH S7A & B regulatory submissions.

    Science.gov (United States)

    Ewart, Lorna; Milne, Aileen; Adkins, Debbie; Benjamin, Amanda; Bialecki, Russell; Chen, Yafei; Ericsson, Ann-Christin; Gardner, Stacey; Grant, Claire; Lengel, David; Lindgren, Silvana; Lowing, Sarah; Marks, Louise; Moors, Jackie; Oldman, Karen; Pietras, Mark; Prior, Helen; Punton, James; Redfern, Will S; Salmond, Ross; Skinner, Matt; Some, Margareta; Stanton, Andrea; Swedberg, Michael; Finch, John; Valentin, Jean-Pierre

    2013-01-01

    Parts A and B of the ICH S7 guidelines on safety pharmacology describe the in vivo studies that must be conducted prior to first time in man administration of any new pharmaceutical. ICH S7A requires a consideration of the sensitivity and reproducibility of the test systems used. This could encompass maintaining a dataset of historical pre-dose values, power analyses, as well as a demonstration of acceptable model sensitivity and robust pharmacological validation. During the process of outsourcing safety pharmacology studies to Charles River Laboratories, AstraZeneca set out to ensure that models were performed identically in each facility and saw this as an opportunity to review the inter-laboratory variability of these essential models. The five in vivo studies outsourced were the conscious dog telemetry model for cardiovascular assessment, the rat whole body plethysmography model for respiratory assessment, the rat modified Irwin screen for central nervous system assessment, the rat charcoal meal study for gastrointestinal assessment and the rat metabolic cage study for assessment of renal function. Each study was validated with known reference compounds and data were compared across facilities. Statistical power was also calculated for each model. The results obtained indicated that each of the studies could be performed with comparable statistical power and could achieve a similar outcome, independent of facility. The consistency of results obtained from these models across multiple facilities was high thus providing confidence that the models can be run in different facilities and maintain compliance with ICH S7A and B. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Pharmacists' and general practitioners' pharmacology knowledge and pharmacotherapy skills

    NARCIS (Netherlands)

    Keijsers, Carolina J P W; Leendertse, Anne J; Faber, Adrianne; Brouwers, Jacobus R B J; de Wildt, Dick J; Jansen, Paul A F

    Understanding differences in the pharmacology knowledge and pharmacotherapy skills of pharmacists and physicians is vital to optimizing interprofessional collaboration and education. This study investigated these differences and the potential influence of work experience. The pharmacology knowledge

  1. Practice Parameters for the Treatment of Narcolepsy and other Hypersomnias of Central Origin An American Academy of Sleep Medicine Report

    Science.gov (United States)

    Morgenthaler, Timothy I.; Kapur, Vishesh K.; Brown, Terry; Swick, Todd J.; Alessi, Cathy; Aurora, R. Nisha; Boehlecke, Brian; Chesson, Andrew L.; Friedman, Leah; Maganti, Rama; Owens, Judith; Pancer, Jeffrey; Zak, Rochelle

    2007-01-01

    These practice parameters pertain to the treatment of hypersomnias of central origin. They serve as both an update of previous practice parameters for the therapy of narcolepsy and as the first practice parameters to address treatment of other hypersomnias of central origin. They are based on evidence analyzed in the accompanying review paper. The specific disorders addressed by these parameters are narcolepsy (with cataplexy, without cataplexy, due to medical condition and unspecified), idiopathic hypersomnia (with long sleep time and without long sleep time), recurrent hypersomnia and hypersomnia due to medical condition. Successful treatment of hypersomnia of central origin requires an accurate diagnosis, individual tailoring of therapy to produce the fullest possible return of normal function, and regular follow-up to monitor response to treatment. Modafinil, sodium oxybate, amphetamine, methamphetamine, dextroamphetamine, methylphenidate, and selegiline are effective treatments for excessive sleepiness associated with narcolepsy, while tricyclic antidepressants and fluoxetine are effective treatments for cataplexy, sleep paralysis, and hypnagogic hallucinations; but the quality of published clinical evidence supporting them varies. Scheduled naps can be beneficial to combat sleepiness in narcolepsy patients. Based on available evidence, modafinil is an effective therapy for sleepiness due to idiopathic hypersomnia, Parkinson's disease, myotonic dystrophy, and multiple sclerosis. Based on evidence and/or long history of use in the therapy of narcolepsy committee consensus was that modafinil, amphetamine, methamphetamine, dextroamphetamine, and methylphenidate are reasonable options for the therapy of hypersomnias of central origin. Citation: Morgenthaler TI; Kapur VK; Brown T; Swick TJ; Alessi C; Aurora RN; Boehlecke B; Chesson AL; Friedman L; Maganti R; Owens J; Pancer J; Zak R; Standards of Practice Committee of the AASM. Practice parameters for the treatment

  2. Pharmacological therapy of spondyloarthritis.

    Science.gov (United States)

    Palazzi, Carlo; D'Angelo, Salvatore; Gilio, Michele; Leccese, Pietro; Padula, Angela; Olivieri, Ignazio

    2015-01-01

    The current pharmacological therapy of spondyloarthritis (SpA) includes several drugs: Non-steroidal anti-inflammatory drugs, corticosteroids, traditional disease-modifying antirheumatic drugs and biologic drugs. A systematic literature search was completed using the largest electronic databases (Medline, Embase and Cochrane), starting from 1995, with the aim to review data on traditional and biologic agents commercialised for SpA treatment. Randomised controlled trials and large observational studies were considered. In addition, studies performed in SpA patients treated with other, still unapproved, drugs (rituximab, anti-IL6 agents, apremilast, IL17 inhibitors and anakinra) were also taken into account. Biologic agents, especially anti-TNF drugs, have resulted in significant progress in improving clinical symptoms and signs, reducing inflammatory features in laboratory tests and imaging findings, and recovering all functional indexes. Anti-TNF drugs have radically changed the evolution of radiographic progression in peripheral joints; the first disappointing data concerning their efficacy on new bone formation of axial SpA has been recently challenged by studies enrolling patients who have been earlier diagnosed and treated. The opportunity to extend the interval of administration or to reduce the doses of anti-TNF agents can favourably influence the costs. Ustekinumab, the first non-anti-TNF biologic drug commercialised for psoriatic arthritis, offers new chances to patients that are unresponsive to anti-TNF.

  3. Intravenous immunoglobulin treatment and screening for hypocretin neuron-specific autoantibodies in recent onset childhood narcolepsy with cataplexy

    DEFF Research Database (Denmark)

    Knudsen, S; Mikkelsen, J D; Bang, B

    2010-01-01

    Narcolepsy with cataplexy (NC) is caused by substantial loss of hypocretin neurons. NC patients carry the HLA-DQB1*0602 allele suggesting that hypocretin neuron loss is due to an autoimmune attack. We tested intravenous immunoglobulin (IVIG) treatment in early onset NC.......Narcolepsy with cataplexy (NC) is caused by substantial loss of hypocretin neurons. NC patients carry the HLA-DQB1*0602 allele suggesting that hypocretin neuron loss is due to an autoimmune attack. We tested intravenous immunoglobulin (IVIG) treatment in early onset NC....

  4. Bioanalysis, metabolism & clinical pharmacology of antiretroviral drugs

    NARCIS (Netherlands)

    Heine, R. ter

    2009-01-01

    The aims of all studies described in this thesis were to develop new bioanalytical and more patient friendly methods for studying the clinical pharmacology of antiretroviral drugs and to ultimately improve antiretroviral treatment.

  5. A feasibility study of a new approach to clinical radiosensitisation: hypothermia and hyperbaric oxygen in combination with pharmacological vasodilatation

    International Nuclear Information System (INIS)

    Sealy, R.; Harrison, G.G.; Morrell, D.; Cape Town Univ.

    1986-01-01

    It is proposed that hyperbaric oxygen fails in the clinical situation due to a high proportion (greater than 33%) of hypoxic cells in human tumours. The means of overcoming this problem are reviewed. Additional to hyperbaric oxygenation, moderate hypothermia (30 0 C) to allow redistribution of oxygen in the tumour is proposed. A system of externally controlled intravenous anaesthesia has been developed for the single-subject hypervaric cylinder. Pharmacological vasodilatation is induced in the anaesthetised patient who is then fluid loaded and cooled. Initial single-sensitising treatments are advocated. Twenty-nine patients with advanced mouth cancer have completed a course of this treatment, of whom five of nine were free of disease after 2 years and 10 of 21 at 1 year, with three intercurrent deaths. Fifteen have experienced local failure. This approach would appear to be practical, safe and promising. (author)

  6. Pharmacology of midazolam.

    Science.gov (United States)

    Pieri, L; Schaffner, R; Scherschlicht, R; Polc, P; Sepinwall, J; Davidson, A; Möhler, H; Cumin, R; Da Prada, M; Burkard, W P; Keller, H H; Müller, R K; Gerold, M; Pieri, M; Cook, L; Haefely, W

    1981-01-01

    8-Chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4]benzodiazepine (midazolam, Ro 21-3981, Dormicum) is an imidazobenzodiazepine whose salts are soluble and stable in aqueous solution. It has a quick onset and, due to rapid metabolic inactivation, a rather short duration of action in all species studied. Midazolam has a similar pharmacologic potency and broad therapeutic range as diazepam. It produces all the characteristic effects of the benzodiazepine class, i.e., anticonvulsant, anxiolytic, sleep-inducing, muscle relaxant, and "sedative" effects. The magnitude of the anticonflict effect of midazolam is smaller than that of diazepam in rats and squirrel monkeys, probably because a more pronounced sedative component interferes with the increase of punished responses. In rodents, surgical anaesthesia is not attained with midazolam alone even in high i.v. doses, whereas this state is obtained in monkeys. The drug potentiates the effect of various central depressant agents. Midazolam is virtually free of effects on the cardiovascular system in conscious animals and produces only slight decreases in cardiac performance in dogs anaesthetized with barbiturates. No direct effects of the drugs on autonomic functions were found, however, stress-induced autonomic disturbances are prevented, probably by an effect on central regulatory systems. All animal data suggest the usefulness of midazolam as a sleep-inducer and i.v. anaesthetic of rapid onset and short duration.

  7. HLA DQB1*06:02 negative narcolepsy with hypocretin/orexin deficiency.

    Science.gov (United States)

    Han, Fang; Lin, Ling; Schormair, Barbara; Pizza, Fabio; Plazzi, Giuseppe; Ollila, Hanna M; Nevsimalova, Sona; Jennum, Poul; Knudsen, Stine; Winkelmann, Juliane; Coquillard, Cristin; Babrzadeh, Farbod; Strom, Tim M; Wang, Chunlin; Mindrinos, Michael; Fernandez Vina, Marcelo; Mignot, Emmanuel

    2014-10-01

    To identify rare allelic variants and HLA alleles in narcolepsy patients with hypocretin (orexin, HCRT) deficiency but lacking DQB1*06:02. China (Peking University People's Hospital), Czech Republic (Charles University), Denmark (Golstrup Hospital), Italy (University of Bologna), Korea (Catholic University), and USA (Stanford University). CSF hypocretin-1, DQB1*06:02, clinical and polysomnographic data were collected in narcolepsy patients (552 with and 144 without cataplexy) from 6 sites. Numbers of cases with and without DQB1*06:02 and low CSF hypocretin-1 were compiled. HLA class I (A, B, C), class II (DRBs, DQA1, DQB1, DPA1, and DPB1), and whole exome sequencing were conducted in 9 DQB1*06:02 negative cases with low CSF hypocretin-1. Sanger sequencing of selected exons in DNMT1, HCRT, and MOG was performed to exclude mutations in known narcolepsy-associated genes. Classic narcolepsy markers DQB1*06:02 and low CSF hypocretin-1 were found in 87.4% of cases with cataplexy, and in 20.0% without cataplexy. Nine cases (all with cataplexy) were DQB1*06:02 negative with low CSF hypocretin-1, constituting 1.7% [0.8%-3.4%] of all cases with cataplexy and 1.8% [0.8%-3.4%] of cases with low CSF hypocretin independent of cataplexy across sites. Five HLA negative subjects had severe cataplexy, often occurring without clear triggers. Subjects had diverse ethnic backgrounds and HLA alleles at all loci, suggesting no single secondary HLA association. The rare subtype DPB1*0901, and homologous DPB1*10:01 subtype, were present in 5 subjects, suggesting a secondary association with HLA-DP. Preprohypocretin sequencing revealed no mutations beyond one previously reported in a very early onset case. No new MOG or DNMT1 mutations were found, nor were suspicious or private variants in novel genes identified through exome sequencing. Hypocretin, MOG, or DNMT1 mutations are exceptional findings in DQB1*06:02 negative cases with hypocretin deficiency. A secondary HLA-DP association may be

  8. Flow cytometry analysis of T-cell subsets in cerebrospinal fluid of narcolepsy type 1 patients with long-lasting disease

    DEFF Research Database (Denmark)

    Moresco, Monica; Lecciso, Mariangela; Ocadlikova, Darina

    2018-01-01

    BACKGROUND: Type 1 narcolepsy (NT1) is a central hypersomnia linked to the destruction of hypocretin-producing neurons. A great body of genetic and epidemiological data points to likely autoimmune disease aetiology. Recent reports have characterized peripheral blood T-cell subsets in NT1, whereas...... data regarding the cerebrospinal fluid (CSF) immune cell composition are lacking. The current study aimed to characterize the T-cell and natural killer (NK) cell subsets in NT1 patients with long disease course. METHODS: Immune cell subsets from CSF and peripheral blood mononuclear cell (PBMC) samples...... were analysed by flow cytometry in two age-balanced and sex-balanced groups of 14 NT1 patients versus 14 healthy controls. The frequency of CSF cell groups was compared with PBMCs. Non-parametric tests were used for statistical analyses. RESULTS: The NT1 patients did not show significant differences...

  9. Comparative efficacy of pharmacological and non-pharmacological interventions for the acute treatment of adult outpatients with anorexia nervosa: study protocol for the systematic review and network meta-analysis of individual data.

    Science.gov (United States)

    Wade, Tracey D; Treasure, Janet; Schmidt, Ulrike; Fairburn, Christopher G; Byrne, Susan; Zipfel, Stephan; Cipriani, Andrea

    2017-01-01

    Outpatient treatment studies of anorexia nervosa (AN) are notoriously hard to conduct given the ambivalence of the patient group and high drop-out rates. It is therefore not surprising that previous meta-analyses of pharmacological and psychological treatments for outpatient treatment of adult AN have proved to be inconclusive. Network meta-analysis (NMA) has the potential to overcome the limitations of pairwise meta-analysis, as this approach can compare multiple treatments using both direct comparisons of interventions within randomized controlled trials (RCTs) and indirect comparisons across trials based on a common comparator. To date there is no published example of this approach with eating disorders and the current study provides a protocol which will use NMA to advance knowledge about what outpatient therapy works best for which patients with AN by conducting both direct and indirect comparisons of different treatments and the moderating variables. Searches of electronic data bases will be supplemented with manual searches for published, unpublished and ongoing RCTs in international registries, and clinical trials registries of regulatory agencies and pharmaceutical companies. Two reviewers will independently extract the data and where possible we will access individual data in order to examine moderators of treatment. Two primary outcomes will be selected: changes to body mass index and changes to global eating disorder psychopathology. The secondary outcome is the total number of patients who, at 12-month post-randomization, attained over the previous 28 day period: (i) BMI > 18.5, and (ii) global eating disorder psychopathology to within 1 SD of community norms. We will also provide a statistical evaluation of consistency, the agreement between direct and indirect evidence. Descriptive statistics across all eligible trials will be provided along with a network diagram, where the size of the nodes will reflect the amount of evidence accumulated for

  10. [PROFESSOR VLADIMIR V. NIKOLAEV AND RUSSIAN PHARMACOLOGY.

    Science.gov (United States)

    Bondarchuk, N G; Fisenko, V P

    2016-01-01

    Various stages of scientific research activity of Prof. Vladimir V. Nikolaev are analyzed. The importance of Prof. Nikolaev's discovery of the two-neuron parasympathetic nervous system and some new methods of pharmacological substances evaluation is shown. Prof. Nikolaev is known as the editor of the first USSR Pharmacopoeia. Peculiarities of pharmacology teaching at the First Moscow Medical institute under conditions of changing social demands are described. Successful research of Prof. Nikolaev with colleagues in studying new mechanisms of drug action and developing original pharmacological substances is summarized.

  11. Problems of pharmacological supply of disaster medicine

    International Nuclear Information System (INIS)

    Sabaev, V.V.; Il'ina, S.L.

    1995-01-01

    The paper reviews a number of pharmacological problems, being important for the disaster medicine, of theoretical and practical nature, the settlement of which would promote more efficient rendering emergency medical aid to the injured persons in the conditions of emergency situations and further expert medical care. On the example of radiation accidents there are studied methodical approaches to organization of drug prophylaxis and therapy of the injured persons in emergency situations. The authors have proved the necessity of arranging proper pharmacological supply of disaster medicine which is to settle the whole complex of scientific-applied and organizational questions relating to the competence of pharmacology and pharmacy. 17 refs

  12. [Contribution of animal experimentation to pharmacology].

    Science.gov (United States)

    Sassard, Jean; Hamon, Michel; Galibert, Francis

    2009-11-01

    Animal experimentation is of considerable importance in pharmacology and cannot yet be avoided when studying complex, highly integrated physiological functions. The use of animals has been drastically reduced in the classical phases of pharmacological research, for example when comparing several compounds belonging to the same pharmacological class. However, animal experiments remain crucial for generating and validating new therapeutic concepts. Three examples of such research, conducted in strict ethical conditions, will be used to illustrate the different ways in which animal experimentation has contributed to human therapeutics.

  13. Narcolepsy Type 1 Is Associated with a Systemic Increase and Activation of Regulatory T Cells and with a Systemic Activation of Global T Cells.

    Directory of Open Access Journals (Sweden)

    Michel Lecendreux

    Full Text Available Narcolepsy is a rare neurologic disorder characterized by excessive daytime sleepiness, cataplexy and disturbed nocturnal sleep patterns. Narcolepsy type 1 (NT1 has been shown to result from a selective loss of hypothalamic hypocretin-secreting neurons with patients typically showing low CSF-hypocretin levels (<110 pg/ml. This specific loss of hypocretin and the strong association with the HLA-DQB1*06:02 allele led to the hypothesis that NT1 could be an immune-mediated pathology. Moreover, susceptibility to NT1 has recently been associated with several pathogens, particularly with influenza A H1N1 virus either through infection or vaccination. The goal of this study was to compare peripheral blood immune cell populations in recent onset pediatric NT1 subjects (post or non-post 2009-influenza A H1N1 vaccination to healthy donors. We demonstrated an increased number of central memory CD4+ T cells (CD62L+ CD45RA- associated to an activated phenotype (increase in CD69 and CD25 expression in NT1 patients. Percentage and absolute count of regulatory T cells (Tregs in NT1 patients were increased associated with an activated phenotype (increase in GITR and LAP expression, and of activated memory phenotype. Cytokine production by CD4+ and CD8+ T cells after activation was not modified in NT1 patients. In H1N1 vaccinated NT1 patients, absolute counts of CD3+, CD8+ T cells, and B cells were increased compared to non-vaccinated NT1 patients. These results support a global T cell activation in NT1 patients and thus support a T cell-mediated autoimmune origin of NT1, but do not demonstrate the pathological role of H1N1 prophylactic vaccination. They should prompt further studies of T cells, particularly of Tregs (such as suppression and proliferation antigen specific assays, and also T-cell receptor sequencing, in NT1.

  14. Narcolepsy Type 1 Is Associated with a Systemic Increase and Activation of Regulatory T Cells and with a Systemic Activation of Global T Cells.

    Science.gov (United States)

    Lecendreux, Michel; Churlaud, Guillaume; Pitoiset, Fabien; Regnault, Armelle; Tran, Tu Anh; Liblau, Roland; Klatzmann, David; Rosenzwajg, Michelle

    2017-01-01

    Narcolepsy is a rare neurologic disorder characterized by excessive daytime sleepiness, cataplexy and disturbed nocturnal sleep patterns. Narcolepsy type 1 (NT1) has been shown to result from a selective loss of hypothalamic hypocretin-secreting neurons with patients typically showing low CSF-hypocretin levels (NT1 could be an immune-mediated pathology. Moreover, susceptibility to NT1 has recently been associated with several pathogens, particularly with influenza A H1N1 virus either through infection or vaccination. The goal of this study was to compare peripheral blood immune cell populations in recent onset pediatric NT1 subjects (post or non-post 2009-influenza A H1N1 vaccination) to healthy donors. We demonstrated an increased number of central memory CD4+ T cells (CD62L+ CD45RA-) associated to an activated phenotype (increase in CD69 and CD25 expression) in NT1 patients. Percentage and absolute count of regulatory T cells (Tregs) in NT1 patients were increased associated with an activated phenotype (increase in GITR and LAP expression), and of activated memory phenotype. Cytokine production by CD4+ and CD8+ T cells after activation was not modified in NT1 patients. In H1N1 vaccinated NT1 patients, absolute counts of CD3+, CD8+ T cells, and B cells were increased compared to non-vaccinated NT1 patients. These results support a global T cell activation in NT1 patients and thus support a T cell-mediated autoimmune origin of NT1, but do not demonstrate the pathological role of H1N1 prophylactic vaccination. They should prompt further studies of T cells, particularly of Tregs (such as suppression and proliferation antigen specific assays, and also T-cell receptor sequencing), in NT1.

  15. Intravenous immunoglobulin treatment and screening for hypocretin neuron-specific autoantibodies in recent onset childhood narcolepsy with cataplexy

    DEFF Research Database (Denmark)

    Knudsen, S; Mikkelsen, J D; Bang, B

    2010-01-01

    Narcolepsy with cataplexy (NC) is caused by substantial loss of hypocretin neurons. NC patients carry the HLA-DQB1*0602 allele suggesting that hypocretin neuron loss is due to an autoimmune attack. We tested intravenous immunoglobulin (IVIG) treatment in early onset NC....

  16. The Directive 2010/63/EU on animal experimentation may skew the conclusions of pharmacological and behavioural studies.

    Science.gov (United States)

    Macrì, Simone; Ceci, Chiara; Altabella, Luisa; Canese, Rossella; Laviola, Giovanni

    2013-01-01

    All laboratory animals shall be provided some form of environmental enrichment (EE) in the nearest future (Directive 2010/63/EU). Displacing standard housing with EE entails the possibility that data obtained under traditional housing may be reconsidered. Specifically, while EE often contrasts the abnormalities of consolidated disease models, it also indirectly demonstrates that their validity depends on housing conditions. We mimicked a situation in which the consequences of a novel pharmacological compound were addressed before and after the adoption of the Directive. We sub-chronically exposed standard- or EE-reared adolescent CD1 mice (postnatal days 23-33) to the synthetic compound JWH-018, and evaluated its short- and long-term potential cannabinoid properties on: weight gain, locomotion, analgesia, motor coordination, body temperature, brain metabolism ((1)H MRI/MRS), anxiety- and depressive-related behaviours. While several parameters are modulated by JWH-018 independently of housing, other effects are environmentally mediated. The transition from standard housing to EE shall be carefully monitored.

  17. CLINICAL PHARMACOLOGY OF DIURETICS

    Directory of Open Access Journals (Sweden)

    I. V. Soldatenko

    2014-06-01

    Full Text Available Clinical pharmacology of diuretics in the international system of ATC (anatomic-therapeutic-chemical is presented. Classification of this group by the action mechanism and caused effects is provided. Pharmacokinetics and pharmacodynamics features, indications and principles of diuretics usage in clinics are considered. Contraindications, side effects and interaction with other drugs of this group are discussed in detail.

  18. Developmental paediatric anaesthetic pharmacology

    DEFF Research Database (Denmark)

    Hansen, Tom Giedsing

    2015-01-01

    Safe and effective drug therapy in neonates, infants and children require detailed knowledge about the ontogeny of drug disposition and action as well how these interact with genetics and co-morbidity of children. Recent advances in developmental pharmacology in children follow the increased...

  19. Sleep-stage transitions during polysomnographic recordings as diagnostic features of type 1 narcolepsy

    DEFF Research Database (Denmark)

    Christensen, Julie Anja Engelhard; Carrillo, Oscar; Leary, Eileen B.

    2015-01-01

    Objective: Type 1 narcolepsy/hypocretin deficiency is characterized by excessive daytime sleepiness, sleep fragmentation, and cataplexy. Short rapid eye movement (REM) latency (≤15 min) during nocturnal polysomnography (PSG) or during naps of the multiple sleep latency test (MSLT) defines a sleep......-onset REM sleep period (SOREMP), a diagnostic hallmark. We hypothesized that abnormal sleep transitions other than SOREMPs can be identified in type 1 narcolepsy. Methods: Sleep-stage transitions (one to 10 epochs to one to five epochs of any other stage) and bout length features (one to 10 epochs) were...... of 19 cases and 708 sleep-clinic patients was used for the validation. Results: (1) ≥5 transitions from ≥5 epochs of stage N1 or W to ≥2 epochs of REM sleep, (2) ≥22 transitions from ≥3 epochs of stage N2 or N3 to ≥2 epochs of N1 or W, and (3) ≥16 bouts of ≥6 epochs of N1 or W were found to be highly...

  20. HLA-DPB1 and HLA class I confer risk of and protection from narcolepsy

    DEFF Research Database (Denmark)

    Ollila, Hanna M; Ravel, Jean-Marie; Han, Fang

    2015-01-01

    Type 1 narcolepsy, a disorder caused by a lack of hypocretin (orexin), is so strongly associated with human leukocyte antigen (HLA) class II HLA-DQA1(∗)01:02-DQB1(∗)06:02 (DQ0602) that very few non-DQ0602 cases have been reported. A known triggering factor for narcolepsy is pandemic 2009 influenza......-class-II-independent associations with HLA-A(∗)11:01 (OR = 1.32 [1.13-1.54], p = 4.92 × 10(-4)), HLA-B(∗)35:03 (OR = 1.96 [1.41-2.70], p = 5.14 × 10(-5)), and HLA-B(∗)51:01 (OR = 1.49 [1.25-1.78], p = 1.09 × 10(-5)) were also seen across ethnic groups in the HLA class I region. These effects might reflect modulation...... of autoimmunity or indirect effects of HLA class I and HLA-DP alleles on response to viral infections such as that of influenza....

  1. Improving the apo-state detergent stability of NTS1 with CHESS for pharmacological and structural studies.

    Science.gov (United States)

    Scott, Daniel J; Kummer, Lutz; Egloff, Pascal; Bathgate, Ross A D; Plückthun, Andreas

    2014-11-01

    The largest single class of drug targets is the G protein-coupled receptor (GPCR) family. Modern high-throughput methods for drug discovery require working with pure protein, but this has been a challenge for GPCRs, and thus the success of screening campaigns targeting soluble, catalytic protein domains has not yet been realized for GPCRs. Therefore, most GPCR drug screening has been cell-based, whereas the strategy of choice for drug discovery against soluble proteins is HTS using purified proteins coupled to structure-based drug design. While recent developments are increasing the chances of obtaining GPCR crystal structures, the feasibility of screening directly against purified GPCRs in the unbound state (apo-state) remains low. GPCRs exhibit low stability in detergent micelles, especially in the apo-state, over the time periods required for performing large screens. Recent methods for generating detergent-stable GPCRs, however, offer the potential for researchers to manipulate GPCRs almost like soluble enzymes, opening up new avenues for drug discovery. Here we apply cellular high-throughput encapsulation, solubilization and screening (CHESS) to the neurotensin receptor 1 (NTS1) to generate a variant that is stable in the apo-state when solubilized in detergents. This high stability facilitated the crystal structure determination of this receptor and also allowed us to probe the pharmacology of detergent-solubilized, apo-state NTS1 using robotic ligand binding assays. NTS1 is a target for the development of novel antipsychotics, and thus CHESS-stabilized receptors represent exciting tools for drug discovery. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. The role of the noradrenergic system in the exploration-exploitation trade-off: a pharmacological study

    Directory of Open Access Journals (Sweden)

    Marieke Jepma

    2010-08-01

    Full Text Available Animal research and computational modeling have indicated an important role for the neuromodulatory locus coeruleus-norepinephrine (LC-NE system in the control of behavior. According to the adaptive gain theory, the LC-NE system is critical for optimizing behavioral performance by regulating the balance between exploitative and exploratory control states. However, crucial direct empirical tests of this theory in human subjects have been lacking. We used a pharmacological manipulation of the LC-NE system to test predictions of this theory in humans. In a double-blind parallel-groups design (N = 52, participants received 4 mg reboxetine (a selective norepinephrine reuptake inhibitor, 30 mg citalopram (a selective serotonin reuptake inhibitor or placebo. The adaptive gain theory predicted that the increased tonic NE levels induced by reboxetine would promote task disengagement and exploratory behavior. We assessed the effects of reboxetine on performance in two cognitive tasks designed to examine task (disengagement and exploitative versus exploratory behavior: a diminishing-utility task and a gambling task with a non-stationary pay-off structure. In contrast to predictions of the adaptive gain theory, we did not find differences in task (disengagement or exploratory behavior between the three experimental groups, despite demonstrable effects of the two drugs on non-specific central and autonomic nervous system parameters. Our findings suggest that the LC-NE system may not be involved in the regulation of the exploration-exploitation trade-off in humans, at least not within the context of a single task. It remains to be examined whether the LC-NE system is involved in random exploration exceeding the current task context.

  3. Punishment, Pharmacological Treatment, and Early Release

    DEFF Research Database (Denmark)

    Ryberg, Jesper

    2013-01-01

    Recent studies have shown that pharmacological treatment may have an impact on aggressive and impulsive behavior. Assuming that these results are correct, would it be morally acceptable to instigate violent criminals to accept pharmacological rehabilitation by offering this treatment in return fo...... relates to the acceptability of the fact that those criminals who accepted the treatment would be exempted from the punishment they rightly deserved. It is argued that none of these reasons succeeds in rejecting this sort of offer....

  4. Pharmacological interactions of vasoconstrictors.

    Science.gov (United States)

    Gómez-Moreno, Gerardo; Guardia, Javier; Cutando, Antonio; Calvo-Guirado, José Luis

    2009-01-01

    This article is the first of a series on pharmacological interactions involving medicaments commonly prescribed and/or used in odontology: vasoconstrictors in local anaesthetics and anti-inflammatory and anti-microbial analgesics. The necessity for the odontologist to be aware of adverse reactions as a result of the pharmacological interactions is due to the increase in medicament consumption by the general population. There is a demographic change with greater life expectancy and patients have increased chronic health problems and therefore have increased medicament intake. The presence of adrenaline (epinephrine) and other vasoconstrictors in local odontological anaesthetics is beneficial in relation to the duration and depth of anaesthesia and reduces bleeding and systemic toxicity of the local anaesthetic. However, it might produce pharmacological interactions between the injected vasoconstrictors and the local anaesthetic and adrenergic medicament administered exogenically which the odontologist should be aware of, especially because of the risk of consequent adverse reactions. Therefore the importance of conducting a detailed clinical history of the general state of health and include all medicaments, legal as well as illegal, taken by the patient.

  5. Pharmacological effects of biotin.

    Science.gov (United States)

    Fernandez-Mejia, Cristina

    2005-07-01

    In the last few decades, more vitamin-mediated effects have been discovered at the level of gene expression. Increasing knowledge on the molecular mechanisms of these vitamins has opened new perspectives that form a connection between nutritional signals and the development of new therapeutic agents. Besides its role as a carboxylase prosthetic group, biotin regulates gene expression and has a wide repertoire of effects on systemic processes. The vitamin regulates genes that are critical in the regulation of intermediary metabolism: Biotin has stimulatory effects on genes whose action favors hypoglycemia (insulin, insulin receptor, pancreatic and hepatic glucokinase); on the contrary, biotin decreases the expression of hepatic phosphoenolpyruvate carboxykinase, a key gluconeogenic enzyme that stimulates glucose production by the liver. The findings that biotin regulates the expression of genes that are critical in the regulation of intermediary metabolism are in agreement with several observations that indicate that biotin supply is involved in glucose and lipid homeostasis. Biotin deficiency has been linked to impaired glucose tolerance and decreased utilization of glucose. On the other hand, the diabetic state appears to be ameliorated by pharmacological doses of biotin. Likewise, pharmacological doses of biotin appear to decrease plasma lipid concentrations and modify lipid metabolism. The effects of biotin on carbohydrate metabolism and the lack of toxic effects of the vitamin at pharmacological doses suggest that biotin could be used in the development of new therapeutics in the treatment of hyperglycemia and hyperlipidemia, an area that we are actively investigating.

  6. Pharmacological approach to acute pancreatitis

    DEFF Research Database (Denmark)

    Bang, Ulrich-Christian; Semb, Synne; Nojgaard, Camilla

    2008-01-01

    -steroidal anti-inflammatory drugs (NSAID) indomethacin and diclofenac have in randomized studies showed potential as prophylaxis against PEP. Interleukin 10 (IL-10) is a cytokine with anti-inflammatory properties but two trials testing IL-10 as prophylaxis to PEP have returned conflicting results. Antibodies...... pharmacological treatment of AP is limited and studies on the effect of potent anti-inflammatory drugs are warranted....... against tumor necrosis factor-alpha (TNF-alpha) have a potential as rescue therapy but no clinical trials are currently being conducted. The antibiotics beta-lactams and quinolones reduce mortality when necrosis is present in pancreas and may also reduce incidence of infected necrosis. Evidence based...

  7. [Pharmacological therapy of obesity].

    Science.gov (United States)

    Pagotto, Uberto; Vanuzzo, Diego; Vicennati, Valentina; Pasquali, Renato

    2008-04-01

    Obesity is reaching epidemic proportions worldwide and it is correlated with various comorbidities, among which the most relevant are diabetes mellitus, arterial hypertension, and cardiovascular diseases. Obesity management is a modern challenge because of the rapid evolution of unfavorable lifestyles and unfortunately there are no effective treatments applicable to the large majority of obese/overweight people. The current medical attitude is to treat the complications of obesity (e.g. dyslipidemia, hypertension, diabetes, and cardiovascular diseases). However, the potential of treating obesity is enormous, bearing in mind that a volitional weight loss of 10 kg is associated with important risk factor improvement: blood pressure -10 mmHg, total cholesterol -10%, LDL cholesterol -15%, triglycerides -30%, fasting glucose -50%, HDL cholesterol +8%. Drug treatment for obesity is an evolving branch of pharmacology, burdened by severe side effects and consequences of the early drugs, withdrawn from the market, and challenged by the lack of long-term data on the effect of medications on obesity-related morbidity and mortality, first of all cardiovascular diseases. In Europe three antiobesity drugs are currently licensed: sibutramine, orlistat, and rimonabant; important trials with clinical endpoints are ongoing for sibutramine and rimonabant. While waiting for their results, it is convenient to evaluate these drugs for their effects on body weight and cardiometabolic risk factors. Sibutramine is a centrally acting serotonin/noradrenaline reuptake inhibitor that mainly increases satiety. At the level of brown adipose tissue, sibutramine can also facilitate energy expenditure by increasing thermogenesis. The long-term studies (five) documented a mean differential weight reduction of 4.45 kg for sibutramine vs placebo. Considering the principal studies, attrition rate was 43%. This drug not only reduces body weight and waist circumference, but it decreases triglycerides and

  8. Pharmacologic therapy for acute pancreatitis

    Science.gov (United States)

    Kambhampati, Swetha; Park, Walter; Habtezion, Aida

    2014-01-01

    While conservative management such as fluid, bowel rest, and antibiotics is the mainstay of current acute pancreatitis management, there is a lot of promise in pharmacologic therapies that target various aspects of the pathogenesis of pancreatitis. Extensive review of preclinical studies, which include assessment of therapies such as anti-secretory agents, protease inhibitors, anti-inflammatory agents, and anti-oxidants are discussed. Many of these studies have shown therapeutic benefit and improved survival in experimental models. Based on available preclinical studies, we discuss potential novel targeted pharmacologic approaches that may offer promise in the treatment of acute pancreatitis. To date a variety of clinical studies have assessed the translational potential of animal model effective experimental therapies and have shown either failure or mixed results in human studies. Despite these discouraging clinical studies, there is a great clinical need and there exist several preclinical effective therapies that await investigation in patients. Better understanding of acute pancreatitis pathophysiology and lessons learned from past clinical studies are likely to offer a great foundation upon which to expand future therapies in acute pancreatitis. PMID:25493000

  9. Interprofessional education in pharmacology using high-fidelity simulation.

    Science.gov (United States)

    Meyer, Brittney A; Seefeldt, Teresa M; Ngorsuraches, Surachat; Hendrickx, Lori D; Lubeck, Paula M; Farver, Debra K; Heins, Jodi R

    2017-11-01

    This study examined the feasibility of an interprofessional high-fidelity pharmacology simulation and its impact on pharmacy and nursing students' perceptions of interprofessionalism and pharmacology knowledge. Pharmacy and nursing students participated in a pharmacology simulation using a high-fidelity patient simulator. Faculty-facilitated debriefing included discussion of the case and collaboration. To determine the impact of the activity on students' perceptions of interprofessionalism and their ability to apply pharmacology knowledge, surveys were administered to students before and after the simulation. Attitudes Toward Health Care Teams scale (ATHCT) scores improved from 4.55 to 4.72 on a scale of 1-6 (p = 0.005). Almost all (over 90%) of the students stated their pharmacology knowledge and their ability to apply that knowledge improved following the simulation. A simulation in pharmacology is feasible and favorably affected students' interprofessionalism and pharmacology knowledge perceptions. Pharmacology is a core science course required by multiple health professions in early program curricula, making it favorable for incorporation of interprofessional learning experiences. However, reports of high-fidelity interprofessional simulation in pharmacology courses are limited. This manuscript contributes to the literature in the field of interprofessional education by demonstrating that an interprofessional simulation in pharmacology is feasible and can favorably affect students' perceptions of interprofessionalism. This manuscript provides an example of a pharmacology interprofessional simulation that faculty in other programs can use to build similar educational activities. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Iomazenil: pharmacological and animal data

    International Nuclear Information System (INIS)

    Beer, H.F.; Blaeuenstein, P.A.; Hasler, P.H.; Schubiger, P.A.; Hunkeler, W.; Bibettu, E.P.; Pieri, L.; Grayson Richards, J.

    1990-01-01

    The flumazenil analogue Ro 16-0154 (Iomazenil), a benzodiazepine partial inverse agonist, has been labelled by halogen exchange to enable SPECT investigations of central benzodiazepine receptors in human brain. The purified 123 I-Ro 16-0154 was found to be stable in rat brain preparations and to be metabolized in rat liver preparations. Its pharmacological properties were comparable to those of flumazenil with the exception of the antagonism of diazepam versus pentylenetetrazol. Biodistribution in rats (1 h p.i.) resulted in a high brain to blood ratio of 16. Clinical studies revealed images of the bezodiazepine receptor density in the brain. (author) 9 figs., 3 tabs., 27 refs

  11. Delirium in the elderly: A systematic review of pharmacological and non-pharmacological treatments

    Directory of Open Access Journals (Sweden)

    Cecília Carboni Tardelli Cerveira

    Full Text Available ABSTRACT Delirium is a common disorder associated with poor prognosis, especially in the elderly. The impact of different treatment approaches for delirium on morbimortality and long-term welfare is not completely understood. OBJECTIVE: To determine the efficacy of pharmacological and non-pharmacological treatments in elderly patients with delirium. METHODS: This systematic review compared pharmacological and non-pharmacological treatments in patients over 60 years old with delirium. Databases used were: MEDLINE (PubMed, EMBASE, Cochrane CENTRAL and LILACS from inception to January 6th, 2016. RESULTS: A total of ten articles were selected. The six non-pharmacological intervention studies showed no impact on duration of delirium, mortality or institutionalization, but a decrease in severity of delirium and improvement in medium-term cognitive function were observed. The most commonly used interventions were temporal-spatial orientation, orientation to self and others, early mobilization and sleep hygiene. The four studies with pharmacological interventions found that rivastigmine reduced the duration of delirium, improved cognitive function and reduced caregiver burden; olanzapine and haloperidol decreased the severity of delirium; droperidol reduced length of hospitalization and improved delirium remission rate. CONCLUSION: Although the pharmacological approach has been used in the treatment of delirium among elderly, there have been few studies assessing its efficacy, involving a small number of patients. However, the improvements in delirium duration and severity suggest these drugs are effective in treating the condition. Once delirium has developed, non-pharmacological treatment seems less effective in controlling symptoms, and there is a lack of studies describing different non-pharmacological interventions.

  12. Temporal Changes in the Cerebrospinal Fluid Level of Hypocretin-1 and Histamine in Narcolepsy.

    Science.gov (United States)

    Lopez, Régis; Barateau, Lucie; Evangelista, Elisa; Chenini, Sofiene; Robert, Philippe; Jaussent, Isabelle; Dauvilliers, Yves

    2017-01-01

    To follow the temporal changes of cerebrospinal fluid (CSF) biomarker levels in narcoleptic patients with unexpected hypocretin level at referral. From 2007 to 2015, 170 human leukocyte antigen (HLA) DQB1*06:02-positive patients with primary narcolepsy and definite (n = 155, 95 males, 60 females, 36 children) or atypical cataplexy (n = 15, 4 males, 3 children) were referred to our center. Cerebrospinal hypocretin deficiency was found in 95.5% and 20% of patients with definitive and atypical cataplexy, respectively. CSF hypocretin-1 (n = 6) and histamine/tele-methylhistamine (n = 5) levels were assessed twice (median interval: 14.4 months) in four patients with definite and in two with atypical cataplexy and hypocretin level greater than 100 pg/mL at baseline. CSF hypocretin levels decreased from normal/intermediate to undetectable levels in three of the four patients with definite cataplexy and remained stable in the other (>250 pg/mL). Hypocretin level decreased from 106 to 27 pg/mL in one patient with atypical cataplexy, and remained stable in the other (101 and 106 pg/mL). CSF histamine and tele-methylhistamine levels remained stable, but for one patient showing increased frequency of cataplexy and a strong decrease (-72.5%) of tele-methylhistamine levels several years after disease onset. No significant association was found between relative or absolute change in hypocretin level and demographic/clinical features. These findings show that in few patients with narcolepsy with cataplexy, symptoms and CSF marker levels can change over time. In these rare patients with cataplexy without baseline hypocretin deficiency, CSF markers should be monitored over time with potential for immune therapies in early stages to try limiting hypocretin neuron loss. © Sleep Research Society 2017. Published by Oxford University Press [on behalf of the Sleep Research Society].

  13. Pharmacological Profile of Quinoxalinone

    Directory of Open Access Journals (Sweden)

    Youssef Ramli

    2014-01-01

    Full Text Available Quinoxalinone and its derivatives are used in organic synthesis for building natural and designed synthetic compounds and they have been frequently utilized as suitable skeletons for the design of biologically active compound. This review covers updated information on the most active quinoxalinone derivatives that have been reported to show considerable pharmacological actions such as antimicrobial, anti-inflammatory, antidiabetic, antiviral, antitumor, and antitubercular activity. It can act as an important tool for chemists to develop newer quinoxalinone derivatives that may prove to be better agents in terms of efficacy and safety.

  14. Diagnostic value of sleep stage dissociation as visualized on a 2-dimensional sleep state space in human narcolepsy

    DEFF Research Database (Denmark)

    Olsen, Anders Vinther; Stephansen, Jens; Leary, Eileen B.

    2017-01-01

    Type 1 narcolepsy (NT1) is characterized by symptoms believed to represent Rapid Eye Movement (REM) sleep stage dissociations, occurrences where features of wake and REM sleep are intermingled, resulting in a mixed state. We hypothesized that sleep stage dissociations can be objectively detected...... through the analysis of nocturnal Polysomnography (PSG) data, and that those affecting REM sleep can be used as a diagnostic feature for narcolepsy. A Linear Discriminant Analysis (LDA) model using 38 features extracted from EOG, EMG and EEG was used in control subjects to select features differentiating...... wake, stage N1, N2, N3 and REM sleep. Sleep stage differentiation was next represented in a 2D projection. Features characteristic of sleep stage differences were estimated from the residual sleep stage probability in the 2D space. Using this model we evaluated PSG data from NT1 and non...

  15. A Review of Pharmacologic Treatment for Compulsive Buying Disorder

    OpenAIRE

    Soares, Célia; Fernandes, Natália; Morgado, Pedro

    2016-01-01

    At present, no treatment recommendations can be made for compulsive buying disorder. Recent studies have found evidence for the efficacy of psychotherapeutic options, but less is known regarding the best pharmacologic treatment. The purpose of this review is to present and analyze the available published evidence on the pharmacological treatment of compulsive buying disorder. To achieve this, we conducted a review of studies focusing on the pharmacological treatment of compulsive buying by se...

  16. CLINICAL-PHARMACOLOGY OF ROCURONIUM (ORG-9426) - STUDY OF THE TIME-COURSE OF ACTION, DOSE REQUIREMENT, REVERSIBILITY, AND PHARMACOKINETICS

    NARCIS (Netherlands)

    VANDENBROEK, L; WIERDA, JMKH; SMEULERS, NJ; VANSANTEN, GJ; LECLERCQ, MGL; HENNIS, PJ

    1994-01-01

    Study Objective: To evaluate the time course of action, dose requirement, reversibility, and pharmacokinetics of rocuronium (Org 9426) under 3 anesthetic techniques (nitrous oxide-fentanyl supplemented with propofol halothane, or isoflurane). Design: Prospective, randomized study. Setting: Operating

  17. Differences in latency to first pharmacological treatment (duration of untreated illness) in anxiety disorders: a study on patients with panic disorder, generalized anxiety disorder and obsessive-compulsive disorder.

    Science.gov (United States)

    Dell'Osso, Bernardo; Camuri, Giulia; Benatti, Beatrice; Buoli, Massimiliano; Altamura, A Carlo

    2013-11-01

    The latency to first pharmacological treatment (duration of untreated illness or 'DUI') is supposed to play a major role in terms of outcome in psychotic conditions. Interest in the field of affective disorders and, in particular, of duration of untreated anxiety, has been recently registered as well. However, a preliminary epidemiologic investigation of the phenomenon is necessary. The present study was aimed to investigate and compare age at onset, age at first pharmacological treatment and DUI in a sample of patients affected by different anxiety disorders. DUI was defined as the interval between the onset of the specific anxiety disorder and the administration of the first adequate pharmacological treatment in compliant subjects. Study sample included 350 patients, of both sexes, with a DSM-IV-TR diagnosis of panic disorder (n = 138), generalized anxiety disorder (n = 127) and obsessive-compulsive disorder (n = 85). Panic disorder was associated with the shortest DUI (39.5 months), whereas obsessive-compulsive disorder was associated with the longest latency to treatment (94.5 months) (F = 13.333; P anxiety disorder showed a mean DUI of 81.6 months. Present results indicate that patients with different anxiety disorders may wait for years (from 3 up to 8) before receiving a first adequate pharmacological treatment. Differences in terms of age at onset, age at the first pharmacological treatment and, ultimately, in DUI in specific anxiety disorders may depend on multiple clinical and environmental factors. Latency to non-pharmacological interventions (e.g. psychoeducation and different forms of psychotherapy) needs to be addressed and correlated with DUI in future studies. © 2013 Wiley Publishing Asia Pty Ltd.

  18. Effects of ¿9-Tetrahydrocannabinol Administration on human encoding and recall memory function: a pharmacological fMRI study

    NARCIS (Netherlands)

    Bossong, M.G.; Jager, G.; Hell, van H.H.; Zuurman, L.; Jansma, J.M.; Mehta, M.A.; Gerven, van J.; Kahn, R.S.; Ramsey, N.F.

    2012-01-01

    Deficits in memory function are an incapacitating aspect of various psychiatric and neurological disorders. Animal studies have recently provided strong evidence for involvement of the endocannabinoid (eCB) system in memory function. Neuropsychological studies in humans have shown less convincing

  19. Internet of Things for Sensing: A Case Study in the Healthcare System

    OpenAIRE

    Syed Aziz Shah; Aifeng Ren; Dou Fan; Zhiya Zhang; Nan Zhao; Xiaodong Yang; Ming Luo; Weigang Wang; Fangming Hu; Masood Ur Rehman; Osamah S. Badarneh; Qammer Hussain Abbasi

    2018-01-01

    Medical healthcare is one of the fascinating applications using Internet of Things (IoTs). The pervasive smart environment in IoTs has the potential to monitor various human activities by deploying smart devices. In our pilot study, we look at narcolepsy, a disorder in which individuals lose the ability to regulate their sleep-wake cycle. An imbalance in the brain chemical called orexin makes the sleep pattern irregular. This sleep disorder in patients suffering from narcolepsy results in the...

  20. Genetic, clinical and pharmacological determinants of out-of-hospital cardiac arrest: rationale and outline of the AmsteRdam Resuscitation Studies (ARREST) registry

    Science.gov (United States)

    Blom, M T; van Hoeijen, D A; Bardai, A; Berdowski, J; Souverein, P C; De Bruin, M L; Koster, R W; de Boer, A; Tan, H L

    2014-01-01

    Introduction Out-of-hospital cardiac arrest (OHCA) is a major public health problem. Recognising the complexity of the underlying causes of OHCA in the community, we aimed to establish the clinical, pharmacological, environmental and genetic factors and their interactions that may cause OHCA. Methods and analysis We set up a large-scale prospective community-based registry (AmsteRdam Resuscitation Studies, ARREST) in which we prospectively include all resuscitation attempts from OHCA in a large study region in the Netherlands in collaboration with Emergency Medical Services. Of all OHCA victims since June 2005, we prospectively collect medical history (through hospital and general practitioner), and current and previous medication use (through community pharmacy). In addition, we include DNA samples from OHCA victims with documented ventricular tachycardia/fibrillation during the resuscitation attempt since July 2007. Various study designs are employed to analyse the data of the ARREST registry, including case–control, cohort, case only and case-cross over designs. Ethics and dissemination We describe the rationale, outline and potential results of the ARREST registry. The design allows for a stable and reliable collection of multiple determinants of OHCA, while assuring that the patient, lay-caregiver or medical professional is not hindered in any way. Such comprehensive data collection is required to unravel the complex basis of OHCA. Results will be published in peer-reviewed journals and presented at relevant scientific symposia. PMID:25332818

  1. Current knowledge of Schisandra chinensis (Turcz.) Baill. (Chinese magnolia vine) as a medicinal plant species: a review on the bioactive components, pharmacological properties, analytical and biotechnological studies.

    Science.gov (United States)

    Szopa, Agnieszka; Ekiert, Radosław; Ekiert, Halina

    2017-01-01

    Schisandra chinensis Turcz. (Baill.) is a plant species whose fruits have been well known in Far Eastern medicine for a long time. However, schisandra seems to be a plant still underestimated in contemporary therapy still in the countries of East Asia. The article presents latest available information on the chemical composition of this plant species. Special attention is given to dibenzo cyclooctadiene lignans. In addition, recent studies of the biological activity of dibenzocyclooctadiene lignans and schisandra fruit extracts are recapitulated. The paper gives a short resume of their beneficial effects in biological systems in vitro, in animals, and in humans, thus underlining their medicinal potential. The cosmetic properties are depicted, too. The analytical methods used for assaying schisandra lignans in the scientific studies and also in industry are also presented. Moreover, special attention is given to the information on the latest biotechnological studies of this plant species. The intention of this review is to contribute to a better understanding of the huge potential of the pharmacological relevance of S. chinensis.

  2. Improving the Clinical Pharmacologic Assessment of Abuse Potential: Part 2: Optimizing the Design of Human Abuse Potential Studies.

    Science.gov (United States)

    Sellers, Edward M

    2018-04-01

    This article discusses the conduct of a human abuse potential study as outlined in the Food and Drug Administration Final Guidance to Industry on Assessment of Abuse Potential. In addition, areas where alternative approaches should be considered are proposed. The design, end points, conduct, and interpretation of the human abuse potential study were reviewed, analyzed, and placed in the context of current scientific knowledge and best practices to mitigate regulatory risk and expedite drug development. The guidance is based on regulatory needs and current scientific practices. However, the reliability and utility of such studies can be improved with better subject selection, data collection, standardization of data collection and staff training, and a better understanding of the measurement properties of the dependent measures. The guidance provides a useful framework for conduct of human abuse potential studies. However, design assumptions, poor choice of end points, failure to consider alternate approaches, and limited experience with interpretation can result in an inadequate study or one that does not fairly represent the abuse potential of a new chemical entity. Methodologic development is needed to strengthen the regulatory framework. The Food and Drug Administration or the National Institutes on Drug Abuse could take a targeted initiative to encourage this work.

  3. Examination of Traditional Medicine and Herbal Pharmacology and the Implications for Teaching and Education: A Ghanaian Case Study

    Science.gov (United States)

    Asabere-Ameyaw, Akwasi; Sefa Dei, George J.; Raheem, Kolawole

    2009-01-01

    This article presents the preliminary findings of a pilot study of the practice, uses, and effectiveness of traditional medicine in Ghana. Based on in-depth interviews with local key practitioners and users of traditional medicine, the article points to some of the educational significance of local cultural knowledge on the environment and the…

  4. Molecular Docking Study, Green Synthesis and Pharmacological Evaluation of 1,3,4-thiadiazole Derivatives as Potential Antiepileptic Agents

    Czech Academy of Sciences Publication Activity Database

    Sahoo, B. M.; Dinda, S. C.; Kumar, B. V. V. R.; Panda, J. R.; Brahmkshatriya, Pathik

    2013-01-01

    Roč. 13, č. 14 (2013), s. 2076-2081 ISSN 1389-5575 Institutional support: RVO:61388963 Keywords : antiepileptic activity * docking study * epilepsy * green synthesis * neurotoxicity * thiadiazole Subject RIV: CC - Organic Chemistry Impact factor: 3.186, year: 2013

  5. A combined phytohemagglutinin and a-ketoglutarate pharmacology study of gut morphology and growth in older adult rats

    DEFF Research Database (Denmark)

    Filip, R.; Harrison, Adrian Paul; Pierzynowski, S.G.

    2008-01-01

    This study has evaluated the effect of phytohaemagglutinin (PHA) in combination with alpha-ketoglutaric acid (AKG), on GI-tract morphology and N balance in adult rats. Rats, aged approx. 15 months, were assigned to one of four experimental groups, (1) Control group, (2) AKG group, (3) AKG+PHA 100...

  6. Non Pharmacological Cognitive Enhancers - Current Perspectives.

    Science.gov (United States)

    Sachdeva, Ankur; Kumar, Kuldip; Anand, Kuljeet Singh

    2015-07-01

    Cognition refers to the mental processes involved in thinking, knowing, remembering, judging, and problem solving. Cognitive dysfunctions are an integral part of neuropsychiatric disorders as well as in healthy ageing. Cognitive Enhancers are molecules that help improve aspects of cognition like memory, intelligence, motivation, attention and concentration. Recently, Non Pharmacological Cognitive Enhancers have gained popularity as effective and safe alternative to various established drugs. Many of these Non Pharmacological Cognitive Enhancers seem to be more efficacious compared to currently available Pharmacological Cognitive Enhancers. This review describes and summarizes evidence on various Non Pharmacological Cognitive Enhancers such as physical exercise, sleep, meditation and yoga, spirituality, nutrients, computer training, brain stimulation, and music. We also discuss their role in ageing and different neuro-psychiatric disorders, and current status of Cochrane database recommendations. We searched the Pubmed database for the articles and reviews having the terms 'non pharmacological and cognitive' in the title, published from 2000 till 2014. A total of 11 results displayed, out of which 10 were relevant to the review. These were selected and reviewed. Appropriate cross-references within the articles along with Cochrane reviews were also considered and studied.

  7. A pharmacological analysis elucidating why, in contrast to (-)-deprenyl (selegiline), alpha-tocopherol was ineffective in the DATATOP study.

    Science.gov (United States)

    Miklya, I; Knoll, B; Knoll, J

    2003-04-25

    The Parkinson Study Group who conducted the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) trial designed their study in the belief that the MAO inhibitor (-)-deprenyl (selegiline), the antioxidant alpha-tocopherol, and the combination of the two compounds will slow the clinical progression of the disease to the extent that MAO activity and the formation of oxygen radicals contribute to the pathogenesis of nigral degeneration. In fact, (-)-deprenyl only delayed the onset of disability associated with early, otherwise untreated Parkinson's disease, however, in contrast to the expectation of the authors, alpha-tocopherol proved to be ineffective in the DATATOP study. Enhancer substances, (-)-deprenyl, (-)-1-phenyl-2-propylaminopentane [(-)-PPAP] the (-)-deprenyl analogue free of MAO inhibitory potency, and R-(-)1-(benzofuran-2-yl)-2-propylaminopentane [(-)-BPAP] the presently known most potent enhancer substance, are peculiar stimulants. They enhance the impulse propagation mediated release of the catecholamines in the brain. Due to their enhancer effect, the amount of catecholamines released from selected discrete brain areas (striatum, substantia nigra, tuberculum olfactorium, locus coeruleus) is significantly higher in rats treated with an enhancer substance than in saline treated rats. We compared the effect of (-)-deprenyl 0.025 and 0.25 mg/kg, (-)-PPAP 0.1 mg/kg, (-)-BPAP 0.0001 mg/kg, and alpha-tocopherol 25 and 50 mg/kg, in this test. The doses of (-)-deprenyl and alpha-tocopherol were selected to be in compliance with the dose given in the DATATOP study. Compared to saline treated rats, the enhancer substances significantly increased the amount of dopamine released from the striatum, substantia nigra and tuberculum olfactorium and the amount of norepinephrine released from the locus coeruleus; alpha-tocopherol was ineffective. The results indicate that alpha-tocopherol was ineffective, because, unlike (-)-deprenyl it dose not enhance

  8. Amide-linked Ethanolamine Conjugate of Gemfibrozil as a Profound HDL Enhancer: Design, Synthesis, Pharmacological Screening and Docking Study.

    Science.gov (United States)

    Rai, Himanshu; Dhaneshwar, Suneela S

    2015-01-01

    Elevated concentration of any or all types of lipids in the plasma including hypertriglyceridemia and hypercholesterolemia leads to atherosclerotic cardiovascular disease. Effective medication needs multiple drug therapy as recommended cholesterol and triglyceride levels are difficult to achieve by monotherapy and frequently require the use of more than one lipid-lowering medication. Gemfibrozil lowers plasma triglyceride-rich lipoproteins mainly VLDL and increases HDL. It is associated with short plasma half-life (1.5h) and GIT distress on long term use. In a study it was found that ethanolamine decreases serum cholesterol, especially VLDL cholesterol and LDL cholesterol in rats fed an HF/HC diet. In the present work, we thought of exploring the effect of co-drug of gemfibrozil with ethanolamine (GE-I) as a potential combination therapy for the management of mixed hyperlipidemia. Synthesis of GE-I was effected by CDI coupling. Structure was confirmed spectrally. Interestingly kinetic studies revealed that GE-I resisted chemical and enzymatic hydrolysis. In tritoninduced hyperlipidemia, significant lowering of serum lipid levels was observed. The hallmark of GEI was its profound effect on HDL level which was raised above the normal level by 15%. Docking study also supported modulatory effect of GE-I (docking score -7.012) on PPAR-α which was comparable to docking score of gemfibrozil (-9.432). These preliminary observations prompt us to consider GE-I as a novel, serendipitous, hybrid anti-hyperlipidemic new chemical entity which needs be studied extensively to prove it as an HDL enhancing anti-hyperlipidemic agent.

  9. The Ehrlich Tumor Induces Pain-Like Behavior in Mice: A Novel Model of Cancer Pain for Pathophysiological Studies and Pharmacological Screening

    Directory of Open Access Journals (Sweden)

    Cassia Calixto-Campos

    2013-01-01

    Full Text Available The Ehrlich tumor is a mammary adenocarcinoma of mice that can be developed in solid and ascitic forms depending on its administration in tissues or cavities, respectively. The present study investigates whether the subcutaneous plantar administration of the Ehrlich tumor cells induces pain-like behavior and initial pharmacological susceptibility characteristics. The Ehrlich tumor cells (1 × 104–107 cells induced dose-dependent mechanical hyperalgesia (electronic version of the von Frey filaments, paw edema/tumor growth (caliper, and flinches compared with the saline group between days 2 and 12. There was no difference between doses of cells regarding thermal hyperalgesia in the hot-plate test. Indomethacin (a cyclooxygenase inhibitor and amitriptyline hydrochloride (a tricyclic antidepressant treatments did not affect flinches or thermal and mechanical hyperalgesia. On the other hand, morphine (an opioid inhibited the flinch behavior and the thermal and mechanical hyperalgesia. These effects of morphine on pain-like behavior were prevented by naloxone (an opioid receptor antagonist treatment. None of the treatments affected paw edema/tumor growth. The results showed that, in addition to tumor growth, administration of the Ehrlich tumor cells may represent a novel model for the study of cancer pain, specially the pain that is susceptible to treatment with opioids, but not to cyclooxygenase inhibitor or to tricyclic antidepressant.

  10. 1-cyclohexyl-x-methoxybenzene derivatives, novel psychoactive substances seized on the internet market. Synthesis and in vivo pharmacological studies in mice.

    Science.gov (United States)

    Fantinati, Anna; Ossato, Andrea; Bianco, Sara; Canazza, Isabella; De Giorgio, Fabio; Trapella, Claudio; Marti, Matteo

    2017-05-01

    Among novel psychoactive substances notified to EMCDDA and Europol were 1-cyclohexyl-x-methoxybenzene stereoisomers (ortho, meta, and para). These substances share some structural characteristics with phencyclidine and tramadol. Nowadays, no information on the pharmacological and toxicological effects evoked by 1-cyclohexyl-x-methoxybenzene are reported. The aim of this study was to investigate the effect evoked by each one stereoisomer on visual stimulation, body temperature, acute thermal pain, and motor activity in mice. Mice were evaluated in behavioral tests carried out in a consecutive manner according to the following time scheme: observation of visual placing response, measures of core body temperature, determination of acute thermal pain, and stimulated motor activity. All three stereoisomers dose-dependent inhibit visual placing response (rank order: meta > ortho > para), induce hyperthermia at lower and hypothermia at higher doses (meta > ortho > para) and cause analgesia to thermal stimuli (para > meta = ortho), while they do not alter motor activity. For the first time, this study demonstrates that systemic administration of 1-cyclohexyl-x-methoxybenzene compounds markedly inhibit visual response, promote analgesia, and induce core temperature alterations in mice. This data, although obtained in animal model, suggest their possible hazard for human health (i.e., hyperthermia and sensorimotor alterations). In particular, these novel psychoactive substances may have a negative impact in many daily activities, greatly increasing the risk factors for workplace accidents and traffic injuries. Copyright © 2017 John Wiley & Sons, Ltd.

  11. Time to lack of persistence with pharmacological treatment among patients with current depressive episodes: a natural study with 1-year follow-up

    Directory of Open Access Journals (Sweden)

    Li K

    2016-10-01

    Full Text Available Kanglai Li,1,* Qinling Wei,2,* Guanying Li,2 Xiangjun He,2 Yingtao Liao,2 Zhaoyu Gan2 1Very Important Patient Department, 2Department of Psychiatry, The Third Affiliated Hospital of Sun Yat-sen University, Tianhe District, Guangzhou, Guangdong, People’s Republic of China *These authors contributed equally to this work Introduction: Medication nonadherence remains a big challenge for depressive patients. This study aims to assess and compare the medication persistence between unipolar depression (UD and bipolar depression (BD. Methods: A total of 146 UD and 187 BD patients were recruited at their first index prescription. Time to lack of persistence with pharmacological treatment (defined as a gap of at least 60 days without taking any medication was calculated, and clinical characteristics were collected. Final diagnosis was made at the end of 1-year follow-up. Results: A total of 101 (69.2% UD and 126 (67.4% BD patients discontinued the treatment, with a median duration of 36 days and 27 days, respectively. No significant difference was found between UD and BD in terms of time to lack of persistence with pharmacological treatment. The highest discontinuation rate (>40% occurred in the first 3 months for both groups of patients. For UD patients, those with a higher risk of suicide (odds ratio [OR] =0.696, P=0.035 or comorbidity of any anxiety disorder (OR =0.159, P<0.001 were less likely to prematurely drop out (drop out within the first 3 months, while those with onset in the summer (OR =4.702, P=0.049 or autumn (OR =7.690, P=0.012 were more likely to prematurely drop out than those with onset in the spring (OR =0.159, P<0.001. For BD patients, being female (OR =2.250, P=0.012 and having a history of spontaneous remission or switch to hypomania (OR =2.470, P=0.004 were risk factors for premature drop out, while hospitalization (OR =0.304, P=0.023 and misdiagnosis as UD (OR =0.283, P<0.001 at the first index prescription were protective

  12. Studies on Impact of Irradiation Treatment on Certain Pharmacological and Biochemical Responses of Naja nigricollis Snake Venom

    International Nuclear Information System (INIS)

    Abd El Hamid, F.Y.A.

    2015-01-01

    Snakebite is a serious medical problem worldwide, especially in the tropics. In Egypt, the Black-neck Spitting Cobra; Naja nigricollis is one of the most venomous snakes distributed in the south part of Egypt. The lethality as well as the immunological, biochemical and histological effects of Naja nigricollis venom at a sublethal dose has been investigated before and after exposure to gamma radiation (1.5 KGy and 3 KGy). The toxicity of irradiated venom decreased as compared to that of the native one. There was no change in the antigenic reactivity between both native and irradiated venom. The effect of ½ LD 50 of native or irradiated (1.5 KGy) was studied on the activities of heart enzymes: CPK, CK-MB, LDH and AST after (1, 2, 4, 24 hours) of envenomation. The present study showed that snake venom envenomation caused significant (p ≤ 0.05) elevation in serum CPK, CK-MB, LDH and AST levels. In contrast, the 1.5 KGy gamma-irradiated venom recorded no significant changes compared to that of normal rats. Histopathological study of heart confirmed these findings. The 1.5 KGy and 3 KGy gamma irradiation decrease the phospholipase activity of the venom. Anticoagulant activity was prominent when re calcification time was tested on human plasma using each venom (native, γ- irradiated venoms) as a test solution. Naja nigricollis venom detoxified by gamma irradiation (1.5 KGy or 3 KGy) was used as toxoid for active immunization of rabbits following a short schedule of immunization with complete Freund's adjuvant. Effective neutralization of venom toxin by immune sera of rabbits was observed.

  13. Comparison of freely-moving telemetry Chinese Miniature Experiment Pigs (CMEPs) to beagle dogs in cardiovascular safety pharmacology studies.

    Science.gov (United States)

    Yuan, Haitao; Zhao, Jing; Guo, Jiabin; Wu, Ruiqin; He, Li; Cui, Yaxiong; Feng, Min; Zhang, Tingfen; Hou, Mingyue; Guo, Qian; Zhang, Lijun; Jia, Li; Huang, Chang; Ye, Lin; Peng, Shuangqing

    2014-01-01

    Telemetry beagle dogs are the most frequently used species in cardiovascular telemetry assessments. However, beagle dogs may not be always suitable for all of the tests. Recently minipigs have received increased attention for these studies. Differences between the two species regarding the response of their cardiovascular systems to environmental stimuli are unclear. This study investigates how the telemetry minipig compares to beagle dog as a test subject and also refines the experimental protocols necessary to obtain accurate data. Beagle dogs and Chinese Miniature Experiment Pigs (CMEPs) were implanted with telemetry transmitters and the influences of gavage, feeding and the circadian cycle on various cardiovascular parameters were investigated. ECG signal quality from CMEPs was superior to that of the beagle dogs. Poor ECG signal quality, elevated HR, BP and locomotor activity associated with gavage and feeding were observed in both species. ECG signal quality, BP and locomotor activity recovered more quickly in the CMEPs than in the beagle dogs. Residual elevation of HR found in CMEPs lasted approximately 4h post-feeding, which has a profound influence on the circadian cycle. A diurnal rhythm in CMEP with a significant increase of body temperature during the dark period and a clear circadian rhythm of locomotor activity in both species were observed. The present data demonstrated that gavage, feeding and circadian cycle were having an enormous influence on BP, HR and locomotor activity in both species. If drug-induced effects are expected rapidly after oral administration and feeding, CMEP seems to be a favorable choice. Also, due to the effects of feeding on HR, CMEPs should fast at least 5h before the start of recording or should not be fed during the study where the Tmax of a given compound might occur very late. It also should be taken into consideration when the test article has a potential effect on body temperature by using CMEPs. In summary, the

  14. In Vivo Evidence of Increased nNOS Activity in Acute MPTP Neurotoxicity: A Functional Pharmacological MRI Study

    Directory of Open Access Journals (Sweden)

    Tiing Yee Siow

    2013-01-01

    Full Text Available 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP is a neurotoxin commonly used to produce an animal model of Parkinson’s disease. Previous studies have suggested a critical role for neuronal nitric oxide (NO synthase- (nNOS- derived NO in the pathogenesis of MPTP. However, NO activity is difficult to assess in vivo due to its extremely short biological half-life, and so in vivo evidence of NO involvement in MPTP neurotoxicity remains scarce. In the present study, we utilized flow-sensitive alternating inversion recovery sequences, in vivo localized proton magnetic resonance spectroscopy, and diffusion-weighted imaging to, respectively, assess the hemodynamics, metabolism, and cytotoxicity induced by MPTP. The role of NO in MPTP toxicity was clarified further by administering a selective nNOS inhibitor, 7-nitroindazole (7-NI, intraperitoneally to some of the experimental animals prior to MPTP challenge. The transient increase in cerebral blood flow (CBF in the cortex and striatum induced by systemic injection of MPTP was completely prevented by pretreatment with 7-NI. We provide the first in vivo evidence of increased nNOS activity in acute MPTP-induced neurotoxicity. Although the observed CBF change may be independent of the toxicogenesis of MPTP, this transient hyperperfusion state may serve as an early indicator of neuroinflammation.

  15. Pharmacological approaches to the study of CHOLINO- and GABA-receptor states in nerve cells after irradiation with low intensity

    International Nuclear Information System (INIS)

    Anan'eva, T.V.; Dvoretskij, A.I.

    2000-01-01

    The peculiarities of functioning specific cholino- and GABA-receptors (ChR and GABA-R) by modeling the effect of synaptic neuromediators, correspondingly acetocholine (ACh) and gamma-aminobutyric acid (GABA), in low concentrations on the K + active transport in the rats cerebral cortex after single-time or chronical total irradiation with the dose of 0.25 Gy are studied. As a result of the study of both the acetocholine (10 -10 and 10 -6 mole/l) and gamma-aminobutyric avid (10 -9 and 10 -5 mole/l) effects on the K + active transport in the rats cerebral cortex slices in presence of any selective antagonists of the choline- and GABA-receptors, it is shown, that after the whole body irradiation with 25 c Gy (1.75 m Gy/min) the metabotropic muscarinic ChR and GABA B - receptors were involved into the processes of neurotransmitter modulation, whereas under ionotropic nicotinic choline- and GAB A - receptors. The observed changes are supposed to be of adaptive character. The post irradiation structural and functional disturbances may be considered as one of the causes of essential distortions in the processes of interneuronal metabolic communication in the central nerve system [ru

  16. Sequential psychological and pharmacological therapies for comorbid and primary insomnia: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Morin, Charles M; Edinger, Jack D; Krystal, Andrew D; Buysse, Daniel J; Beaulieu-Bonneau, Simon; Ivers, Hans

    2016-03-03

    Chronic insomnia is a prevalent disorder associated with significant psychosocial, health, and economic impacts. Cognitive behavioral therapies (CBTs) and benzodiazepine receptor agonist (BzRA) medications are the most widely supported therapeutic approaches for insomnia management. However, few investigations have directly compared their relative and combined benefits, and even fewer have tested the benefits of sequential treatment for those who do not respond to initial insomnia therapy. Moreover, insomnia treatment studies have been limited by small, highly screened study samples, fixed-dose, and fixed-agent pharmacotherapy strategies that do not represent usual clinical practices. This study will address these limitations. This is a two-site randomized controlled trial, which will enroll 224 adults who meet the criteria for a chronic insomnia disorder with or without comorbid psychiatric disorders. Prospective participants will complete clinical assessments and polysomnography and then will be randomly assigned to first-stage therapy involving either behavioral therapy (BT) or zolpidem. Treatment outcomes will be assessed after 6 weeks, and treatment remitters will be followed for the next 12 months on maintenance therapy. Those not achieving remission will be offered randomization to a second, 6-week treatment, again involving either pharmacotherapy (zolpidem or trazodone) or psychological therapy (BT or cognitive therapy (CT)). All participants will be re-evaluated 12 weeks after the protocol initiation and at 3-, 6-, 9-, and 12-month follow-ups. Insomnia remission, defined categorically as a score Insomnia Severity Index, a patient-reported outcome, will serve as the primary endpoint for treatment comparisons. Secondary outcomes will include sleep parameters derived from daily sleep diaries and from polysomnography, subjective measures of fatigue, mood, quality of life, and functional impairments; and measures of adverse events; dropout rates; and treatment

  17. A study on pharmacology and redistribution of a myocardial imaging agent 99TcmN (NOEt)2

    International Nuclear Information System (INIS)

    Wang Jincheng; Zhang Junbo; Mi Hongzhi; Wang Xuebin; Wang Qian

    2002-01-01

    Objective: To study the biological properties of the myocardial imaging agent 99 Tc m N(NOEt) 2 and compare its redistribution characters with 201 Tl. Methods: The 99 Tc m N(NOEt) 2 was prepared. Blood clearance, biodistribution, imaging and redistribution imaging with 99 Tc m N(NOEt) 2 or 201 Tl were studied in 5 dogs. Results: Radiochemical purity of 99 Tc m N(NOEt) 2 was (98.41 +- 0.46)%, blood clearance T(α) 1/2 (2.8 +- 0.1) min, T(β 1/2 = (142.7 +- 32.7) min, Cl = (292.3 +- 117.1) mL/h. Imaging studies demonstrated that 99 Tc m N(NOEt) 2 was distributed rapidly in the myocardium of the dogs, disappearance of pulmonary uptake was faster than that of myocardial uptake, the uptake was higher in liver. At 10, 30, 60, 90 and 120 min after injection the myocardial uptakes were (4.27 +- 0.21), (5.3 +- 1.48), (5.3 +- 0.66), (4.0 +- 0.53) and (3.67 +- 0.35)% ID; the heart-to-lung ratios and the heart-to-liver ratios of these time points were 1.24 +- 0.31, 2.03 +- 0.45, 2.33 +- 0.31, 2.23 +- 0.5, 2.07 +- 0.49, 0.94 +- 0.08, 0.78 +- 0.15, 0.56 +- 0.22, 0.53 +- 0.22, 0.38 +- 0.15, respectively, the myocardial images were most distinct at 30 and 60 min postinjection. The results of redistribution in ischemic myocardium of dogs with 99 Tc m N(NOEt) 2 or 201 Tl were about the same. Conclusion: 99 Tc m N(NOEt) 2 is very worth to be one of the new myocardial imaging agents, it has the re-distributive character just as that of 201 Tl

  18. Pharmacological Evaluation of the Antidiarrhoeal Activity of ...

    African Journals Online (AJOL)

    This study presents the pharmacological evaluation of the effects of intraperitoneal injection of aqueous seed extract of Aframomum melegueta (AM) on diarrhoea, intestinal fluid secretion and gastrointestinal transit time, induced by castor oil in rodents. The results of the study revealed that AM (50-200 mg/kg) produced a ...

  19. Pharmacological and spectral studies of synthetic biomimetic copper complexes derived from 3-hydroxyflavone derivatives as anti-inflammatory agents

    Directory of Open Access Journals (Sweden)

    K. Nagashri

    2016-09-01

    Full Text Available Novel biomimetic ligands were synthesized by the condensation of 3-hydroxyflavone, 2-aminophenol(L1/2-aminobenzoic acid (L2 and-aminothiazole (L3. Their Cu(II complexes have also been synthesized and characterized on the basis of 1H NMR, IR, UV–Vis spectra, elemental analyses, molar conductivity, ESR, electrochemical behaviour and thermal analyses. The antimicrobial activities (MIC values of the ligands, copper complexes and standard drugs have been evaluated using the serial dilution technique against the bacterial species Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris and Pseudomonas aeruginosa and fungal species Aspergillus niger, Rhizopus stolonifer, Aspergillus flavus, Rhizoctonia bataicola and Candida albicans. The anti-inflammatory and SOD activities of the investigated compounds are also promising and allow the selection of a lead compound for further biological studies.

  20. In Vivo Study on the Pharmacological Interactions between a Chinese Herbal Formula ELP and Antiresorptive Drugs to Counteract Osteoporosis

    Directory of Open Access Journals (Sweden)

    Chun-Hay Ko

    2012-01-01

    Full Text Available Antiresorptive drugs, alendronate and raloxifene, are effective in lowering bone mineral density (BMD loss in postmenopausal women. However, long-term treatment may be associated with serious side effects. Our research group has recently discovered that a Chinese herbal formula, ELP, could significantly reduce BMD loss in animal and human studies. Therefore, the present study aimed to investigate the potential synergistic bone-protective effects of different herb-drug combinations using ovariectomized rats. To assess the efficacy of different combinations, the total BMD was monitored biweekly in the 8-week course of daily oral treatment. Bone microarchitecture, bone strength, and deoxypyridinoline level were also determined after 8 weeks. From our results, coadministration of ELP and raloxifene increased the total tibial BMD by 5.26% (2.5 mg/kg/day of raloxifene; P=0.014 and 5.94% (0.25 mg/kg/day of raloxifene; P=0.026 when compared with the respective dosage groups with raloxifene alone. Similar synergistic effects were also observed in BMD increase at distal femur (0.25 mg/kg/day; P=0.001 and reduction in urinary deoxypyridinoline crosslink excretion (2.5 and 0.25 mg/kg/day; both P=0.02. However, such interactions could not be observed in all alendronate-treated groups. Our data provide first evidence that ELP could synergistically enhance the therapeutic effects of raloxifene, so that the clinical dosage of raloxifene could be reduced.

  1. Pharmacological study of the possible protective effect of certain natural products against irradiation-induced bone loss in female rats

    International Nuclear Information System (INIS)

    Elsabbagh, W.M.A.

    2007-01-01

    osteoporosis is a common human bone disease characterized by decreased bone mass and increased risk of fractures . it is associated with numerous risk factors; post menopausal oestrogen loss is the major factor. on another hand, exposure to γ -radiation may be responsible for the late reduction in bone mass following radiotherapy. research in nutrition suggests that diet can help to achieve optimal health specifically that human diet that contain macro nutrients and phytochemicals which have antioxidant and anti-inflammatory properties. the present study has been constructed to identify the effect of radiation exposure on bone, and to investigate the possible protective effect of garlic oil and parsley extract against bone loss induced in female virgin rats(180-200 g) either by ovariectomization or by exposure to γ -radiation. a pilot lest was carried first in this study on 2 groups of female virgin rats to estimate the degree of bone loss induced by exposure to fractionated doses of γ -radiation . the 1 st group's rats were normal non-irradiated and served as control normal group. in the 2 nd group, female rats were exposed to total dose of 15 Gy fractionated over 5 weeks (1 Gy 3 times weekly for 5 weeks), and measurements of urinary calcium and urinary hydroxyproline were carried out periodically after 4,8,11 and 15 weeks from the 1 st day of exposure to γ -radiation doses . the highest values were detected after 11 weeks i.e. after 6 weeks from the last exposure to γ -radiation

  2. Pharmacological Evaluation of Antidepressant-Like Effect of Genistein and Its Combination with Amitriptyline: An Acute and Chronic Study

    Directory of Open Access Journals (Sweden)

    Gaurav Gupta

    2015-01-01

    Full Text Available The present study was designed to evaluate the acute and chronic antidepressant effect of genistein in combination with amitriptyline in mice. Animals were divided into six groups (n=6 for treatment with water, genistein, or amitriptyline, either alone or in combination for ten days. Animals were subjected to locomotor activity testing; tail suspension test (TST; and forced swim test (FST and immobility time was recorded on day one and day ten. Acute treatment of all treatment groups did not significantly reduce the immobility time (p>0.05. Chronic treatment of combination of genistein (10 mg/kg and amitriptyline (5 mg/kg and 10 mg/kg significantly reduced the immobility time as compared to control group (p<0.001 and was comparable to amitriptyline alone (10 mg/kg. However, no changes in anti-immobility activity in combination of subeffective doses of genistein (5 mg/kg and amitriptyline (5 mg/kg were observed. Genistein at its standard dose (10 mg/kg rendered synergistic effects in combination with subeffective dose of amitriptyline (5 mg/kg and additive effects in combination with therapeutic dose of amitriptyline (10 mg/kg.

  3. Gamma-aminobutyric acid esters. 1. Synthesis, brain uptake, and pharmacological studies of aliphatic and steroid esters of gamma-aminobutyric acid

    International Nuclear Information System (INIS)

    Shashoua, V.E.; Jacob, J.N.; Ridge, R.; Campbell, A.; Baldessarini, R.J.

    1984-01-01

    Labeled and unlabeled aliphatic and steroid esters of gamma-amino[U- 14 C]butyric acid (GABA) were synthesized and tested for their capacity to penetrate the blood-brain barrier and for evidence of central neuropharmacological activity in rodents. The uptake of the labeled 9,12,15-octadecatrienyl (linolenyl), 3-cholesteryl, 1-butyl, and the 9-fluoro-11 beta,17-dihydroxy-16 alpha-methyl-3,20-dioxopregna -1,4-dien-21-yl (dexamethasone) esters of GABA into mouse brain increased 2-, 25-, 74-, and 81-fold over GABA, respectively. The cholesteryl ester of GABA depressed the general motor activity of mice and rats in a dose-dependent manner, whereas the 1-butyl, linolenyl, and dexamethasone esters were inactive by this test. Studies of the rates of hydrolysis, GABA receptor binding capacity, and octanol/water partition coefficients indicated that pharmacological activity of the esters after entry into the central nervous system (CNS) was dependent on their capacity to release GABA by enzymatic hydrolysis and their lipid solubility

  4. Human pharmacology of current and new treatments for schizophrenia

    NARCIS (Netherlands)

    Liem-Moolenaar, Marieke

    2012-01-01

    The studies in this thesis together show different ways of studying human pharmacology, give an impression of the current drug development in schizophrenia, and provide examples how human pharmacology can be applied in an early stage of drug development in healthy volunteers. The investigated

  5. Pharmacological and non- pharmacological treatment of hypertension: A review article

    Directory of Open Access Journals (Sweden)

    Marjan Seyedmazhari

    2013-01-01

    Full Text Available BACKGROUND: Hypertension is a worldwide epidemic disease. It is more common and more severe in elderly persons. Various studies however have estimated 41.9 million men and 27.8 million women to have prehypertension. Diagnosis and early treatment of prehypertension are of utmost importance. Although hypertension is usually divided into 2 general categories of essential (primary and secondary hypertension, the initial treatment for hypertension often depends on its stage which is determined by systolic and diastolic blood pressure. Lifestyle modification is the first step in treating stage one hypertension. Pharmaceutical treatments including diuretics, angiotensin converting enzyme (ACE inhibitors, calcium blockers, beta blockers, and angiotensin receptor blockers will be recommended if lifestyle modification fails to control blood pressure.    METHODS: The PubMed database was searched by a number of keywords including hypertension, pharmaceutical treatment, and non-pharmaceutical treatment. The results were limited by determining a date range of 2008-11.    RESULTS: High blood pressure causes major health problems for many people around the world. It should be controlled because of its high mortality and morbidity. However, in order to select an appropriate treatment modality, it is initially important to diagnose the kinds and stages of hypertension. Pharmaceutical or non-pharmaceutical treatments can then be employed to control this serious disease.    CONCLUSION: Treating hypertension depends on the kinds and stages of this disease. Several tips should be considered when selecting a method of treatment.       Keywords: Hypertension, Pharmacological treatment, Non-pharmacological treatment

  6. A systematic review assessing non-pharmacological conservative treatment studies for people with non-inflammatory multi-joint pain: clinical outcomes and research design considerations.

    Science.gov (United States)

    Comer, C; Smith, T O; Drew, B; Raja, R; Kingsbury, S R; Conaghan, Philip G

    2018-03-01

    To systematically review the evidence to determine the clinical outcomes and the important methodological quality features of interventional studies on adults with non-inflammatory multi-joint pain (MJP). Systematic search of published and unpublished literature using the databases: AMED, CINAHL, MEDLINE, EMBASE, psycINFO, SPORTDiscus, PEDro, OpenGrey, the EU Clinical Trials Register, World Health Organization International Clinical Trial Registry Platform, ClinicalTrials.gov and the ISRCTN registry (search: inception to 19th October 2017). All papers reporting the clinical outcomes of non-pharmacological interventions for people with non-inflammatory MJP were included. Studies were critically appraised using the Downs and Black Critical Appraisal and the TIDieR reporting checklists. Data were analysed using a Best Evidence Synthesis approach. From 3824 citations, four papers satisfied the eligibility criteria. Three studies reported outcomes from multidisciplinary rehabilitation programmes and one study reported the findings of a spa therapy intervention. All interventions significantly improved pain, function and quality of life in the short-term. There was limited reporting of measures for absenteeism, presenteeism and psychosocial outcomes. The evidence was 'weak', and due to a lack of controlled trials, there is limited evidence to ascertain treatment effectiveness. Design consideration for future trials surround improved reporting of participant characteristics, interventions and the standardisation of core outcome measures. There is insufficient high-quality trial data to determine the effectiveness of treatments for non-inflammatory MJP. Given the significant health burden which this condition presents on both individuals and wider society, developing and testing interventions and accurately reporting these, should be a research priority. Registration PROSPERO (CRD42013005888).

  7. Pharmacology of human experimental anxiety

    Directory of Open Access Journals (Sweden)

    F.G. Graeff

    2003-04-01

    Full Text Available This review covers the effect of drugs affecting anxiety using four psychological procedures for inducing experimental anxiety applied to healthy volunteers and patients with anxiety disorders. The first is aversive conditioning of the skin conductance responses to tones. The second is simulated public speaking, which consists of speaking in front of a video camera, with anxiety being measured with psychometric scales. The third is the Stroop Color-Word test, in which words naming colors are painted in the same or in a different shade, the incongruence generating a cognitive conflict. The last test is a human version of a thoroughly studied animal model of anxiety, fear-potentiated startle, in which the eye-blink reflex to a loud noise is recorded. The evidence reviewed led to the conclusion that the aversive conditioning and potentiated startle tests are based on classical conditioning of anticipatory anxiety. Their sensitivity to benzodiazepine anxiolytics suggests that these models generate an emotional state related to generalized anxiety disorder. On the other hand, the increase in anxiety determined by simulated public speaking is resistant to benzodiazepines and sensitive to drugs affecting serotonergic neurotransmission. This pharmacological profile, together with epidemiological evidence indicating its widespread prevalence, suggests that the emotional state generated by public speaking represents a species-specific response that may be related to social phobia and panic disorder. Because of scant pharmacological data, the status of the Stroop Color-Word test remains uncertain. In spite of ethical and economic constraints, human experimental anxiety constitutes a valuable tool for the study of the pathophysiology of anxiety disorders.

  8. [Pharmacological treatment of obesity].

    Science.gov (United States)

    Gomis Barbará, R

    2004-01-01

    The pharmacological treatment of obesity should be considered when cannot be achieved a 10% weight loss with diet therapy and physical activity. The drugs effective in obesity treatment may act by different mechanisms such as reduction in food intake, inhibition of fat absorption, increase of thermogenesis and stimulation of adipocyte apoptosis. At present, we only have two marketed drugs for obesity treatment. Sibutramine is an inhibitor of norepinephrine, dopamine and serotonina reuptake which inhibits food intake and increases thermogenesis. Sibutramine administration for a year can induce a weight loss of 4-7%. Its main side effects are hypertension, headache, insomnia and constipation. Orlistat is an inhibitor of pancreatic lipase which is able to block the absorption of 30% of ingested fat. Its administration induces weight loss and reduction of ulterior weight regain. Also, this drug improves hypertension dyslipdaemia and helps to prevent diabetes in 52% of cases when administered over four years. The increase in frequency of stools and interference with vitamin absorption are its main side effects. Glucagon-like peptide 1, which increases insulin sensitivity and satiety, adiponectin and PPAR-gamma agonists which reduce insulin resistance and modulates adipocyte generation are the basis for future therapeutic approaches of obesity. Phosphatase inhibitors induce PPAR-gamma phosphorylation and UCP-1 expression leading to an increase in thermogenesis and reduction in appetite.

  9. Pharmacology of pediatric resuscitation.

    Science.gov (United States)

    Ushay, H M; Notterman, D A

    1997-02-01

    The resuscitation of children from cardiac arrest and shock remains a challenging goal. The pharmacologic principles underlying current recommendations for intervention in pediatric cardiac arrest have been reviewed. Current research efforts, points of controversy, and accepted practices that may not be most efficacious have been described. Epinephrine remains the most effective resuscitation adjunct. High-dose epinephrine is tolerated better in children than in adults, but its efficacy has not received full analysis. The preponderance of data continues to point toward the ineffectiveness and possible deleterious effects of overzealous sodium bicarbonate use. Calcium chloride is useful in the treatment of ionized hypocalcemia but may harm cells that have experienced asphyxial damage. Atropine is an effective agent for alleviating bradycardia induced by increased vagal tone, but because most bradycardia in children is caused by hypoxia, improved oxygenation is the intervention of choice. Adenosine is an effective and generally well-tolerated agent for the treatment of supraventricular tachycardia. Lidocaine is the drug of choice for ventricular dysrhythmias, and bretylium, still relatively unexplored, is in reserve. Many pediatricians use dopamine for shock in the postresuscitative period, but epinephrine is superior. Most animal research on cardiac arrest is based on models with ventricular fibrillation that probably are not reflective of cardiac arrest situations most often seen in pediatrics.

  10. Jatropha Tanjorensis - Review of Phytochemistry, Pharmacology ...

    African Journals Online (AJOL)

    Based on the findings of this work, future study on the phytochemistry and chemical constituents in relation to certain other biological activities are required to fully understand the phytochemical and complex pharmacological effect of the plant specie. Further work to isolate active compounds from the plant is also necessary.

  11. Clinical pharmacology of novel anticancer drug formulations

    NARCIS (Netherlands)

    Stuurman, F.E.

    2013-01-01

    Studies outlined in this thesis describe the impact of drug formulations on pharmacology of anticancer drugs. It consists of four parts and starts with a review describing the mechanisms of low oral bioavailability of anti-cancer drugs and strategies for improvement of the bioavailability. The

  12. Neurofeedback in children with attention-deficit/hyperactivity disorder (ADHD)--a controlled multicenter study of a non-pharmacological treatment approach.

    Science.gov (United States)

    Holtmann, Martin; Pniewski, Benjamin; Wachtlin, Daniel; Wörz, Sonja; Strehl, Ute

    2014-08-13

    Attention-deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder of childhood and has often a chronic course persisting into adulthood. However, up to 30% of children treated with stimulants either fail to show an improvement or suffer adverse side effects, including decreased appetite, insomnia and irritability and there is no evidence of long term efficacy of stimulants for ADHD. A series of studies has shown that neurofeedback is an effective additional or alternative treatment for children with ADHD, leading to e.g. significant and stable improvement in behavior, attention and IQ. Significant treatment effects of neurofeedback have also been verified in meta-analyses. Most of the trials, however, have been criticized for methodological difficulties, particularly lacking appropriate control conditions and number of patients included. This randomized study examines the efficacy of slow cortical potentials (SCP) -neurofeedback, controlling unspecific effects of the setting by comparing two active treatment modalities. A total of 144 patients with ADHD, older than six and younger than ten years, in some cases with additional pharmacological treatment, are included in this trial. In five trial centres patients are treated either with SCP-feedback or electromyographic (EMG) -feedback in 25 sessions within 3 months. A comprehensive test battery is conducted before and after treatment and at follow-up 6 month later, to assess core symptoms of ADHD, general psychopathology, attentional performance, comorbid symptoms, intelligence, quality of life and cortical arousal. The efficacy of SCP-feedback training for children with ADHD is evaluated in this randomized controlled study. In addition to behavior ratings and psychometric tests neurophysiological parameters serve as dependent variables. Further, the choice of EMG-biofeedback as an active control condition is debated. Current Controlled Trials ISRCTN76187185. Registered 5 February 2009.

  13. Pharmacological studies of the mechanism and function of interleukin-1β-induced miRNA-146a expression in primary human airway smooth muscle

    Directory of Open Access Journals (Sweden)

    Jiang Xiaoying

    2010-06-01

    Full Text Available Abstract Background Despite the widespread induction of miR-146a during the innate immune response little is known regarding its biogenesis, function and mechanism. We have therefore examined the role of miR-146a during the interleukin (IL-1β-stimulated IL-6 and IL-8 release and proliferation in primary human airway smooth muscle (HASM cells. Methods HASM cells were isolated from human lung re-section, cultured to a maximum of 3 - 6 passages and then exposed to IL-1β. miR-146a expression were determined by qRT-PCR, IL-6 and IL-8 release by ELISA and proliferation using bromodeoxyuridine incorporation. The role of NF-κB and the MAP kinase pathways was assessed using pharmacological inhibitors of IKK2 (TPCA-1, JNK (SP600125, p38 MAP kinase (SB203580 and MEK-1/2 (PD98059. miR-146a function was determined following transfection of HASM with inhibitors and mimics using Amaxa electroporation. Results IL-1β induced a time-dependent and prolonged 100-fold induction in miR-146a expression, which correlated with release of IL-6 and IL-8. Exposure to IL-1β had no effect upon HASM proliferation. Pharmacological studies showed that expression of primary miR-146a was regulated at the transcriptional levels by NF-κB whilst post-transcriptional processing to mature miR-146a was regulated by MEK-1/2 and JNK-1/2. Functional studies indicated that IL-1β-induced miR-146a expression does not negatively regulate IL-6 and IL-8 release or basal proliferation. However, inhibition of IL-1β-induced IL-6 and IL-8 release was observed at the super-maximal intracellular miR-146a levels obtained by transfection with miR-146a mimics and indicates that studies using miRNA mimics can produce false positive results. Mechanistic studies showed that in the presence of super-maximal levels, the action of miR-146a mimics was mediated at a step following IL-6 and IL-8 mRNA transcription and not through down-regulation of IL-1 receptor associated kinase 1 (IRAK-1 and TNF

  14. Carotenoids: biochemistry, pharmacology and treatment.

    Science.gov (United States)

    Milani, Alireza; Basirnejad, Marzieh; Shahbazi, Sepideh; Bolhassani, Azam

    2017-06-01

    Carotenoids and retinoids have several similar biological activities such as antioxidant properties, the inhibition of malignant tumour growth and the induction of apoptosis. Supplementation with carotenoids can affect cell growth and modulate gene expression and immune responses. Epidemiological studies have shown a correlation between a high carotenoid intake in the diet with a reduced risk of breast, cervical, ovarian, colorectal cancers, and cardiovascular and eye diseases. Cancer chemoprevention by dietary carotenoids involves several mechanisms, including effects on gap junctional intercellular communication, growth factor signalling, cell cycle progression, differentiation-related proteins, retinoid-like receptors, antioxidant response element, nuclear receptors, AP-1 transcriptional complex, the Wnt/β-catenin pathway and inflammatory cytokines. Moreover, carotenoids can stimulate the proliferation of B- and T-lymphocytes, the activity of macrophages and cytotoxic T-cells, effector T-cell function and the production of cytokines. Recently, the beneficial effects of carotenoid-rich vegetables and fruits in health and in decreasing the risk of certain diseases has been attributed to the major carotenoids, β-carotene, lycopene, lutein, zeaxanthin, crocin (/crocetin) and curcumin, due to their antioxidant effects. It is thought that carotenoids act in a time- and dose-dependent manner. In this review, we briefly describe the biological and immunological activities of the main carotenoids used for the treatment of various diseases and their possible mechanisms of action. This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc. © 2016 The British Pharmacological Society.

  15. The pharmacology of regenerative medicine.

    Science.gov (United States)

    Christ, George J; Saul, Justin M; Furth, Mark E; Andersson, Karl-Erik

    2013-07-01

    Regenerative medicine is a rapidly evolving multidisciplinary, translational research enterprise whose explicit purpose is to advance technologies for the repair and replacement of damaged cells, tissues, and organs. Scientific progress in the field has been steady and expectations for its robust clinical application continue to rise. The major thesis of this review is that the pharmacological sciences will contribute critically to the accelerated translational progress and clinical utility of regenerative medicine technologies. In 2007, we coined the phrase "regenerative pharmacology" to describe the enormous possibilities that could occur at the interface between pharmacology, regenerative medicine, and tissue engineering. The operational definition of regenerative pharmacology is "the application of pharmacological sciences to accelerate, optimize, and characterize (either in vitro or in vivo) the development, maturation, and function of bioengineered and regenerating tissues." As such, regenerative pharmacology seeks to cure disease through restoration of tissue/organ function. This strategy is distinct from standard pharmacotherapy, which is often limited to the amelioration of symptoms. Our goal here is to get pharmacologists more involved in this field of research by exposing them to the tools, opportunities, challenges, and interdisciplinary expertise that will be required to ensure awareness and galvanize involvement. To this end, we illustrate ways in which the pharmacological sciences can drive future innovations in regenerative medicine and tissue engineering and thus help to revolutionize the discovery of curative therapeutics. Hopefully, the broad foundational knowledge provided herein will spark sustained conversations among experts in diverse fields of scientific research to the benefit of all.

  16. A before and after study of medical students' and house staff members' knowledge of ACOVE quality of pharmacologic care standards on an acute care for elders unit.

    Science.gov (United States)

    Jellinek, Samantha P; Cohen, Victor; Nelson, Marcia; Likourezos, Antonios; Goldman, William; Paris, Barbara

    2008-06-01

    The Assessing Care of Vulnerable Elders (ACOVE) comprehensive set of quality assessment tools for ill older persons is a standard designed to measure overall care delivered to vulnerable elders (ie, those aged > or =65 years) at the level of a health care system or plan. The goal of this research was to quantify the pretest and posttest results of medical students and house staff participating in a pharmacotherapist-led educational intervention that focused on the ACOVE quality of pharmacologic care standards. This was a before and after study assessing the knowledge ofACOVE standards following exposure to an educational intervention led by a pharmacotherapist. It was conducted at the 29-bed Acute Care for Elders (ACE) unit of Maimonides Medical Center, a 705-bed, independent teaching hospital located in Brooklyn, New York. Participants included all medical students and house staff completing a rotation on the ACE unit from August 2004 through May 2005 who completed both the pre-and posttests. A pharmacotherapist provided a 1-hour active learning session reviewing the evidence supporting the quality indicators and reviewed case-based questions with the medical students and house staff. Educational interventions also occurred daily through pharmacotherapeutic consultations and during work rounds. Medical students and house staff were administered the same 15-question, patient-specific, case-based, multiple-choice pre-and posttest to assess knowledge of the standards before and after receiving the intervention. A total of 54 medical students and house staff (median age, 28.58 years; 40 men, 14 women) completed the study. Significantly higher median scores were achieved on the multiple-choice test after the intervention than before (median scores, 14/15 [93.3%] vs 12/15 [80.0%], respectively; P = 0.001). A pharmacotherapist-led educational intervention improved the scores of medical students and house staff on a test evaluating knowledge of evidence

  17. Pharmacological effects of two cytolysins isolated from the sea ...

    Indian Academy of Sciences (India)

    Sticholysins I and II (St I/II) are cytolysins purified from the sea anemone Stichodactyla helianthus. In this study, we show their pharmacological action on guinea-pig and snail models in native and pH-denatured conditions in order to correlate the pharmacological findings with the pore-forming activity of both isoforms.

  18. Pharmacology of sexually compulsive behavior.

    Science.gov (United States)

    Codispoti, Victoria L

    2008-12-01

    In a meta-analysis on controlled outcomes evaluations of 22,000 sex offenders, Losel and Schmucker found 80 comparisons between treatment and control groups. The recidivism rate averaged 19% in treated groups, and 27% in controls. Most other reviews reported a lower rate of sexual recidivism in treated sexual offenders. Of 2039 citations in this study (including literature in five languages), 60 studies held independent comparisons. Problematic issues included the control groups; various hormonal, surgical, cognitive behavioral, and psychotherapeutic treatments; and sample sizes. In the 80 studies compared after the year 2000, 32% were reported after 2000, 45% originated in the United States, 45% were reported in journals, and 36% were unpublished. Treatment characteristics showed a significant lack of pharmacologic treatment (7.5%), whereas use cognitive and classical behavioral therapy was 64%. In 68% of the studies, no information was available on the integrity of the treatment implementation; 36% of the treatment settings were outpatient only, 31% were prison settings, and 12% were mixed settings (prison, hospital, and outpatient). Integrating research interpretations is complicated by the heterogeneity of sex offenders, with only 56% being adult men and 17.5% adolescents. Offense types reported included 74% child molestation, 48% incest, and 30% exhibitionism. Pedophilia was not singled out. Follow-up periods varied from 12 months to greater than 84 months. The definition of recidivism ran the gamut from arrest (24%), conviction (30%), charges (19%), and no indication (16%). Results were difficult to interpret because of the methodological problems with this type of study. Overall, a positive outcome was noted with sex offender treatment. Cognitive-behavioral and hormonal treatment were the most promising. Voluntary treatment led to a slightly better outcome than mandatory participation. When accounting for a low base rate of sexual recidivism, the reduction

  19. Dual Nicotinic Acetylcholine Receptor α4β2 Antagonists/α7 Agonists: Synthesis, Docking Studies, and Pharmacological Evaluation of Tetrahydroisoquinolines and Tetrahydroisoquinolinium Salts

    DEFF Research Database (Denmark)

    Crestey, François; Jensen, Anders A; Soerensen, Christian

    2018-01-01

    We describe the synthesis of tetrahydroisoquinolines and tetrahydroisoquinolinium salts together with their pharmacological properties at various nicotinic acetylcholine receptors. In general, the compounds were α4β2 nAChR antagonists, with the tetrahydroisoquinolinium salts being more potent than...

  20. Genetic, clinical and pharmacological determinants of out-of-hospital cardiac arrest : rationale and outline of the AmsteRdam Resuscitation Studies (ARREST) registry

    NARCIS (Netherlands)

    Blom, M T; van Hoeijen, D A; Bardai, A; Berdowski, J; Souverein, P C; De Bruin, M L; Koster, R W; de Boer, A; Tan, H L

    2014-01-01

    INTRODUCTION: Out-of-hospital cardiac arrest (OHCA) is a major public health problem. Recognising the complexity of the underlying causes of OHCA in the community, we aimed to establish the clinical, pharmacological, environmental and genetic factors and their interactions that may cause OHCA.

  1. Pharmacologic and non-pharmacologic treatments for chronic pain in individuals with HIV: a systematic review

    Science.gov (United States)

    Merlin, Jessica S.; Bulls, Hailey W.; Vucovich, Lee A.; Edelman, E. Jennifer; Starrels, Joanna L.

    2016-01-01

    Chronic pain occurs in as many as 85% of individuals with HIV and is associated with substantial functional impairment. Little guidance is available for HIV providers seeking to address their patients’ chronic pain. We conducted a systematic review to identify clinical trials and observational studies that examined the impact of pharmacologic or non-pharmacologic interventions on pain and/or functional outcomes among HIV-infected individuals with chronic pain in high-development countries. Eleven studies met inclusion criteria and were mostly low or very low quality. Seven examined pharmacologic interventions (gabapentin, pregabalin, capsaicin, analgesics including opioids) and four examined non-pharmacologic interventions (cognitive behavioral therapy, self-hypnosis, smoked cannabis). The only controlled studies with positive results were of capsaicin and cannabis, and had short-term follow-up (≤12 weeks). Among the seven studies of pharmacologic interventions, five had substantial pharmaceutical industry sponsorship. These findings highlight several important gaps in the HIV/chronic pain literature that require further research. PMID:27267445

  2. Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology.

    Science.gov (United States)

    Pirazzini, Marco; Rossetto, Ornella; Eleopra, Roberto; Montecucco, Cesare

    2017-04-01

    The study of botulinum neurotoxins (BoNT) is rapidly progressing in many aspects. Novel BoNTs are being discovered owing to next generation sequencing, but their biologic and pharmacological properties remain largely unknown. The molecular structure of the large protein complexes that the toxin forms with accessory proteins, which are included in some BoNT type A1 and B1 pharmacological preparations, have been determined. By far the largest effort has been dedicated to the testing and validation of BoNTs as therapeutic agents in an ever increasing number of applications, including pain therapy. BoNT type A1 has been also exploited in a variety of cosmetic treatments, alone or in combination with other agents, and this specific market has reached the size of the one dedicated to the treatment of medical syndromes. The pharmacological properties and mode of action of BoNTs have shed light on general principles of neuronal transport and protein-protein interactions and are stimulating basic science studies. Moreover, the wide array of BoNTs discovered and to be discovered and the production of recombinant BoNTs endowed with specific properties suggest novel uses in therapeutics with increasing disease/symptom specifity. These recent developments are reviewed here to provide an updated picture of the biologic mechanism of action of BoNTs, of their increasing use in pharmacology and in cosmetics, and of their toxicology. Copyright © 2017 by The Author(s).

  3. Measuring the effectiveness of pharmacology teaching in undergraduate medical students.

    Science.gov (United States)

    Urrutia-Aguilar, Maria Esther; Martinez-Gonzalez, Adrian; Rodriguez, Rodolfo

    2012-03-01

    Information overload and recent curricular changes are viewed as important contributory factors to insufficient pharmacological education of medical students. This study was designed to assess the effectiveness of pharmacology teaching in our medical school. The study subjects were 455 second-year medical students, class of 2010, and 26 pharmacology teachers at the National University of Mexico Medical School. To assess pharmacological knowledge, students were required to take 3 multiple-choice exams (70 questions each) as part of their evaluation in the pharmacology course. A 30-item questionnaire was used to explore the students' opinion on teaching. Pharmacology professors evaluated themselves using a similar questionnaire. Students and teachers rated each statement on a 5-point Likert scale. The groups' exam scores ranged from 54.5% to 90.0% of correct responses, with a mean score of 77.3%. Only 73 (16%) of 455 students obtained an exam score of 90% and higher. Students' evaluations of faculty and professor self-ratings were very high (90% and 96.2%, of the maximal response, respectively). Student and professor ratings were not correlated with exam scores (r = 0.291). Our study shows that knowledge on pharmacology is incomplete in a large proportion of second-year medical students and indicates that there is an urgent need to review undergraduate training in pharmacology. The lack of relationship between the subjective ratings of teacher effectiveness and objective exam scores suggests the use of more demanding measures to assess the effectiveness of teaching.

  4. Pharmacology Portal: An Open Database for Clinical Pharmacologic Laboratory Services.

    Science.gov (United States)

    Karlsen Bjånes, Tormod; Mjåset Hjertø, Espen; Lønne, Lars; Aronsen, Lena; Andsnes Berg, Jon; Bergan, Stein; Otto Berg-Hansen, Grim; Bernard, Jean-Paul; Larsen Burns, Margrete; Toralf Fosen, Jan; Frost, Joachim; Hilberg, Thor; Krabseth, Hege-Merete; Kvan, Elena; Narum, Sigrid; Austgulen Westin, Andreas

    2016-01-01

    More than 50 Norwegian public and private laboratories provide one or more analyses for therapeutic drug monitoring or testing for drugs of abuse. Practices differ among laboratories, and analytical repertoires can change rapidly as new substances become available for analysis. The Pharmacology Portal was developed to provide an overview of these activities and to standardize the practices and terminology among laboratories. The Pharmacology Portal is a modern dynamic web database comprising all available analyses within therapeutic drug monitoring and testing for drugs of abuse in Norway. Content can be retrieved by using the search engine or by scrolling through substance lists. The core content is a substance registry updated by a national editorial board of experts within the field of clinical pharmacology. This ensures quality and consistency regarding substance terminologies and classification. All laboratories publish their own repertoires in a user-friendly workflow, adding laboratory-specific details to the core information in the substance registry. The user management system ensures that laboratories are restricted from editing content in the database core or in repertoires within other laboratory subpages. The portal is for nonprofit use, and has been fully funded by the Norwegian Medical Association, the Norwegian Society of Clinical Pharmacology, and the 8 largest pharmacologic institutions in Norway. The database server runs an open-source content management system that ensures flexibility with respect to further development projects, including the potential expansion of the Pharmacology Portal to other countries. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

  5. Structural Exploration of Quinazolin-4(3H)-ones as Anticonvulsants: Rational Design, Synthesis, Pharmacological Evaluation, and Molecular Docking Studies.

    Science.gov (United States)

    Ugale, Vinod G; Bari, Sanjay B

    2016-11-01

    Anticonvulsants effective against multiple seizures are of wide interest as antiepileptic drugs, especially if active against pharmaco-resistant seizures. Herein, we synthesized 16 different, rationally designed 2-((6,7-dimethoxy-4-oxo-2-phenylquinazolin-3(4H)-yl)amino)-N-(substituted phenyl)acetamides and screened for anticonvulsant activities through in vivo experiments. Compound 4d emerged as prototype with excellent anti-seizure action in mice against electroshock, chemically induced and pharmaco-resistant 6-Hz seizure models with no symptoms of neurotoxicity and hepatotoxicity (ED 50  = 23.5 mg/kg, MES, mice, i.p.; ED 50  = 32.6 mg/kg, scPTZ, mice, i.p.; ED 50  = 45.2 mg/kg, 6-Hz, mice, i.p.; TD 50  = 325.9 mg/kg, mice, i.p.). In addition, investigation of compound 4l in mice for its pharmacological profile proved it as safer anticonvulsant, devoid of the side effects such as motor dysfunction and hepatotoxicity of classical antiepileptic drugs (ED 50  = 26.1 mg/kg, MES, mice, i.p.; ED 50  = 79.4 mg/kg, scPTZ, mice, i.p.; TD 50  = 361.2 mg/kg, mice, i.p.). We also predicted physiochemical and pharmacokinetic properties of structurally optimized quinazolin-4(3H)-ones by a computational protocol. A combination of in vivo anticonvulsant profile, ex vivo toxicity, and in silico studies suggested that the synthesized compounds may be useful as broad-spectrum anti-seizure drug candidates with favorable pharmacokinetic parameters. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. A validated HPLC-MS/MS assay for quantifying unstable pharmacologically active metabolites of clopidogrel in human plasma: application to a clinical pharmacokinetic study.

    Science.gov (United States)

    Furlong, Michael T; Savant, Ishani; Yuan, Moucun; Scott, Laura; Mylott, William; Mariannino, Thomas; Kadiyala, Pathanjali; Roongta, Vikram; Arnold, Mark E

    2013-05-01

    Clopidogrel is prescribed for the treatment of Acute Coronary Syndrome and recent myocardial infarction, recent stroke, or established peripheral arterial disease. A sensitive and reliable high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) assay was developed and validated to enable reliable quantification of four diastereomeric and chemically reactive thiol metabolites, two of which are pharmacologically active, in human plasma. The metabolites were stabilized by alkylation of their reactive thiol moieties with 2-bromo-3'-methoxyacetophenone (MPB). Following organic solvent mediated-protein precipitation in a 96-well plate format, chromatographic separation was achieved by gradient elution on an Ascentis Express RP-amide column. Chromatographic conditions were optimized to ensure separation of the four derivatized active metabolites. Derivatized metabolites and stable isotope-labeled internal standards were detected by positive ion electrospray tandem mass spectrometry. The HPLC-MS/MS assay was validated over concentration ranges of 0.125-125 ng/mL for metabolites H1-H3 and 0.101-101 ng/mL for H4. Intra- and inter-assay precision values for replicate quality control samples were within 14.3% for all analytes during the assay validation. Mean quality control accuracy values were within ±6.3% of nominal values for all analytes. Assay recoveries were high (>79%). The four derivatized analytes were stable in human blood for at least 2 h at room temperature and on ice. The analytes were also stable in human plasma for at least 25 h at room temperature, 372 days at -20 °C and -70 °C, and following at least five freeze-thaw cycles. The validated assay was successfully applied to the quantification of all four thiol metabolites in human plasma in support of a human pharmacokinetic study. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Diretrizes brasileiras para o diagnóstico de narcolepsia Brazilian guidelines for the diagnosis of narcolepsy

    Directory of Open Access Journals (Sweden)

    Flávio Alóe

    2010-09-01

    Full Text Available Este artigo relata as conclusões da reunião de consenso com médicos especialistas sobre diagnóstico de narcolepsia baseada na revisão dos artigos sobre narcolepsia listados no Medline entre 1980 e 2010. A narcolepsia é uma doença crônica de início entre a primeira e segunda décadas de vida do indivíduo. Os sintomas essenciais são cataplexia e sonolência excessiva. A cataplexia é definida como episódios súbitos, recorrentes e reversíveis de fraqueza da musculatura esquelética desencadeados por situações de conteúdo emocional. Os sintomas acessórios são alucinações hipnagógicas, paralisia do sono e sono fragmentado. Critérios de diagnóstico clínico de acordo com a Classificação Internacional dos Transtornos do Sono são de sonolência excessiva e cataplexia. Recomenda-se a realização de polissonografia seguida do teste de latência múltipla do sono em um laboratório de sono para confirmação e diagnóstico de comorbidades. Quando não houver cataplexia, deve haver duas ou mais sonecas com sono REM no teste de latência múltipla do sono. Tipagem HLA-DQB1*0602 positiva com níveis de hipocretina-1 abaixo de 110pg/mL devem estar presentes para o diagnóstico de narcolepsia sem cataplexia e sem sonecas com sono REM.This manuscript contains the conclusion of the consensus meeting on the diagnosis of narcolepsy based on the review of Medline publications between 1980-2010. Narcolepsy is a chronic disorder with age at onset between the first and second decade of life. Essential narcolepsy symptoms are cataplexy and excessive sleepiness. Cataplexy is defined as sudden, recurrent and reversible attacks of muscle weakness triggered by emotions. Accessory narcolepsy symptoms are hypnagogic hallucinations, sleep paralysis and nocturnal fragmented sleep. The clinical diagnosis according to the International Classification of Sleep Disorders is the presence of excessive sleepiness and cataplexy. A full in-lab polysomnography

  8. Fuzzy pharmacology: theory and applications.

    Science.gov (United States)

    Sproule, Beth A; Naranjo, Claudio A; Türksen, I Burhan

    2002-09-01

    Fuzzy pharmacology is a term coined to represent the application of fuzzy logic and fuzzy set theory to pharmacological problems. Fuzzy logic is the science of reasoning, thinking and inference that recognizes and uses the real world phenomenon that everything is a matter of degree. It is an extension of binary logic that is able to deal with complex systems because it does not require crisp definitions and distinctions for the system components. In pharmacology, fuzzy modeling has been used for the mechanical control of drug delivery in surgical settings, and work has begun evaluating its use in other pharmacokinetic and pharmacodynamic applications. Fuzzy pharmacology is an emerging field that, based on these initial explorations, warrants further investigation.

  9. Monitoring pharmacologically induced immunosuppression by immune repertoire sequencing to detect acute allograft rejection in heart transplant patients: a proof-of-concept diagnostic accuracy study.

    Directory of Open Access Journals (Sweden)

    Christopher Vollmers

    2015-10-01

    Full Text Available It remains difficult to predict and to measure the efficacy of pharmacological immunosuppression. We hypothesized that measuring the B-cell repertoire would enable assessment of the overall level of immunosuppression after heart transplantation.In this proof-of-concept study, we implemented a molecular-barcode-based immune repertoire sequencing assay that sensitively and accurately measures the isotype and clonal composition of the circulating B cell repertoire. We used this assay to measure the temporal response of the B cell repertoire to immunosuppression after heart transplantation. We selected a subset of 12 participants from a larger prospective cohort study (ClinicalTrials.gov NCT01985412 that is ongoing at Stanford Medical Center and for which enrollment started in March 2010. This subset of 12 participants was selected to represent post-heart-transplant events, with and without acute rejection (six participants with moderate-to-severe rejection and six without. We analyzed 130 samples from these patients, with an average follow-up period of 15 mo. Immune repertoire sequencing enables the measurement of a patient's net state of immunosuppression (correlation with tacrolimus level, r = -0.867, 95% CI -0.968 to -0.523, p = 0.0014, as well as the diagnosis of acute allograft rejection, which is preceded by increased immune activity with a sensitivity of 71.4% (95% CI 30.3% to 94.9% and a specificity of 82.0% (95% CI 72.1% to 89.1% (cell-free donor-derived DNA as noninvasive gold standard. To illustrate the potential of immune repertoire sequencing to monitor atypical post-transplant trajectories, we analyzed two more patients, one with chronic infections and one with amyloidosis. A larger, prospective study will be needed to validate the power of immune repertoire sequencing to predict rejection events, as this proof-of-concept study is limited to a small number of patients who were selected based on several criteria including the

  10. The pharmacology of gynaecology.

    Science.gov (United States)

    Tothill, A

    1980-09-01

    Focus in this discussion of the pharmacology of gynecology is on the following: vaginal infections; genital herpes; genital warts; pelvic inflammatory disease; urinary infections; pruritus vulvae; menstrual problems; infertility; oral contraception; and hormone replacement therapy. Doctors in England working in Local Authority Family Planning Clinics are debarred from prescribing, and any patient with a vaginal infection has to be referred either to a special clinic or to her general practitioner which is often preferable as her medical history will be known. Vaginal discharge is a frequent complaint, and it is necessary to obtain full details. 1 of the most common infections is vaginal candidosis. Nystatin pessaries have always been a useful 1st-line treatment and are specific for this type of infection. Trichomonas infection also occurs frequently and responds well to metronidazole in a 200 mg dosage, 3 times daily for 7 days. It is necessary to treat the consort at the same time. Venereal diseases such as syphilis and gonorrhea always require vigorous treatment. Patients are now presenting with herpes genitalis far more often. The only treatment which is currently available, and is as good as any, is the application of warm saline to the vaginal area. Genital warts may be discovered on routine gynecological examination or may be reported to the doctor by the patient. 1 application of a 20% solution of podophyllum, applied carefully to each wart, usually effects a cure. Pelvic inflammatory disease seems to be on the increase. Provided any serious disease is ruled out a course of systemic antibiotics is often effective. Urinary infections are often seen in the gynecologic clinic, and many of these will respond well to 2 tablets of co-trimoxazole, 2 times daily for 14 days. In pruritus vulvae it is important to determine whether the cause is general or local. Menstrual problems regularly occur and have been increased by the IUD and the low-dose progesterone pill

  11. Genome wide analysis of narcolepsy in China implicates novel immune loci and reveals changes in association prior to versus after the 2009 H1N1 influenza pandemic.

    Directory of Open Access Journals (Sweden)

    Fang Han

    2013-10-01

    Full Text Available Previous studies in narcolepsy, an autoimmune disorder affecting hypocretin (orexin neurons and recently associated with H1N1 influenza, have demonstrated significant associations with five loci. Using a well-characterized Chinese cohort, we refined known associations in TRA@ and P2RY11-DNMT1 and identified new associations in the TCR beta (TRB@; rs9648789 max P = 3.7 × 10(-9 OR 0.77, ZNF365 (rs10995245 max P = 1.2 × 10(-11 OR 1.23, and IL10RB-IFNAR1 loci (rs2252931 max P = 2.2 × 10(-9 OR 0.75. Variants in the Human Leukocyte Antigen (HLA- DQ region were associated with age of onset (rs7744020 P = 7.9×10(-9 beta -1.9 years and varied significantly among cases with onset after the 2009 H1N1 influenza pandemic compared to previous years (rs9271117 P = 7.8 × 10(-10 OR 0.57. These reflected an association of DQB1*03:01 with earlier onset and decreased DQB1*06:02 homozygosity following 2009. Our results illustrate how genetic association can change in the presence of new environmental challenges and suggest that the monitoring of genetic architecture over time may help reveal the appearance of novel triggers for autoimmune diseases.

  12. A comparison of medical and pharmacy students' knowledge and skills of pharmacology and pharmacotherapy

    NARCIS (Netherlands)

    Keijsers, Carolina J P W; Brouwers, Jacobus R B J; de Wildt, Dick J; Custers, Eugene J F M; Ten Cate, Olle Th J; Hazen, Ankie C M; Jansen, Paul A F

    2014-01-01

    AIM: Pharmacotherapy might be improved if future pharmacists and physicians receive a joint educational programme in pharmacology and pharmacotherapeutics. This study investigated whether there are differences in the pharmacology and pharmacotherapy knowledge and skills of pharmacy and medical

  13. Electronic cigarettes and nicotine clinical pharmacology

    OpenAIRE

    Schroeder, Megan J; Hoffman, Allison C

    2014-01-01

    Objective To review the available literature evaluating electronic cigarette (e-cigarette) nicotine clinical pharmacology in order to understand the potential impact of e-cigarettes on individual users, nicotine dependence and public health. Methods Literature searches were conducted between 1 October 2012 and 30 September 2013 using key terms in five electronic databases. Studies were included in the review if they were in English and publicly available; non-clinical studies, conference abst...

  14. Pharmacological interventions to treat phlebitis: systematic review.

    Science.gov (United States)

    dos Reis, Paula Elaine Diniz; Silveira, Renata Cristina de Campos Pereira; Vasques, Christiane Inocêncio; de Carvalho, Emilia Campos

    2009-01-01

    This study presents a systematic review for evaluating effective pharmacological actions for the treatment of phlebitis stemming from infusion therapy. The studies reviewed were categorized according to the type of therapeutic approach proposed by the author and by the level of evidence presented. The review found that topical nitroglycerin and notoginseny were more effective in the reduction of the inflammatory process when compared with other proposed alternatives. Nevertheless, the development of research related to possible alternatives for the treatment of phlebitis is important.

  15. Cardiovascular Safety Pharmacology of Sibutramine.

    Science.gov (United States)

    Yun, Jaesuk; Chung, Eunyong; Choi, Ki Hwan; Cho, Dae Hyun; Song, Yun Jeong; Han, Kyoung Moon; Cha, Hey Jin; Shin, Ji Soon; Seong, Won-Keun; Kim, Young-Hoon; Kim, Hyung Soo

    2015-07-01

    Sibutramine is an anorectic that has been banned since 2010 due to cardiovascular safety issues. However, counterfeit drugs or slimming products that include sibutramine are still available in the market. It has been reported that illegal sibutramine-contained pharmaceutical products induce cardiovascular crisis. However, the mechanism underlying sibutramine-induced cardiovascular adverse effect has not been fully evaluated yet. In this study, we performed cardiovascular safety pharmacology studies of sibutramine systemically using by hERG channel inhibition, action potential duration, and telemetry assays. Sibutramine inhibited hERG channel current of HEK293 cells with an IC50 of 3.92 μM in patch clamp assay and increased the heart rate and blood pressure (76 Δbpm in heart rate and 51 ΔmmHg in blood pressure) in beagle dogs at a dose of 30 mg/kg (per oral), while it shortened action potential duration (at 10 μM and 30 μM, resulted in 15% and 29% decreases in APD50, and 9% and 17% decreases in APD90, respectively) in the Purkinje fibers of rabbits and had no effects on the QTc interval in beagle dogs. These results suggest that sibutramine has a considerable adverse effect on the cardiovascular system and may contribute to accurate drug safety regulation.

  16. Right unilateral electroconvulsive therapy does not cause more cognitive impairment than pharmacologic treatment in treatment-resistant bipolar depression: A 6-month randomized controlled trial follow-up study.

    Science.gov (United States)

    Bjoerke-Bertheussen, Jeanette; Schoeyen, Helle; Andreassen, Ole A; Malt, Ulrik F; Oedegaard, Ketil J; Morken, Gunnar; Sundet, Kjetil; Vaaler, Arne E; Auestad, Bjoern; Kessler, Ute

    2017-12-21

    Electroconvulsive therapy is an effective treatment for bipolar depression, but there are concerns about whether it causes long-term neurocognitive impairment. In this multicenter randomized controlled trial, in-patients with treatment-resistant bipolar depression were randomized to either algorithm-based pharmacologic treatment or right unilateral electroconvulsive therapy. After the 6-week treatment period, all of the patients received maintenance pharmacotherapy as recommended by their clinician guided by a relevant treatment algorithm. Patients were assessed at baseline and at 6 months. Neurocognitive functions were assessed using the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery, and autobiographical memory consistency was assessed using the Autobiographical Memory Interview-Short Form. Seventy-three patients entered the trial, of whom 51 and 26 completed neurocognitive assessments at baseline and 6 months, respectively. The MATRICS Consensus Cognitive Battery composite score improved by 4.1 points in both groups (P = .042) from baseline to 6 months (from 40.8 to 44.9 and from 41.9 to 46.0 in the algorithm-based pharmacologic treatment and electroconvulsive therapy groups, respectively). The Autobiographical Memory Interview-Short Form consistency scores were reduced in both groups (72.3% vs 64.3% in the algorithm-based pharmacologic treatment and electroconvulsive therapy groups, respectively; P = .085). This study did not find that right unilateral electroconvulsive therapy caused long-term impairment in neurocognitive functions compared to algorithm-based pharmacologic treatment in bipolar depression as measured using standard neuropsychological tests, but due to the low number of patients in the study the results should be interpreted with caution. ClinicalTrials.gov: NCT00664976. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. CD4+ T cell autoimmunity to hypocretin/orexin and cross-reactivity to a 2009 H1N1 influenza A epitope in narcolepsy

    DEFF Research Database (Denmark)

    De la Herrán-Arita, Alberto K; Kornum, Birgitte Rahbek; Mahlios, Josh

    2013-01-01

    the wake-promoting neuropeptide hypocretin (HCRT) (orexin). We identified two DQ0602-binding HCRT epitopes, HCRT56-68 and HCRT87-99, that activated a subpopulation of CD4(+) T cells in narcolepsy patients but not in DQ0602-positive healthy control subjects. Because of the established association...... to the 2009 H1N1 strain, pHA1275-287, with homology to HCRT56-68 and HCRT87-99. In vitro stimulation of narcolepsy CD4(+) T cells with pH1N1 proteins or pHA1275-287 increased the frequency of HCRT56-68- and HCRT87-99-reactive T cells. Our data indicate the presence of CD4(+) T cells that are reactive to HCRT...... of narcolepsy with the 2009 H1N1 influenza A strain (pH1N1), we administered a seasonal influenza vaccine (containing pH1N1) to patients with narcolepsy and found an increased frequency of circulating HCRT56-68- and HCRT87-99-reactive T cells. We also identified a hemagglutinin (HA) pHA1 epitope specific...

  18. Pharmacological study of 99mTc-CO-MIBI, a new mycoardial perfusion imaging agent comparison to 99mTc-MIBI

    International Nuclear Information System (INIS)

    Zhao Jiandong; Wang Jincheng; Mi Hongzhi

    2004-01-01

    For many years, 99m Tc-MIBI has been widely used for the diagnosis of ischemic heart disease. Although it has been regarded as a successful myocardial imaging agent, it has a notable defect of high liver radioactivities due to high uptake and slowly excrete. Recently, researchers had developed a new intermediate [ 99m Tc(CO) 3 (OH 2 ) 3 ] + , considering 99m Tc-MIBI excellent biodistribution, they synthesized a new class of compound- 99m Tc-CO-MIBI with [ 99m Tc(CO) 3 ] + core and ligand MIBI. Previous studies have preliminary demonstrated the following favorable properties: rapid blood-pool clearance, high myocardial extraction and rapid clearance kinetics from liver that indicated 99m Tc-CO-MIBI a promising new myocardial perfusion imaging agent. Furthermore, researchers separated the compound by changing liquid pH value and prepared single alkaline component 99m Tc-CO-MIBI. The pharmacological experiments in rat have provided better results on its biodistribution in vivo and much faster clearance kinetics from liver compared to 99mTc-MIBI. To evaluate the potential application of 99m Tc-CO-MIBI, further investigations are necessary to determine the evidence for enhanced ability in clinical decision making as a novel new myocardial perfusion imaging agent. Objective: Here, perform pharmacological experiment of 99m Tc-CO-MIBI, a new technetium-99m-labeled myocardial imaging agent compared to 99m Tc-MIBI in canines. To identify whether it is feasible in clinical application as a novel myocardial imaging agent, or not. Results: Accordingly, prepared the single alkaline component of 99m Tc-CO-MIBI. The complex was stable up to at least 7 hours after synthesized in vitro at either room temperature or 37 degree C water bath. Labeling yield and radiochemical purity (RCP) of the complex were evaluated by TLC and HPLC, the labeling percent was 93%-97% and the RCP was over 90%. Then administer 555MBq to every dog each times. A total of 5 dogs were involved. The data of

  19. Conception of pharmacological knowledge and needs amongst ...

    African Journals Online (AJOL)

    Students who are taking/have taken the medical pharmacology course completed an 18-question survey within 10min by marking one/more choices from ... and 31.1% different drugs in a group; 45.8% prefer to study lecturers' notes, 26.7% textbooks, 9.8% the Internet, and 2.7% journals; 46.7% use standard textbooks, ...

  20. Results from a pooled analysis of two European, randomized, placebo-controlled, phase 3 studies of ATX-101 for the pharmacologic reduction of excess submental fat.

    Science.gov (United States)

    McDiarmid, James; Ruiz, Jesus Benito; Lee, Daniel; Lippert, Susanne; Hartisch, Claudia; Havlickova, Blanka

    2014-10-01

    The injectable adipocytolytic drug ATX-101 is the first nonsurgical treatment for the reduction of submental fat (SMF) to undergo comprehensive clinical evaluation. This study aimed to confirm the efficacy and safety of ATX-101 for SMF reduction through a post hoc pooled analysis of two large phase 3 studies. Patients with unwanted SMF were randomized to receive 1 or 2 mg/cm(2) of ATX-101 or a placebo injected into their SMF during a maximum of four treatment sessions spaced approximately 28 days apart, with a 12-week follow-up period. The proportions of patients with reductions in SMF of one point or more on the Clinician-Reported SMF Rating Scale (CR-SMFRS) and the proportions of patients satisfied with the appearance of their face and chin [Subject Self-Rating Scale (SSRS) score ≥4] were reported overall and in subgroups. Other efficacy measures included improvements in the Patient-Reported SMF Rating Scale (PR-SMFRS), calliper measurements of SMF thickness, and assessment of skin laxity [Skin Laxity Rating Scale (SLRS)]. Adverse events and laboratory test results were recorded. Significantly greater proportions of the patients had improvements in clinician-reported measures (≥1-point improvement in CR-SMFRS: 58.8 and 63.8 % of the patients who received ATX-101 1 and 2 mg/cm(2), respectively, and 28.6 % of the placebo recipients; p < 0.001 for both ATX-101 doses vs. placebo) and patient-reported measures (≥1-point improvement in PR-SMFRS: 60.0 and 63.1 % of the patients who received ATX-101 1 and 2 mg/cm(2), respectively, vs. 34.3 % of the placebo recipients; p < 0.001 for both), analyzed alone or in combination, with ATX-101 versus placebo. These improvements correlated moderately with patient satisfaction regarding face and chin appearance (SSRS score ≥4: 60.8 and 65.4 % of the patients who received ATX-101 1 and 2 mg/cm(2), respectively, vs. 29.0 % of the placebo recipients; p < 0.001 for both). In this study, ATX-101 was effective irrespective of

  1. Arformoterol Tartrate: A Review of Pharmacology, Analysis and ...

    African Journals Online (AJOL)

    Erah

    suggest the potentially enhanced efficacy of this drug in the treatment of COPD including ... pharmacology, pharmacokinetics, clinical studies, analytical techniques, drug-drug interactions, ..... accordance with the United States Food and. Drug ...

  2. Pharmacology profiling of chemicals and proteins

    DEFF Research Database (Denmark)

    Kringelum, Jens Vindahl

    between pharmaceuticals and proteins in vivo potential leads to unwanted adverse effects, toxicity and reduced half-life, but can also lead to novel therapeutic effects of already approved pharmaceuticals. Hence identification of in vivo targets is of importance in discovery, development and repurposing....... This limitation complicates adverse effect assessment in the early drug-development phase, thus contributing to drugattrition. Prediction models offer the possibility to close these gaps and provide more complete pharmacology profiles, however improvements in performances are required for these tools to serve...... to its nonself origin, which potentially alters the pharmacology profile of the substance. The neutralization of biopharmaceuticals by antidrug antibodies (ADAs) is an important element in the immune response cascade, however studies of ADA binding site on biopharmaceuticals, referred to as B...

  3. Pharmacological evaluation of bee venom and melittin

    Directory of Open Access Journals (Sweden)

    Camila G. Dantas

    Full Text Available The objective of this study was to identify the pharmacological effects of bee venom and its major component, melittin, on the nervous system of mice. For the pharmacological analysis, mice were treated once with saline, 0.1 or 1.2 mg/kg of bee venom and 0.1 mg/kg of melittin, subcutaneously, 30 min before being submitted to behavioral tests: locomotor activity and grooming (open-field, catalepsy, anxiety (elevated plus-maze, depression (forced swimming test and apomorphine-induced stereotypy. Haloperidol, imipramine and diazepam were administered alone (positive control or as a pre-treatment (haloperidol.The bee venom reduced motor activity and promoted cataleptic effect, in a similar manner to haloperidol.These effects were decreased by the pretreatment with haloperidol. Both melittin and bee venom decreased the apomorphine-induced stereotypies. The data indicated the antipsychotic activity of bee venom and melittin in a murine model.

  4. How research in behavioral pharmacology informs behavioral science.

    Science.gov (United States)

    Branch, Marc N

    2006-05-01

    Behavioral pharmacology is a maturing science that has made significant contributions to the study of drug effects on behavior, especially in the domain of drug-behavior interactions. Less appreciated is that research in behavioral pharmacology can have, and has had, implications for the experimental analysis of behavior, especially its conceptualizations and theory. In this article, I outline three general strategies in behavioral pharmacology research that have been employed to increase understanding of behavioral processes. Examples are provided of the general characteristics of the strategies and of implications of previous research for behavior theory. Behavior analysis will advance as its theories are challenged.

  5. The pharmacological mechanisms of omalizumab in patients with very high IgE levels—Clues from studies on atopic dermatitis

    Directory of Open Access Journals (Sweden)

    Tse Wen Chang

    2012-12-01

    Full Text Available Seventeen case series investigating the effects of omalizumab on patients with atopic dermatitis included patients whose pretreatment serum IgE was above 700 IU/ml, the upper inclusion limit specified in the product label. In all, 107 patients received omalizumab at doses of ≤375 mg every 2 weeks, which is recommended for patients with IgE <700 IU/ml. Among them, 87 improved in clinical symptoms and some did so after the first dose. Among these 87 patients, 35 and 12 had pretreatment serum IgE in the range 700–7000 IU/ml and 7000–121,000 IU/ml, respectively. These results not only suggest the pathogenic roles of IgE and the potential utility of omalizumab in atopic dermatitis, but also raise questions concerning the pharmacological mechanisms of omalizumab in patients with very high IgE levels. If omalizumab at regular doses is proven to treat patients with ultra high IgE (e.g. above 7000 IU/ml effectively, it probably achieves this without neutralizing most of the IgE produced in the patients and downregulating the high-affinity IgE-Fc receptors on basophils and mast cells. Herein, we propose that a potential main pharmacological mechanism of omalizumab in patients with ultra high IgE is the ability of the rapidly accumulated IgE:omalizumab complexes to trap allergens.

  6. Did hypocretin receptor 2 autoantibodies cause narcolepsy with hypocretin deficiency in Pandemrix-vaccinated children? Comment on “Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2”

    OpenAIRE

    Vassalli Anne

    2015-01-01

    Abstract Did hypocretin receptor 2 auto antibodies cause narcolepsy with hypocretin deficiency in Pandemrix vaccinated children as suggested by Ahmed et al.? Using newly developed mouse models to report and inactivate hypocretin receptor expression Vassalli et al. now show that hypocretin neurons (whose loss causes narcolepsy) do not express hypocretin autoreceptors raising questions to the interpretation of Ahmed et al.’s findings. Mouse Genome Informatics: www.informatics.jax.org/reference/...

  7. Pharmacology Experiments on the Computer.

    Science.gov (United States)

    Keller, Daniel

    1990-01-01

    A computer program that replaces a set of pharmacology and physiology laboratory experiments on live animals or isolated organs is described and illustrated. Five experiments are simulated: dose-effect relationships on smooth muscle, blood pressure and catecholamines, neuromuscular signal transmission, acetylcholine and the circulation, and…

  8. Pharmacology of Marihuana (Cannabis sativa)

    Science.gov (United States)

    Maickel, Roger P.

    1973-01-01

    A detailed discussion of marihuana (Cannabis sativa) providing the modes of use, history, chemistry, and physiologic properties of the drug. Cites research results relating to the pharmacologic effects of marihuana. These effects are categorized into five areas: behavioral, cardiovascular-respiratory, central nervous system, toxicity-toxicology,…

  9. Chemotaxonomy and pharmacology of Gentianaceae

    DEFF Research Database (Denmark)

    Jensen, Søren Rosendal; Schripsema, Jan

    2002-01-01

    the remaining six are members of the Gentianeae. Based on the above results, a tentative list of chemical characteristics for the tribes of the Gentianaceae is presented. Finally, some pharmacologically interesting properties of plant extracts or compounds from taxa within Gentianaceae are listed....

  10. Pharmacological Effects of Biotin in Animals.

    Science.gov (United States)

    Riveron-Negrete, Leticia; Fernandez-Mejia, Cristina

    2017-01-01

    In recent decades, it was found that vitamins affect biological functions in ways other than their long-known functions; niacin is the best example of a water-soluble vitamin known to possess multiple actions. Biotin, also known as vitamin B7 or vitamin H, is a water-soluble B-complex vitamin that serves as a covalently-bound coenzyme of carboxylases. It is now well documented that biotin has actions other than participating in classical enzyme catalysis reactions. Several lines of evidence have demonstrated that pharmacological concentrations of biotin affect glucose and lipid metabolism, hypertension, reproduction, development, and immunity. The effect of biotin on these functions is related to its actions at the transcriptional, translational, and post-translational levels. The bestsupported mechanism involved in the genetic effects of biotin is the soluble guanylate cyclase/protein kinase G (PKG) signaling cascade. Although there are commercially-available products containing pharmacological concentrations of biotin, the toxic effects of biotin have been poorly studied. This review summarizes the known actions and molecular mechanisms of pharmacological doses of biotin in animals and current information regarding biotin toxicity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Neurovascular pharmacology of migraine

    NARCIS (Netherlands)

    MaassenVanDenBrink, Antoinette; Chan, Kayi Y.

    2008-01-01

    Migraine is a paroxysmal neurovascular disorder, which affects a significant proportion of the population. Since dilation of cranial blood vessels is likely to be responsible for the headache experienced in migraine, many experimental models for the study of migraine have focussed on this feature.

  12. Flow cytometry analysis of T-cell subsets in cerebrospinal fluid of narcolepsy type 1 patients with long-lasting disease.

    Science.gov (United States)

    Moresco, Monica; Lecciso, Mariangela; Ocadlikova, Darina; Filardi, Marco; Melzi, Silvia; Kornum, Birgitte Rahbek; Antelmi, Elena; Pizza, Fabio; Mignot, Emmanuel; Curti, Antonio; Plazzi, Giuseppe

    2018-04-01

    Type 1 narcolepsy (NT1) is a central hypersomnia linked to the destruction of hypocretin-producing neurons. A great body of genetic and epidemiological data points to likely autoimmune disease aetiology. Recent reports have characterized peripheral blood T-cell subsets in NT1, whereas data regarding the cerebrospinal fluid (CSF) immune cell composition are lacking. The current study aimed to characterize the T-cell and natural killer (NK) cell subsets in NT1 patients with long disease course. Immune cell subsets from CSF and peripheral blood mononuclear cell (PBMC) samples were analysed by flow cytometry in two age-balanced and sex-balanced groups of 14 NT1 patients versus 14 healthy controls. The frequency of CSF cell groups was compared with PBMCs. Non-parametric tests were used for statistical analyses. The NT1 patients did not show significant differences of CSF immune cell subsets compared to controls, despite a trend towards higher CD4 + terminally differentiated effector memory T cells. T cells preferentially displayed a memory phenotype in the CSF compared to PBMCs. Furthermore, a reduced frequency of CD4 + terminally differentiated effector memory T cells and an increased frequency of NK CD56 bright cells was observed in PBMCs from patients compared to controls. Finally, the ratio between CSF and peripheral CD4 + terminally differentiated effector memory T cells was two-fold increased in NT1 patients versus controls. Significant differences in PBMCs and in CSF/PBMC ratios of immune cell profile were found in NT1 patients compared to healthy controls. These differences might have arisen from the different HLA status, or be primary or secondary to hypocretin deficiency. Further functional studies in patients close to disease onset are required to understand NT1 pathophysiology. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Nematode cholinergic pharmacology

    International Nuclear Information System (INIS)

    Segerberg, M.A.

    1989-01-01

    Nematode acetylcholine (ACh) receptors were characterized using both biochemical and electrophysiological techniques, including: (1) receptor binding studies in crude homogenates of the free-living nematode Caenorhabditis elegans and the parasitic nematode Ascaris lumbricoides with the high-affinity probe [ 3 H]N-methylscopolamine ([ 3 H]NMS) which binds to muscarinic receptors in many vertebrate and invertebrate tissues (2) measurement of depolarization and contraction induced by a variety of cholinergic agents, including N-methylscopolamine (NMS), in an innervated dorsal muscle strip preparation of Ascaris; (3) examination of the antagonistic actions of d-tubocurarine (dTC) and NMS at dorsal neuromuscular junction; (4) measurement of input resistance changes in Ascaris commissural motorneurons induced by ACh, dTC, NMS, pilocarpine and other cholinergic drugs

  14. Pharmacological potentials of betalains.

    Science.gov (United States)

    Kaur, Ginpreet; Thawkar, Baban; Dubey, Shivangi; Jadhav, Priyanka

    2018-06-06

    Betalains are water soluble plant pigments in plants of the order Caryophyllales, which are widely used as colorants. Several preclinical studies reported that betanin reveals antioxidants, anti-inflammatory, hepatoprotective, anticancer, anti-diabetes, anti-lipid emic, antimicrobial activity, radio protective and anti-proliferative activity. They are isolated from sources such as red beetroot, amaranth, prickly pear, red pitahaya, etc. Betalains are divided into two groups based on the colour and confer either the betacyanins (purple reddish) or betaxanthins (yellowish orange). Betalain is one of the promising nutraceuticals which can provide beneficial effects for prevention and cure of various diseases. The purpose of this review is to focus on nutraceutical facts of betalains by focusing on the ongoing treatment using betalains and to address its future nutraceuticals implications.

  15. Pharmacological enhancement of treatment for amblyopia

    Directory of Open Access Journals (Sweden)

    Rashad MA

    2012-03-01

    Full Text Available Mohammad A RashadOphthalmology Department, Faculty of Medicine, Ain Shams University, Cairo, EgyptBackground: The purpose of this study was to compare a weight-adjusted dose of carbidopa-levodopa as treatment adjunctive to occlusion therapy with occlusion therapy alone in children and adults with different types of amblyopia.Methods: This prospective study included 63 patients with amblyopia classified into two groups, ie, an occlusion group which included 35 patients who received occlusion therapy only and a pharmacological enhancement group which included 28 patients who received oral carbidopa-levodopa together with occlusion therapy for 6 weeks.Results: The mean logarithm of the minimal angle of resolution (logMAR of the eyes with amblyopia was not significantly different in the occlusion group (0.52, 0.52, and 0.51 than in the pharmacological enhancement group (0.58, 0.49, and 0.56 at three follow-up visits (at months 1, 3, and 12, respectively. There was a highly significant improvement in mean logMAR of amblyopic eyes compared with baseline in both occlusion groups (from 0.68 to 0.52, from 0.68 to 0.52, and from 0.68 to 0.51 and in the pharmacological enhancement group (from 0.81 to 0.58, from 0.81 to 0.49, and from 0.81 to 0.56 at the month 1, 3, and 12 visits (P = 0.01, P = 0.01, and P = 0.001, respectively. The improvement of mean logMAR in the subgroup of patients older than 12 years was greater in the pharmacological enhancement group (42.5% than in the occlusion group (30%. The improvement of mean logMAR in the subgroup of patients with severe amblyopia was greater in the pharmacological enhancement group (34.3% than in the occlusion group (22%.Conclusion: Significant improvement was reported in both groups at all follow-up visits over 1 year. Regardless of the etiology of amblyopia, levodopa-carbidopa may be added to part-time occlusion in older patients as a means of increasing the plasticity of the visual cortex. Levodopa may add

  16. Pharmacological enhancement of treatment for amblyopia

    Science.gov (United States)

    Rashad, Mohammad A

    2012-01-01

    Background The purpose of this study was to compare a weight-adjusted dose of carbidopa- levodopa as treatment adjunctive to occlusion therapy with occlusion therapy alone in children and adults with different types of amblyopia. Methods This prospective study included 63 patients with amblyopia classified into two groups, ie, an occlusion group which included 35 patients who received occlusion therapy only and a pharmacological enhancement group which included 28 patients who received oral carbidopa-levodopa together with occlusion therapy for 6 weeks. Results The mean logarithm of the minimal angle of resolution (logMAR) of the eyes with amblyopia was not significantly different in the occlusion group (0.52, 0.52, and 0.51) than in the pharmacological enhancement group (0.58, 0.49, and 0.56) at three follow-up visits (at months 1, 3, and 12, respectively). There was a highly significant improvement in mean logMAR of amblyopic eyes compared with baseline in both occlusion groups (from 0.68 to 0.52, from 0.68 to 0.52, and from 0.68 to 0.51) and in the pharmacological enhancement group (from 0.81 to 0.58, from 0.81 to 0.49, and from 0.81 to 0.56) at the month 1, 3, and 12 visits (P = 0.01, P = 0.01, and P = 0.001, respectively). The improvement of mean logMAR in the subgroup of patients older than 12 years was greater in the pharmacological enhancement group (42.5%) than in the occlusion group (30%). The improvement of mean logMAR in the subgroup of patients with severe amblyopia was greater in the pharmacological enhancement group (34.3%) than in the occlusion group (22%). Conclusion Significant improvement was reported in both groups at all follow-up visits over 1 year. Regardless of the etiology of amblyopia, levodopa-carbidopa may be added to part-time occlusion in older patients as a means of increasing the plasticity of the visual cortex. Levodopa may add to the effect of occlusion in severe amblyopia and bilateral amblyopia. PMID:22536029

  17. Contemporary pharmacological obesity treatments

    Directory of Open Access Journals (Sweden)

    Kaszubska Katarzyna

    2016-06-01

    Full Text Available In the last few years, obesity has become a global epidemic. Consequently, worldwide costs associated with managing obesity and obesity-related comorbidities are huge. Numerous studies have focused on discerning the appropriate proper treatment of weight related problems such as overweight and obesity. Moreover, many clinical trials have been conducted for many years in order to introduce effective anti-obesity drugs. The aim of the present review is to provide an overview of current and future pharmacotherapy for obesity, and to provide the reader with a determination of the concentration and composition of long and short term anti-obesity drugs, doing so by placing emphasis on pharmacotherapy and up-to-day solutions. It should be noted that, currently, the worldwide pharmacotherapy is represented by phendimetrazine, benzphetamine and diethylpropion, as well as by orlistat, lorcaserin, phentermine/topiramate, naltrexone/bupropion and liraglutide. In our paper, individual cases of patients’ needs are thoroughly illustrated by way of examples. Medical prescriptions and contraindications are also described.

  18. PHARMACOLOGY OF CANNABINOIDS

    Directory of Open Access Journals (Sweden)

    Ilonka Ferjan

    2015-06-01

    Full Text Available The discovery of cannabinoid receptors and endocannabinoid system has led to the potential therapeutic use of cannabis derivatives. Cannabinoids acting through the CB1 receptors modulate the release of other neurotransmitters in central nervous system, whereas the activation of peripheral CB2 receptors results in decreased inflammatory response and increased apoptosis of some tumor cells populations. The cannabinoids have been authorized for chemotherapy-induced nausea and vomiting; stimulation of appetite; to alleviate neuropathic pain and spasticity in multiple sclerosis, and to reduce pain in cancer patients. Efficacy in other diseases and clinical conditions should be proven in ongoing or future clinical trials. Isolation and identification of different cannabinoids from cannabis and synthesis of novel, more selective, derivatives widens their therapeutic potential. However, there are numerous adverse effects reported, especially when cannabinoids formulations with unknown quantitative and qualitative composition are used. Addiction, tolerance, withdrawal symptoms, increased risk of acute myocardial re-infarction, and increased risk of psychosis or worsening of psychosis are the most common adverse effects of cannabinoids. Acute adverse effects e. g. severe central nervous system depression, are more pronounced in children than in adults. Potential cannabinoid medicines should be subject to the same regulations as other potential drugs. Safety and efficacy of any potential drug candidate, regardless whether it is plant-derived or synthesized, should be proven in non-clinical studies and clinical trials, as well as the marketing authorization must be issued by the appropriate drug authority. Patients deserve a quality manufactured product, which always contains the specified amount of "Remedium cardinale."

  19. Clinical pharmacology of homoharringtonine

    International Nuclear Information System (INIS)

    Savaraj, N.; Lu, K.; Dimery, I.; Feun, L.G.; Burgess, M.; Keating, M.; Loo, T.L.

    1986-01-01

    Clinical pharmacokinetics of homoharringtonine (HHT) were studied in eight patients who received uniformly labeled HHT at 3-4 mg/m2 (150 mu Ci) by continuous 6-hour infusion. The drug and metabolites were quantified by radiochemical and high-performance liquid chromatographic techniques. Computerized nonlinear least-square regression and curve stripping were used to characterize HHT and total [ 3 H]HHT equivalent pharmacokinetics. Unchanged HHT in the plasma declined biphasically, with an alpha-half-life of 0.5 +/- 0.1 hours and a beta-half-life of 9.3 +/- 1.4 hours. The total clearance of HHT was 177.4 +/- 27.7 ml X hour-1 X kg-1, and the apparent volume of distribution, estimated from the area under the drug concentration versus time curve, was 2.4 +/- 0.4 L X kg-1. Correspondingly, the total [ 3 H]HHT equivalent disappeared from the plasma in a triphasic manner. Compared with the pharmacokinetic parameters of unchanged HHT, the terminal half-life of total 3 H was 67.5 +/- 7.5 hours, 7.4 times longer; the total clearance was 30.9 +/- 3.1 ml X hour-1 X kg-1, 5.5 times slower; but the volume of distribution by area was 2.7 +/- 0.1 L X kg-1, nearly the same. The 72-hour cumulative urinary excretion of total tritium was 28.2% of the administered dose and only 38.3% of this resided in unchanged HHT. Thus, urinary excretion was not a major route of elimination of HHT. Moreover, HHT underwent extensive metabolism; one major and two minor unidentified products were detected in both plasma and urine

  20. Pharmacological Properties of Melanin and its Function in Health.

    Science.gov (United States)

    ElObeid, Adila Salih; Kamal-Eldin, Afaf; Abdelhalim, Mohamed Anwar K; Haseeb, Adil M

    2017-06-01

    The biological pigment melanin is present in most of the biological systems. It manifests a host of biological and pharmacological properties. Its role as a molecule with special properties and functions affecting general health, including photoprotective and immunological action, are well recognized. Its antioxidant, anti-inflammatory, immunomodulatory, radioprotective, hepatic, gastrointestinal and hypoglycaemic benefits have only recently been recognized and studied. It is also associated with certain disorders of the nervous system. In this MiniReview, we consider the steadily increasing literature on the bioavailability and functional activity of melanin. Published literature shows that melanin may play a number of possible pharmacological effects such as protective, stimulatory, diagnostic and curative roles in human health. In this MiniReview, possible health roles and pharmacological effects are considered. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  1. Breastfeeding information in pharmacology textbooks: a content analysis.

    Science.gov (United States)

    Amir, Lisa H; Raval, Manjri; Hussainy, Safeera Y

    2013-07-01

    Women often need to take medicines while breastfeeding and pharmacists need to provide accurate information in order to avoid undue caution about the compatibility of medicines and breastfeeding. The objective of this study was to review information provided about breastfeeding in commonly used pharmacology textbooks. We asked 15 Australian universities teaching pharmacy courses to provide a list of recommended pharmacology textbooks in 2011. Ten universities responded, generating a list of 11 textbooks that we analysed for content relating to breastfeeding. Pharmacology textbooks outline the mechanisms of actions of medicines and their use: however, only a small emphasis is placed on the safety/compatibility of medicines for women during breastfeeding. Current pharmacology textbooks recommended by Australian universities have significant gaps in their coverage of medicine use in breastfeeding. Authors of textbooks should address this gap, so academic staff can recommend texts with the best lactation content.

  2. Narcolepsy, REM sleep behavior disorder, and supranuclear gaze palsy associated with Ma1 and Ma2 antibodies and tonsillar carcinoma.

    Science.gov (United States)

    Adams, Chris; McKeon, Andrew; Silber, Michael H; Kumar, Rajeev

    2011-04-01

    To describe a patient with diencephalic and mesencephalic presentation of a Ma1 and Ma2 antibody-associated paraneoplastic neurological disorder. Case report. The Colorado Neurological Institute Movement Disorders Center in Englewood, Colorado, and the Mayo Clinic in Rochester, Minnesota. A 55-year-old man with a paraneoplastic neurological disorder characterized by rapid eye movement sleep behavior disorder, narcolepsy, and a progressive supranuclear palsy-like syndrome in the setting of tonsillar carcinoma. Immunotherapy for paraneoplastic neurological disorder, surgery and radiotherapy for cancer, and symptomatic treatment for parkinsonism and sleep disorders. Polysomnography, multiple sleep latency test, and neurological examination. The cancer was detected at a limited stage and treatable. After oncological therapy and immunotherapy, symptoms stabilized. Treatment with modafinil improved daytime somnolence. Rapid onset and progression of multifocal deficits may be a clue to paraneoplastic etiology. Early treatment of a limited stage cancer (with or without immunotherapy) may possibly slow progression of neurological symptoms. Symptomatic treatment may be beneficial.

  3. Pharmacological Treatment for Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    Kaoru Sugi, MD PhD

    2005-01-01

    Full Text Available Pharmacological treatment for atrial fibrillation has a variety of purposes, such as pharmacological defibrillation, maintenance of sinus rhythm, heart rate control to prevent congestive heart failure and prevention of both cerebral infarction and atrial remodeling. Sodium channel blockers are superior to potassium channel blockers for atrial defibrillation, while both sodium and potassium channel blockers are effective in the maintenance of sinus rhythm. In general, digitalis or Ca antagonists are used to control heart rate during atrial fibrillation to prevent congestive heart failure, while amiodarone or bepridil also reduce heart rates during atrial fibrillation. Anticoagulant therapy with warfarin is recommended to prevent cerebral infarction and angiotensin converting enzyme antagonists or angiotensin II receptor blockers are also used to prevent atrial remodeling. One should select appropriate drugs for treatment of atrial fibrillation according to the patient's condition.

  4. Pharmacological interventions for acute pancreatitis.

    Science.gov (United States)

    Moggia, Elisabetta; Koti, Rahul; Belgaumkar, Ajay P; Fazio, Federico; Pereira, Stephen P; Davidson, Brian R; Gurusamy, Kurinchi Selvan

    2017-04-21

    the remaining comparisons in these outcomes or for any of the remaining primary outcomes (the proportion of participants experiencing at least one serious adverse event and the occurrence of infected pancreatic necrosis). None of the trials reported heath-related quality of life. Very low-quality evidence suggests that none of the pharmacological treatments studied decrease short-term mortality in people with acute pancreatitis. However, the confidence intervals were wide and consistent with an increase or decrease in short-term mortality due to the interventions. We did not find consistent clinical benefits with any intervention. Because of the limitations in the prognostic scoring systems and because damage to organs may occur in acute pancreatitis before they are clinically manifest, future trials should consider including pancreatitis of all severity but power the study to measure the differences in the subgroup of people with severe acute pancreatitis. It may be difficult to power the studies based on mortality. Future trials in participants with acute pancreatitis should consider other outcomes such as complications or health-related quality of life as primary outcomes. Such trials should include health-related quality of life, costs, and return to work as outcomes and should follow patients for at least three months (preferably for at least one year).

  5. Pharmacological challenges in chronic pancreatitis

    OpenAIRE

    Olesen, Anne Estrup; Brokjaer, Anne; Fisher, Iben Wendelboe; Larsen, Isabelle Myriam

    2013-01-01

    Drug absorption in patients with chronic pancreatitis might be affected by the pathophysiology of the disease. The exocrine pancreatic insufficiency is associated with changes in gastrointestinal intraluminal pH, motility disorder, bacterial overgrowth and changed pancreatic gland secretion. Together these factors can result in malabsorption and may also affect the efficacy of pharmacological intervention. The lifestyle of chronic pancreatitis patients may also contribute to gastrointestinal ...

  6. Applications of stable isotopes in clinical pharmacology

    NARCIS (Netherlands)

    Schellekens, Reinout C A; Stellaard, Frans; Woerdenbag, Herman J; Frijlink, Henderik W; Kosterink, Jos G W

    2011-01-01

    This review aims to present an overview of the application of stable isotope technology in clinical pharmacology. Three main categories of stable isotope technology can be distinguished in clinical pharmacology. Firstly, it is applied in the assessment of drug pharmacology to determine the

  7. Scaling down of a clinical three-dimensional perfusion multicompartment hollow fiber liver bioreactor developed for extracorporeal liver support to an analytical scale device useful for hepatic pharmacological in vitro studies.

    Science.gov (United States)

    Zeilinger, Katrin; Schreiter, Thomas; Darnell, Malin; Söderdahl, Therese; Lübberstedt, Marc; Dillner, Birgitta; Knobeloch, Daniel; Nüssler, Andreas K; Gerlach, Jörg C; Andersson, Tommy B

    2011-05-01

    Within the scope of developing an in vitro culture model for pharmacological research on human liver functions, a three-dimensional multicompartment hollow fiber bioreactor proven to function as a clinical extracorporeal liver support system was scaled down in two steps from 800 mL to 8 mL and 2 mL bioreactors. Primary human liver cells cultured over 14 days in 800, 8, or 2 mL bioreactors exhibited comparable time-course profiles for most of the metabolic parameters in the different bioreactor size variants. Major drug-metabolizing cytochrome P450 activities analyzed in the 2 mL bioreactor were preserved over up to 23 days. Immunohistochemical studies revealed tissue-like structures of parenchymal and nonparenchymal cells in the miniaturized bioreactor, indicating physiological reorganization of the cells. Moreover, the canalicular transporters multidrug-resistance-associated protein 2, multidrug-resistance protein 1 (P-glycoprotein), and breast cancer resistance protein showed a similar distribution pattern to that found in human liver tissue. In conclusion, the down-scaled multicompartment hollow fiber technology allows stable maintenance of primary human liver cells and provides an innovative tool for pharmacological and kinetic studies of hepatic functions with small cell numbers.

  8. Pharmacological chaperoning: a primer on mechanism and pharmacology.

    Science.gov (United States)

    Leidenheimer, Nancy J; Ryder, Katelyn G

    2014-05-01

    Approximately forty percent of diseases are attributable to protein misfolding, including those for which genetic mutation produces misfolding mutants. Intriguingly, many of these mutants are not terminally misfolded since native-like folding, and subsequent trafficking to functional locations, can be induced by target-specific, small molecules variably termed pharmacological chaperones, pharmacoperones, or pharmacochaperones (PCs). PC targets include enzymes, receptors, transporters, and ion channels, revealing the breadth of proteins that can be engaged by ligand-assisted folding. The purpose of this review is to provide an integrated primer of the diverse mechanisms and pharmacology of PCs. In this regard, we examine the structural mechanisms that underlie PC rescue of misfolding mutants, including the ability of PCs to act as surrogates for defective intramolecular interactions and, at the intermolecular level, overcome oligomerization deficiencies and dominant negative effects, as well as influence the subunit stoichiometry of heteropentameric receptors. Not surprisingly, PC-mediated structural correction of misfolding mutants normalizes interactions with molecular chaperones that participate in protein quality control and forward-trafficking. A variety of small molecules have proven to be efficacious PCs and the advantages and disadvantages of employing orthostatic antagonists, active-site inhibitors, orthostatic agonists, and allosteric modulator PCs are considered. Also examined is the possibility that several therapeutic agents may have unrecognized activity as PCs, and this chaperoning activity may mediate/contribute to therapeutic action and/or account for adverse effects. Lastly, we explore evidence that pharmacological chaperoning exploits intrinsic ligand-assisted folding mechanisms. Given the widespread applicability of PC rescue of mutants associated with protein folding disorders, both in vitro and in vivo, the therapeutic potential of PCs is vast

  9. Leveraging model-based study designs and serial micro-sampling techniques to understand the oral pharmacokinetics of the potent LTB4 inhibitor, CP-105696, for mouse pharmacology studies.

    Science.gov (United States)

    Spilker, Mary E; Chung, Heekyung; Visswanathan, Ravi; Bagrodia, Shubha; Gernhardt, Steven; Fantin, Valeria R; Ellies, Lesley G

    2017-07-01

    1. Leukotriene B4 (LTB4) is a proinflammatory mediator important in the progression of a number of inflammatory diseases. Preclinical models can explore the role of LTB4 in pathophysiology using tool compounds, such as CP-105696, that modulate its activity. To support preclinical pharmacology studies, micro-sampling techniques and mathematical modeling were used to determine the pharmacokinetics of CP-105696 in mice within the context of systemic inflammation induced by a high-fat diet (HFD). 2. Following oral administration of doses > 35 mg/kg, CP-105696 kinetics can be described by a one-compartment model with first order absorption. The compound's half-life is 44-62 h with an apparent volume of distribution of 0.51-0.72 L/kg. Exposures in animals fed an HFD are within 2-fold of those fed a normal chow diet. Daily dosing at 100 mg/kg was not tolerated and resulted in a >20% weight loss in the mice. 3. CP-105696's long half-life has the potential to support a twice weekly dosing schedule. Given that most chronic inflammatory diseases will require long-term therapies, these results are useful in determining the optimal dosing schedules for preclinical studies using CP-105696.

  10. Chemistry and Pharmacology of Citrus sinensis

    Directory of Open Access Journals (Sweden)

    Juan Manuel J. Favela-Hernández

    2016-02-01

    Full Text Available Presently the search for new drugs from natural resources is of growing interest to the pharmaceutical industry. Natural products have been the source of new drugs since ancient times. Plants are a good source of secondary metabolites which have been found to have beneficial properties. The present study is a review of the chemistry and pharmacology of Citrus sinensis. This review reveals the therapeutic potential of C. sinensis as a source of natural compounds with important activities that are beneficial for human health that could be used to develop new drugs.

  11. [Pharmacological aspects of pain research in Germany].

    Science.gov (United States)

    Niederberger, E; Kuner, R; Geißlinger, G

    2015-10-01

    In spite of several approved analgesics, the therapy of pain still constitutes a challenge due to the fact that the drugs do not exert sufficient efficacy or are associated with severe side effects. Therefore, the development of new and improved painkillers is still of great importance. A number of highly qualified scientists in Germany are investigating signal transduction pathways in pain, effectivity of new drugs and the so far incompletely investigated mechanisms of well-known analgesics in preclinical and clinical studies. The highlights of pharmacological pain research in Germany are summarized in this article.

  12. Electronic cigarettes and nicotine clinical pharmacology.

    Science.gov (United States)

    Schroeder, Megan J; Hoffman, Allison C

    2014-05-01

    To review the available literature evaluating electronic cigarette (e-cigarette) nicotine clinical pharmacology in order to understand the potential impact of e-cigarettes on individual users, nicotine dependence and public health. Literature searches were conducted between 1 October 2012 and 30 September 2013 using key terms in five electronic databases. Studies were included in the review if they were in English and publicly available; non-clinical studies, conference abstracts and studies exclusively measuring nicotine content in e-cigarette cartridges were excluded from the review. Nicotine yields from automated smoking machines suggest that e-cigarettes deliver less nicotine per puff than traditional cigarettes, and clinical studies indicate that e-cigarettes deliver only modest nicotine concentrations to the inexperienced e-cigarette user. However, current e-cigarette smokers are able to achieve systemic nicotine and/or cotinine concentrations similar to those produced from traditional cigarettes. Therefore, user experience is critically important for nicotine exposure, and may contribute to the products' ability to support and maintain nicotine dependence. Knowledge about e-cigarette nicotine pharmacology remains limited. Because a user's e-cigarette experience may significantly impact nicotine delivery, future nicotine pharmacokinetic and pharmacodynamic studies should be conducted in experienced users to accurately assess the products' impact on public health.

  13. Electronic cigarettes and nicotine clinical pharmacology

    Science.gov (United States)

    Schroeder, Megan J; Hoffman, Allison C

    2014-01-01

    Objective To review the available literature evaluating electronic cigarette (e-cigarette) nicotine clinical pharmacology in order to understand the potential impact of e-cigarettes on individual users, nicotine dependence and public health. Methods Literature searches were conducted between 1 October 2012 and 30 September 2013 using key terms in five electronic databases. Studies were included in the review if they were in English and publicly available; non-clinical studies, conference abstracts and studies exclusively measuring nicotine content in e-cigarette cartridges were excluded from the review. Results Nicotine yields from automated smoking machines suggest that e-cigarettes deliver less nicotine per puff than traditional cigarettes, and clinical studies indicate that e-cigarettes deliver only modest nicotine concentrations to the inexperienced e-cigarette user. However, current e-cigarette smokers are able to achieve systemic nicotine and/or cotinine concentrations similar to those produced from traditional cigarettes. Therefore, user experience is critically important for nicotine exposure, and may contribute to the products’ ability to support and maintain nicotine dependence. Conclusions Knowledge about e-cigarette nicotine pharmacology remains limited. Because a user's e-cigarette experience may significantly impact nicotine delivery, future nicotine pharmacokinetic and pharmacodynamic studies should be conducted in experienced users to accurately assess the products’ impact on public health. PMID:24732160

  14. Geriatric pharmacology and pharmacotherapy education for health professionals and students: a systematic review

    Science.gov (United States)

    Keijsers, Carolina J P W; van Hensbergen, Larissa; Jacobs, Lotte; Brouwers, Jacobus R B J; de Wildt, Dick J; ten Cate, Olle Th J; Jansen, Paul A F

    2012-01-01

    AIMS Given the reported high rates of medication errors, especially in elderly patients, we hypothesized that current curricula do not devote enough time to the teaching of geriatric pharmacology. This review explores the quantity and nature of geriatric pharmacology education in undergraduate and postgraduate curricula for health professionals. METHODS Pubmed, Embase and PsycINFO databases were searched (from 1 January 2000 to 11 January 2011), using the terms ‘pharmacology’ and ‘education’ in combination. Articles describing content or evaluation of pharmacology education for health professionals were included. Education in gen