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Sample records for manejo con haloperidol

  1. Doses of olanzapine, risperidone, and haloperidol used in clinical practice: results of a prospective pharmacoepidemiologic study. EFESO Study Group. Estudio Farmacoepidemiologico en la Esquizofrenia con Olanzapina.

    PubMed

    Sacristán, J A; Gómez, J C; Montejo, A L; Vieta, E; Gregor, K J

    2000-05-01

    The objectives of this study were to determine the doses of olanzapine (OLZ), risperidone (RIS), and haloperidol (HAL) used in clinical practice in outpatients with schizophrenia and the rates of occurrence of extrapyramidal symptoms (EPS) and other adverse events, clinical response, and use of concomitant medications. The present study involved a subset of patients from a 6-month, open-label, prospective observational study. Data were collected by 293 psychiatrists at mental health centers and other outpatient treatment facilities in Spain. Medications and doses used, occurrence of EPS and other adverse events, and scores on the Clinical Global Impression (CGI) of Severity Scale and Global Assessment of Function (GAF) were recorded. Clinical response was defined as a decrease of > or = 2 points on the CGI, with a final CGI score < or = 4. A total of 2657 patients were included in the analysis. The initial and overall mean daily doses for the 3 groups were as follows: OLZ, 12.2 and 13.0 mg, respectively; RIS, 5.2 and 5.4 mg; and HAL, 13.9 and 13.6 mg. Initial and overall median daily doses were the same in each group: OLZ, 10 mg; RIS, 6 mg; and HAL, 10 mg. A significantly lower proportion of OLZ-treated patients (36.9%) experienced EPS compared with RIS-treated (49.6%) and HAL-treated (76.0%) patients (P < or = 0.001). A significantly lower proportion of patients in the OLZ group (47.8%) experienced adverse events compared with patients in the RIS (57.2%) and HAL (79.8%) groups (P < or = 0.001). A significantly greater proportion of OLZ-treated patients (37.3%) were responders compared with RIS-treated patients (31.5%) (P < 0.05). In all 3 groups, patients who had an initial CGI score > or = 5 received significantly higher overall mean daily doses than did patients with an initial CGI score < 5 (P < 0.001). A significantly lower proportion of OLZ-treated patients (10.2%) were receiving concomitant anticholinergic medication at the end of the study (month 6

  2. Classics in Chemical Neuroscience: Haloperidol.

    PubMed

    Tyler, Marshall W; Zaldivar-Diez, Josefa; Haggarty, Stephen J

    2017-02-15

    The discovery of haloperidol catalyzed a breakthrough in our understanding of the biochemical basis of schizophrenia, improved the treatment of psychosis, and facilitated deinstitutionalization. In doing so, it solidified the role for chemical neuroscience as a means to elucidate the molecular underpinnings of complex neuropsychiatric disorders. In this Review, we will cover aspects of haloperidol's synthesis, manufacturing, metabolism, pharmacology, approved and off-label indications, and adverse effects. We will also convey the fascinating history of this classic molecule and the influence that it has had on the evolution of neuropsychopharmacology and neuroscience.

  3. Does haloperidol block methylphenidate? Motivation or attention?

    PubMed

    Levy, F; Hobbes, G

    1996-07-01

    The effect of methylphenidate preceded by a moderate dose of haloperidol on reaction times over the duration of a continuous performance test (CPT), was investigated in ten male children, with a DSM-III diagnosis of attention deficit disorder with hyperactivity disorder (ADDH). Using a within-subject double-blind design, the effects of methylphenidate preceded by haloperidol on reaction time during the first and second blocks of CPT test were compared. Methylphenidate maintained a significantly improved reaction time in the second block of the CPT test. When methylphenidate, preceded by placebo, was preceded by haloperidol this effect was not observed, suggesting opposing effects on attentional systems by methylphenidate versus haloperidol. The study is the first to examine the "blocking" effect of haloperidol over the course of a CPT. The results suggest that dopamine systems are involved in the maintenance of the CPT response, and support an "incentive motivation" theory of sustained attention.

  4. Haloperidol

    MedlinePlus

    ... movements) and verbal tics (uncontrollable need to repeat sounds or words) in adults and children who have ... is important to keep all medication out of sight and reach of children as many containers (such ...

  5. Is topical haloperidol a useful glaucoma treatment?

    PubMed Central

    Lavin, M. J.; Andrews, V.

    1986-01-01

    A randomised, double blind, single dose study of topical haloperidol, a dopamine receptor blocking drug, was performed on 20 healthy volunteers. After its administration a modest reduction in intraocular pressure was recorded over the six-hour study period, but the difference was not significant at the p less than 0.05 level. Although dopamine blocking agents are effective in reducing intraocular pressure in experimental animals, topical haloperidol appears unlikely to be clinically useful in the treatment of glaucoma. PMID:3718908

  6. Molindone and haloperidol in tardive dyskinesia.

    PubMed

    Glazer, W M; Hafez, H M; Benarroche, C L

    1985-08-01

    Preliminary results are described from a study of 11 outpatients manifesting exacerbated tardive dyskinesia after tapering and withdrawal of neuroleptic medications. Patients were randomly assigned to molindone or haloperidol under double-blind placebo-controlled conditions to compare the masking effects of the two drugs. Haloperidol treatment masked withdrawal-exacerbated tardive dyskinesia more than molindone did; this difference (measured by percent change in AIMS scores) was significant (p = .04) when the dose was 200% but not 100% of the prestudy neuroleptic dose. Despite several limitations to the study, the results suggest that molindone may have less dyskinetogenic potential than haloperidol. Further research in the area of site-specificity of molindone is indicated.

  7. Haloperidol-induced suppression of carotid chemoreception in vitro.

    PubMed

    Nolan, W F; Donnelly, D F; Smith, E J; Dutton, R E

    1985-09-01

    Effects of antagonism of endogenous dopamine with haloperidol on single-unit frequency, interspike interval distribution, and interval serial dependency of the cat sinus nerve were tested using an in vitro carotid body-sinus nerve superfusion technique. A dose dependency of inhibition by haloperidol (0.05-2.0 microgram/ml) was observed. Superfusion with 1-2 microgram/ml haloperidol significantly reduced frequency within 5 min (P less than 0.05) and caused a complete cessation of firing within 25 min in 5 of 10 chemoreceptor units. Frequency recovered to control during drug washout. Acetylcholine (10-micrograms/ml superfusion or 500-micrograms bolus) increased sinus nerve activity under control conditions but not during superfusion with haloperidol. No effect of haloperidol on impulse serial dependency was detected. However, interval distribution was significantly altered by haloperidol in five of six chemoreceptor units. Our results suggest an excitatory role for dopamine in carotid chemoreception.

  8. [18F]haloperidol binding in baboon brain in vivo.

    PubMed

    Yousef, K A; Fowler, J S; Volkow, N D; Dewey, S L; Shea, C; Schlyer, D J; Gatley, S J; Logan, J; Wolf, A P

    1996-01-01

    The binding of [18F]haloperidol to dopamine D2 and to sigma recognition sites in baboon brain was examined using positron emission tomography (PET). Studies were performed at baseline and after treatment with either haloperidol (to evaluate saturability), (+)-butaclamol (which has specificity for dopamine D2 receptors) or (-)-butaclamol (which has specificity for sigma sites). Binding was widespread. Treatment with (-)-butaclamol had no effect, whereas (+)-butaclamol selectively reduced the uptake in striatum. Haloperidol increased the clearance rate from all brain regions. These results indicate that the binding profile of [18F]haloperidol does not permit the selective examination of either dopamine D2 or sigma sites using PET.

  9. [Elimination of haloperidol from erythrocytes surfaces supernatant and blood plasma].

    PubMed

    Shanidze, L A

    2005-01-01

    The aim of the study was to investigate the adsorption rate of haloperidol on erythrocytes surfaces. The pharmacokinetic and pharmacodynamic parameters of haloperidol were monitored in the experiment. The neuroleptic was administered to 12 adult dogs and the blood samples were collected for further analysis following 20, 30, 60, 180, 240, 360, 420 and 480 minutes after the injection. The groups of samples (blood plasma and supernatant) were monitored during this period. The differences between haloperidol concentration in the supernatant and blood plasma were compared. Our data have shown that dynamics of the elimination of intact and acidified forms of haloperidol from the supernatant and the blood serum are not the same. Intact and acidified forms are differently regulated by plasma. albumines and globulines. The process of redistribution of haloperidol between the both substrates takes place, while the supernatant has a donor function for the free form of haloperidol and represents the acceptor of the haloperidol's metabolites. This provides the possibility to develop multidiscipline approach to the optimization to the prescription of haloperidol.

  10. Anandamide attenuates haloperidol-induced vacuous chewing movements in rats.

    PubMed

    Röpke, Jivago; Busanello, Alcindo; Leal, Caroline Queiroz; de Moraes Reis, Elizete; de Freitas, Catiuscia Molz; Villarinho, Jardel Gomes; Figueira, Fernanda Hernandes; Mello, Carlos Fernando; Ferreira, Juliano; Fachinetto, Roselei

    2014-10-03

    Antipsychotics may cause tardive dyskinesia in humans and orofacial dyskinesia in rodents. Although the dopaminergic system has been implicated in these movement disorders, which involve the basal ganglia, their underlying pathomechanisms remain unclear. CB1 cannabinoid receptors are highly expressed in the basal ganglia, and a potential role for endocannabinoids in the control of basal ganglia-related movement disorders has been proposed. Therefore, this study investigated whether CB1 receptors are involved in haloperidol-induced orofacial dyskinesia in rats. Adult male rats were treated for four weeks with haloperidol decanoate (38mg/kg, intramuscularly - i.m.). The effect of anandamide (6nmol, intracerebroventricularly - i.c.v.) and/or the CB1 receptor antagonist SR141716A (30μg, i.c.v.) on haloperidol-induced vacuous chewing movements (VCMs) was assessed 28days after the start of the haloperidol treatment. Anandamide reversed haloperidol-induced VCMs; SR141716A (30μg, i.c.v.) did not alter haloperidol-induced VCM per se but prevented the effect of anandamide on VCM in rats. These results suggest that CB1 receptors may prevent haloperidol-induced VCMs in rats, implicating CB1 receptor-mediated cannabinoid signaling in orofacial dyskinesia. Copyright © 2014. Published by Elsevier Inc.

  11. Invariom based electron density studies on the C/Si analogues haloperidol/sila-haloperidol and venlafaxine/sila-venlafaxine.

    PubMed

    Luger, Peter; Dittrich, Birger; Tacke, Reinhold

    2015-09-14

    The subjects of this study are the structures and electron densities of the carbon/silicon analogues haloperidol/sila-haloperidol (1a/1b) and venlafaxine/sila-venlafaxine (2a/2b). The parent carbon compounds 1a (an antipsychotic agent) and 2a (an antidepressant) are both in clinical use. For haloperidol/sila-haloperidol, three published structures were studied in more detail: the structures of haloperidol hydrochloride (1a·HCl), haloperidol hydropicrate (1a·HPic) and sila-haloperidol hydrochloride (1b·HCl). For venlafaxine/sila-venlafaxine, the published structures of venlafaxine (2a), venlafaxine hydrochloride (2a·HCl; as orthorhombic (2a·HCl-ortho) and monoclinic polymorph (2a·HCl-mono)) and sila-venlafaxine hydrochloride (2b·HCl) were investigated. Based on these structures, the molecular electron densities were reconstructed by using the invariom formalism. They were further analysed in terms of Bader's quantum theory of atoms in molecules, electrostatic potentials mapped onto electron density isosurfaces and Hirshfeld surfaces. These studies were performed with a special emphasis on the comparison of the corresponding carbon/silicon analogues.

  12. Rapid tranquillisation in psychiatric emergency settings in Brazil: pragmatic randomised controlled trial of intramuscular haloperidol versus intramuscular haloperidol plus promethazine

    PubMed Central

    Coutinho, E S F; Adams, C E

    2007-01-01

    Objective To determine whether haloperidol alone results in swifter and safer tranquillisation and sedation than haloperidol plus promethazine. Design Pragmatic randomised open trial (January-July 2004). Setting Psychiatric emergency room, Rio de Janeiro, Brazil. Participants 316 patients who needed urgent intramuscular sedation because of agitation, dangerous behaviour, or both. Interventions Open treatment with intramuscular haloperidol 5-10 mg or intramuscular haloperidol 5-10 mg plus intramuscular promethazine up to 50 mg; doses were at the discretion of the prescribing clinician. Main outcome measures The primary outcome was proportion tranquil or asleep by 20 minutes. Secondary outcomes were asleep by 20 minutes; tranquil or asleep by 40, 60, and 120 minutes; physically restrained or given additional drugs within 2 hours; severe adverse events; another episode of agitation or aggression; additional visit from the doctor during the subsequent 24 hours; overall antipsychotic load in the first 24 hours; and still in hospital after 2 weeks. Results Primary outcome data were available for 311 (98.4%) people, 77% of whom were thought to have a psychotic illness. Patients allocated haloperidol plus promethazine were more likely to be tranquil or asleep by 20 minutes than those who received intramuscular haloperidol alone (relative risk 1.30, 95% confidence interval 1.10 to 1.55; number needed to treat 6, 95% confidence interval 4 to 16; P=0.002). No differences were found after 20 minutes. However, 10 cases of acute dystonia occurred, all in the haloperidol alone group. Conclusions Haloperidol plus promethazine is a better option than haloperidol alone in terms of speed of onset of action and safety. Enough data are now available to change guidelines that continue to recommend treatments that leave people exposed to longer periods of aggression than necessary and patients vulnerable to distressing and unsafe adverse effects. Trial registration Current Controlled

  13. Simultaneous Spectrophotometric Estimation of Haloperidol and Trihexyphenidyl in Tablets

    PubMed Central

    Wate, S. P.; Borkar, A. A.

    2010-01-01

    The combination of haloperidol and trihexyphenidyl is a dosage form to be used as antidyskinetic agent. Literature revealed that there is no single method for the simultaneous estimation of these drugs in tablet dosage form, which prompted us to develop a simple, rapid, accurate, economical and sensitive spectrophotometric method. The simultaneous estimation method is based on the principle of additivity of absorbance, for the determination of haloperidol and trihexyphenidyl in tablet formulation. The absorption maxima of the drugs were found to be at 245.0 nm and 206.0 nm respectively for haloperidol and trihexyphenidyl in methanol and 0.1N HCl (90:10). The obeyance of Beer Lambert’s law was observed in the concentration range of 2.5-12.5 µg/ml for haloperidol and 1.0-5.0 µg/ml for trihexyphenidyl. The accuracy and reproducibility of the proposed method was statistically validated by recovery studies. PMID:20838539

  14. Simultaneous spectrophotometric estimation of haloperidol and trihexyphenidyl in tablets.

    PubMed

    Wate, S P; Borkar, A A

    2010-03-01

    The combination of haloperidol and trihexyphenidyl is a dosage form to be used as antidyskinetic agent. Literature revealed that there is no single method for the simultaneous estimation of these drugs in tablet dosage form, which prompted us to develop a simple, rapid, accurate, economical and sensitive spectrophotometric method. The simultaneous estimation method is based on the principle of additivity of absorbance, for the determination of haloperidol and trihexyphenidyl in tablet formulation. The absorption maxima of the drugs were found to be at 245.0 nm and 206.0 nm respectively for haloperidol and trihexyphenidyl in methanol and 0.1N HCl (90:10). The obeyance of Beer Lambert's law was observed in the concentration range of 2.5-12.5 µg/ml for haloperidol and 1.0-5.0 µg/ml for trihexyphenidyl. The accuracy and reproducibility of the proposed method was statistically validated by recovery studies.

  15. Clinical Comparison of Haloperidol with Chlorpromazine in Mentally Retarded Children

    ERIC Educational Resources Information Center

    LeVann, Leonard J.

    1971-01-01

    In an 8-week double-blind comparison, haloperidol reduced the severity of the target symptoms impulsiveness, hostility, and aggressiveness in significantly more mentally retarded children than did chlorpromazine. (Author)

  16. Clinical Comparison of Haloperidol with Chlorpromazine in Mentally Retarded Children

    ERIC Educational Resources Information Center

    LeVann, Leonard J.

    1971-01-01

    In an 8-week double-blind comparison, haloperidol reduced the severity of the target symptoms impulsiveness, hostility, and aggressiveness in significantly more mentally retarded children than did chlorpromazine. (Author)

  17. Brain and liver oxidative stress after sertraline and haloperidol treatment in mice.

    PubMed

    Abdel-Salam, Omar M E; Youness, Eman R; Khadrawy, Yasser Ashry; Sleem, Amany A

    2013-01-01

    Haloperidol is a classic antipsychotic drug known for its propensity to cause extrapyramidal side effects. Sertraline is an antidepressant drug which has been reported to cause extrapyramidal symptoms. We aimed to see whether treatment with sertraline would worsen the effect of haloperidol on oxidative stress in the brains of mice. Sertraline (10 or 20 mg/kg), haloperidol (2 mg/kg), haloperidol combined with sertraline or saline was administered daily via the subcutaneous route and mice were euthanized 10 days later when biochemical assays were carried out. Malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (nitrite) levels, total antioxidant capacity (TAC), acetylcholinesterase (AChE), catalase and paraoxonase 1 (PON1) activities were determined in the brain and liver. Sertraline monotherapy did not alter GSH, MDA, TAC or nitrite in the brain. Haloperidol decreased GSH and TAC and increased MDA and nitrite. The combined treatment with sertraline and haloperidol resulted in increased MDA, but to a lesser extent than haloperidol monotherapy. A significant increase in GSH and TAC and decreased nitrite was observed after the combination treatment was compared with haloperidol monotherapy. Catalase activity decreased with sertraline or haloperidol treatment. PON1 activity decreased with sertraline and haloperidol monotherapy and showed a further decrease with the combination therapy compared with haloperidol monotherapy. AChE activity decreased after haloperidol and increased with the combination treatment compared with haloperidol monotherapy. In the liver, GSH was unaltered after sertraline, haloperidol or their combination. MDA increased with sertraline, haloperidol and their combination. TAC decreased after combination therapy. Nitric oxide increased after sertraline, haloperidol or their combination. PON1 activity decreased with sertraline, haloperidol and with sertraline-haloperidol co-treatment. Sertraline did not worsen brain oxidative stress

  18. Use of haloperidol in PCP-intoxicated individuals.

    PubMed

    MacNeal, James J; Cone, David C; Sinha, Vinnita; Tomassoni, Anthony J

    2012-11-01

    Emergency medical workers often experience violence while performing their job functions. Phencyclidine (PCP)-intoxicated patients are often violent and difficult to control physically. A chemical restraint is frequently needed to assist in protecting both patients and staff from agitated persons. This study evaluated haloperidol as a chemical restraint in PCP-intoxicated patients. This is a retrospective case series of all PCP-positive patients who received haloperidol for behavioral control from April 2008 to April 2011 at a single large (944 bed), urban, tertiary-care hospital. All patients receiving haloperidol and having a toxicology screen positive for PCP were identified using an electronic medical record. Identified cases were then manually reviewed by investigators for adverse events. Subjects included 59 adult patients who were acutely agitated requiring chemical restraint or sedation with haloperidol, and who tested positive for PCP. There were 20 females and 39 males, ranging in age from 19 to 54 years. Patients received haloperidol via the PO, IM, or IV routes in doses ranging from 1 to 10 mg. There were two adverse events (mild hypoxia and mild hypotension) found during chart review; neither were serious nor required change in patient disposition. In this study, haloperidol does not seem to cause harm when used in the management of PCP-intoxicated patients. Caution must always be exercised in the use of chemical restraint; further prospective study is warranted.

  19. A comparative study of parenteral molindone and haloperidol in the acutely psychotic patient.

    PubMed

    Binder, R; Glick, I; Rice, M

    1981-05-01

    This study compares the efficacy of intramuscular haloperidol with intramuscular molindone, a newer antipsychotic medication. Molindone appears to be comparable in efficacy to haloperidol in acutely agitated and psychotic patients.

  20. Dyskinesias evoked in monkeys by weekly administration of haloperidol.

    PubMed

    Weiss, B; Santelli, S

    1978-05-19

    In two cebus (Cebus albifrons) monkeys given weekly oral doses of 0.25 milligram of haloperidol per kilogram, movement disorders appeared 1 to 8 hours after drug administration following the tenth weekly dose. These disorders included oral movements, peculiar postures, writhing, and stretching. Such reactions faded in intensity after the next two doses. Increasing the dose to 0.5 milligram per kilogram has elicited the disorders reliably after each weekly dose for almost 2 years. Similar reactions also developed in a squirrel monkey (Saimiri sciurea) treated weekly with haloperidol and in a third cebus monkey previously maintained for a year on a regimen of 0.25 milligram of haloperidol per kilogram on 5 days per week. These findings suggest an experimental model for determining the etiology of drug-induced movement disorders. They also suggest an unrecognized clinical problem.

  1. Haloperidol versus risperidone on rat "early onset" vacuous chewing.

    PubMed

    Marchese, Giorgio; Bartholini, Francesco; Casu, Maria Antonietta; Ruiu, Stefania; Casti, Paola; Congeddu, Elena; Tambaro, Simone; Pani, Luca

    2004-02-04

    Similarly to acute rat catalepsy, "early onset" vacuous chewing movements (VCMs) induced by subchronic treatment with antipsychotic have recently been proposed as a model of human extrapyramidal symptoms. In the present study, the propensities of haloperidol and risperidone in inducing rat "early onset" VCMs were compared using doses of the two antipsychotics that acutely induce similar catalepsy. Comparable rat catalepsy states were observed when the effects produced by 0.1, 0.5, and 1mg/kg of haloperidol were compared with those induced by 1, 4, and 10mg/kg of risperidone, respectively. These doses of the two antipsychotics were then administered twice a day for 4 weeks and VCMs scored after 12h, 5 days, or 3 weeks of drug withdrawal. Among the haloperidol-treated groups, only those rats injected with 0.5 and 1mg/kg showed high levels of VCMs after 12h and 5 days of drug withdrawal when compared to vehicle-treated rats, while basal levels of VCMs were reached after 3 weeks from the last injection. High VCMs levels were observed in risperidone-treated rats only at the dose of 10mg/kg and after 12h of drug withdrawal, but not after 5 days or 3 weeks. The present results indicated that haloperidol possessed a much higher propensity to induce rat "early onset" VCMs than risperidone.

  2. Brain Targeting of a Water Insoluble Antipsychotic Drug Haloperidol via the Intranasal Route Using PAMAM Dendrimer.

    PubMed

    Katare, Yogesh K; Daya, Ritesh P; Sookram Gray, Christal; Luckham, Roger E; Bhandari, Jayant; Chauhan, Abhay S; Mishra, Ram K

    2015-09-08

    Delivery of therapeutics to the brain is challenging because many organic molecules have inadequate aqueous solubility and limited bioavailability. We investigated the efficiency of a dendrimer-based formulation of a poorly aqueous soluble drug, haloperidol, in targeting the brain via intranasal and intraperitoneal administration. Aqueous solubility of haloperidol was increased by more than 100-fold in the developed formulation. Formulation was assessed via different routes of administration for behavioral (cataleptic and locomotor) responses, and for haloperidol distribution in plasma and brain tissues. Dendrimer-based formulation showed significantly higher distribution of haloperidol in the brain and plasma compared to a control formulation of haloperidol administered via intraperitoneal injection. Additionally, 6.7 times lower doses of the dendrimer-haloperidol formulation administered via the intranasal route produced behavioral responses that were comparable to those induced by haloperidol formulations administered via intraperitoneal injection. This study demonstrates the potential of dendrimer in improving the delivery of water insoluble drugs to brain.

  3. Aripiprazole and haloperidol in the treatment of delirium.

    PubMed

    Boettger, Soenke; Friedlander, Miriam; Breitbart, William; Passik, Steven

    2011-06-01

    To compare the efficacy and tolerability of aripiprazole and haloperidol in the amelioration of distressing symptoms of delirium and its motoric subtypes. At Memorial Sloan-Kettering Cancer Center, we prospectively collected sociodemographic and medical data and systematically rated all patients diagnosed with delirium with the Memorial Delirium Assessment Scale (MDAS), Karnofsky Performance Scale (KPS) and the abbreviated Udvalg Kliniske Undersogelser Side Effect Rating Scale (UKU) at the initial diagnosis of delirium (T1), after 48-72 h (T2) and 7 days later (T3). All collected information was entered into a delirium database. For our analysis, we subsequently extracted data on aripiprazole (ARI) treated patients to compare to case-matched haloperidol (HAL) treated patients. We retrieved 21 patients treated with aripiprazole and 21 case-matched patients treated with haloperidol. Initial MDAS scores did not significantly differ between the groups. Over the course of treatment (T1 to T3), MDAS scores improved from 18.1 to 8.3 for ARI and 19.9 to 6.8 for HAL. The delirium resolution rate was 76.2% for ARI and 76.2% for HAL. For patients with hypoactive delirium, the MDAS scores improved from 15.6 to 5.7 for ARI and 18.8 to 8.1 for HAL. Delirium resolution rates for patients with hypoactive delirium were 100% for ARI and 77.8% for HAL. For patients experiencing hyperactive delirium, the MDAS scores improved from 19.9 to 6.8 for ARI and 20.8 to 5.8 for HAL. Delirium resolution rates for patients with hyperactive delirium were 58.3% for ARI and 75% for HAL. There were no significant differences in treatment results between ARI and HAL. Treatment with HAL caused more extrapyramidal side effects. From our secondary analysis, aripiprazole may be as effective as haloperidol in the management of delirium and its subtypes. Treatment with haloperidol resulted in more side effects.

  4. Pharmacodynamics and pharmacokinetics of haloperidol and reduced haloperidol in schizophrenic patients.

    PubMed

    Chang, W H; Lin, S K; Jann, M W; Lam, Y W; Chen, T Y; Chen, C T; Hu, W H; Yeh, E K

    1989-07-01

    Twelve male chronic schizophrenic inpatients, neuroleptic-free for at least 4 weeks, were given an oral test dose of 10 mg haloperidol (HAL) and reduced HAL (RHAL) in a random order, with a 2-week interval. Two weeks after the last test dose, the patients were given HAL, 5 mg orally twice daily for 7 days. Blood samples were drawn at baseline and between 0.5 and 24 hr after the test doses, and during HAL treatment as well. Plasma drug concentrations and homovanillic acid (HVA) levels were measured with high-performance liquid chromatography using electrochemical detection. HAL, but not RHAL, produced increments in plasma HVA (pHVA) levels at 24 hr after a test dose. pHVA levels remained higher than baseline during HAL treatment. Detectable interconversion between HAL and RHAL was observed in eight patients. The capacity of the reductive drug-metabolizing enzyme system, however, was greater than that of the oxidative processes. The plasma RHAL:HAL ratios on days 6 and 7 were higher than and positively correlated with those at Tmax after a single dose of HAL and were negatively correlated with the HAL:RHAL ratios at Tmax after a single dose of RHAL. Thus, both reductive and oxidative drug-metabolizing systems probably contribute to individual differences in plasma RHAL:HAL ratios in HAL-treated schizophrenic patients.

  5. A comparison of haloperidol, lithium carbonate and their combination in the treatment of mania.

    PubMed

    Garfinkel, P E; Stancer, H C; Persad, E

    1980-12-01

    Previous investigations of the treatment of mania have resulted in uncertainty about the efficacy of lithium versus a neuroleptic. In addition there have been reports of toxicity with a haloperidol--lithium combination. In order to determine the comparative efficacy of lithium vs haloperidol vs a combination of haloperidol--lithium, we studied 21 severely ill manic patients who all met rigorous criteria for bipolar illness and who required in hospital treatment. Subjects were randomly assigned to 3 groups: (A) Lithium plus placebo (B) Placebo plus haloperidol and (C) Lithium plus haloperidol. The study was conducted in double blind fashion for 3 weeks with the dosages of the medications varied according to clinical response or untoward effects. Subjects on haloperidol and placebo or the haloperidol--lithium combination were significantly improved after 7 days in comparison to the lithium-treated group. Groups B and C did not differ from each other, either in degree of improvement or in side effects. Inspite of the relatively small sample size the results suggest (1) that haloperidol is superior to lithium for treating severely ill acute mania and (2) that while a haloperidol--lithium combination does not result in a significant increase in side effects, it is not superior to haloperidol alone.

  6. Movement disorders induced in monkeys by chronic haloperidol treatment.

    PubMed

    Weiss, B; Santelli, S; Lusink, G

    1977-08-16

    After several months of treatment, Cebus apella, Cebus albifrons, and Saimiri sciurea monkeys maintained on haloperidol, in doses of 0.5 or 1.0 mg/kg orally 5 days per week, began to display severe movement disorders, typically 1-6 h post-drug. Cebus monkeys exhibited violent, uncontrolled movements that flung the animals about the cage. Such episodes usually lasted only a few minutes, recurring several times during the period following drug ingestion. Writhing and bizarre postures dominated the response in S. sciurea. Cessation of drug treatment produced no distinctive after-effects. When tested as long as 508 days after the last administration, however, Cebus monkeys responded to haloperidol with several episodes of hyperkinesis, even at challenge doses considerably lower than those in the original treatment.

  7. Haloperidol and chlorpheniramine interaction in inhibitory avoidance in goldfish.

    PubMed

    Faganello, F R; Medalha, C C; Mattioli, R

    2003-12-17

    The purpose of this study was to investigate a possible interaction between histaminergic and dopaminergic systems in learning and memory processes, in an inhibitory avoidance test in goldfish. Haloperidol, a dopaminergic antagonist, was administrated pre-training and the chlorpheniramine (CPA), a histaminergic antagonist, post-training. The inhibitory avoidance procedure was performed in 3 days, using a rectangular aquarium divided into two compartments (black and white), with a central door. On the first day, the animals were habituated for 10 min. On the second day, they were injected with 2 mg/kg of haloperidol or dimethyl sulfoxide (DMSO) 20 min before training. Then, the animals were placed in the white compartment, the central door was opened and the time spent for crossing between compartments was recorded. After the fish crossed the line between compartments a 45 g weight was dropped. This procedure was done five times in a row. Immediately after the fifth trial, the fish were injected intraperitoneally (i.p.) with either saline or CPA (0.4, 1.0, 4.0, 8.0 or 16 mg/kg). On the next day (test) the time to cross was recorded again. On the training trials, the animals treated with DMSO or haloperidol presented a significant increase in the latencies indicating learning (Friedman P = 0.0062 and 0.0001). The latencies in the test day showed that groups pre-treated with haloperidol and treated with CPA presented a dose-dependent increase in latencies, and those treated with the 16 mg/kg CPA group showed a significant increase (ANOVA two-way followed by Student-Newman-Keuls (SNK) P < 0.01). Thus, it can be suggested that the facilitatory action occurs due to an additive interaction between both systems, in a dose-dependent way.

  8. Efficacy of phenelzine and haloperidol in borderline personality disorder.

    PubMed

    Soloff, P H; Cornelius, J; George, A; Nathan, S; Perel, J M; Ulrich, R F

    1993-05-01

    To compare the efficacy of a neuroleptic (haloperidol) to a monoamine oxidase inhibitor antidepressant (phenelzine sulfate) against the affective, cognitive, and impulsive-aggressive symptoms of criteria-defined borderline inpatients in an effort to dissect apart affective and schizotypal symptom patterns or subtypes using medication response. Randomized, double-blind, placebo-controlled trial. Inpatient unit of a tertiary care university psychiatric hospital serving a large public catchment area. One hundred eight consecutively admitted borderline inpatients defined by Gunderson's Diagnostic Interview for Borderline Patients and DSM-III-R criteria, randomly assigned to 38 phenelzine, 36 haloperidol, and 34 placebo trials. Following 1 week free of medication, haloperidol (average dose, 4 mg/d), phenelzine sulfate (average dose, 60 mg/d), or placebo were given for 5 weeks with weekly symptom ratings and plasma drug level determinations. Efficacy was measured on depression (Hamilton Rating Scale, Beck Depression Inventory), global severity (Global Assessment Scale, Symptom Checklist-90 items [SCL-90]), anxiety, anger-hostility (SCL-90, Inpatient Multidimensional Psychiatric Scale [IMPS], Buss-Durkee Hostility Inventory), psychoticism (Schizotypal Symptom Inventory, SCL-90, IMPS), impulsivity (Ward Scale, Barratt Impulsiveness Scale, Self-Report Test of Impulse Control), and borderline psychotherapy (Borderline Syndrome Index). Three-way comparisons between groups indicated superior efficacy for phenelzine, followed by placebo and haloperidol on measures of depression, borderline psychopathologic symptoms, and anxiety. Pairwise comparisons between medication and placebo revealed significant efficacy for phenelzine against anger and hostility but no efficacy against atypical depression or hysteroid dysphoria. We were unable to replicate prior reports of efficacy for the neuroleptic. Pharmacologic dissection of borderline personality disorder patients into affective and

  9. Haloperidol response and plasma catecholamines and their metabolites.

    PubMed

    Green, A I; Alam, M Y; Boshes, R A; Waternaux, C; Pappalardo, K M; Fitzgibbon, M E; Tsuang, M T; Schildkraut, J J

    1993-06-01

    Eleven acutely psychotic patients with schizophrenia or schizoaffective disorder underwent a 5-7 day drug-washout period (with lorazepam allowed) prior to participating in a 6-week controlled dose haloperidol trial. Patients were evaluated longitudinally with clinical ratings and with plasma measures of the catecholamines dopamine (pDA) and norepinephrine (pNE) and their metabolites, homovanillic acid (pHVA) and 3-methoxy-4-hydroxyphenylglycol (pMHPG). All patients exhibited clinical improvement with haloperidol; the decrease in their Brief Psychiatric Rating Scale (BPRS) scores ranged from 32 to 89%. Measures of pHVA increased within the first week of treatment and returned to baseline by week 5. The pattern of change of pDA resembled that of pHVA. The pattern of change of pNE and pMHPG revealed a decrease over the course of treatment. The early increase and the subsequent decrease in pHVA were strongly correlated with improvement in positive symptoms on the BPRS. These data are consistent with previous reports on the change in pHVA and pMHPG during clinical response to haloperidol. The data on change of pDA and pNE further describe the nature of the biochemical response to this drug.

  10. Effects of haloperidol and phentolamine on the crustacean cardiac ganglion.

    PubMed

    Berlind, A

    2001-09-01

    Haloperidol (a dopamine D2 blocker in vertebrates) and phentolamine (an alpha-adrenergic blocker) alter the pattern of bursting by the isolated cardiac ganglion of the lobster when perfused at concentrations of 10(-6)-10(-5) mol/l. Both drugs decrease the frequency of bursting and increase burst duration. They are most effective in slowing the ganglion when applied selectively to the anterior ganglionic trunk, the same region of the ganglion where dopamine (DA) and 5-hydroxytryptamine (5HT) are most effective in speeding up bursting. When exogenous monoamine transmitters are applied in the presence of 3x10(-6) mol/l haloperidol, the effect of 5HT, but not of DA, is significantly reduced. At the same concentration, phentolamine does not suppress the actions of DA, 5HT or noradrenaline (NA). Both haloperidol and phentolamine significantly alter the properties of endogenous burst-organizing potentials (driver potentials) generated by motorneurons in the ganglion. It is possible that the effects of these drugs on bursting reflect alteration of endogenous electrical properties of the constituent neurons, rather than receptor antagonism.

  11. Chronic haloperidol increases voltage-gated Na+ currents in mouse cortical neurons.

    PubMed

    Chen, Weiqiang; Zhu, Fangfang; Guo, Jingfang; Sheng, Jiangtao; Li, Wenli; Zhao, Xiangfeng; Wang, Gefei; Li, Kangsheng

    2014-07-18

    Typical antipsychotics are characterized by extrapyramidal syndrome (EPS). Previous studies demonstrated that typical antipsychotics could inhibit neuronal voltage-gated sodium channel (VGSC). However, EPS typically emerge only upon prolonged exposure. As a result, we examined effects of haloperidol, a prototype typical antipsychotic, on neuronal VGSC upon incubation for varying duration. Briefly, VGSC currents were activated and recorded using a whole-cell patch-clamp technique in primary culture of mouse cortical neurons. VGSC activity was inhibited by acute haloperidol exposure (for minutes), but enhanced in a time- and concentration-dependent manner by chronic haloperidol exposure (for hours). The effects of chronic haloperidol were associated with increased expression of VGSC subunits as well as corresponding electrophysiological channel properties. In summary, we found enhanced VGSC currents upon chronic haloperidol exposure in cortical neurons in contrast to inhibition by acute haloperidol exposure. Such a results may contribute to EPS of typical antipsychotics.

  12. Biperiden and haloperidol plasma levels and extrapyramidal side effects in schizophrenic patients.

    PubMed

    Meszaros, K; Lenzinger, E; Hornik, K; Schönbeck, G; Hatzinger, R; Langer, G; Sieghart, W; Aschauer, H N

    1997-01-01

    Anticholinergic drugs such as biperiden are used for the treatment of extrapyramidal side effects (EPS) induced by neuroleptics such as haloperidol. The effects of biperiden and haloperidol plasma levels on EPS were studied in 29 chronically ill schizophrenics. The results show relationships between biperiden dose and biperiden plasma levels (BPL), and between BPL and haloperidol plasma levels (HPL). Neither BPL nor HPL seem to influence EPS.

  13. Activation of retinal tyrosine hydroxylase: tolerance induced by chronic treatment with haloperidol does not modify response to light

    SciTech Connect

    Cohen, J.; Neff, N.H.

    1982-05-01

    A single dose of haloperidol administered to rats in the dark increases the activity of retinal tyrosine hydroxylase. The ability of haloperidol to activate the enzyme is diminished 24 hr after terminating 22 to 30 days of treatment with haloperidol. The retinal enzyme is also tolerant to activation by treatment with chlorpromazine. In contrast, exposure of the animals to light activates the enzyme to the same extent in chronic haloperidol-treated and control animals. Thus, chronic haloperidol treatment does not modify the ability of the retinal enzyme system to respond to the physiological stimulus, light. Apparently, activation of retinol tyrosine hydroxylase by haloperidol and light occurs by independent mechanisms.

  14. Amelioration of the haloperidol-induced memory impairment and brain oxidative stress by cinnarizine

    PubMed Central

    Abdel-Salam, Omar M.E.; El-Sayed El-Shamarka, Marwa; Salem, Neveen A.; El-Mosallamy, Aliaa E.M.K.; Sleem, Amany A.

    2012-01-01

    Haloperidol is a classic antipsychotic drug known for its propensity to cause extrapyramidal symptoms and impaired memory, owing to blockade of striatal dopamine D2 receptors. Cinnarizine is a calcium channel blocker with D2 receptor blocking properties which is widely used in treatment of vertiginous disorders. The present study aimed to see whether cinnarizine would worsen the effect of haloperidol on memory function and on oxidative stress in mice brain. Cinnarizine (5, 10 or 20 mg/kg), haloperidol, or haloperidol combined with cinnarizine was administered daily via the subcutaneous route and mice were examined on weekly basis for their ability to locate a submerged plate in the water maze test. Mice were euthanized 30 days after starting drug injection. Malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (nitrite/nitrate) were determined in brain. Haloperidol substantially impaired water maze performance. The mean time taken to find the escape platform (latency) was significantly delayed by haloperidol (2 mg/kg, i.p.) on weeks 1-8 of the test, compared with saline control group. In contrast, those treated with haloperidol and cinnarizine showed significantly shorter latencies, which indicated that learning had occurred immediately. Haloperidol resulted in increased MDA in cortex, striatum, cerebellum and midbrain. GSH decreased in cortex, striatum and cerebellum and nitric oxide increased in cortex. Meanwhile, treatment with cinnarizine (20 mg/kg) and haloperidol resulted in significant decrease in MDA cortex, striatum, cerebellum and midbrain and an increase in GSH in cortex and striatum, compared with haloperidol group. These data suggest that cinnarizine improves the haloperidol induced brain oxidative stress and impairment of learning and memory in the water maze test in mice. PMID:27540345

  15. Is haloperidol the wonder drug for cannabinoid hyperemesis syndrome?

    PubMed

    Inayat, Faisal; Virk, Hafeez Ul Hassan; Ullah, Waqas; Hussain, Qulsoom

    2017-01-04

    Cannabinoid hyperemesis syndrome (CHS) is a rare clinical syndrome characterised by nausea, cyclic vomiting and severe abdominal pain in association with chronic cannabis use. It is often under-recognised or misdiagnosed, resulting in the unnecessary workup and frequent hospitalisations. Long-term treatment of CHS is abstinence from cannabis, but acute symptomatic management has been a struggle for many clinicians. The present report highlights the use of haloperidol as an agent that successfully and safely treats the unrelenting symptoms of CHS. 2017 BMJ Publishing Group Ltd.

  16. Tourette Syndrome Associated with Mental Retardation: A Single-Subject Treatment Study with Haloperidol.

    ERIC Educational Resources Information Center

    Rosenquist, Peter B.; And Others

    1997-01-01

    A study of a 35-year-old woman with severe mental retardation and Tourette syndrome examined the efficacy of haloperidol in the treatment of Tourette syndrome. Results indicate that the haloperidol treatment produced significant reduction of all tic topographies. Improvement was also seen in tic severity, hyperactivity, and compulsive behaviors.…

  17. El manejo de la caoba define la agenda de conservación.

    Treesearch

    A. E. Lugo

    2005-01-01

    Los artículos en este número especial documentan un cambio en el enfoque de aprovechamiento maderero, de la explotación minera al manejo sostenible por parte de las comunidades rurales que ahora cuentan con más información y conocimiento de sus derechos.

  18. Importance of the cytochrome P450 2D6 genotype for the drug metabolic interaction between chlorpromazine and haloperidol.

    PubMed

    Suzuki, Y; Someya, T; Shimoda, K; Hirokane, G; Morita, S; Yokono, A; Inoue, Y; Takahashi, S

    2001-08-01

    The authors studied the interactive effects of the coadministration of haloperidol and chlorpromazine on plasma concentrations of haloperidol and reduced haloperidol. The subjects were 43 Japanese male schizophrenic inpatients who were concomitantly treated with chlorpromazine before or after monotherapy with haloperidol. Coadministration of chlorpromazine produced significant increases in the plasma concentrations of haloperidol (P < 0.01) and reduced haloperidol (P < 0.001) by an average of 28.5% +/- 83.3% and 160.8% +/- 288.9%, respectively. However, there were marked interindividual variations in the interactive effects of chlorpromazine. The authors analyzed the importance of five CYP2D6 genotypes, *1/ *1, *1/ *10, *10/ *10, *1/*5, and *5/*10 on the percentage of change in plasma concentrations of haloperidol and reduced haloperidol. Patients with the CYP2D6*5 allele (n = 4) showed a significantly smaller increase in plasma concentrations of haloperidol (P < 0.05) and a slightly smaller increase in those of reduced haloperidol (P = 0.074) in response to the coadministration of chlorpromazine compared than those with the CYP2D6*1/*1 genotype (n = 8). Those with the CYP2D6*1/*1 genotype (n = 8) showed a trend toward greater increases in plasma concentrations of haloperidol than those with other genotypes (P = 0.087).

  19. Supersolubilization and amorphization of a model basic drug, haloperidol, by interaction with weak acids.

    PubMed

    Singh, Saumya; Parikh, Tapan; Sandhu, Harpreet K; Shah, Navnit H; Malick, A Waseem; Singhal, Dharmendra; Serajuddin, Abu T M

    2013-06-01

    To present a novel approach of greatly enhancing aqueous solubility of a model weakly basic drug, haloperidol, by using weak acids that would not form salts with the drug and to attain physically stable form of amorphous drug by drying such aqueous solutions. Aqueous solubility of haloperidol in presence of increasing concentrations of four different weak organic acids (malic, tartaric, citric, fumaric) were determined. Several concentrated aqueous solutions with differing drug-to-acid molar ratios were dried in vacuum oven, and dried materials were characterized by DSC, powder XRD, dissolution testing, and stability study. Acids were selected such that they would not form salts with haloperidol. Haloperidol solubility increased greatly with increased concentrations of malic, tartaric and citric acids, reaching >300 mg/g of solution. In contrast to the haloperidol HCl aqueous solubility of 4 mg/g, this may be called supersolubilization. Fumaric acid did not cause such solubilization as it had low water solubility. Dried solids formed dispersions of amorphous haloperidol in acids that were either amorphous or partially crystalline. Amorphous haloperidol was physically stable and had better dissolution rate than HCl salt. A novel method of drug solubilization in aqueous media by acid-base interaction is presented. Physically stable amorphous systems of drugs may also be prepared by using this organic solvent-free approach.

  20. Metabolic syndrome and drug discontinuation in schizophrenia: a randomized trial comparing aripiprazole olanzapine and haloperidol.

    PubMed

    Parabiaghi, A; Tettamanti, M; D'Avanzo, B; Barbato, A

    2016-01-01

    To determine whether the prescription of aripiprazole, compared with olanzapine and haloperidol, was associated with a lower frequency of metabolic syndrome (MS) and treatment discontinuation at 1 year. Patients were randomly assigned to be treated open-label and according to usual clinical practice with either aripiprazole, olanzapine, or haloperidol and followed up for 1 year. Three hundred out-patients with persistent schizophrenia were recruited in 35 mental health services. The intention-to-treat (ITT) analysis found no significant differences in the rate of MS between aripiprazole (37%), olanzapine (47%), and haloperidol (42%). Treatment discontinuation for any cause was higher for aripiprazole (52%) than for olanzapine (33%; OR, 0.41; P = 0.004), or haloperidol (37%; OR, 0.51; P = 0.030). No significant difference was found between olanzapine and haloperidol. Time to discontinuation for any cause was longer for olanzapine than for aripiprazole (HR, 0.55; P < 0.001). No significant differences were found between haloperidol and aripiprazole, or between olanzapine and haloperidol. The prescription of aripiprazole did not significantly reduce the rates of MS, but its treatment retention was worse. Aripiprazole cannot be considered the safest and most effective drug for maintenance treatment of schizophrenia in routine care, although it may have a place in antipsychotic therapy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. 19F-magnetic resonance spectroscopy and chemical shift imaging for schizophrenic patients using haloperidol decanoate.

    PubMed

    Sassa, Takeshi; Suhara, Tetsuya; Ikehira, Hiroo; Obata, Takayuki; Girard, Franck; Tanada, Shuji; Okubo, Yoshiro

    2002-12-01

    Haloperidol decanoate is widely used in the maintenance treatment of schizophrenia and other psychotic disorders, but knowledge concerning its pharmacokinetics at the injected region is very limited. Because the chemical structure of haloperidol contains fluorine, in vivo 19F-magnetic resonance (MR) spectroscopy (repetition time (TR) = 1 s) and chemical shift imaging (CSI; TR = 1 s, pixel size = 15 x 15 mm) were performed in schizophrenic patients who were treated with haloperidol decanoate (three men and one woman) to measure its diachronic change at the injection point and visualize its local distribution after intramuscular injection. 19F signals (T1 time = 365 ms) were obtained at the haloperidol decanoate-injected region. The decrease rate of the signal-to-noise ratio (SNR) by 19F-MR spectroscopy seemed large in comparison with that of the plasma haloperidol concentration. The distribution was clearly visualized by 19F-CSI for a few days after the injection, but after 1 week could no longer be seen. Although the slow-release characteristics of depot neuroleptics have been explained by the slow diffusion of esterified neuroleptics from the oil vehicle, this result may suggest that there are other mechanisms involved in maintaining the plasma haloperidol concentration. In vivo 19F-MR spectroscopy and CSI are potentially applicable for the pharmacokinetic analysis of haloperidol and other drugs containing fluorine in their structure.

  2. Pharmacokinetic and pharmacodynamic interactions among haloperidol, carteolol hydrochloride and biperiden hydrochloride.

    PubMed

    Isawa, S; Murasaki, M; Miura, S; Yoshioka, M; Uchiumi, M; Kumagai, Y; Aoki, S; Hisazumi, H; Kudo, S

    1999-07-01

    A beta-adrenoceptor blocker and an anticholinergic agent are often prescribed concomitantly for the treatment of neuroleptic-induced akathisia. The aim of this study was to investigate possible pharmacokinetic interactions of neuroleptic haloperidol with the beta-blocker carteolol and the anticholinergic biperiden. In a 5-step, open-labeled, oral single-dose study, eight healthy male volunteers received 2 mg haloperidol, 10 mg carteolol hydrochloride, and 2 mg biperiden hydrochloride: first each drug alone, then a combination of haloperidol and carteolol, and then all three drugs concurrently. Serum concentrations of haloperidol, carteolol, and biperiden were determined up to 24 hr postdosing, and a safety evaluation was conducted throughout the study. Carteolol increased the area under the haloperidol serum concentration-time curve (AUC0-t) 1.4-fold (P = 0.0014) and decreased the serum clearance of haloperidol up to 67% (P = 0.0127). Biperiden reduced the serum haloperidol concentrations increased by the administration of carteolol. No significant changes of the serum pharmacokinetics of carteolol and biperiden were found as a result of any drug combinations. Adverse events of the central nervous system such as sleepiness and changes in pupil size were observed, but all were mild with clinical insignificance.

  3. Contribution of the central histaminergic transmission in the cataleptic and neuroleptic effects of haloperidol.

    PubMed

    Jain, Nishant S; Tandi, Lakshyapati; Verma, Lokesh

    2015-12-01

    The antipsychotic properties of haloperidol are primarily attributed to its ability to block dopamine D2 receptors. Histaminergic transmission modulates some of the behavioral effects of haloperidol. Hence, the present study investigated the contribution of central histaminergic transmission in the cataleptic and neuroleptic effect of haloperidol respectively, using bar test and conditioned avoidance response (CAR) in a two-way shuttle box. The studies revealed that haloperidol (0.50 or 1 mg/kg, i.p.) exhibited cataleptic behavior and inhibited conditioned avoidance response (CAR) in the doses 0.25 or 0.50 mg in rats. The rats, pretreated centrally (i.c.v.) with histamine precursor, L-histidine (1, 2.5 μg) or histamine neuronal inducer (H3 receptor antagonist), thioperamide (20, 50 μg/rat), showed an enhanced cataleptic effect with sub-maximal dose of haloperidol (0.5 mg/kg, i.p.). Similarly, the neuroleptic effect of haloperidol (0.25 mg/kg, i.p.) in CAR was also potentiated in the rats pretreated with L-histidine (2.5 μg) or thioperamide (50 μg/rat). Further, the cataleptic effect of haloperidol (1 mg/kg, i.p.) was attenuated in rats pretreated with the H1 receptor antagonist, chlorpheniramine (60, 80 μg/rat, i.c.v.) or H2 receptor antagonist, ranitidine (60 μg/rat, i.c.v.). However, the neuroleptic effect of haloperidol (0.5 mg/kg, i.p.) was completely reversed by pretreatment with ranitidine (60 μg/rat, i.c.v.), and partially attenuated by chlorpheniramine (80 μg/rat, i.c.v.). These findings suggest the possible involvement of histaminergic transmission in the cataleptic and neuroleptic effects of haloperidol probably via H1 or H2 receptor stimulation.

  4. Effects of semax against the background of dopaminergic receptor blockade with haloperidol.

    PubMed

    Sebentsova, E A; Levitskaya, N G; Andreeva, L A; Alfeeva, L Yu; Kamenskii, A A; Myasoedov, N F

    2006-02-01

    We studied the neurotropic effects of ACTH(4-10) analog semax against the background of dopaminergic receptors blockade with haloperidol. Intranasal administration of semax (0.05, 0.2, and 0.6 mg/kg) produced virtually no effect on disturbances of orientation and exploratory reactions and motor activity caused by intraperitoneal injection of 0.2 mg/kg haloperidol. By contrast, preliminary administration of 0.05 mg/kg semax prevented haloperidol-induced disturbances in active avoidance conditioning.

  5. Effects of debrisoquin and haloperidol on plasma homovanillic acid concentration in schizophrenic patients.

    PubMed

    Davidson, M; Losonczy, M F; Mohs, R C; Lesser, J C; Powchik, P; Freed, L B; Davis, B M; Mykytyn, V V; Davis, K L

    1987-12-01

    Plasma levels of the dopamine metabolite homovanillic acid (pHVA) may potentially reflect upon central dopamine activity. This study examines the effects of debrisoquin, haloperidol, and the two drugs combined on pHVA concentrations of schizophrenic patients. Debrisoquin is a drug that suppresses the peripheral formation of homovanillic acid without affecting the central formation. Acute haloperidol administration consistently increased pHVA concentrations in patients pretreated or not pretreated with debrisoquin, suggesting that this increment reflects haloperidol's central and not peripheral effects.

  6. An adverse drug interaction of haloperidol with levodopa.

    PubMed

    Lucca, Jisha M; Ramesh, Madhan; Parthasarathi, Gurumurthy; Raman, Rajesh

    2015-01-01

    Drug interactions are known to play a significant role in the incidence of adverse drug reactions (ADRs) both in the community and in hospitals. Both the newer atypical antipsychotics and their more traditional counterparts are subject to drug - drug interactions amongst themselves, with other psychotropics, and with the agents used in the treatment of various physical ailments. The most common interactions encountered in clinical practice are pharmacodynamic in nature. It is well established that antipsychotic drugs reduce the efficacy of levodopa in parkinson's disease by blockade of dopamine receptors in the corpus striatum. The case reported here illustrates a common pharmacodynamic drug interaction of haloperidol with levodopa in a 60-year-old female patient.

  7. Effect of prenatal haloperidol exposure on behavioral alterations in rats.

    PubMed

    Singh, K P; Singh, Mandavi

    2002-01-01

    Pregnant Charles-Foster rats were exposed to haloperidol (HAL), a neuroleptic drug that binds to and blocks dopamine (DA) receptor subtypes at a dose of 2.5 mg/kg body weight (intraperitoneally) from Gestation Day (GD) 12 to 20. The animals from both treated as well as vehicle control groups were allowed to deliver on GD 21. The offspring culled at birth on the basis of sex and weight were subjected to behavioral tests at the age of 8 weeks. The HAL-treated rat offspring showed a significant increase in anxiogenic behavior on the open field, elevated plus-maze and elevated zero-maze tests when compared with the vehicle-treated (control) rat offspring of the same age group. These findings suggest that prenatal exposure to HAL during a critical period of brain development leaves a lasting imprint on the brain, resulting in abnormal anxiety states, possibly through dopaminergic neurotransmission mechanisms.

  8. Haloperidol, dynamics of choice, and the parameters of the matching law.

    PubMed

    Aparicio, Carlos F

    2007-06-01

    The idea that dopamine mediates the reinforcing effects of stimuli persists in the field of neurosciences. The present study shows that haloperidol, a dopamine antagonist, does not eliminate the reinforcing value of food reinforcers. The ratio of reinforcers changed seven times across two levers within sessions, modeling a dynamic environment. The magnitude of the reinforcer was manipulated independently of the reinforcer ratio. Four doses of intraperitoneal haloperidol were assessed over periods of 12 daily sessions. Haloperidol did not impair the discrimination that the rats established between rich and lean levers; the response distributions favored the lever associated with the higher probability of reinforcement and the larger pellets. The parameters of the generalized matching law (bias and sensitivity) were used to estimate effects of haloperidol upon the motor system and upon the rats' motivation for food reinforcers.

  9. Serum albumin and the haloperidol pharmacokinectics. A study using a computational model

    NASA Astrophysics Data System (ADS)

    de Morais e Coura, Carla Patrícia; Paulino, Erica Tex; Cortez, Celia Martins; da Silva Fragoso, Viviane Muniz

    2016-12-01

    Here we are studying the binding of haloperidol with human and bovine sera albumins applying a computational model, based on spectrofluorimetry, statistical and mathematical knowledge. Haloperidol is one of the oldest antipsychotic drug in use for therapy of patients with acute and chronic schizophrenia. It was found that the fluorescence of HSA was quenched in 18.0 (± 0.2)% and for BSA it was 24.0 (± 0.9)%, for a ratio of 1/1000 of haloperidol/albumin. Results suggested that the primary binding site is located in the subdomain IB. Quenching constants of the albumin fluorescence by haloperidol were in the order of 107, approximately 100-fold higher than that found for risperidone, and about 1000-fold higher than that estimated for chlorpromazine and sulpiride.

  10. Changes at cholecystokinin receptors induced by long-term treatment with diazepam and haloperidol.

    PubMed

    Vasar, E; Soosaar, A; Harro, J; Lang, A

    1992-12-01

    Fourteen days administration of haloperidol (1 mg/kg daily) prevented the motor depressant effect of caerulein (an agonist at cholecystokinin receptors, 15 micrograms/kg) and the antagonistic effect of caerulein (100 micrograms/kg) against (+)-amphetamine (5 mg/kg) induced hyperlocomotion in mice. The antiaggressive effect of caerulein (40 micrograms/kg) in saline-treated mice was replaced by increased aggressiveness after long-term haloperidol and diazepam (5 mg/kg daily) treatment. The anticonvulsant effect of caerulein (125 micrograms/kg) against picrotoxin (10 mg/kg) induced seizures was abolished after 14 days diazepam, but not after haloperidol, treatment. The above described changes in the mouse behaviour are probably related to the development of subsensitivity at CCKA receptors, whereas the CCKB receptor subtype becomes more sensitized to the action of caerulein after long-term haloperidol and diazepam treatment.

  11. Effects of Cannabis sativa extract on haloperidol-induced catalepsy and oxidative stress in the mice

    PubMed Central

    Abdel-Salam, Omar M.E.; El-Sayed El-Shamarka, Marawa; Salem, Neveen A.; El-Din M. Gaafar, Alaa

    2012-01-01

    Haloperidol is a classic antipsychotic drug known for its propensity to cause extrapyramidal symptoms due to blockade of dopamine D2 receptors in the striatum. Interest in medicinal uses of cannabis is growing. Cannabis sativa has been suggested as a possible adjunctive in treatment of Parkinson's disease. The present study aimed to investigate the effect of repeated administration of an extract of Cannabis sativa on catalepsy and brain oxidative stress induced by haloperidol administration in mice. Cannabis extract was given by subcutaneous route at 5, 10 or 20 mg/kg (expressed as Δ9-tetrahydrocannabinol) once daily for 18 days and the effect on haloperidol (1 mg/kg, i.p.)-induced catalepsy was examined at selected time intervals using the bar test. Mice were euthanized 18 days after starting cannabis injection when biochemical assays were carried out. Malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (the concentrations of nitrite/nitrate) were determined in brain and liver. In saline-treated mice, no catalepsy was observed at doses of cannabis up to 20 mg/kg. Mice treated with haloperidol at the dose of 1 mg/kg, exhibited significant cataleptic response. Mice treated with cannabis and haloperidol showed significant decrease in catalepsy duration, compared with the haloperidol only treated group. This decrease in catalepsy duration was evident on days 1-12 after starting cannabis injection. Later the effect of cannabis was not apparent. The administration of only cannabis (10 or 20 mg/kg) decreased brain MDA by 17.5 and 21.8 %, respectively. The level of nitric oxide decreased by 18 % after cannabis at 20 mg/kg. Glucose in brain decreased by 20.1 % after 20 mg/kg of cannabis extract. The administration of only haloperidol increased MDA (22.2 %), decreased GSH (25.7 %) and increased brain nitric oxide by 44.1 %. The administration of cannabis (10 or 20 mg/kg) to haloperidol-treated mice resulted in a significant decrease in brain MDA and nitric

  12. Effects of Cannabis sativa extract on haloperidol-induced catalepsy and oxidative stress in the mice.

    PubMed

    Abdel-Salam, Omar M E; El-Sayed El-Shamarka, Marawa; Salem, Neveen A; El-Din M Gaafar, Alaa

    2012-01-01

    Haloperidol is a classic antipsychotic drug known for its propensity to cause extrapyramidal symptoms due to blockade of dopamine D2 receptors in the striatum. Interest in medicinal uses of cannabis is growing. Cannabis sativa has been suggested as a possible adjunctive in treatment of Parkinson's disease. The present study aimed to investigate the effect of repeated administration of an extract of Cannabis sativa on catalepsy and brain oxidative stress induced by haloperidol administration in mice. Cannabis extract was given by subcutaneous route at 5, 10 or 20 mg/kg (expressed as Δ(9)-tetrahydrocannabinol) once daily for 18 days and the effect on haloperidol (1 mg/kg, i.p.)-induced catalepsy was examined at selected time intervals using the bar test. Mice were euthanized 18 days after starting cannabis injection when biochemical assays were carried out. Malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (the concentrations of nitrite/nitrate) were determined in brain and liver. In saline-treated mice, no catalepsy was observed at doses of cannabis up to 20 mg/kg. Mice treated with haloperidol at the dose of 1 mg/kg, exhibited significant cataleptic response. Mice treated with cannabis and haloperidol showed significant decrease in catalepsy duration, compared with the haloperidol only treated group. This decrease in catalepsy duration was evident on days 1-12 after starting cannabis injection. Later the effect of cannabis was not apparent. The administration of only cannabis (10 or 20 mg/kg) decreased brain MDA by 17.5 and 21.8 %, respectively. The level of nitric oxide decreased by 18 % after cannabis at 20 mg/kg. Glucose in brain decreased by 20.1 % after 20 mg/kg of cannabis extract. The administration of only haloperidol increased MDA (22.2 %), decreased GSH (25.7 %) and increased brain nitric oxide by 44.1 %. The administration of cannabis (10 or 20 mg/kg) to haloperidol-treated mice resulted in a significant decrease in brain MDA and nitric

  13. /sup 3/H and /sup 125/I radioimmunoassays of haloperidol compared with fluoroimmunoassay involving antibody coupled to magnetizable solid phase

    SciTech Connect

    Rowell, F.J.; Hui, S.M.; Kamel, S.R.

    1981-07-01

    Radioimmunoassays for haloperidol are described, involving use of tritium- or 125I-labeled drug or tritium-labeled spiroperidol, and a rabbit antiserum to a drug/bovine serum albumin conjugate. The 125I-labeled drug was prepared by the Chloramine T iodination technique. A fluoroimmunoassay for haloperidol is also described in which the antiserum is coupled to magnetizable solid-phase medium, and fluorescein-labeled haloperidol is used. The assays have acceptable accuracy, precision, and reproducibility, and are specific for haloperidol and similar butyrophenones, with no significant interference from known metabolites and other drugs. Only the radioimmunoassays have sufficient sensitivity to cover the whole range of haloperidol concentrations in serum. The fluoroimmunoassay can be used to monitor high concentrations of haloperidol in 150-microL samples or the complete concentration range of 1-mL serum samples that are extracted and concentrated before assay.

  14. /sup 3/H and /sup 125/I radioimmunoassays of haloperidol compared with fluoroimmunoassay involving antibody coupled to magnetizable solid phase

    SciTech Connect

    Rowell, F.J.; Hui, S.M.; Kamel, S.R.

    1981-07-01

    Radioimmunoassays for haloperidol are described, involving use of tritium-or /sup 125/I-labeled drug or tritium-labeled spiroperidol, and a rabbit antiserum to a drug/bovine serum albumin conjugate. The /sup 125/I-labeled drug was prepared by the Chloramine T iodination technique. A fluoroimmunoassay for haloperidol is also described in which the antiserum is coupled to magnetizable solid-phase medium, and fluorescein-labeled haloperidol is used. The assays have acceptable accuracy, precision, and reproducibility, and are specific for haloperidol and similar butyrophenones, with no significant interference from known metabolites and other drugs. Only the radioimmunoassays have sufficient sensitivity to cover the whole range of haloperidol concentrations in serum. The fluoroimmunoassay can be used to monitor high concentrations of haloperidol in 150 ..mu..L samples or the complete concentration range of 1-mL serum samples that are extracted and concentrated before assay.

  15. Chronic treatment with clozapine, unlike haloperidol, does not induce changes in striatal D-2 receptor function in the rat.

    PubMed

    Rupniak, N M; Hall, M D; Mann, S; Fleminger, S; Kilpatrick, G; Jenner, P; Marsden, C D

    1985-08-01

    Comparison has been made of the effects on brain dopamine function of chronic administration of haloperidol or clozapine to rats for up to 12 months. In rats treated for 1-12 months with haloperidol (1.4-1.6 mg/kg/day), purposeless chewing jaw movements emerged. These movements were only observed after 12 months' treatment with clozapine (24-27 mg/kg/day). Apomorphine-induced (0.125-0.25 mg/kg) stereotyped behaviour was inhibited during 12 months treatment with haloperidol. Clozapine treatment was without effect. After 12 months, stereotypy induced by higher doses of apomorphine (0.5-1.0 mg/kg) was enhanced in haloperidol, but not clozapine, treated rats. Bmax for striatal 3H-spiperone binding was elevated throughout 12 months of haloperidol administration, but was not altered by clozapine treatment. Bmax for striatal 3H-NPA binding was only elevated after 12 months of haloperidol treatment; clozapine treatment was without effect. Bmax for 3H-piflutixol binding was not altered by haloperidol treatment, but was increased after 9 and 12 months of clozapine treatment. Dopamine (50 microM)-stimulated adenylate cyclase activity was inhibited after 1 month's haloperidol treatment but normal thereafter. Adenylate cyclase activity was not altered by chronic clozapine treatment. Striatal acetylcholine content was increased after 3 and 12 months of haloperidol or clozapine intake. These findings indicate that the chronic administration of the atypical neuroleptic clozapine does not produce changes in brain dopamine function which mirror those of the typical neuroleptic haloperidol. In particular, chronic administration of clozapine, unlike haloperidol, does not appear to induce striatal D-2 receptor supersensitivity. Unexpectedly, clozapine treatment, unlike haloperidol, altered D-1 receptor function.

  16. Haloperidol versus low-potency first-generation antipsychotic drugs for schizophrenia.

    PubMed

    Tardy, Magdolna; Huhn, Maximilian; Kissling, Werner; Engel, Rolf R; Leucht, Stefan

    2014-07-09

    Antipsychotic drugs are the core treatment for schizophrenia. Treatment guidelines state that there is no difference in efficacy between antipsychotic compounds, however, low-potency antipsychotic drugs are often clinically perceived as less efficacious than high-potency compounds, and they also seem to differ in their side-effects. To review the effects in clinical response of haloperidol and low-potency antipsychotics for people with schizophrenia. We searched the Cochrane Schizophrenia Group Trials Register (July 2010). We included all randomised trials comparing haloperidol with first-generation low-potency antipsychotic drugs for people with schizophrenia or schizophrenia-like psychosis. We extracted data independently. For dichotomous data, we calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. For continuous data, we calculated mean differences (MD), again based on a random-effects model. The review currently includes 17 randomised trials and 877 participants. The size of the included studies was between 16 and 109 participants. All studies were short-term with a study length between two and 12 weeks. Overall, sequence generation, allocation procedures and blinding were poorly reported. We found no clear evidence that haloperidol was superior to low-potency antipsychotic drugs in terms of clinical response (haloperidol 40%, low-potency drug 36%, 14 RCTs, n = 574, RR 1.11, CI 0.86 to 1.44 lowquality evidence). There was also no clear evidence of benefit for either group in acceptability of treatment with equivocal difference in the number of participants leaving the studies early due to any reason (haloperidol 13%, low-potency antipsychotics 17%, 11 RCTs, n = 408, RR 0.82, CI 0.38 to 1.77, low quality evidence). Similar equivocal results were found between groups for experiencing at least one adverse effect (haloperidol 70%, low-potency antipsychotics 35%, 5 RCTs n = 158, RR 1

  17. Differential effects of continuous administration for 1 year of haloperidol or sulpiride on striatal dopamine function in the rat.

    PubMed

    Rupniak, N M; Mann, S; Hall, M D; Fleminger, S; Kilpatrick, G; Jenner, P; Marsden, C D

    1984-01-01

    Administration of haloperidol (1.4-1.6 mg/kg/day) for up to 12 months or sulpiride (102-109 mg/kg/day) for between 6 and 12 months increased the frequency of purposeless chewing jaw movements in rats. N,n-propylnorapomorphine (NPA) (0.25-2.0 mg/kg SC) did not induce hypoactivity in haloperidol-treated rats at any time; sulpiride treatment for 9 and 12 months caused a reduction in the ability of NPA to induce hypoactivity. Haloperidol, but not sulpiride, treatment enduringly inhibited low dose apomorphine effects (0.125 mg/kg SC). After 12 months, stereotypy induced by high doses of apomorphine (0.5-1.0 mg/kg) was exaggerated in haloperidol-, but not sulpiride-treated rats. Bmax for specific striatal 3H-spiperone binding was increased by haloperidol, but not sulpiride, treatment throughout the study. Bmax for 3H-piflutixol binding was not altered by chronic haloperidol or sulpiride treatment. Striatal dopamine-stimulated adenylate cyclase activity was inhibited for the 1st month of haloperidol treatment, thereafter returning to control levels; dopamine stimulation was increased after 12 months of sulpiride treatment. Striatal acetylcholine content was increased after 3 and 12 months of treatment with haloperidol, but was not affected by sulpiride. Chronic administration of sulpiride does not induce identical changes in striatal dopamine function to those caused by haloperidol.

  18. Therapeutic window of serum haloperidol concentration in acute schizophrenia and schizoaffective disorder.

    PubMed

    Ulrich, S; Neuhof, S; Braun, V; Meyer, F P

    1998-09-01

    Although several studies have been performed on the serum level-therapeutic effect relationship of neuroleptic drugs, the application of therapeutic drug-monitoring of neuroleptics is still a matter of controversy. Until now, haloperidol provided the most promising results. For this reason, an investigation of the dependence of clinical improvement on haloperidol serum levels was conducted in an acute psychiatric ward (Landeskrankenhaus Bernburg). In an open clinical trial haloperidol serum levels were measured in 57 acute schizophrenic patients for at least three weeks and correlated with clinical outcome (percent change of Brief Psychiatric Rating Scale, BPRS). A bisigmoidal model was used for data analysis. After three weeks of treatment, the major result proved to be a significant relationship between haloperidol serum level and therapeutic effect with pseudo-r2=0.316 and p=0.0031. Clinical improvement is enhanced by increasing haloperidol concentration up to about 10 ng/ml. It attains a maximum at about 10 ng/ml and decreases at haloperidol serum levels in a range of 10 ng/ml to 50 ng/ml. A simulation of this dependence of clinical improvement on serum levels, mediated by the variable dose design, can be excluded because of the results of a retrospective analysis of dosing behavior. Further evidence is thus provided for the dependence of therapeutic effect on the serum haloperidol concentration in acute schizophrenia. For practical application the position of a therapeutic window can be defined by a lower threshold level of about 5 ng/ml and an upper threshold of about 17 ng/ml. However, a maximal therapeutic effect is assured at 10 ng/ml. This should be the target value in serum level-guided dose adjustments.

  19. A prospective study of ketamine versus haloperidol for severe prehospital agitation.

    PubMed

    Cole, Jon B; Moore, Johanna C; Nystrom, Paul C; Orozco, Benjamin S; Stellpflug, Samuel J; Kornas, Rebecca L; Fryza, Brandon J; Steinberg, Lila W; O'Brien-Lambert, Alex; Bache-Wiig, Peter; Engebretsen, Kristin M; Ho, Jeffrey D

    2016-08-01

    Ketamine is an emerging drug for the treatment of acute undifferentiated agitation in the prehospital environment, however no prospective comparative studies have evaluated its effectiveness or safety in this clinical setting. We hypothesized 5 mg/kg of intramuscular ketamine would be superior to 10 mg of intramuscular haloperidol for severe prehospital agitation, with time to adequate sedation as the primary outcome measure. This was a prospective open label study of all patients in an urban EMS system requiring chemical sedation for severe acute undifferentiated agitation that were subsequently transported to the EMS system's primary Emergency Department. All paramedics were trained in the Altered Mental Status Scale and prospectively recorded agitation scores on all patients. Two 6-month periods where either ketamine or haloperidol was the first-line therapy for severe agitation were prospectively compared primarily for time to adequate sedation. Secondary outcomes included laboratory data and adverse medication events. 146 subjects were enrolled; 64 received ketamine, 82 received haloperidol. Median time to adequate sedation for the ketamine group was 5 minutes (range 0.4-23) vs. 17 minutes (range 2-84) in the haloperidol group (difference 12 minutes, 95% CI 9-15). Complications occurred in 49% (27/55) of patients receiving ketamine vs. 5% (4/82) in the haloperidol group. Complications specific to the ketamine group included hypersalivation (21/56, 38%), emergence reaction (5/52, 10%), vomiting (5/57, 9%), and laryngospasm (3/55, 5%). Intubation was also significantly higher in the ketamine group; 39% of patients receiving ketamine were intubated vs. 4% of patients receiving haloperidol. Ketamine is superior to haloperidol in terms of time to adequate sedation for severe prehospital acute undifferentiated agitation, but is associated with more complications and a higher intubation rate.

  20. Crocin prevents haloperidol-induced orofacial dyskinesia: possible an antioxidant mechanism

    PubMed Central

    Kamyar, Marzyeh; Razavi, Bibi Marjan; Hasani, Faezeh Vahdati; Mehri, Soghra; Foroutanfar, Amir; Hosseinzadeh, Hossein

    2016-01-01

    Objective(s): Long-term treatment with antipsychotics causes serious side effects such as tardive dyskinesia that characterized by abnormal movements in the orofacial region. Oxidative stress in the brain specific area is implicated in the pathophysiology of tardive dyskinesia. In this study the protective effect of crocin on haloperidol-induced orofacial dyskinesia was evaluated. Materials and Methods: Haloperidol (1 mg/kg, IP) and crocin (10, 20 and 40 mg/kg, IP) were administrated to rats for 21 days. Behavioral assessments such as orofacial dyskinesia movements, open field test and elevated plus maze (EPM) were evaluated every week. Malondealdehyde (MDA) and glutathione (GSH) levels in the hippocampus, cortex and striatum were also measured. Results: Haloperidol increased vacuous chewing movements (VCMs) and tongue protrusions (TPs) in rats and co-administration of crocin (20 and 40 mg/kg) significantly reduced them. Furthermore, haloperidol decreased the locomotor and exploratory activities (rearing) in the open field test and decreased the percentage of entries into open arms and the percentage of the time spent on open arms in the EPM. Pretreatment with crocin (10 mg/kg) modified haloperidol effects on these behavioral parameters. Haloperidol induced lipid peroxidation in three brain regions, whereas crocin co-administration reduced the MDA and restored the decreased GSH levels. Conclusion: Our finding suggests that oxidative stress has an important role in the development of tardive dyskinesia. Crocin showed protective effect against haloperidol induced tardive dyskinesia and as a potent naturally antioxidant could be a new and useful drug and a possible therapeutic option for the treatment of tardive dyskinesia. PMID:27872703

  1. Glutamatergic neurotransmission in the inferior colliculus influences intrastriatal haloperidol-induced catalepsy.

    PubMed

    Medeiros, P; Viana, M B; Barbosa-Silva, R C; Tonelli, L C; Melo-Thomas, L

    2014-07-15

    The inferior colliculus (IC) is an important midbrain relay station for the integration of descending and ascending auditory information. In addition, it has also been implicated in the processing of acoustic information of aversive nature, as well as in sensory-motor gating. There is evidence that glutamate-mediated mechanisms at the IC level influence haloperidol-induced catalepsy. The present study investigated the influence of glutamate-mediated mechanisms in the IC on catalepsy induced by intrastriatal microinjection of haloperidol (10 μg/0.5 μl). Male Wistar rats received bilateral intracollicular microinjections of the glutamate receptor agonist NMDA (10 or 20 nmol/0.5 μl), the NMDA receptor antagonists MK-801 (15 or 30 nmol/0.5 μl) or physiological saline (0.5 μl), followed by bilateral microinjections of haloperidol (10 μg/0.5 μl) or vehicle (0.5 μl) into the dorso-rostral or ventro-rostral striatum. The catalepsy test was performed positioning both forepaws of the rats on an elevated horizontal wooden bar and recording the time during which the animal remained in this position. The results showed that the administration of physiological saline in the IC followed by the microinjection of haloperidol in the dorso-rostral region of the striatum was not able to induce catalepsy. However, when the bilateral administration of NMDA into the IC was followed by microinjection of haloperidol into the dorso-rostral striatum, catalepsy was observed. The microinjection of haloperidol into the ventro-rostral striatum induced catalepsy, counteracted by previous administration of MK-801 into the IC. These findings suggest that glutamate-mediated mechanisms in the IC can influence the intrastriatal haloperidol-induced catalepsy and that the IC plays an important role as a sensorimotor interface.

  2. A double blind comparison of zuclopenthixol acetate with haloperidol in the management of acutely disturbed schizophrenics.

    PubMed

    Chin, C N; Hamid, A R; Philip, G; Ramlee, T; Mahmud, M; Zulkifli, G; Loh, C C; Zakariah, M S; Norhamidah, M S; Suraya, Y; Roslan, K A; Chandramohan, P; Cheah, Y C; Leonard, A O

    1998-12-01

    The aim of this study was to evaluate the efficacy and side effects of zuclopenthixol acetate compared with haloperidol in the management of the acutely disturbed schizophrenic patient. Suitable subjects diagnosed as having schizophreniform disorder or acute exacerbation of schizophrenia admitted to the psychiatric wards Hospital Kuala Lumpur were randomised to receive either zuclopenthixol acetate or haloperidol. They were rated blind for three consecutive days using the Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI) and UKU Side Effects Scale. Apart from repeat injections of the same medication, no other anti-psychotic was given for the duration of the study. 50 subjects entered the study of which 44 completed. 23 were given zuclopenthixol acetate and 21 haloperidol. Both groups significantly reduced BPRS and CGI scores on all 3 days compared to the initial rating (p < 0.001). There was however no difference between the zuclopenthixol acetate and haloperidol group scores on all days (p > 0.05). More subjects on haloperidol than zuclopenthixol required more than 1 injection during the study. Both groups had minimal side effects. Zuclopenthixol acetate was effective in the management of the acutely disturbed schizophrenic.

  3. [Involvement of cytochromeP4503A4 in the metabolism of haloperidol and bromperidol].

    PubMed

    Furukori, H

    1998-02-01

    To clarify the involvement of cytochromeP450 (CYP) 3A4 in the metabolism of haloperidol and bromperidol in humans, the effects of itraconazole, a potent inhibitor of CYP3A4, on steady-state plasma concentrations of both drugs and their reduced metabolites were investigated using 21 schizophrenic patients. Patients treated with haloperidol 12 or 24 mg/day (n = 13) or bromperidol 12 or 24 mg/day (n = 8) for at least 2 weeks were then given itraconazole 200 mg/day for 7 days. Blood samplings were performed before administration, 1 week during itraconazole coadministration and 1 week after its discontinuation together with clinical assessments. Plasma concentrations of haloperidol and bromperidol and their reduced metabolites were significantly higher during itraconazole treatment (P < 0.01). Deterioration in the neurological side effects of haloperidol was observed during itraconazole coadministration. Thus, this study suggests that itraconazole inhibits the metabolism of haloperidol and bromperidol, and that CYP3A4 is involved in the metabolism of both drugs.

  4. Parkinson's disease: low-dose haloperidol increases dopamine receptor sensitivity and clinical response.

    PubMed

    Hudson, Craig J; Seeman, Philip; Seeman, Mary V

    2014-01-01

    Background. It is known that ultra-low doses of haloperidol can cause dopamine supersensitivity of dopamine D2 receptors and related behaviour in animals. Objective. The objective was to determine whether a daily ultra-low dose of 40 micrograms of haloperidol could enhance the clinical action of levodopa in Parkinson's disease patients. Method. While continuing their daily treatment with levodopa, 16 patients with Parkinson's disease were followed weekly for six weeks. They received an add-on daily dose of 40 micrograms of haloperidol for the first two weeks only. The SPES/SCOPA scale (short scale for assessment of motor impairments and disabilities in Parkinson's disease) was administered before treatment and weekly throughout the trial. Results. The results showed a mean decrease in SPES/SCOPA scores after one week of the add-on treatment. Conclusion. SCOPA scores decreased after the addition of low-dose haloperidol to the standard daily levodopa dose. This finding is consistent with an increase in sensitivity of dopamine D2 receptors induced by haloperidol. Such treatment for Parkinson's disease may possibly permit the levodopa dose to be reduced and, thus, delay the onset of levodopa side effects.

  5. Evolution of plasma homovanillic acid (HVA) in chronic schizophrenic patients treated with haloperidol.

    PubMed

    Galinowski, A; Poirier, M F; Aymard, N; Leyris, A; Beauverie, P; Bourdel, M C; Loo, H

    1998-06-01

    In a 4-week study of 14 drug-free schizophrenic patients (according to DSM-III-R), free and conjugated fractions of plasma homovanillic acid (pHVA) were repeatedly measured. Free HVA levels decreased during the first 2 h of haloperidol intake (P < 0.03). Conjugated HVA levels slowly decreased during the following weeks (P < 0.05), while free HVA levels remained stable. After 4 weeks, free HVA levels remained unchanged 2 h after morning haloperidol intake, but conjugated HVA levels tended to increase. In haloperidol responders, at baseline the free/total HVA ratio was significantly higher than that in non-responders (P < 0.01). Tolerant patients, i.e. those whose post-treatment free HVA levels decreased below pre-treatment levels, were not found to respond better to haloperidol than non-tolerant patients. The balance between free and conjugated pHVA may be a better reflection of the action of haloperidol than free pHVA levels and it may be of prognostic value in terms of drug response.

  6. Changes caused by haloperidol are blocked by music in Wistar rat.

    PubMed

    Tasset, Inmaculada; Quero, Ismael; García-Mayórgaz, Ángel D; del Río, Manuel Causse; Túnez, Isaac; Montilla, Pedro

    2012-06-01

    This study sought to evaluate the effect of classical music, using Mozart's sonata for two pianos (K. 448), on changes in dopamine (DA) levels in the striatal nucleus (SN), prefrontal cortex (PFC) and mesencephalon, and on prolactin (PRL) and corticosterone secretion in adult male Wistar rats. Rats were divided into four groups: (1) control, (2) haloperidol treatment (single dose of 2 mg/kg s.c.), (3) music (two 2-h sessions per day) and (4) haloperidol plus music. Rats were sacrificed 2 h after haloperidol injection. Music prompted a fall in plasma PRL and corticosterone levels in healthy rats (P < 0.05) and prevented the increase in levels triggered by haloperidol (P < 0.001). Moreover, exposure to music was associated with a significant increase in DA levels in all groups, with the increase being particularly marked in PFC and SN (P < 0.001). Haloperidol is a recognised D2 receptor antagonist, and these findings suggest that music, by contrast, enhances DA activity and turnover in the brain. The results obtained here bear out reports that music triggers a reduction in systolic pressure and an increase in mesencephalon dopamine levels in human and rats treated with ecstasy, through a calmodulin-dependent system.

  7. Haloperidol-induced extra pyramidal symptoms attenuated by imipramine in rats.

    PubMed

    Samad, Noreen; Haleem, Darakhshan Jabeen

    2014-09-01

    Effects of administration of imipramine (IMI) are determined on haloperidol-induced extrapyramidal symptoms (EPS). Haloperidol is administered orally at a dose of 0.2 mg/rat/day in rats for a period of 5 weeks, by this treatment rats developed vacuous chewing movements (VCMs) after 2 weeks, which increased in a time dependent manner as the treatment continued for 5 weeks. Motor coordination (assess on rota rod activity) impaired maximally after 3 weeks and tolerance was developed in the haloperidol induced motor impairment after 5 weeks of treatment. Motor activity in an open field or activity box was not altered. The administration of IMI (intraperitoneally, for 5 weeks) did not affect motor activity or motor coordination. Co-administration of IMI at a dose of 5 mg/ml/kg/day attenuated the induction of haloperidol elicited VCMs (Quantitative orofacial dyskinesia) as well impairment of motor coordination. Results are discussed in the context of the mechanism involved by which imipramine attenuated haloperidol-induced EPS.

  8. Beneficial effect of candesartan and lisinopril against haloperidol-induced tardive dyskinesia in rat.

    PubMed

    Thakur, Kuldeep Singh; Prakash, Atish; Bisht, Rohit; Bansal, Puneet Kumar

    2015-12-01

    Tardive dyskinesia is a serious motor disorder of the orofacial region, resulting from chronic neuroleptic treatment of schizophrenia. Candesartan (AT1 antagonist) and lisinopril (ACE inhibitor) has been reported to possess antioxidant and neuroprotective effects. The present study is designed to investigate the effect of candesartan and lisinopril on haloperidol-induced orofacial dyskinesia and oxidative damage in rats. Tardive dyskinesia was induced by administering haloperidol (1 mg/kg i.p.) and concomitantly treated with candesartan (3 and 5 mg/kg p.o.) and lisinopril (10 and 15 mg/kg p.o.) for 3 weeks in male Wistar rats. Various behavioral parameters were assessed on days 0, 7, 14 and 21 and biochemical parameters were estimated at day 22. Chronic administration of haloperidol significantly increased stereotypic behaviors in rats, which were significantly improved by administration of candesartan and lisinopril. Chronic administration of haloperidol significantly increased oxidative stress and neuro-inflammation in the striatum region of the rat's brain. Co-administration of candesartan and lisinopril significantly attenuated the oxidative damage and neuro-inflammation in the haloperidol-treated rat. The present study supports the therapeutic use of candesartan and lisinopril in the treatment of typical antipsychotic-induced orofacial dyskinesia and possible antioxidant and neuro-inflammatory mechanisms. © The Author(s) 2014.

  9. Delta-9-tetrahydrocannabinol differently affects striatal c-Fos expression following haloperidol or clozapine administration.

    PubMed

    Marchese, Giorgio; Sanna, Angela; Casu, Gianluca; Casti, Paola; Spada, Gabriele Pinna; Ruiu, Stefania; Pani, Luca

    2008-11-19

    It was previously shown that haloperidol, but not clozapine, induced intense rat catalepsy when co-administered with delta-9-tetrahydrocannabinol. The present study investigated whether similar alterations could be observed on striatal c-Fos immunoreactivity after administration of the same drug combinations. Western Blot and immunocytochemistry stereological analyses indicated that delta-9-tetrahydrocannabinol (0.5 mg/kg) increased striatal c-Fos immunoreactivity induced by haloperidol (0.1 mg/kg). Conversely, no significant alterations of striatal c-Fos immunoreactivity were observed after injections of clozapine (10 mg/kg)+vehicle, clozapine+delta-9-tetrahydrocannabinol or vehicle+delta-9-tetrahydrocannabinol. The present results indicate that the behavioral effects induced by delta-9-tetrahydrocannabinol in haloperidol- and clozapine-treated rats are associated with different striatal c-Fos expressions.

  10. A comparison of masking effects of haloperidol versus molindone in tardive dyskinesia.

    PubMed

    Glazer, W M; Hafez, H

    1990-01-01

    An experimental method was utilized to compare the masking effects of two neuroleptic agents--molindone and haloperidol--on 18 neuroleptic-treated schizophrenic patients exhibiting operationally defined withdrawal-exacerbated tardive dyskinesia. After a week on one of these two medications at preestablished doses equivalent to that of the pre-study neuroleptic, molindone-masked total AIMS scores by significantly less (12%) than haloperidol (27%). Similarly, during a second week when the dose of these neuroleptics was equivalent to 200% that of the pre-study dose, molindone masked the total AIMS score significantly less (23%) as compared to haloperidol (53%). Several interpretations of this finding are considered. This study demonstrates the feasibility of a method that may offer a model for understanding pharmacological differences among neuroleptic medications.

  11. Molindone compared to haloperidol in a guinea-pig model of tardive dyskinesia.

    PubMed

    Koller, W; Curtin, J; Fields, J

    1984-10-01

    Molindone was compared with haloperidol in animal models of tardive dyskinesia. Treatment with molindone for 14 days at 3, 6, 20 and 40 mg/kg, enhanced the stereotyped behavioral response induced by apomorphine and increased the numbered of D-2 dopamine receptors in the striatum (Bmax) labelled by high affinity (Kd = 40 pmol) binding or [3H] spiroperidol in the guinea-pig. Molindone at 1 mg/kg, caused no behavioral supersensitivity or change in the binding of dopamine receptors. Chronic administration of haloperidol (0.1, 0.5 and 5.0 mg/kg) also increased both the behavioral response to apomorphine and the number of dopamine receptors. Haloperidol, at 0.02 and 0.004 mg/kg, had no effect. Molindone potentiated dopaminergic activity in animal models in a similar way to other neuroleptics, suggesting that its use may also result in tardive dyskinesia.

  12. Effects of atypical (risperidone) and typical (haloperidol) antipsychotic agents on astroglial functions.

    PubMed

    Quincozes-Santos, André; Bobermin, Larissa Daniele; Tonial, Rafaela Pestana Leques; Bambini-Junior, Victorio; Riesgo, Rudimar; Gottfried, Carmem

    2010-09-01

    Although classical and atypical antipsychotics may have different neurotoxic effects, their underlying mechanisms remain to be elucidated, especially regarding neuroglial function. In the present study, we compared the atypical antipsychotic risperidone (0.01-10 μM) with the typical antipsychotic haloperidol (0.01-10 μM) regarding different aspects such as glutamate uptake, glutamine synthetase (GS) activity, glutathione (GSH) content, and intracellular reactive oxygen species (ROS) production in C6 astroglial cells. Risperidone significantly increased glutamate uptake (up to 27%), GS activity (14%), and GSH content (up to 17%). In contrast, haloperidol was not able to change any of these glial functions. However, at concentration of 10 μM, haloperidol increased (12%) ROS production. Our data contribute to the clarification of different hypothesis concerning the putative neural responses after stimulus with different antipsychotics, and may establish important insights about how brain rewiring could be enhanced.

  13. Differential Antagonism of Cocaine Self-Administration and Cocaine-Induced Disruptions of Learning by Haloperidol in Rhesus Monkeys

    ERIC Educational Resources Information Center

    Winsauer, Peter J.; Moerschbaecher, Joseph M.; Roussell, Alison M.

    2008-01-01

    Six rhesus monkeys responding under a three-component multiple schedule were administered haloperidol to determine its effects on cocaine self-administration and on cocaine's disruptive effects on the repeated acquisition and performance of response chains. In the absence of haloperidol, 0.0032 - 0.032 mg/kg/infusion of cocaine increased response…

  14. Differential Antagonism of Cocaine Self-Administration and Cocaine-Induced Disruptions of Learning by Haloperidol in Rhesus Monkeys

    ERIC Educational Resources Information Center

    Winsauer, Peter J.; Moerschbaecher, Joseph M.; Roussell, Alison M.

    2008-01-01

    Six rhesus monkeys responding under a three-component multiple schedule were administered haloperidol to determine its effects on cocaine self-administration and on cocaine's disruptive effects on the repeated acquisition and performance of response chains. In the absence of haloperidol, 0.0032 - 0.032 mg/kg/infusion of cocaine increased response…

  15. The consolidation of neuroleptic therapy: Janssen, the discovery of haloperidol and its introduction into clinical practice.

    PubMed

    López-Muñoz, Francisco; Alamo, Cecilio

    2009-04-29

    The discovery of haloperidol at the end of the 1950s constitutes one of the greatest advances of 20th century psychiatry. This antipsychotic drug has their origin in the research process of central analgesic molecules derived from pethidine and methadone, carried out by the Belgian company Janssen Phamaceutica. After the synthesis of phenoperidine, numerous analogues of this compound were studied, and chemists at Janssen took the decision to substitute the propiophenone group for a butyrophenone group. One of these compounds went the R-1625, a stronger agent with specifically neuroleptic properties but lacking morphine-like activity. This substance was synthesized on the 11th February 1958 and received the generic name of haloperidol because of the two halogenated substitutes incorporated into the molecule. Clinical development of haloperidol was conducted, primarily, by psychiatric research team at the University of Liège that confirmed its efficacy in the treatment of various psychiatric disorders such as acute and chronic paranoid psychosis, mania, or chronic treatment-resistant schizophrenia. Under the brand name Haldol((R)), haloperidol was licensed and marketed in Belgium in October 1959. The direct and differed consequences of its introduction into the psychiatric practice have been multiple, involving different areas of socio-sanitary reality. Moreover, haloperidol has contributed substantially to the development of biological psychiatry and currently neuroscience, because it made possible the development of new experimental models for predicting the effects of antipsychotics, and allowed the postulate of the firsts biological hypotheses about the schizophrenia etiology. Haloperidol has been included in the World Health Organisation's list of essential medicines.

  16. Comparative effects of sertraline, haloperidol or olanzapine treatments on ketamine-induced changes in mouse behaviours.

    PubMed

    Onaolapo, O J; Paul, T B; Onaolapo, A Y

    2017-05-15

    Effects of sertraline, haloperidol or olanzapine administration on ketamine-induced behaviours in mice were examined. The aim was to ascertain the degree of reversal of such behaviours by sertraline, and compare its effectiveness to haloperidol and olanzapine. Ten-week old mice (N = 120) were equally divided into main groups; 1 (open-field, radial-arm maze and elevated plus maze {EPM} tests), and 2 (social interaction test). Mice in each main group were assigned into six groups of ten (n = 10) each. Group 1 received intraperitoneal (i.p) injection of vehicle, while groups 2-6 received i.p ketamine at 15 mg/kg daily for 10 days. From day 11 to 24, mice in group 1 (vehicle) were given distilled water (i.p at 2 ml/kg and oral at 10 ml/kg), group 2 (ketamine control) received daily i.p ketamine and oral distilled water; while animals in groups 3-6 received daily i.p. ketamine and oral haloperidol (4 mg/kg), olanzapine (2 mg/kg), or one of two doses of sertraline (SERT) (2.5 or 5 mg/kg), respectively. Treatments were administered daily, and behaviours assessed on days 11 and 24. Results showed that repeated ketamine administration caused hyperlocomotion, increased self-grooming, memory loss and social withdrawal. Administration of sertraline (both doses), haloperidol, and olanzapine reversed ketamine-induced behavioural changes. However, in the EPM, sertraline and olanzapine were anxiolytic, while haloperidol was anxiogenic. Sertraline's effect on behaviours tested was comparable to olanzapine and better than haloperidol. In conclusion, this study shows that sertraline's ability to counteract ketamine-induced behavioural changes in mice is comparable to known antipsychotics.

  17. Beta-glucan from Saccharomyces cerevisiae reduces plasma lipid peroxidation induced by haloperidol.

    PubMed

    Dietrich-Muszalska, Anna; Olas, Beata; Kontek, Bogdan; Rabe-Jabłońska, Jolanta

    2011-07-01

    Since oxidative stress observed in schizophrenia may be caused partially by the treatment of patients with various antipsychotics, the aim of the study was to establish the effects of beta-d-glucan, polysaccharide derived from the yeast cell walls of species such as Saccharomyces cerevisiae, and the antipsychotics (the first generation antipsychotic (FGA) - haloperidol and the second generation antipsychotic (SGA) - amisulpride) action on plasma lipid peroxidation in vitro. Lipid peroxidation in human plasma was measured by the level of thiobarbituric acid reactive species (TBARS). The samples of plasma from healthy subjects were incubated with haloperidol or amisulpride in the presence of beta-glucan (4 μg/ml). The action of beta-d-glucan was also compared with the properties of a well characterized commercial monomeric polyphenol - resveratrol (3,4',5-trihydroxystilbene, the final concentration - 4 μg/ml). The two-way analysis variance showed that the differences in TBARS levels were depended on the type of tested drugs (p=7.9 × 10(-6)). We observed a statistically increase of the level of biomarker of lipid peroxidation such as TBARS after 1 and 24h incubation of plasma with haloperidol compared to the control samples (p<0.01, p<0.02, respectively). Amisulpride, contrary to haloperidol (after 1 and 24h) did not cause plasma lipid peroxidation (p>0.05). We showed that in the presence of beta-glucan, lipid peroxidation in plasma samples treated with haloperidol was significantly decreased. Moreover, we did not observe the synergistic action of beta-glucan and amisulpride on the inhibition of plasma lipid peroxidation. However, the beta-d-glucan was found to be more effective antioxidant, than the solution of pure resveratrol. The presented results indicate that beta-glucan seems to have distinctly protective effects against the impairment of plasma lipid molecules induced by haloperidol.

  18. Olanzapine Is Faster than Haloperidol in Inducing Metabolic Abnormalities in Schizophrenic and Bipolar Patients.

    PubMed

    Fabrazzo, Michele; Monteleone, Palmiero; Prisco, Vincenzo; Perris, Francesco; Catapano, Francesco; Tortorella, Alfonso; Monteleone, Alessio Maria; Steardo, Luca; Maj, Mario

    2015-01-01

    The effects of olanzapine and haloperidol on metabolic parameters in bipolar patients have been evaluated much less comprehensively than in schizophrenic patients. Therefore, in this study, medical records of 343 schizophrenic and bipolar patients treated with haloperidol or olanzapine for 1 year were retrospectively reviewed and metabolic outcomes were evaluated. After 12 months of follow-up, 25.9% of patients showed ≥3 metabolic abnormalities with a point prevalence of 27.2% in the bipolar and 24.9% in the schizophrenic group: 22.0% of the schizophrenic patients treated with haloperidol and 29.8% of those treated with olanzapine achieved ≥3 metabolic alterations; in bipolar patients, these percentages were 15.8% of those treated with haloperidol and 37.8% of those treated with olanzapine (p < 0.0001). Significant changes were reported over time in fasting glucose, triglycerides and cholesterol blood levels, systolic and diastolic blood pressure, body weight, and BMI. Overall, a significant number of schizophrenic and bipolar patients treated with olanzapine showed ≥3 metabolic alterations in the first month of treatment when compared to those treated with haloperidol. Moreover, the number of olanzapine-treated patients developing metabolic changes in the first month was significantly higher in both diagnostic groups when compared to those who reached metabolic abnormal values in the subsequent 11 months. These data suggest that both antipsychotics could increase the metabolic risk in schizophrenic and bipolar patients with a higher prevalence in olanzapine-treated patients. On the other hand, olanzapine-treated patients seem to achieve metabolic abnormalities faster than haloperidol-treated subjects in both diagnostic groups.

  19. Reversal of haloperidol-induced motor deficits by mianserin and mesulergine in rats.

    PubMed

    Shireen, Erum; Haleem, Darakhshan J

    2011-01-01

    Although haloperidol is widely prescribed for the treatment of schizophrenia, its beneficial effects are accompanied by extrapyramidal side effects (EPS). Role of 5-HT-2A/2C receptors in the attenuation of acute Parkinsonian-like effects of typical antipsychotics is investigated by prior administration of mianserin and mesulergine to rats injected with haloperidol. In the first part of study effects of various doses of haloperidol (0.5, 1.0, 2.5 and 5.0 mg/kg) were determined on motor activity and a selected dose (1 mg/kg) was used to monitor attenuation of parkinsonian effects by two different doses of 5-HT-2A/2C receptor antagonists mianserin (2.5 & 5.0 mg/kg) and mesulergine (1.0 & 3.0 mg/kg). Rats treated with haloperidol at doses of 0.5-5.0 mg/kg exhibited impaired motor coordination and a decrease in exploratory activity in an open field. The dose response curve showed that at a dose of 1 mg/kg significant and submaximal effects are produced on motor coordination and exploratory activity. Coadministration of mianserin and mesulergine attenuated and reversed haloperidol-induced motor deficits in a dose dependent manner. The mechanism involved in the attenuation / reversal of haloperidol-induced parkinsonian like symptoms by mianserin and mesulergine is discussed. Prior administration of mianserin or mesulergine may be of use in the alleviation of EPS induced by conventional antipsychotic drugs.The findings have potential implication in the treatment of schizophrenia and motor disorders.

  20. Beneficial effects of lycopene against haloperidol induced orofacial dyskinesia in rats: Possible neurotransmitters and neuroinflammation modulation.

    PubMed

    Datta, Swati; Jamwal, Sumit; Deshmukh, Rahul; Kumar, Puneet

    2016-01-15

    Tardive Dyskinesia is a severe side effect of chronic neuroleptic treatment consisting of abnormal involuntary movements, characterized by orofacial dyskinesia. The study was designed to investigate the protective effect of lycopene against haloperidol induced orofacial dyskinesia possibly by neurochemical and neuroinflammatory modulation in rats. Rats were administered with haloperidol (1mg/kg, i.p for 21 days) to induce orofacial dyskinesia. Lycopene (5 and 10mg/kg, p.o) was given daily 1hour before haloperidol treatment for 21 days. Behavioral observations (vacuous chewing movements, tongue protrusions, facial jerking, rotarod activity, grip strength, narrow beam walking) were assessed on 0th, 7th(,) 14th(,) 21st day after haloperidol treatment. On 22nd day, animals were killed and striatum was excised for estimation of biochemical parameters (malondialdehyde, nitrite and endogenous enzyme (GSH), pro-inflammatory cytokines [Tumor necrosis factor, Interleukin 1β, Interleukin 6] and neurotransmitters level (dopamine, serotonin, nor epinephrine, 5-Hydroxyindole acetic acid (5-HIAA), Homovanillic acid, 3,4- dihydroxyphenylacetic acid. Haloperidol treatment for 21 days impaired muscle co-ordination, motor activity and grip strength with an increased in orofacial dyskinetic movements. Further free radical generation increases MDA and nitrite levels, decreasing GSH levels in striatum. Neuroinflammatory markers were significantly increased with decrease in neurotransmitters levels. Lycopene (5 and 10mg/kg, p.o) treatment along with haloperidol significantly attenuated impairment in behavioral, biochemical, neurochemical and neuroinflammatory markers. Results of the present study attributed the therapeutic potential of lycopene in the treatment (prevented or delayed) of typical antipsychotic induced orofacial dyskinesia.

  1. Comparative effectiveness of quetiapine and haloperidol in delirium: A single blind randomized controlled study

    PubMed Central

    Grover, Sandeep; Mahajan, Sudhir; Chakrabarti, Subho; Avasthi, Ajit

    2016-01-01

    AIM To evaluate the effectiveness of quetiapine and haloperidol in patients of delirium referred to psychiatry consultation liaison services. METHODS The study followed a single blind randomised controlled trial design. Thirty-two patients in the haloperidol group and 31 patients in the quetiapine group were assessed at the baseline and 6 consecutive days. Flexible dosing regimen (haloperidol: 0.25-1.25 mg; quetiapine 12.5-75 mg/d) was used. Delirium Rating Scale-Revised-98 (DRS-R-98) and mini mental status examination (MMSE) were the primary and secondary efficacy measures respectively. RESULTS Baseline DRS-R-98 severity score and MMSE scores did not differ between the 2 study groups. From baseline to day 6, there was significant reduction in the total DRS-R-98 scores, DRS-R-98 cognitive domain scores, DRS-R-98 non-cognitive domain scores and significant increase in the MMSE scores in both the groups. Both the groups did not differ on any of the assessments in terms of DRS-R98 and MMSE scores. The effectiveness of both the medications was similar in adult and elderly (≥ 60 years) patients. At the end of the trial, 68.75% and 67.74% of subjects in the haloperidol and quetiapine group respectively had mean DRS-R-98 scores below 10. By 6th day, 12 (37.5%) patients in haloperidol group and 9 (29.03%) patients in the quetiapine group had DRS-R98 score of “0” with no significant difference between the two groups (P = 0.47). CONCLUSION Quetiapine is as effective as haloperidol in the management of delirium. PMID:27679777

  2. Economic evaluation of zuclopenthixol acetate compared with injectable haloperidol in schizophrenic patients with acute psychosis.

    PubMed

    Laurier, C; Kennedy, W; Lachaine, J; Gariepy, L; Tessier, G

    1997-01-01

    Zuclopenthixol acetate is a rapid-acting, injectable neuroleptic drug with a duration of action that allows for administration once every 2 to 3 days, in contrast to injectable haloperidol, which may require administration more than once daily. To assess the place of zuclopenthixol acetate in the treatment of acute episodes of schizophrenia, a cost-consequence analysis was performed comparing this new medication with short-acting, injectable haloperidol. The perspective of the Quebec health care system was adopted. The study population comprised patients diagnosed with schizophrenia who experienced an acute episode of psychosis and who were treated with intramuscular (i.m.) haloperidol. The study assessed patients for 9 days after the start of treatment. The literature was the principal source of comparative data about the clinical outcomes of the two treatments. The total cost associated with zuclopenthixol acetate i.m. or haloperidol i.m. was modeled using a decision tree built around the number of i.m. injections required to achieve stabilization. To establish costs, expert panels were consulted and patients' files were reviewed for a sample of schizophrenic patients who had been hospitalized in a large psychiatric or general hospital subsequent to a visit to the emergency department and had received a short-acting i.m. neuroleptic drug. Only a direct medical records costs were considered. Because zuclopenthixol acetate was not on the market at the time of the study, the file review did not allow for a direct estimate of its related costs but did provide an account of haloperidol use. The literature shows that zuclopenthixol acetate is similar to haloperidol with respect to the control of psychotic episodes; however, zuclopenthixol acetate is associated with increased sedation and a lower incidence of extrapyramidal symptoms. Using the base-case estimate for the number of injections required for stabilization, the incremental cost of zuclopenthixol acetate 50 mg

  3. Haloperidol: a possible medication for the treatment of exacerbation of intractable psychogenic sneezing.

    PubMed

    Guner, Sukru Nail; Gokcen, Cem; Gokturk, Bahar; Topal, Ozgul

    2010-10-01

    Sneezing is one of the physiological defense mechanisms that develops generally due to nasal irritation. But intractable sneezing episodes are uncommon and generally detected among the adolescents. It is difficult to distinguish physiologic sneezing from psychogenic sneezing. Herein, we report a 12-year-old girl who was complaint with intractable sneezing. She was diagnosed as intractable psychogenic sneezing and haloperidol treatment was started. All symptoms had resolved completely within 2 weeks. As a result, haloperidol can be considered as a different treatment modality for intractable psychogenic sneezing.

  4. Differential Effects of Intermittent versus Continuous Haloperidol Treatment throughout Adolescence on Haloperidol Sensitization and Social Behavior in Adulthood

    PubMed Central

    Gao, Jun; Li, Ming

    2014-01-01

    Animal work on the behavioral effects of antipsychotic treatment suggests that different dosing regimens could affect drug sensitivity differently, with an intermittent treatment regimen tending to cause a sensitization effect, while a continuous treatment causing a tolerance. In this study, we explored how haloperidol (HAL) sensitization induced throughout adolescence and tested in adulthood was differentially impacted by these two dosing regimens in the conditioned avoidance response (CAR) test. We also examined how these two dosing regiments affected social interaction and social memory in adulthood. Male adolescent Sprague-Dawley rats were treated with HAL via either osmotic minipump (HAL-0.25 CONT; 0.25 mg/kg/day, n = 14) or daily injection (HAL-0.05 INT; 0.05 mg/kg/injection/day, sc, n = 14), or sterile water (n = 14) from postnatal days (PND) 44 to 71. HAL sensitization was assessed in a challenge test in which all rats were injected with HAL (0.025 and 0.05 mg/kg, sc) on PND 80 and PND 82. Two days later, half of the rats from each group (n = 7/group) were assayed in two 4-trial social interaction tests in which a subject rat was given four 5-min social encounters with a familiar or novel juvenile rat (PND 35–40) at 10 min intervals. Another half were tested in a quinpirole-induced hyperlocomotion assay to assess the potential HAL-induced change in D2-mediated function. Results show that only the intermittent dosing group under the HAL 0.05 mg/kg challenge showed a robust sensitization effect as rats in this group made significantly fewer avoidance responses than those in the vehicle and HAL-0.25 CONT groups. Adolescent HAL treatment did not affect social behavior and social memory, as rats from all 3 groups exhibited a similar level of social interaction and showed a similar level of sensitivity to the change of social stimuli. Similarly, adolescent HAL treatment also did not produce a long-lasting change in D2 function, as all 3 groups exhibited a

  5. Effects of the Antipsychotic Drug, Haloperidol, on Reproduction in the Fathead Minnow

    EPA Science Inventory

    Haloperidol is a butyrophenone antipsychotic drug used for the treatment of human hyperactive and manic disorders, agitation, and schizophrenia. The drug is thought to act through antagonism of dopaminergic receptors. We have studied a variety of endocrine-disrupting chemicals wi...

  6. Co-administration of haloperidol and drugs affecting the angiotensin pathway: effect on the extrapyramidal system.

    PubMed

    Pemminati, Sudhakar; Swati, B; Shreyasi, C; Gopalakrishna, H N; Nair, Vinod; Pai, M R S M

    2012-02-01

    The present study investigates the extrapyramidal effects of co-administration of enalapril (angiotensin-converting enzyme inhibitor) or losartan (angiotensin receptor blocker) with haloperidol in mice. Enalapril/losartan (as a suspension in 1% gum acacia) was administered by oral gavage and haloperidol was administered as an intraperitoneal injection to all the animals for seven days. Catalepsy was measured 30 min after the administration of haloperidol (1 mg/kg i.p.) on days 1 and 7. Observations on day 1 constituted the acute study (single dose administration) and observations on day 7, constituted the chronic study (repeated dose administration). Both acute and chronic administration of enalapril/losartan produced an increase in the duration of haloperidol induced catalepsy at the highest dose (20 mg/kg). Enalapril produced a more pronounced increase in the duration of catalepsy as compared to losartan on both acute and chronic administration. Results of our study suggest that co-administration of anti-psychotics and drugs affecting the angiotensin system can lead to an increase in motor side effects and therefore should be used with caution in patients with these co-morbid conditions.

  7. Effects of the Antipsychotic Drug, Haloperidol, on Reproduction in the Fathead Minnow

    EPA Science Inventory

    Haloperidol is a butyrophenone antipsychotic drug used for the treatment of human hyperactive and manic disorders, agitation, and schizophrenia. The drug is thought to act through antagonism of dopaminergic receptors. We have studied a variety of endocrine-disrupting chemicals wi...

  8. Does haloperidol prophylaxis reduce ketamine-induced emergence delirium in children?

    PubMed

    Amr, Mostafa A M; Shams, Tarek; Al-Wadani, Hamid

    2013-05-01

    Ketamine is a non-barbiturate agent with rapid action onset that induces profound sedation; however, some emergency physicians tend not to use ketamine because of the risk of emergence delirium (ED). This study aimed to evaluate the effectiveness of haloperidol prophylaxis in postoperative ketamine delirium in children. Prospective data relating to any emergence dreams, delirium, hallucinations, agitation, crying, altered perceptions, and necessary interventions were recorded in consecutive cases of ketamine delirium in patients attending Mansoura University Hospital, Egypt, from June 2010 to May 2011. A total of 537 records were available for analysis. Of those, 267 received prophylactic haloperidol (49.7%). There were significant differences between the two groups regarding post-anaesthetic care unit behaviour. The ketamine-haloperidol groups included more patients who were sleepy, calm (P ≤0.01) and less irritable (P ≤0.01), with a lower incidence of crying (P ≤0.01) and disorientation (P ≤0.01). We found that preoperative administration of haloperidol decreases the incidence of postoperative delirium in a sample of Egyptian children undergoing minor surgery. This is congruent with earlier work conducted in adults. This work carries great hope to decrease and even prevent ED in hospitalised, non-surgical patients.

  9. Epicatechin inhibits human plasma lipid peroxidation caused by haloperidol in vitro.

    PubMed

    Dietrich-Muszalska, Anna; Kontek, Bogdan; Olas, Beata; Rabe-Jabłońska, Jolanta

    2012-03-01

    Epicatechin belongs to flavonoids protecting cells against oxidative/nitrative stress. Oxidative/nitrative stress observed in schizophrenia may be caused partially by the treatment of patients with various antipsychotics. The aim of our study was to establish the effects of epicatechin and antipsychotics action (the first generation antipsychotic (FGA)--haloperidol and the second generation antipsychotic (SGA)--amisulpride) on peroxidation of plasma lipids in vitro. Lipid peroxidation in human plasma was measured by the level of thiobarbituric acid reactive species (TBARS). The properties of epicatechin were also compared with the action of a well characterized antioxidative commercial polyphenol-resveratrol (3,4',5-trihydroxystilbene) and quercetin (3,5,7,3',4'-pentahydroxyflavone). Amisulpride, contrary to haloperidol (after 1 and 24 h) does not significantly influence the increase of plasma TBARS level in comparison with control samples (P > 0.05). After incubation (1 and 24 h) of plasma with haloperidol in the presence of epicatechin we observed a significantly decreases the level of TBARS (P < 0.001, P < 0.001, respectively). In our other experiments, we found that epicatechin also decreased the amount of TBARS in human plasma treated with amisulpride. In conclusion, the presented results indicate that epicatechin-the major polyphenolic component of green tea reduced significantly human plasma lipid peroxidation caused by haloperidol. Moreover, epicatechin was found to be a more effective antioxidant, than the solution of pure resveratrol or quercetin.

  10. Interaction of dopamine and haloperidol with O2 and CO2 chemoreception in carotid body.

    PubMed

    Lahiri, S; Nishino, T; Mokashi, A; Mulligan, E

    1980-07-01

    Effects of dopamine and of a dopaminergic blocker, haloperidol, on the responses of carotid body chemoreceptors to hypoxia and hypercapnia were investigated in 16 anesthetized cats. Intravenous infusion of dopamine (10-20 micrograms.min-1) decreased carotid body chemoreceptor responses to hypoxia and hypercapnia. The effect was greater at higher levels of arterial oxygen and carbon dioxide tension (PaO2 and PaCO2) stimulus. Thus, the magnitude of the dopamine effect depended on the degree of both PO2- and PCO2-mediated excitation of the receptors. Haloperidol potentiated responses to both hypoxia and hypercapnia but apparently did not stimulate the receptors in the absence of these stimuli. Potentiation by haloperidol and inhibition by dopamine of excitatory effects due to PaO2 decrease and PaCO2 increase are complementary. The data suggest that chemoreception of dopamine, O2, and CO2 converge at some site in the carotid body. Persistence of hypoxic and hypercapnic responses, following dopamine-blocking doses of haloperidol, does not support the theory that regulation of dopamine release is responsible for O2 and CO2 chemoreception in carotid body of the cat.

  11. Effects of haloperidol and clozapine administration on oxidative stress in rat brain, liver and serum.

    PubMed

    Andreazza, Ana C; Barakauskas, Vilte E; Fazeli, Salar; Feresten, Abigail; Shao, Li; Wei, Vivien; Wu, Che Hsuan; Barr, Alasdair M; Beasley, Clare L

    2015-03-30

    Antipsychotics remain the standard of care for individuals with schizophrenia, despite their association with adverse effects including extrapyramidal symptoms, metabolic syndrome and agranulocytosis. While the biological mechanisms underlying these side effects remain unresolved, it has been proposed that oxidative stress may play a role in their development. The aim of this study was to evaluate markers of oxidative stress associated with first- and second-generation antipsychotics, focusing on protein and lipid oxidation and expression of the antioxidant proteins peroxiredoxin-2 and peroxiredoxin-6. Following 28-day administration of haloperidol, clozapine or saline to adult rats, brain grey matter, white matter, serum and liver samples were obtained and lipid peroxidation, protein oxidation, peroxiredoxin-2 and peroxiredoxin-6 levels quantified. In grey matter, peroxiredoxin-6 was significantly increased in the haloperidol-exposed animals, with a trend towards increased lipid peroxidation also observed in this group. In liver, lipid peroxidation was increased in the clozapine-exposed animals, with a similar trend noted in the haloperidol group. Antipsychotics did not produce significant changes in serum or white matter. Our results suggest that haloperidol and clozapine may induce oxidative stress in brain and liver, respectively, consistent with the documented adverse effects of these agents. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Risk management of QTc-prolongation in patients receiving haloperidol: an epidemiological study in a University hospital in Belgium.

    PubMed

    Vandael, Eline; Vandenberk, Bert; Vandenberghe, Joris; Spriet, Isabel; Willems, Rik; Foulon, Veerle

    2016-04-01

    Many drugs, including haloperidol, are linked with a risk of QTc-prolongation, which can lead to Torsade de Pointes and sudden cardiac death. To investigate the prevalence of concomitant risk factors for QTc-prolongation in patients treated with haloperidol, and the use of safety measures to minimize this risk. University Hospitals of Leuven, Belgium. Methods A retrospective epidemiological study was performed. On 15 consecutive Mondays, all patients with a prescription for haloperidol were included. A risk score for QTc-prolongation, inspired by the pro-QTc score of Haugaa et al., was calculated based on gender, comorbidities, lab results and concomitant QTc-prolonging drugs (each factor counting for one point). Available electrocardiograms before and during the treatment of haloperidol were registered. Management of the risk of QTc-prolongation. Two hundred twenty-two patients were included (59.0 % men, median age 77 years) of whom 26.6 % had a risk score of ≥4 (known to significantly increase the mortality). Overall, 24.3 % received haloperidol in combination with other drugs with a known risk of Torsade de Pointes. Half of the patients had an electrocardiogram in the week before the start of haloperidol; only in one-third a follow-up electrocardiogram during haloperidol treatment was performed. Of the patients with a moderately (n = 41) or severely (n = 14) prolonged QTc-interval before haloperidol, 48.8 % and 42.9 % respectively had a follow-up electrocardiogram. In patients with a risk score ≥4, significantly more electrocardiograms were taken before starting haloperidol (p = 0.020). Although many patients had risk factors for QTc-prolongation (including the use of other QTc-prolonging drugs) or had a prolonged QTc on a baseline electrocardiogram, follow-up safety measures were limited. Persistent efforts should be taken to develop decision support systems to manage this risk.

  13. Pharmacovigilance in Hospice/Palliative Care: Net Effect of Haloperidol for Nausea or Vomiting.

    PubMed

    Digges, Madeline; Hussein, Akram; Wilcock, Andrew; Crawford, Gregory B; Boland, Jason W; Agar, Meera R; Sinnarajah, Aynharan; Currow, David C; Johnson, Miriam J

    2017-08-03

    Haloperidol is widely prescribed as an antiemetic in patients receiving palliative care, but there is limited evidence to support and refine its use. To explore the immediate and short-term net clinical effects of haloperidol when treating nausea and/or vomiting in palliative care patients. A prospective, multicenter, consecutive case series. Twenty-two sites, five countries: consultative, ambulatory, and inpatient services. When haloperidol was started in routine care as an antiemetic, data were collected at three time points: baseline; 48 hours (benefits); day seven (harms). Clinical effects were assessed using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE). Data were collected (May 2014-March 2016) from 150 patients: 61% male; 86% with cancer; mean age 72 (standard deviation 11) years and median Australian-modified Karnofsky Performance Scale 50 (range 10-90). At baseline, nausea was moderate (88; 62%) or severe (11; 8%); 145 patients reported vomiting, with a baseline NCI CTCAE vomiting score of 1.0. The median (range) dose of haloperidol was 1.5 mg/24 hours (0.5-5 mg/24 hours) given orally or parenterally. Five patients (3%) died before further data collection. At 48 hours, 114 patients (79%) had complete resolution of their nausea and vomiting, with greater benefit seen in the resolution of nausea than vomiting. At day seven, 37 (26%) patients had a total of 62 mild/moderate harms including constipation 25 (40%); dry mouth 13 (21%); and somnolence 12 (19%). Haloperidol as an antiemetic provided rapid net clinical benefit with low-grade, short-term harms.

  14. Haloperidol modifies instrumental aspects of slot machine gambling in pathological gamblers and healthy controls.

    PubMed

    Tremblay, Anne-Marie; Desmond, Renée C; Poulos, Constantine X; Zack, Martin

    2011-07-01

    Instrumental conditioning has been implicated in persistence at slot machine gambling, but its specific role remains unclear. Dopamine (DA) mediates aspects of instrumental responding, and D2 antagonists reliably alter this process. This study investigated the effects of the preferential D2 antagonist, haloperidol (3 mg) on reward-related betting behavior in 20 subjects with pathological gambling (PG) and 18 healthy controls. Hierarchical regression assessed the prospective relationship between Payoff and Bet Size on consecutive trials, along with potential moderating effects of Cumulative Winnings and Phase of game (early/late) under drug and placebo. Payoff predicted Bet Size on the next trial regardless of other factors, consistent with an instrumental view of slot machine gambling. Under placebo, this correlation varied as a function of Winnings and Phase in PG subjects but was strong and invariant in Controls. Under haloperidol, the Payoff-Bet Size correlation in PG subjects resembled the invariant pattern of Controls under placebo. In contrast, the Payoff-Bet Size correlation rose then fell sharply over trials under haloperidol in controls. The correlation of Payoff with Bet Size is remarkable given that there is no actual contingency between winning and betting, and suggests that reward expectancies largely drive slot machine gambling. By blocking inhibitory D2 receptors, haloperidol may have reversed 'tolerance' to monetary reward mediated by increased tonic DA in PG subjects. Disturbance of the Payoff-Bet Size correlation in controls may reflect indiscriminate reward signaling under haloperidol in subjects with normal DA function. Indirect enhancement of DA transmission may reduce undue reward-related responding in PG subjects. © 2010 The Authors. Journal compilation © 2010 Society for the Study of Addiction.

  15. A comparison of the central nervous system effects of haloperidol, chlorpromazine and sulpiride in normal volunteers.

    PubMed Central

    McClelland, G R; Cooper, S M; Pilgrim, A J

    1990-01-01

    1. Twelve healthy male volunteers participated in four experimental occasions during each of which they were dosed with one of the following anti-psychotic drugs: chlorpromazine (50 mg), haloperidol (3 mg), sulpiride (400 mg) and placebo. Drugs were allocated to subjects in a double-blind, crossover fashion. 2. The subject's mood state, psychometric performance and electroencephalogram (EEG) were assessed pre-dose, and at 2, 4, 6, 8, 24 and 48 h post-dose. Mood states were assessed using 16 visual analogue scales and psychomotor performance was measured using the following tests: elapsed time estimation, tapping rate, choice reaction times, a rapid information processing task, flash fusion threshold, a manipulative motor task, digit span, body sway and tremor. 3. Chlorpromazine and haloperidol significantly reduced subjective ratings of 'alertness' and 'contentedness', and haloperidol significantly reduced feelings of 'calmness'. Sulpiride did not significantly affect any of the visual analogue scales. 4. All three anti-psychotic drugs had similar EEG effects with peak effect 2 to 4 h postdose. The profile was characterised by an increase in the proportion of slow wave activity (delta and theta) as well as decreased alpha (8-14 Hz) and faster (beta) wave activity. 5. Chlorpromazine reduced tapping rate and increased choice reaction movement times. Haloperidol reduced the flash fusion threshold frequency at 6 h post-dose. Sulpiride prolonged the duration of the manipulative motor task, particularly at 48 h post-dose. 6. All three anti-psychotic drugs impaired performance on the rapid information processing task. Chlorpromazine significantly reduced the number of correct letter pair identifications at 2, 4 and 6 h post-dose, haloperidol at 4, 6, 8, 24 and 48 h post-dose, and sulpiride at 24 h post-dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2288826

  16. Antipsychotics, chlorpromazine and haloperidol inhibit voltage-gated proton currents in BV2 microglial cells.

    PubMed

    Shin, Hyewon; Song, Jin-Ho

    2014-09-05

    Microglial dysfunction and neuroinflammation are thought to contribute to the pathogenesis of schizophrenia. Some antipsychotic drugs have anti-inflammatory activity and can reduce the secretion of pro-inflammatory cytokines and reactive oxygen species from activated microglial cells. Voltage-gated proton channels on the microglial cells participate in the generation of reactive oxygen species and neuronal toxicity by supporting NADPH oxidase activity. In the present study, we examined the effects of two typical antipsychotics, chlorpromazine and haloperidol, on proton currents in microglial BV2 cells using the whole-cell patch clamp method. Chlorpromazine and haloperidol potently inhibited proton currents with IC50 values of 2.2 μM and 8.4 μM, respectively. Chlorpromazine and haloperidol are weak bases that can increase the intracellular pH, whereby they reduce the proton gradient and affect channel gating. Although the drugs caused a marginal positive shift of the activation voltage, they did not change the reversal potential. This suggested that proton current inhibition was not due to an alteration of the intracellular pH. Chlorpromazine and haloperidol are strong blockers of dopamine receptors. While dopamine itself did not affect proton currents, it also did not alter proton current inhibition by the two antipsychotics, indicating dopamine receptors are not likely to mediate the proton current inhibition. Given that proton channels are important for the production of reactive oxygen species and possibly pro-inflammatory cytokines, the anti-inflammatory and antipsychotic activities of chlorpromazine and haloperidol may be partly derived from their ability to inhibit microglial proton currents. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Adenosine A2 receptors modulate haloperidol-induced catalepsy in rats.

    PubMed

    Mandhane, S N; Chopde, C T; Ghosh, A K

    1997-06-11

    The effect of adenosine A1 and A2 receptor agonists and antagonists was investigated on haloperidol-induced catalepsy in rats. Pretreatment (i.p.) with the non-selective adenosine receptor antagonist, theophylline, or the selective adenosine A2 receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX), significantly reversed haloperidol-induced catalepsy, whereas the selective adenosine A1 receptor antagonists, 8-phenyltheophylline and 8-cyclopentyl-1,3-dipropylxanthine produced no effect. Similar administration of the adenosine A2 receptor agonists, 5'-(N-cyclopropyl)-carboxamidoadenosine and 5'-N-ethylcarboxamidoadenosine (NECA), and the mixed agonists with predominantly A1 site of action, N6-(2-phenylisopropyl) adenosine or 2-chloroadenosine, potentiated haloperidol-induced catalepsy. Higher doses of the adenosine agonists produced catalepsy when given alone. However, N6-cyclopentyladenosine, a highly selective adenosine A1 receptor agonist, was ineffective in these respects. The per se cataleptic effect of adenosine agonists was blocked by DMPX and the centrally acting anticholinergic agent, scopolamine. Scopolamine also attenuated the potentiation of haloperidol-induced catalepsy by adenosine agonists. Further, i.c.v. administration of NECA and DMPX produced a similar effect as that produced after their systemic administration. These findings demonstrate the differential influence of adenosine A1 and A2 receptors on haloperidol-induced catalepsy and support the hypothesis that the functional interaction between adenosine and dopamine mechanisms might occur through adenosine A2 receptors at the level of cholinergic neurons. The results suggest that adenosine A2, but not A1, receptor antagonists may be of potential use in the treatment of Parkinson's disease.

  18. Haloperidol and sudden cardiac death in dementia: autopsy findings in psychiatric inpatients.

    PubMed

    Ifteni, Petru; Grudnikoff, Eugene; Koppel, Jeremy; Kremen, Neil; Correll, Christoph U; Kane, John M; Manu, Peter

    2015-12-01

    Treatment with haloperidol has been shown, in studies using death certificates and prescription files, to be associated with an excess of sudden cardiac deaths, and regulatory warnings highlight this risk in patients with dementia. We used autopsy findings to determine whether the rate of sudden cardiac death is greater in cases of unexpected deaths of patients with dementia treated with haloperidol. From 1989 through 2013, 1219 patients with a primary diagnosis of dementia with behavioral disturbance were admitted to a psychiatric hospital, and 65 (5.3%) died suddenly. Sixty-five patients (5.3%) died unexpectedly. Complete post-mortem examinations after the sudden death were performed in 55 (84.6%) patients. Twenty-seven of the autopsied cases (49.1%) had been treated with haloperidol orally (2.2 mg ± 2.1 mg/day), the only antipsychotic used in this cohort. Univariable comparisons and multivariable regression analyses compared the groups of patients with or without sudden cardiac death. The leading causes of death were sudden cardiac death (32.7%), myocardial infarction (25.5% of patients), pneumonia (23.6%), and stroke (10.9%). Patients with sudden cardiac death and those with anatomically established cause of death were similar regarding the use of haloperidol (p = 0.5). Sudden cardiac death patients were more likely to suffer from Alzheimer's dementia (p = 0.027) and to have a past history of heart disease (p = 0.0094), and less likely to have been treated with a mood stabilizer (p = 0.024), but none of these variables were independent predictors of sudden cardiac death. Autopsy data suggest that oral haloperidol is not associated with increased risk of sudden cardiac death in psychiatric inpatients with dementia. Copyright © 2015 John Wiley & Sons, Ltd.

  19. Clinical and biological outcomes of prolonged treatment with haloperidol in schizophrenia.

    PubMed

    Mutică, Mihai; Marinescu, Ileana; Militaru, Felicia; Pîrlog, Mihail Cristian; Udriştoiu, Ion

    2016-01-01

    Paranoid schizophrenia with long-term course is a challenge for the clinical and therapeutic research, particularly because chronic course is difficult to identify due to the high rate of mortality in this category of patients. The therapeutic stability on an antipsychotic molecule (haloperidol) is indeed an exception, since the current trend in the case of unfavorable course is based on therapeutic versatility and polypharmacy. Haloperidol is the first-generation antipsychotic that is referred in the therapeutic guidelines as the "golden standard" regarding its efficacy on positive symptoms. The research in fundamental and molecular psychopharmacology has shown the aggressivity of this molecule on the secondary and tertiary signaling chains, including mitochondrial alterations. On male patients with paranoid schizophrenia (positive symptoms) and a chronic course of more than 35 years who received exclusively haloperidol, our study demonstrated an negative outcome with the loss of social functioning, persistence of positive symptoms, chronic extrapyramidal symptoms and mild cognitive impairment. The neuroimaging evaluations have shown atrophy in the temporal poles, posterior ventriculomegaly, cerebellar atrophy and calcification on choroid plexus and pineal gland. The difference between the histological changes induced by haloperidol on animal model and the ones on the patients in our study is located in the frontal cortex, thus suggesting the presence of two neurobiological models of schizophrenia in men: fronto-striatal and temporal-limbic-striatal. The persistence of extrapyramidal symptoms during the treatment with haloperidol may be considered as a clinical marker of the risk for negative outcome and a potential indication for the therapeutic switch.

  20. The neuroleptic activity of haloperidol increases after its solubilization in surfactant micelles. Micelles as microcontainers for drug targeting.

    PubMed

    Kabanov, A V; Chekhonin, V P; Alakhov VYu; Batrakova, E V; Lebedev, A S; Melik-Nubarov, N S; Arzhakov, S A; Levashov, A V; Morozov, G V; Severin, E S

    1989-12-04

    It has been suggested to use surfactant micelles as microcontainers for increasing the efficiency of neuroleptic targeting from blood flow into the brain. The neuroleptic action of haloperidol, intraperitoneally injected into mice in micellar solution of non-ionic block copolymer surfactant (pluronic P-85) in water, increased several-fold if compared with that observed for haloperidol aqueous solution. Incorporation of brain-specific antibodies into haloperidol-containing micelles resulted in additional drastic increase (more than by 2 orders of magnitude) in the drug effect.

  1. Haloperidol and Clozapine Differentially Affect the Expression of Arrestins, Receptor Kinases, and Extracellular Signal-Regulated Kinase Activation

    PubMed Central

    Ahmed, Mohamed Rafiuddin; Gurevich, Vsevolod V.; Dalby, Kevin N.; Benovic, Jeffrey L.; Gurevich, Eugenia V.

    2009-01-01

    Dopamine and other G protein-coupled receptors (GPCRs) represent the major target of antipsychotic drugs. GPCRs undergo desensitization via activation-dependent phosphorylation by G protein-coupled receptor kinases (GRKs) followed by arrestin binding. Arrestins and GRKs are major regulators of GPCR signaling. We elucidated changes in expression of two arrestins and four GRKs following chronic (21 days) treatment with haloperidol (1 mg/kg i.p.) or clozapine (20 mg/kg i.p.) 2 or 24 h after the last injection in 11 brain regions. Haloperidol decreased GRK3 in ventrolateral caudate-putamen and transiently down-regulated GRK5 in globus pallidus and caudal caudate-putamen. Clozapine also caused a short-term suppression of the GRK5 expression in the caudal caudate-putamen and globus pallidus, but, unlike haloperidol, elevated GRK5 in the caudal caudate-putamen after 24 h. Unlike haloperidol, clozapine decreased arrestin2 and GRK3 in hippocampus and GRK3 in globus pallidus but increased arrestin2 in the core of nucleus accumbens and ventrolateral caudate-putamen and GRK2 in prefrontal cortex. Clozapine, but not haloperidol, induced long-term activation of extracellular signal-regulated kinase (ERK) 2 in ventrolateral caudate-putamen and transient in prefrontal cortex. The data demonstrate that haloperidol and clozapine differentially affect the expression of arrestins and GRKs and ERK activity, which may play a role in determining their clinical profile. PMID:18178904

  2. Haloperidol Suppresses NF-kappaB to Inhibit Lipopolysaccharide-Induced Pro-Inflammatory Response in RAW 264 Cells.

    PubMed

    Yamamoto, Shunsuke; Ohta, Noriyuki; Matsumoto, Atsuhiro; Horiguchi, Yu; Koide, Moe; Fujino, Yuji

    2016-02-04

    BACKGROUND Haloperidol, a tranquilizing agent, is administered both to treat symptoms of psychotic disorders and to sedate agitated and delirious patients. Notably, haloperidol has been suggested to inhibit the immune response through unknown mechanisms. We hypothesized that the sedative modulates the immune response via NF-κB. MATERIAL AND METHODS Using flow cytometry, we analyzed the effects of haloperidol on expression CD80 and CD86 in RAW 264 cells and in primary macrophages derived from bone marrow. Secretion of interleukin (IL)-1β, IL-6, and IL-12 p40 was measured by enzyme-linked immunosorbent assay. In addition, NF-κB activation was evaluated using a reporter assay based on secretory embryonic alkaline phosphatase. Finally, synthetic antagonists were used to identify the dopamine receptor that mediates the effects of haloperidol. RESULTS Haloperidol inhibited NF-κB activation, and thereby suppressed expression of CD80, as well as secretion of IL-1β, IL-6, and IL-12 p40. CD80 and IL-6 levels were similarly attenuated by a D2-like receptor antagonist, but not by a D1-like receptor antagonist. CONCLUSIONS The data strongly suggest that haloperidol inhibits the immune response by suppressing NF-kB signaling via the dopamine D2 receptor.

  3. The effect of haloperidol on maternal behavior in WAG/Rij rats and its consequences in the offspring.

    PubMed

    Dobryakova, Yulia V; Dubynin, Vyacheslav A; Luijtelaar, Gilles van

    2011-01-01

    Haloperidol treatment during pre- and post-natal period affects maternal behavior and this may have long-term effects on the offspring. We examined whether early haloperidol administration to Wistar-Albino-Glaxo dams from Rijswijk (WAG/Rij) and in Wistar control rats would affect maternal care and as a consequence, seizure susceptibility and behavior in the WAG/Rij's offspring at 3-4 months of age. Nursing dams of this well-validated genetic animal model of absence epilepsy and control dams were injected with haloperidol or saline at PPD 1 to 6. Maternal behavior was evaluated at PPD 7 to 9. Haloperidol-injected WAG/Rij dams showed more pup carryings compared with saline-injected mothers, this effect was not noticed in control Wistar dams. The offspring of haloperidol-treated WAG/Rij dams, tested during adulthood, showed heightened behavioral activity (time spent into the open arms, head dips) in the elevated plus-maze, as well as shorter spike-wave discharges (SWD) as measured in their electroencephalographic activity compared with saline-treated rats. Overall, it can be concluded that deviancies in the DA system as induced by haloperidol facilitates pup carrying/retrieval behavior in WAG/Rij rats and reduces seizure activity of the offspring in adulthood. Therefore, inter-individual differences in seizure properties and behavior in genetically predisposed animals may be due to differences in maternal behavior of the dams.

  4. Effects of haloperidol and aripiprazole on the human mesolimbic motivational system: A pharmacological fMRI study.

    PubMed

    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.

  5. Comparison of injectable molindone and haloperidol followed by oral dosage forms in acutely ill schizophrenics.

    PubMed

    Escobar, J I; Mann, J J; Keller, J; Wilkins, J; Mason, B; Mills, M J

    1985-08-01

    The comparative efficacy of molindone and haloperidol, given by injection for the first 2-3 days of hospitalization and then continued orally for up to 4 weeks, is reported from an ongoing double-blind study. Efficacy and side effects were assessed by the Brief Psychiatric Rating Scale, Clinical Global Impressions, Treatment Emergent Symptom Scale, and Target Symptom Ratings. Analyses based on the first 35 patients who entered the study indicate that both drugs were effective and well tolerated. There were slight advantages for molindone early during the injectable phase of treatment and for haloperidol late during the oral portion of the study, but these differences were not clinically significant. No significant differences in side effects were found between the two drugs.

  6. Effect of prenatal diazepam, phenobarbital, haloperidol and fluoxetine exposure on foot shock induced aggression in rats.

    PubMed

    Singh, Y; Jaiswal, A K; Singh, M; Bhattacharya, S K

    1998-10-01

    Different groups of pregnant rats were treated with diazepam (10 mg/kg), phenobarbital (10 mg/kg), haloperidol (0.1 mg/kg), fluoxetine (10 mg/kg) and vehicle (normal saline) intraperitoneally once a day during gestation days 13 to 21. After birth these pups were culled to 8 pups/dam and foster-nursed by lactating mothers for 3 weeks and were reared in colony cages thereafter. Sex and weight matched pairs of rat offsprings were subjected to foot shock induced aggression test at 8 weeks of age. Two parameters of aggressive behaviour were recorded namely, the latency to fight and total number of fighting bouts. The results indicate that prenatal exposure to diazepam, phenobarbital, haloperidol and fluoxetine caused significantly enhanced aggression in terms of number of fighting bouts.

  7. Chronic atypical antipsychotics, but not haloperidol, increase neurogenesis in the hippocampus of adult mouse.

    PubMed

    Chikama, Koji; Yamada, Hidetaka; Tsukamoto, Tatsuo; Kajitani, Kosuke; Nakabeppu, Yusaku; Uchimura, Naohisa

    2017-09-09

    It is suggested that altered neuroplasticity contributes to the pathophysiology of schizophrenia and antipsychotics may exhibit some of their therapeutic efficacies by improving neurogenesis and/or proliferation of neural progenitors. The aim of this study is to investigate whether chronic antipsychotics treatment affect neurogenesis in adult mouse hippocampus. Animals were administered olanzapine, quetiapine, clozapine, risperidone, aripiprazole, or haloperidol via the osmotic minipump for 21 days and then injected with 5-bromo-2'-deoxyuridine (BrdU) to label mitotic cells. BrdU-positive cells in the hippocampus were quantified by stereology. Aripiprazole, quetiapine, clozapine, and olanzapine significantly increased density of BrdU-positive cells in the hippocampus. Interestingly, other antipsychotic drugs had tendency to increasing BrdU-positive cells, whereas haloperidol had propensity to decrease with a marginal significance. These results suggest that differences of neurogenesis among these drugs may, at least in part, account for their pharmacological profiles. Copyright © 2017. Published by Elsevier B.V.

  8. Ramipril and haloperidol as promising approaches in managing rheumatoid arthritis in rats.

    PubMed

    Fahmy Wahba, Mariam Gamal; Shehata Messiha, Basim Anwar; Abo-Saif, Ali Ahmed

    2015-10-15

    Rheumatoid arthritis (RA) is a challenging autoimmune disorder, whose treatments usually cause severe gastrointestinal, renal and other complications. We aimed to evaluate the beneficial anti-arthritic effects of an angiotensin converting enzyme (ACE) inhibitor, ramipril and a dopamine receptor blocker, haloperidol, on Complete Freund's Adjuvant-induced RA in adult female albino rats. Rats were allocated into a normal control group, an arthritis control group, two reference treatment groups receiving dexamethasone (1.5 mg/kg/day) and methotrexate (1 mg/kg/day), and two treatment groups receiving ramipril (0.9 mg/kg/day) and haloperidol (1 mg/kg/day). Serum rheumatoid factor, matrix metalloprotinease-3 (MMP-3) and cartilage oligomeric matrix protein as specific rheumatoid biomarkers, serum immunoglobulin G and antinuclear antibody as immunological biomarkers, serum tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) as immunomodulatory cytokines, serum myeloperoxidase and C-reactive protein as inflammatory biomarkers, as well as malondialdehyde and glutathione reduced (GSH) as oxidative stress biomarkers were assessed. A histopathological study on joints and spleens was performed to support the results of biochemical estimations. Ramipril administration significantly corrected all the measured biomarkers, being restored back to normal levels except for MMP-3, TNF-α and IL-10. Haloperidol administration restored all the measured biomarkers back to normal levels except for TNF-α, IL-10 and GSH. In conclusion, ACE inhibitors represented by ramipril and dopamine receptor blockers represented by haloperidol may represent new promising protective strategies against RA, at least owing to their immunomodulatory, anti-inflammatory and antioxidant potentials.

  9. Contextual and behavioral control of antipsychotic sensitization induced by haloperidol and olanzapine

    PubMed Central

    Zhang, Chen; Li, Ming

    2011-01-01

    Repeated administration of haloperidol and olanzapine causes a progressively enhanced disruption of conditioned avoidance response (CAR) and a progressively enhanced inhibition of phencyclidine (PCP)-induced hyperlocomotion in rats (termed antipsychotic sensitization). Both actions are thought to reflect intrinsic antipsychotic activity. The present study examined to the extent to which antipsychotic-induced sensitization in one model (e.g. CAR) can be transferred or maintained in another (e.g. PCP hyperlocomotion) as a means of investigating the contextual and behavioral controls of antipsychotic sensitization. Well-trained male Sprague-Dawley rats were first repeatedly tested in the CAR or PCP (3.2 mg/kg, sc) hyperlocomotion model under haloperidol or olanzapine for five consecutive days. Then they were switched to the other model and tested for the expression of sensitization. Finally, all rats were switched back to the original model and retested for the expression of sensitization. Repeated haloperidol or olanzapine treatment progressively disrupted avoidance responding and decreased PCP-induced hyperlocomotion, indicating a robust sensitization. When tested in a different model, rats previously treated with haloperidol or olanzapine did not show a stronger inhibition of CAR or PCP-induced hyperlocomotion than those treated with these drugs for the first time; however, they did show such an effect when tested in the original model in which they received repeated antipsychotic treatment. These findings suggest that the expression of antipsychotic sensitization is strongly influenced by the testing environment and/or selected behavioral response under certain experimental conditions. Distinct contextual cues and behavioral responses may enter an association with unconditional drug effects via a Pavlovian conditioning process. They may also serve as occasion-setters to modulate the expression of sensitized responses. Because antipsychotic sensitization mimics

  10. Neurochemical Metabolomics Reveals Disruption to Sphingolipid Metabolism Following Chronic Haloperidol Administration.

    PubMed

    McClay, Joseph L; Vunck, Sarah A; Batman, Angela M; Crowley, James J; Vann, Robert E; Beardsley, Patrick M; van den Oord, Edwin J

    2015-09-01

    Haloperidol is an effective antipsychotic drug for treatment of schizophrenia, but prolonged use can lead to debilitating side effects. To better understand the effects of long-term administration, we measured global metabolic changes in mouse brain following 3 mg/kg/day haloperidol for 28 days. These conditions lead to movement-related side effects in mice akin to those observed in patients after prolonged use. Brain tissue was collected following microwave tissue fixation to arrest metabolism and extracted metabolites were assessed using both liquid and gas chromatography mass spectrometry (MS). Over 300 unique compounds were identified across MS platforms. Haloperidol was found to be present in all test samples and not in controls, indicating experimental validity. Twenty-one compounds differed significantly between test and control groups at the p < 0.05 level. Top compounds were robust to analytical method, also being identified via partial least squares discriminant analysis. Four compounds (sphinganine, N-acetylornithine, leucine and adenosine diphosphate) survived correction for multiple testing in a non-parametric analysis using false discovery rate threshold < 0.1. Pathway analysis of nominally significant compounds (p < 0.05) revealed significant findings for sphingolipid metabolism (p = 0.015) and protein biosynthesis (p = 0.024). Altered sphingolipid metabolism is suggestive of disruptions to myelin. This interpretation is supported by our observation of elevated N-acetyl-aspartyl-glutamate in the haloperidol-treated mice (p = 0.004), a marker previously associated with demyelination. This study further demonstrates the utility of murine neurochemical metabolomics as a method to advance understanding of CNS drug effects.

  11. Neurochemical metabolomics reveals disruption to sphingolipid metabolism following chronic haloperidol administration

    PubMed Central

    McClay, Joseph L.; Vunck, Sarah A.; Batman, Angela M.; Crowley, James J.; Vann, Robert E.; Beardsley, Patrick M.; van den Oord, Edwin J.

    2015-01-01

    Haloperidol is an effective antipsychotic drug for treatment of schizophrenia, but prolonged use can lead to debilitating side effects. To better understand the effects of long-term administration, we measured global metabolic changes in mouse brain following 3 mg/kg/day haloperidol for 28 days. These conditions lead to movement-related side effects in mice akin to those observed in patients after prolonged use. Brain tissue was collected following microwave tissue fixation to arrest metabolism and extracted metabolites were assessed using both liquid and gas chromatography mass spectrometry (MS). Over 300 unique compounds were identified across MS platforms. Haloperidol was found to be present in all test samples and not in controls, indicating experimental validity. Twenty-one compounds differed significantly between test and control groups at the p < 0.05 level. Top compounds were robust to analytical method, also being identified via partial least squares discriminant analysis. Four compounds (sphinganine, N-acetylornithine, leucine and adenosine diphosphate) survived correction for multiple testing in a non-parametric analysis using false discovery rate threshold < 0.1. Pathway analysis of nominally significant compounds (p < 0.05) revealed significant findings for sphingolipid metabolism (p = 0.02) and protein biosynthesis (p = 0.03). Altered sphingolipid metabolism is suggestive of disruptions to myelin. This interpretation is supported by our observation of elevated N-acetylaspartylglutamate in the haloperidol-treated mice (p = 0.004), a marker previously associated with demyelination. This study further demonstrates the utility of murine neurochemical metabolomics as a method to advance understanding of CNS drug effects. PMID:25850894

  12. Methamphetamine-Associated Psychosis and Treatment With Haloperidol and Risperidone: A Pilot Study

    PubMed Central

    Samiei, Mercede; Vahidi, Mohammad; Rezaee, Omid; Yaraghchi, Azadeh; Daneshmand, Reza

    2016-01-01

    Background Different studies have suggested that antipsychotic medications of the first generation have better effectiveness for the treatment of psychotic symptoms compared with antipsychotic medications of the second generation. Objectives The current study was the first pilot study in Iran that compared Haloperidol with Risperidone in the treatment of positive symptoms of psychosis among a group of methamphetamine-dependent patients. Materials and Methods This randomized clinical trial was designed and conducted in 2012. Overall, 44 patients who met the diagnostic and statistical manual of mental disorders, fourth edition-text revised (DSM.IV-TR) criteria for methamphetamine-associated psychosis (MAP) and were hospitalized at Razi psychiatric hospital in Tehran were selected. Patients (1: 1) were randomly divided to two groups. Overall, 22 subjects received Haloperidol (5 - 20 mg) and 22 subjects received Risperidone (2 - 8 mg). All subjects were assessed at baseline, during three consecutive weeks of treatment and one week after treatment (i.e., follow-up). Scale of assessment of positive symptoms (SAPS) was completed for each subject. Results The study findings indicated that both Haloperidol (< 0.05) and Risperidone (< 0.05) were similarly applicable in the treatment of MAP but no differential effectiveness was found between the two medications. The treatment effects of both medications increased in the first two weeks of treatment and remained stable in the second two weeks. Conclusions Risperidone and Haloperidol are two effective antipsychotic medications for the treatment of positive symptoms of MAP but other aspects of these two neuroleptic medications such as the long-term treatment effects should be studied. Further studies with more samples and longer follow-ups are suggested. PMID:27822286

  13. Effects of risperidone on phencyclidine-induced behaviors: comparison with haloperidol and ritanserin.

    PubMed

    Kitaichi, K; Yamada, K; Hasegawa, T; Furukawa, H; Nabeshima, T

    1994-10-01

    In this study, we investigated whether risperidone, a serotonin-S2A (5-HT2A)/dopamine-D2 (D2)-receptor antagonist, inhibits phencyclidine (PCP)-induced stereotyped behaviors in comparison with haloperidol and ritanserin. Moreover, we also attempted to investigate the effects of these antipsychotics on the contents of dopamine, serotonin (5-HT) and their metabolites in rat striatum and frontal cortex. In rats, PCP (5 mg/kg, i.p.) caused hyperlocomotion and stereotyped behaviors, including sniffing, head-weaving, backpedalling and turning. Both resperidone (0.8-2.4 mg/kg, p.o.) and haloperidol (0.3-1.0 mg/kg, p.o.) inhibited these behaviors, except for backpedalling, in a dose-dependent manner. PCP (10 mg/kg, i.p.) produced hyperlocomotion and stereotyped behaviors, including rearing, sniffing head-twitch, backpedalling and turning. Risperidone (0.8-2.4 mg/kg, p.o.) inhibited both hyperlocomotion and PCP-induced behaviors, except for backpedalling, while ritanserin (3-10 mg/kg, p.o.) inhibited only the head-twitch. These results suggest that risperidone may have an antipsychotic effect on schizophrenia as well as PCP psychosis in humans by exerting a mixed 5-HT2A/D2 antagonism. Neurochemically, the increasing effects of risperidone on the content of DOPAC and the ratio of DOPAC to dopamine in the striatum were lower than those of haloperidol. These findings may support the view that the extrapyramidal side effects of risperidone are lower than those of haloperidol in clinical situations.

  14. Dopamine dynamics during emotional cognitive processing: Implications of the specific actions of clozapine compared with haloperidol.

    PubMed

    Kawano, Masahiko; Oshibuchi, Hidehiro; Kawano, Takaaki; Muraoka, Hiroyuki; Tsutsumi, Takahiro; Yamada, Makiko; Inada, Ken; Ishigooka, Jun

    2016-06-15

    Clozapine has improved efficacy relative to typical antipsychotics in schizophrenia treatment, particularly regarding emotional symptoms. However, the mechanisms underlying its therapeutic benefits remain unclear. Using a methamphetamine-sensitised rat model, we measured changes in dopamine levels in the amygdalae in response to a fear-conditioned cue, serving as a biochemical marker of emotional cognitive processing disruption in psychosis, for analysing the biochemical mechanisms associated with the clinical benefits of clozapine. We also compared how clozapine and haloperidol affected basal dopamine levels and phasic dopamine release in response to the fear-conditioned cue. Extracellular dopamine was collected from the amygdalae of freely moving rats via microdialysis and was analysed by high-performance liquid chromatography. Clozapine or haloperidol was injected during microdialysis, followed by exposure to the fear-conditioned cue. We analysed the ratio of change in dopamine levels from baseline. Haloperidol treatment increased the baseline dopamine levels in both non-sensitised and sensitised rats. Conversely, clozapine only increased the basal dopamine levels in the non-sensitised rats, but not in the sensitised rats. Although both antipsychotics attenuated phasic dopamine release in both the non-sensitised and sensitised rats, the attenuation extent was greater for clozapine than for haloperidol under both dopaminergic conditions. Our findings indicate that stabilized dopamine release in the amygdalae is a common therapeutic mechanism of antipsychotic action during emotional processing. However, the specific dopaminergic state-dependent action of clozapine on both basal dopamine levels and stress-induced dopamine release may be the underlying mechanism for its superior clinical effect on emotional cognitive processing in patients with schizophrenia.

  15. Pavlovian conditional tolerance to haloperidol catalepsy: evidence of dynamic adaptation in the dopaminergic system.

    PubMed

    Poulos, C X; Hinson, R

    1982-10-29

    An experiment with rats has demonstrated that Pavlovian conditioning factors determine the occurrence of tolerance to haloperidol catalepsy. Rats exhibited tolerance only in the environment previously associated with the drug. Previous research involving receptor binding techniques implicated an increase in the number of brain dopamine receptors as the mediator of neuroleptic tolerance. The present findings demonstrate that this change, by itself, cannot account for the conditional occurrence of such tolerance.

  16. Neuropeptide Y mRNA expression levels following chronic olanzapine, clozapine and haloperidol administration in rats.

    PubMed

    Huang, X-F; Deng, Chao; Zavitsanou, Katerina

    2006-06-01

    Using quantitative in situ hybridization, this study examined regional changes in rat brain mRNA levels encoding neuropeptide Y (NPY) following olanzapine, clozapine and haloperidol administration (1.2, 1.5 and 2.0 mg/kg, oral) for 36 days. The NPY mRNA expression levels and patterns were examined after the last drug administration at both time points enabling the measurement of immediate effect at 2h and the effects after 48 h of drug administration. It was found that all these drugs had an immediate effect on NPY mRNA expression, while virtually all these changes normalized 48 h after the drug treatments. A similarity in altered NPY mRNA expression patterns was seen between the olanzapine and clozapine groups; however, haloperidol was very different. Olanzapine and clozapine administration decreased NPY mRNA levels in the nucleus accumbens, striatum and anterior cingulate cortex (from -60% to -77%, p<0.05). Haloperidol decreased NPY mRNA expression in the amygdala and hippocampus (-69%, -64%, p<0.05). In the lateral septal nucleus, NPY mRNA levels significantly decreased in the olanzapine group (-66%, p<0.05), a trend toward a decrease was observed in the clozapine group, and no change was found in the haloperidol treated group. These results suggest that the different effects of atypical and typical antipsychotics on NPY systems may reflect the neural chemical mechanisms responsible for the differences between these drugs in their effects in treating positive and negative symptoms of schizophrenia. The immediate decrease of NPY mRNA levels suggests an immediate reduction of NPY biosynthesis in response to these drugs.

  17. Haloperidol versus first-generation antipsychotics for the treatment of schizophrenia and other psychotic disorders.

    PubMed

    Dold, Markus; Samara, Myrto T; Li, Chunbo; Tardy, Magdolna; Leucht, Stefan

    2015-01-16

    Haloperidol is worldwide one of the most frequently used antipsychotic drugs with a very high market share. Previous narrative, unsystematic reviews found no differences in terms of efficacy between the various first-generation ("conventional", "typical") antipsychotic agents. This established the unproven psychopharmacological assumption of a comparable efficacy between the first-generation antipsychotic compounds codified in textbooks and treatment guidelines. Because this assumption contrasts with the clinical impression, a high-quality systematic review appeared highly necessary. To compare the efficacy, acceptability, and tolerability of haloperidol with other first-generation antipsychotics in schizophrenia and schizophrenia-like psychosis. In October 2011 and July 2012, we searched the Cochrane Schizophrenia Group's Trials Register, which is based on regular searches of CINAHL, BIOSIS, AMED, EMBASE, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. To identify further relevant publications, we screened the references of all included studies and contacted the manufacturers of haloperidol for further relevant trials and missing information on identified studies. Furthermore, we contacted the corresponding authors of all included trials for missing data. We included all randomised controlled trials (RCTs) that compared oral haloperidol with another oral first-generation antipsychotic drug (with the exception of the low-potency antipsychotics chlorpromazine, chlorprothixene, levopromazine, mesoridazine, perazine, prochlorpromazine, and thioridazine) in schizophrenia and schizophrenia-like psychosis. Clinically important response to treatment was defined as the primary outcome. Secondary outcomes were global state, mental state, behaviour, overall acceptability (measured by the number of participants leaving the study early due to any reason), overall efficacy (attrition due to inefficacy of treatment), overall tolerability (attrition due to adverse

  18. Interaction of morphine and haloperidol on agonistic and motor behaviors of male mice.

    PubMed

    Rodríguez-Arias, M; Miñarro, J; Simón, V M

    1997-09-01

    To further clarify the interaction between opioid and dopaminergic systems, the effects of simultaneous administration of morphine hydrochloride (1.25 or 2.5 mg/kg) and haloperidol (0.1 mg/kg) on aggressive behavior of male mice were explored. Isolated male mice (experimental animals) were confronted in a neutral area with anosmic, group-housed consepecifics (standard opponents) 30 min after injection of both compounds, and aggression was evaluated by estimation of times allocated to 11 different behavioral categories. In the first experiment (which functioned as a pilot study), the two doses of morphine were explored. In the second one, incorporating a more complete experimental design, only the lowest morphine dose was used and the animals were preselected by a previous aggression test. In attack behavior, morphine added to haloperidol counteracted, at least partially, the antiaggressive effect of the neuroleptic. In contrast, the impairing effects of haloperidol on motor activity were increased by the addition of morphine. These results show that the behavioral effects of dopaminergic antagonists are modulated by opioid influences and that opiates and dopaminergic agents interact in a different manner on motor and on aggressive behaviors.

  19. Differences in the time course of dopaminergic supersensitivity following chronic administration of haloperidol, molindone, or sulpiride.

    PubMed

    Prosser, E S; Pruthi, R; Csernansky, J G

    1989-01-01

    The onset and persistence of changes in 3H-spiroperidol binding to dopamine (DA) D2 receptors were examined in rat mesolimbic and striatal brain regions following daily administration of haloperidol, molindone, or sulpiride for 3, 7, 14, or 28 days. Neuroleptic dose equivalencies were determined by inhibition of 3H-spiroperidol in vivo binding in several rat brain regions. Changes in locomotor and stereotyped responses to the specific DA D2 agonist quinpirole were examined 3 days after the last treatment dose. Haloperidol or molindone administration increased mean stereotypy scores and striatal DA D2 receptor densities throughout the 28-day treatment period. In contrast, mesolimbic DA D2 receptor densities were transiently increased and returned to control values, after 28 days of haloperidol or molindone treatment. Sulpiride treatment increased mean stereotypy scores and striatal Bmax values, but had no effect on locomotion or mesolimbic dopamine receptor density. Additionally, the magnitude of change in the various measures of brain DA function varied among the three neuroleptic treatment groups. Results from this study suggest that mesolimbic and striatal brain regions differ in their response to long-term neuroleptic administration and that drug choice may influence the magnitude of neuroleptic-induced dopaminergic supersensitivity.

  20. Risperidone versus haloperidol for perception of emotion in treatment-resistant schizophrenia: preliminary findings.

    PubMed

    Kee, K S; Kern, R S; Marshall, B D; Green, M F

    1998-05-25

    Currently, little is known about the pharmacological effects of the new generation of antipsychotic medications on perception of emotion in schizophrenia. The present study was designed to compare the effects of risperidone versus haloperidol on the ability to perceive emotion in 20 treatment-resistant schizophrenia patients, using a double-blind design. Measures of emotion perception included a facial emotion identification test (still photographs presented on videotape), a voice emotion identification test (audiotape), and an affect perception test (brief interpersonal vignettes presented on videotape). These measures were administered during the final week of baseline and after 8 weeks of double-blind medication. Risperidone treatment produced a greater effect on patients' ability to perceive emotion compared with haloperidol treatment. Additionally, all patients who received risperidone demonstrated improvement in performance between baseline and retest, compared with four of the nine patients who received haloperidol. When changes in positive symptoms were statistically controlled, the results remained significant. These findings suggest that resperidone may facilitate patients' ability to accurately perceive emotion, an effect which may be mediated either directly by risperidone's pharmacological action or perhaps indirectly by its influence on basic neurocognition.

  1. A prospective naturalistic multicentre study of intravenous medications in behavioural emergencies: haloperidol versus flunitrazepam.

    PubMed

    Hatta, Kotaro; Nakamura, Mitsuru; Yoshida, Kenichi; Hamakawa, Hiroshi; Wakejima, Toru; Nishimura, Takao; Furuta, Ko; Kawabata, Toshitaka; Hirata, Toyoaki; Usui, Chie; Nakamura, Hiroyuki; Sawa, Yutaka

    2010-06-30

    A prospective naturalistic multicentre study for deep sedation was conducted in intensive care with continuous electrocardiogram (ECG) monitoring. Clinical purpose was enough sedation, which made uncooperative and disrupted patients receive brain computed tomography (CT), magnetic resonance imaging (MRI), or fluid therapy, with minimum drug doses. A first infusion was either haloperidol (HAL group) or flunitrazepam (FNP group). If enough sedation was not achieved, a second infusion, which was the opposite drug to the first infusion, was given. The proportion requiring a second infusion was higher in the HAL group than in the FNP group (82% vs. 36%, P<0.0001). The mean reduction of the Excited Component for Positive and Negative syndrome scale at 15 min was greater for the FNP first group (FNP+HAL group) than the HAL first group (HAL+FNP group) (68% [S.D. 17] vs. 54% [S.D. 31], P=0.02). The mean dose of flunitrazepam in the HAL+FNP group was significantly lower than that in the FNP+HAL-group (1.3 mg vs. 3.5 mg, P=0.0003). Thus, in terms of monotherapy and speed of action, flunitrazepam has advantages over haloperidol as a first infusion for deep sedation. Regarding drug dosages, haloperidol has an advantage over flunitrazepam as a first infusion in safety.

  2. Reversal of haloperidol induced motor deficits in rats exposed to repeated immobilization stress.

    PubMed

    Shireen, Erum; Pervez, Sidra; Masroor, Maria; Ali, Wafa Binte; Rais, Qudsia; Khalil, Samira; Tariq, Anum; Haleem, Darakshan Jabeen

    2014-09-01

    Stress is defined as a non specific response of body to any physiological and psychological demand. Preclinical studies have shown that an uncontrollable stress condition produces neurochemical and behavioral deficits. The present study was conducted to test the hypothesis that a decrease in the responsiveness of somatodendritic 5-hydroxytryptamine (5-HT)-1A receptors following adaptation to stress could attenuate haloperidol induced acute parkinsonian like effect. Results showed that single exposure (2h) to immobilization stress markedly decreased food intake, growth rate and locomotor activity but these stress-induced behavioral deficits were not observed following repeated (2h/day for 5 days) exposure of immobilization stress suggesting behavioral tolerance occurs to similar stress. An important finding of present study is a reversal of haloperidol-induced motor deficits in animals exposed to repeated immobilization stress than respective control animals. It is suggested that stress induced possible desensitization of somatodendritic 5-HT-1A as well as 5-HT-2C receptors could release dopamine system from the inhibitory influence of serotonin. On the other hand, an increase in the effectiveness of postsynaptic 5-HT-1A receptors elicits a direct stimulatory influence on the activity of dopaminergic neuron and is possibly involved in the reversal of haloperidol-induced parkinsonian like symptoms in repeatedly immobilized rats.

  3. Haloperidol, risperidone, olanzapine and aripiprazole in the management of delirium: A comparison of efficacy, safety, and side effects.

    PubMed

    Boettger, Soenke; Jenewein, Josef; Breitbart, William

    2015-08-01

    The aim of this study was to compare the efficacy and side-effect profile of the typical antipsychotic haloperidol with that of the atypical antipsychotics risperidone, olanzapine, and aripiprazole in the management of delirium. The Memorial Delirium Assessment Scale (MDAS), the Karnofsky Performance Status (KPS) scale, and a side-effect rating were recorded at baseline (T1), after 2-3 days (T2), and after 4-7 days (T3). Some 21 cases were case-matched by age, preexisting dementia, and baseline MDAS scores, and subsequently analyzed. The baseline characteristics of the medication groups were not different: The mean age of the patients ranged from 64.0 to 69.6 years, dementia was present in between 23.8 and 28.6%, and baseline MDAS scores were 19.9 (haloperidol), 18.6 (risperidone), 19.4 (olanzapine), and 18.0 (aripiprazole). The doses of medication at T3 were 5.5 mg haloperidol, 1.3 mg risperidone, 7.1 mg olanzapine, and 18.3 mg aripiprazole. Over one week, the decline in MDAS scores between medications was equal, and no differences between individual MDAS scores existed at T2 or T3. After one week, the MDAS scores were 6.8 (haloperidol), 7.1 (risperidone), 11.7 (olanzapine), and 8.3 (aripiprazole). At T2, delirium resolution occurred in 42.9-52.4% of cases and at T3 in 61.9-85.7%; no differences in assessments between medications existed. Recorded side effects were extrapyramidal symptoms (EPSs) in haloperidol- and risperidone-managed patients (19 and 4.8%, respectively) and sedation with olanzapine (28.6%). Haloperidol, risperidone, aripiprazole, and olanzapine were equally effective in the management of delirium; however, they differed in terms of their side-effect profile. Extrapyramidal symptoms were most frequently recorded with haloperidol, and sedation occurred most frequently with olanzapine.

  4. Efficacy and safety of haloperidol for in-hospital delirium prevention and treatment: A systematic review of current evidence.

    PubMed

    Schrijver, E J M; de Graaf, K; de Vries, O J; Maier, A B; Nanayakkara, P W B

    2016-01-01

    Haloperidol is generally considered the drug of choice for in-hospital delirium management. We conducted a systematic review to evaluate the evidence for the efficacy and safety of haloperidol for the prevention and treatment of delirium in hospitalized patients. PubMed, Embase, Cumulative Index to Nursing and Allied Health (CINAHL), PsycINFO, and the Cochrane Library were systematically searched up to April 21, 2015. We included English full-text randomized controlled trials using haloperidol for the prevention or treatment of delirium in adult hospitalized patients reporting on delirium incidence, duration, or severity as primary outcome. Quality of evidence was graded. Meta-analysis was not conducted because of between-study heterogeneity. Twelve studies met our inclusion criteria, four prevention and eight treatment trials. Methodological limitations decreased the graded quality of included studies. Results from placebo-controlled prevention studies suggest a haloperidol-induced protective effect for delirium in older patients scheduled for surgery: two studies reported a significant reduction in ICU delirium incidence and one study found a significant reduction in delirium severity and duration. Although placebo-controlled trials are missing, pharmacological treatment of established delirium reduced symptom severity. Haloperidol administration was not associated with treatment-limiting side-effects, but few studies used a systematic approach to identify adverse events. Although results on haloperidol for delirium management seem promising, current prevention trials lack external validity and treatment trials did not include a placebo arm on top of standard nonpharmacological care. We therefore conclude that the current use of haloperidol for in-hospital delirium is not based on robust and generalizable evidence. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  5. A Randomized Controlled Trial of Intravenous Haloperidol vs. Intravenous Metoclopramide for Acute Migraine Therapy in the Emergency Department.

    PubMed

    Gaffigan, Matthew E; Bruner, David I; Wason, Courtney; Pritchard, Amy; Frumkin, Kenneth

    2015-09-01

    Emergency Department (ED) headache patients are commonly treated with neuroleptic antiemetics like metoclopramide. Haloperidol has been shown to be effective for migraine treatment. Our study compared the use of metoclopramide vs. haloperidol to treat ED migraine patients. A prospective, double-blinded, randomized control trial of 64 adults aged 18-50 years with migraine headache and no recognized risks for QT-prolongation. Haloperidol 5 mg or metoclopramide 10 mg was given intravenously after 25 mg diphenhydramine. Pain, nausea, restlessness (akathisia), and sedation were assessed with 100-mm visual analog scales (VAS) at baseline and every 20 min, to a maximum of 80 min. The need for rescue medications, side effects, and subject satisfaction were recorded. QTc intervals were measured prior to and after treatment. Follow-up calls after 48 h assessed satisfaction and recurrent or persistent symptoms. Thirty-one subjects received haloperidol, 33 metoclopramide. The groups were similar on all VAS measurements, side effects, and in their satisfaction with therapy. Pain relief averaged 53 mm VAS over both groups, with equal times to maximum improvement. Subjects receiving haloperidol required rescue medication significantly less often (3% vs. 24%, p < 0.02). Mean QTcs were equal and normal in the two groups and did not change after treatment. In telephone follow-up, 90% of subjects contacted were "happy with the medication" they had received, with haloperidol-treated subjects experiencing more restlessness (43% vs. 10%). Intravenous haloperidol is as safe and effective as metoclopramide for the ED treatment of migraine headaches, with less frequent need for rescue medications. Published by Elsevier Inc.

  6. Efecto del Programa de Entrenamiento “Manejo del Dolor” en la Documentación de Enfermería en el Expediente Electrónico

    PubMed Central

    Monsiváis, María Guadalupe Moreno; Guzmán, Ma. Guadalupe Interial; Flores, Paz Francisco Sauceda; Arreola, Leticia Vázquez

    2012-01-01

    Resumen En el presente trabajo se muestra la importancia de entrenar al personal de enfermería para mejorar la documentación en el expediente electrónico. Se eligió el manejo del dolor por ser un área prioritaria; una alta proporción de pacientes en período post operatorio cursa con dolor, por lo tanto, la documentación debe ser útil para la toma de decisiones clínicas. Se implementó un programa de entrenamiento denominado “Manejo del Dolor” dirigido al personal de enfermería. Se utilizó la tecnología de la información como herramienta para fortalecer el conocimiento con base en la revisión sistemática de la literatura; el personal de enfermería participante seleccionó la mejor evidencia; posteriormente se trabajó en la transferencia de este conocimiento a la práctica a través del diseño de un protocolo para el manejo del dolor. Se concluye que el conocimiento del manejo del dolor es fundamental para que enfermería documente con mayor precisión sus intervenciones. PMID:24199106

  7. Inhibition by memantine of the development of persistent oral dyskinesias induced by long-term haloperidol treatment of rats.

    PubMed Central

    Andreassen, O. A.; Aamo, T. O.; Jøorgensen, H. A.

    1996-01-01

    1. Tardive dyskinesia (TD) is a serious side-effect of long-term treatment with neuroleptics. To investigate if neuroleptic-induced excessive stimulation of striatal glutamate receptors may underlie TD development, the effect of the NMDA antagonist, memantine (1-amino-3,5-dimethyladamantane), was studied in a rat model of TD. 2. In an acute experiment, six groups of rats were treated daily for 1 week with either vehicle or memantine 20 or 40 mg kg-1 day-1, and on the seventh day they received one injection of either haloperidol 1.0 mg kg-1 i.p. or saline i.p. In a subsequent long-term experiment lasting 20 weeks, the same treatment was continued, except that haloperidol was injected i.m. as decanoate (38 mg kg-1 every 4 weeks) and control rats received sesame oil. The behaviour was videotaped and scored at intervals during both experiments, and for 16 weeks after cessation of the long-term treatment. 3. In the acute experiment, haloperidol decreased motor activity and memantine increased moving and tended to attenuate the immobility induced by haloperidol. Memantine also enhanced the haloperidol-induced increase in the putative TD-analogue vacuous chewing movements (VCM). 4. In the long-term experiment, the most marked effect of haloperidol was a gradual increase in VCM and the increase persisted significantly for 12 weeks after cessation of treatment. Memantine dose-dependently increased VCM and moving during long-term treatment. However, only one week after stopping treatment, both these effects of memantine disappeared. In contrast to rats previously treated with haloperidol alone, rats co-treated with memantine (both doses) and haloperidol had VCM at the level of controls two weeks after stopping treatment. The blood levels of drugs were within the therapeutic range achieved in human subjects. 5. These results suggest that long-lasting changes induced by haloperidol are prevented by memantine, which supports the theory that excessive NMDA receptor stimulation

  8. First-Generation Antipsychotic Haloperidol Alters the Functionality of the Late Endosomal/Lysosomal Compartment in Vitro.

    PubMed

    Canfrán-Duque, Alberto; Barrio, Luis C; Lerma, Milagros; de la Peña, Gema; Serna, Jorge; Pastor, Oscar; Lasunción, Miguel A; Busto, Rebeca

    2016-03-18

    First- and second-generation antipsychotics (FGAs and SGAs, respectively), have the ability to inhibit cholesterol biosynthesis and also to interrupt the intracellular cholesterol trafficking, interfering with low-density lipoprotein (LDL)-derived cholesterol egress from late endosomes/lysosomes. In the present work, we examined the effects of FGA haloperidol on the functionality of late endosomes/lysosomes in vitro. In HepG2 hepatocarcinoma cells incubated in the presence of 1,1'-dioctadecyl-3,3,3,3'-tetramethylindocarbocyanineperchlorate (DiI)-LDL, treatment with haloperidol caused the enlargement of organelles positive for late endosome markers lysosome-associated membrane protein 2 (LAMP-2) and LBPA (lysobisphosphatidic acid), which also showed increased content of both free-cholesterol and DiI derived from LDL. This indicates the accumulation of LDL-lipids in the late endosomal/lysosomal compartment caused by haloperidol. In contrast, LDL traffic through early endosomes and the Golgi apparatus appeared to be unaffected by the antipsychotic as the distribution of both early endosome antigen 1 (EEA1) and coatomer subunit β (β-COP) were not perturbed. Notably, treatment with haloperidol significantly increased the lysosomal pH and decreased the activities of lysosomal protease and β-d-galactosidase in a dose-dependent manner. We conclude that the alkalinization of the lysosomes' internal milieu induced by haloperidol affects lysosomal functionality.

  9. Subjective response to antipsychotic treatment and compliance in schizophrenia. A naturalistic study comparing olanzapine, risperidone and haloperidol (EFESO Study)

    PubMed Central

    García-Cabeza, Ignacio; Gómez, Juan-Carlos; Sacristán, Jose A; Edgell, Eric; González de Chavez, Manuel

    2001-01-01

    Background In order to compare the effectiveness of different antipsychotic drugs in the treatment of schizophrenia it is very important to evaluate subjective response and compliance in patient cohorts treated according to routine clinical practice. Method Outpatients with schizophrenia entered this prospective, naturalistic study when they received a new prescription for an antipsychotic drug. Treatment assignment was based on purely clinical criteria, as the study did not include any experimental intervention. Patients treated with olanzapine, risperidone or haloperidol were included in the analysis. Subjective response was measured using the 10-item version of the Drug Attitude Inventory (DAI-10), and treatment compliance was measured using a physician-rated 4 point categorical scale. Results A total of 2128 patients initiated treatment (as monotherapy) with olanzapine, 417 with risperidone, and 112 with haloperidol. Olanzapine-treated patients had significantly higher DAI-10 scores and significantly better treatment compliance compared to both risperidone- and haloperidol-treated patients. Risperidone-treated patients had a significantly higher DAI-10 score compared to haloperidol-treated patients. Conclusion Subjective response and compliance were superior in olanzapine-treated patients, compared to patients treated with risperidone and haloperidol, in routine clinical practice. Differences in subjective response were explained largely, but not completely, by differences in incidence of EPS. PMID:11835695

  10. Haloperidol prophylaxis for preventing aggravation of postoperative delirium in elderly patients: a randomized, open-label prospective trial.

    PubMed

    Fukata, Shinji; Kawabata, Yasuji; Fujishiro, Ken; Kitagawa, Yuichi; Kuroiwa, Kojiro; Akiyama, Hirotoshi; Takemura, Marie; Ando, Masahiko; Hattori, Hideyuki

    2017-07-01

    The aim of this study was to evaluate the safety and efficacy of the early administration haloperidol in preventing the aggravation of postoperative delirium in elderly patients. A total of 201 patients (age ≥75 years) who underwent elective surgery were enrolled. The patients were divided into two groups: the intervention group (n = 101) received prophylactic haloperidol (5 mg); the control group (n = 100) did not. Haloperidol was administered daily during postoperative days 0-5 to the patients who presented with NEECHAM scores of 20-24 when measured at 18:00. The primary endpoint was the incidence of severe postoperative delirium. The incidence of severe postoperative delirium in all patients was 25.1%. The incidence of severe postoperative delirium in the intervention group (18.2%) was significantly lower than that in the control group (32.0%) (p = 0.02). The difference between the two groups was larger when the analysis was limited to the 70 patients who had NEECHAM scores of 20-24 for at least one day during postoperative days 0-5. No adverse effects of the haloperidol were observed. The prophylactic administration of haloperidol at the early stage of delirium significantly reduced the incidence of severe postoperative delirium in elderly patients. Clinical Trial Registration UMIN000007204.

  11. First-Generation Antipsychotic Haloperidol Alters the Functionality of the Late Endosomal/Lysosomal Compartment in Vitro

    PubMed Central

    Canfrán-Duque, Alberto; Barrio, Luis C.; Lerma, Milagros; de la Peña, Gema; Serna, Jorge; Pastor, Oscar; Lasunción, Miguel A.; Busto, Rebeca

    2016-01-01

    First- and second-generation antipsychotics (FGAs and SGAs, respectively), have the ability to inhibit cholesterol biosynthesis and also to interrupt the intracellular cholesterol trafficking, interfering with low-density lipoprotein (LDL)-derived cholesterol egress from late endosomes/lysosomes. In the present work, we examined the effects of FGA haloperidol on the functionality of late endosomes/lysosomes in vitro. In HepG2 hepatocarcinoma cells incubated in the presence of 1,1′-dioctadecyl-3,3,3,3′-tetramethylindocarbocyanineperchlorate (DiI)-LDL, treatment with haloperidol caused the enlargement of organelles positive for late endosome markers lysosome-associated membrane protein 2 (LAMP-2) and LBPA (lysobisphosphatidic acid), which also showed increased content of both free-cholesterol and DiI derived from LDL. This indicates the accumulation of LDL-lipids in the late endosomal/lysosomal compartment caused by haloperidol. In contrast, LDL traffic through early endosomes and the Golgi apparatus appeared to be unaffected by the antipsychotic as the distribution of both early endosome antigen 1 (EEA1) and coatomer subunit β (β-COP) were not perturbed. Notably, treatment with haloperidol significantly increased the lysosomal pH and decreased the activities of lysosomal protease and β-d-galactosidase in a dose-dependent manner. We conclude that the alkalinization of the lysosomes’ internal milieu induced by haloperidol affects lysosomal functionality. PMID:26999125

  12. Carnitine congener mildronate protects against stress- and haloperidol-induced impairment in memory and brain protein expression in rats.

    PubMed

    Beitnere, Ulrika; Dzirkale, Zane; Isajevs, Sergejs; Rumaks, Juris; Svirskis, Simons; Klusa, Vija

    2014-12-15

    The present study investigates the efficacy of mildronate, a carnitine congener, to protect stress and haloperidol-induced impairment of memory in rats and the expression of brain protein biomarkers involved in synaptic plasticity, such as brain-derived neurotrophic factor (BDNF), acetylcholine esterase and glutamate decarboxylase 67 (GAD67). Two amnesia models were used: 2h immobilization stress and 3-week haloperidol treatment. Stress caused memory impairment in the passive avoidance test and induced a significant 2-fold BDNF elevation in hippocampal and striatal tissues that was completely inhibited by mildronate. Mildronate decreased the level of GAD67 (but not acetylcholine esterase) expression by stress. Haloperidol decrease by a third hippocampal BDNF and acetylcholine esterase (but not GAD67) expression, which was normalized by mildronate; it also reversed the haloperidol-induced memory impairment in Barnes test. The results suggest the usefulness of mildronate as protector against neuronal disturbances caused by stress or haloperidol. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Determination of haloperidol in biological samples using molecular imprinted polymer nanoparticles followed by HPLC-DAD detection.

    PubMed

    Ebrahimzadeh, Homeira; Dehghani, Zahra; Asgharinezhad, Ali Akbar; Shekari, Nafiseh; Molaei, Karam

    2013-09-10

    In this study an extraction procedure using molecular imprinted polymer nanoparticles for the determination of haloperidol in biological samples is proposed. The haloperidol imprinted polymer nanoparticles were synthesized successfully by precipitation polymerization in a flask containing haloperidol as a template, ethyleneglycoldimethacrylate as a crosslinking agent, methacrylic acid as a functional monomer, and 2,2'-azobisisobutyronitrile as an initiator. The leached and unleached polymer nanoparticles have been characterized by infrared spectroscopy and scanning electron microscopy. The effect of different variables such as the pH of solution, uptake and elution time, type, and the least amount of eluent for elution of haloperidol from polymer was evaluated. Extraction efficiencies more than 97% were obtained by elution of the polymer with 1.5 mL of methanol-acetic acid-trifluoroacetic acid 79.9:20:0.1. Under optimal conditions maximum adsorption capacity was obtained 153.84 mg g(-1). The detection limit of the proposed procedure was between 0.2 and 0.35 μg L(-1). Finally this method was applied to the determination of haloperidol in plasma and urine samples and satisfactory results were achieved (RSD<6.9%).

  14. Oral administration of haloperidol at clinically recommended doses elicits smaller parkinsonian effects but more tardive dyskinesia in rats.

    PubMed

    Shireen, Erum; Naeem, Sadaf; Inam, Qurrat-ul-Aen; Haleem, Darakhshan Jabeen

    2013-03-01

    The present study was designed to monitor extrapyramidal symptoms (EPS) elicited by the oral administration of haloperidol at clinically recommended doses and to compare it with EPS produced when the drug is injected intraperitoneally at doses used in animal research. Rats injected with haloperidol at a dose of 1 mg/kg daily for 5 weeks exhibited akinesia in an open field and impaired motor coordination. Effects of the drug on motor coordination but not on open field akinesia were attenuated gradually from 2-5 weeks of treatment. Oral administration of haloperidol in drinking water at clinically recommended dose exhibited decreased exploratory activity without producing akinesia. Motor coordination was impaired maximally after 3 weeks and tolerance was developed in the drug induced motor impairment after 5 weeks of treatment. Intensity of vacuous chewing movements (VCMs) and tardive VCMs was greater by oral administration than intraperitoneal injections of haloperidol. The present results showed that oral administration of haloperidol expected to produce sustained effect may result in tolerance in acute parkinsonian like effects but more intensity of tardive dyskinesia. We suggest that drugs which may helpful in alleviating tardive dyskinesia may be more useful if person is on oral drug therapy.

  15. Amisulpride the 'atypical' atypical antipsychotic--comparison to haloperidol, risperidone and clozapine.

    PubMed

    Natesan, Sridhar; Reckless, Greg E; Barlow, Karren B L; Nobrega, José N; Kapur, Shitij

    2008-10-01

    Amisulpride's high and selective affinity for dopamine D2/3 (Ki 1.3/2.4 nM) receptors, lack of affinity for serotonin receptors, and its unusually high therapeutic doses (400-800 mg/day) makes it unique among atypical antipsychotics and prompted us to compare its actions with other antipsychotics in animal models. Amisulpride's effects on amphetamine and phencyclidine induced locomotor activity (AIL/PIL), conditioned avoidance response, catalepsy (CAT), subcortical Fos expression, and plasma prolactin was correlated to its time-course striatal D2/3 and prefrontal 5-HT2 receptor occupancy (D(2/3)/5-HT2RO); in comparison to haloperidol, clozapine, and risperidone. Unlike the atypicals clozapine and risperidone, amisulpride lacked 5-HT2RO and showed a 'delayed' pattern of D2/3RO: 43, 60 and 88% after 1, 2 and 6 h (100 mg/kg), respectively, despite a quick onset (1 h) and decline (6 h) of prolactin elevation. While haloperidol and risperidone were effective at D2RO>60%, clozapine at D2/3RO<50%, amisulpride was effective only when its D2RO exceeded 60% with a delayed latency and lasted longer than other antipsychotics. CAT was observed for haloperidol and risperidone when D2RO exceeded 80%, while in the case of amisulpride, CAT was not observed even when doses exceeded 90% D2/3RO. Amisulpride also displayed functional limbic selectivity in Fos expression like the other atypicals. Amisulpride's "delayed" functional profile on acute administration and the need for high doses is most likely due to its poor blood-brain-barrier penetration; however, it is distinct from other atypicals in showing low motor side-effects, activity against phencyclidine, and a mesolimbic preference, despite no action on serotonin receptors.

  16. The effects of neuroleptics (haloperidol and chlorpromazine) on the pharmacokinetics of valproic acid in schizophrenic patients.

    PubMed

    Ishizaki, T; Chiba, K; Saito, M; Kobayashi, K; Iizuka, R

    1984-10-01

    The steady state trough concentrations (Cmin) and pharmacokinetics of valproic acid were investigated in schizophrenic patients during the treatment of valproic acid, 200 mg, twice daily and after the one dose of 400 mg, respectively, with and without haloperidol (6 to 10 mg/day, N = 6) or chlorpromazine (100 to 300 mg/day, N = 6). Four to 5 Cmin were monitored just before the morning valproic acid dose for 3 to 4 days preceding the kinetic study. The overall Cmin of valproic acid with chlorpromazine (33.2 +/- 1.7 micrograms/ml, N = 25) was significantly (p less than 0.01) greater than without (27.1 +/- 1.4 micrograms/ml, N = 25). The majority of the mean valproic acid concentrations observed after the 400-mg dose were significantly (p less than 0.05 to 0.01) greater during the chlorpromazine treatment as compared to those without the phenothiazine. The mean t1/2 was shortened from 15.4 +/- 1.4 to 13.5 +/- 1.2 hours (p less than 0.05) with a comparable increase in the clearance from 7.18 +/- 0.38 to 8.32 +/- 0.34 ml/hour/kg (p less than 0.01) after the discontinuation of chlorpromazine. All the patients revealed an increase in the valproic acid clearance after the chlorpromazine therapy was discontinued. When viewed overall, such a trend as found in the chlorpromazine group was not observed in the haloperidol group. The results suggest that chlorpromazine, but not haloperidol, inhibits the metabolism of valproic acid. However, the clinical significance of the interaction awaits future study.

  17. Drug combinations in syringe drivers: the compatibility and stability of diamorphine with cyclizine and haloperidol.

    PubMed

    Grassby, P F; Hutchings, L

    1997-05-01

    The compatibility and stability of 2B combinations of diamorphine hydrochloride (5-100 mg/ml) with cyclizine lactate (5-50 mg/ml), eight combinations of diamorphine (10-100 mg/ml) with haloperidol (2-4 mg/ml) and eight combinations of all three drugs was assessed after storage in 1 ml polypropylene syringes. Samples were stored for periods up to seven days in the light and at room temperature (22 degrees C). Five combinations of diamorphine with cyclizine precipitated immediately upon preparation. After analysis and determination of t90% values (the time taken for 10% degradation). 16 of the remaining 23 combinations were judged to be compatible (no signs of crystallization or precipitation) and stable (less than 10% loss of potency of either drug) after storage for 24 h. After seven days storage only four remained compatible and stable. The results indicate that ratios of diamorphine to cyclizine of 1:1 are stable at concentrations up to 20 mg/ml. An increase in diamorphine concentration necessitates a reduction in cyclizine to 10 mg/ml, and an increase in cyclizine concentration necessitates a reduction in concentration of diamorphine to 15 mg/ml to maintain stability over 24 h. All the combinations of diamorphine with haloperidol remained compatible and stable for seven days. The addition of haloperidol (2 mg/ml) to the diamorphine and cyclizine combinations had no detrimental effect on their compatibility and stability. A stability curve is included as an easy way for palliative care personnel to avoid potential problems with incompatibilities and reduced stability when using these combinations. Furthermore, to reduce the possibility of precipitation with mixtures containing cyclizine, the use of 0.9% sodium chloride should be avoided.

  18. The differential effects of chlorpromazine and haloperidol on latent inhibition in healthy volunteers.

    PubMed

    McCartan, D; Bell, R; Green, J F; Campbell, C; Trimble, K; Pickering, A; King, D J

    2001-06-01

    Latent inhibition (LI) is a measure of reduced learning about a stimulus to which there has been prior exposure without any consequence. It therefore requires a comparison between a pre-exposed (PE) and a non-pre-exposed (NPE) condition. Since, in animals, LI is disrupted by amphetamines and enhanced by antipsychotics, LI disruption has been proposed as a measure of the characteristic attentional deficit in schizophrenia: the inability to ignore irrelevant stimuli. The findings in humans are, however, inconsistent. In particular, a recent investigation suggested that since haloperidol disrupted LI in healthy volunteers, and LI was normal in non-medicated patients with schizophrenia, the previous findings in schizophrenic patients were entirely due to the negative effects of their medication on LI (Williams et al., 1998). We conducted two studies of antipsychotic drug effects on auditory LI using a within-subject, parallel group design in healthy volunteers. In the first of these, single doses of haloperidol (1 mg. i.v.) were compared with paroxetine (20 mg p.o.) and placebo, and in the second, chlorpromazine (100 mg p.o.) was compared with lorazepam (2 mg. p.o.) and placebo. Eye movements, neuropsychological test performance (spatial working memory (SWM), Tower of London and intra/extra dimensional shift, from the CANTAB test battery) and visual analogue rating scales, were also included as other measures of attention and frontal lobe function. Haloperidol was associated with a non-significant reduction in LI scores, and dysphoria/akathisia (Barnes Akathisia Rating Scale) in three-quarters of the subjects. The LI finding may be explained by increased distractibility which was indicated by an increase in antisaccade directional errors in this group. In contrast, LI was significantly increased by chlorpromazine but not by an equally sedative dose of lorazepam (both drugs causing marked decreases in peak saccadic velocity). Paroxetine had no effect on LI, eye

  19. Two cases of Gilles de la Tourette's syndrome treated with haloperidol.

    PubMed

    Perera, H V

    1975-10-01

    Two cases of Gilles de la Tourette's syndrome occurring in Sri Lanka are reported. Both patients had the characteristics of the syndrome as described by Fernando (1967): (1) Childhood onset (below 16 years of age); (2) Multiple motor tics; (3) Unprovoked vocal utterances which may progress to coprolalia. Both responded to haloperidol, withdrawal of medication being followed by relapse, and reintroduction by remission. The literature on the aetiology of the condition has been reviewed. The weight of evidence favours an organic cause, although psychological precipitation cannot be ruled out.

  20. Successful Treatment of Suspected Cannabinoid Hyperemesis Syndrome Using Haloperidol in the Outpatient Setting

    PubMed Central

    Abernathy, Karen E.

    2016-01-01

    Chronic use of cannabis can result in a syndrome of hyperemesis characterized by cyclical vomiting without any other identifiable causes. Cannabinoid hyperemesis syndrome (CHS) is seldom responsive to traditional antiemetic therapies. Despite frequent nausea and vomiting, patients may be reluctant to discontinue use of cannabis. We report a case of severe, refractory CHS with complete resolution of nausea and vomiting after treatment with haloperidol in the outpatient setting. After review of the literature, we believe this is the first reported successful outpatient treatment of CHS and suggests a potential treatment for refractory patients. PMID:27597918

  1. Specific 3H-haloperidol binding to dopamine receptors in the anterior byssus retractor muscle of Mytilus edulis.

    PubMed

    Ishii, Y; Takayanagi, I

    1982-12-01

    The anterior byssus retractor muscle (ABRM) of Mytilus edulis has specific dopamine receptors. We carried out a radioligand binding assay for dopamine receptors in ABRM using (3H)-haloperidol as the radioligand. High affinity binding of (3H)-haloperidol has been shown. Scatchard analysis showed a single component of binding with an apparent equilibrium constant (KD) of 1.6 nM and a maximal number of binding sites (Bmax) of 219 fmoles/mg protein. Some dopamine antagonists displaced 3 nM (3H)-haloperidol binding, and the IC50 and Ki-value of these drugs were calculated. Considering these results, this muscle is thought to be suitable for a study of the dopamine receptors.

  2. Administration of haloperidol with biperiden reduces mRNAs related to the ubiquitin-proteasome system in mice.

    PubMed

    Iwata, Shin-Ichi; Morioka, Hirofumi; Iwabuchi, Mika; Shinohara, Kazuya; Maeda, Maki; Shimizu, Takao; Miyata, Atsuro

    2005-06-15

    In order to find molecules affected by administration of an antipsychotic drug with an antimuscarinic drug, which is a common prescription used to prevent extrapyramidal adverse effects caused by the antipsychotic drugs, gene expression profiling in the frontal cortex was studied in mice. After 14 days of administration with 2 mg/kg haloperidol, a typical antipsychotic drug, and 2 mg/kg biperiden, a high-affinity antagonist for muscarinic receptors in the brain, approximately 500 mRNAs related to synaptic function were investigated. The levels of the mRNAs related to the ubiquitin-related systems were significantly reduced after the combined administration. However, the separate administration of either haloperidol or biperiden had little effect on the levels of the mRNAs. This result suggests that coadministration of haloperidol and biperiden specifically affects the ubiquitin-related system.

  3. Haloperidol treatment at pre-exposure phase reduces the disturbance of latent inhibition in rats with neonatal ventral hippocampus lesions.

    PubMed

    Ouhaz, Zakaria; Ba-M'hamed, Saadia; Bennis, Mohamed

    2014-10-01

    Animals with neonatal ventral hippocampal lesions develop during or after adolescence abnormal behaviors related to schizophrenia such as anxiety and latent inhibition disruption. The aim of this study was to test whether haloperidol injection prior to pre-exposure session in the latent inhibition test would facilitate latent inhibition. Lesioned animals showed a significant decrease in the number and duration of social interactions, a decrease in the marbles buried, a significant increase in locomotor activity, and a disruption of latent inhibition. In the conditioned taste aversion test, injection of haloperidol produced the recovery of latent inhibition. These findings demonstrate that neonatal lidocaine lesion of the ventral hippocampus can induce behavioral changes related to schizophrenia, and injection of haloperidol, when restricted only to a three-day pre-exposure, is sufficient to facilitate latent inhibition. Copyright © 2014 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  4. The comparative effects of clozapine versus haloperidol on initiation and maintenance of alcohol drinking in male alcohol-preferring P rat.

    PubMed

    Chau, David T; Khokhar, Jibran Y; Dawson, Ree; Ahmed, Jayme; Xie, Haiyi; Green, Alan I

    2013-12-01

    Alcohol use disorder, characterized by modest levels of alcohol use, commonly occurs in patients with schizophrenia and dramatically worsens their course. Recent data indicate that the atypical antipsychotic clozapine, but not the typical antipsychotic haloperidol, decreases alcohol drinking both in patients with schizophrenia and also in the Syrian golden hamster, an animal model of moderate alcohol drinking. The present study was designed to assess the comparative effects of clozapine and haloperidol in the alcohol-preferring (P) rat, an animal model of alcoholism. First, the study investigated the comparative effects of clozapine and haloperidol on initiation of alcohol consumption in P rats, which models the early stage of alcoholism. Second, the study assessed the comparative effects of clozapine and haloperidol on maintenance of chronic alcohol consumption in P rats to provide a clue as to whether either drug may also limit alcohol consumption in alcohol-dependent patients. Clozapine attenuated the initiation of alcohol drinking and development of alcohol preference while haloperidol did not. However, neither clozapine nor haloperidol attenuated maintenance of chronic alcohol drinking. Taken together, the current data suggest that clozapine, but not haloperidol, may be effective at reducing alcohol abuse or non-dependent drinking and the P rat, used within an alcohol initiation paradigm, and may differentiate the effects of clozapine and haloperidol on alcohol drinking.

  5. Haloperidol-loaded polysorbate-coated polymeric nanocapsules decrease its adverse motor side effects and oxidative stress markers in rats.

    PubMed

    Benvegnú, Dalila Moter; Barcelos, Raquel Cristine Silva; Boufleur, Nardeli; Pase, Camila Simonetti; Reckziegel, Patrícia; Flores, Fernanda Cramer; Ourique, Aline Ferreira; Nora, Magali Dalla; da Silva, Cristiane de Bona; Beck, Ruy Carlos Ruver; Bürger, Marilise Escobar

    2012-10-01

    Haloperidol is the most widely used antipsychotic drug in the treatment of psychiatric disorders. Despite its satisfactory therapeutic effect, its chronic use is related to severe motor side effects. Here, we investigate the incidence of motor side effects of haloperidol-loaded nanocapsules when compared to free haloperidol and the relation with oxidative stress (OS) development. Both vehicle (B-NcFO) and haloperidol loaded polysorbate-coated nanocapsules suspension (H-NcFO) prepared with fish oil as core showed uniform and rounded particles, nanometric size, negative zeta potential, low polydispersity indices and high encapsulation efficiency. Wistar rats received a single dose of free haloperidol (FH), B-NcFO or H-NcFO (0.2 mg/kg ip) and were submitted to acute motor side effects evaluation 1 h after the injection. Lower catalepsy time and oral dyskinesia were observed in H-NcFO-treated group than in FH group; however, both formulations decreased animals' locomotor activity. In a experiment performed subchronically, rats injected daily with H-NcFO (0.2 mg/kg-ip) for 28 days showed decreased oral dyskinesia frequency and catalepsy time and no impairment on locomotor activity as compared to FH group (0.2 mg/kg-ip). FH group showed higher OS, as observed by increased lipid peroxidation and reduced glutathione levels and catalase activity in extrapyramidal region. Our findings showed that nanocapsules may be an efficient form to prevent or minimize haloperidol motor side effects, which are related to OS development, ameliorating psychiatric patients' quality of life. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Aripiprazole versus haloperidol in combination with clozapine for treatment-resistant schizophrenia in routine clinical care: a randomized, controlled trial.

    PubMed

    Barbui, Corrado; Accordini, Simone; Nosè, Michela; Stroup, Scott; Purgato, Marianna; Girlanda, Francesca; Esposito, Eleonora; Veronese, Antonio; Tansella, Michele; Cipriani, Andrea

    2011-06-01

    This multisite study was conducted to compare the efficacy and tolerability of combination treatment with clozapine plus aripiprazole versus combination treatment with clozapine plus haloperidol in patients with schizophrenia who do not have an optimal response to clozapine. Patients continued to take clozapine and were randomly assigned to receive daily augmentation with aripiprazole or haloperidol. Physicians prescribed the allocated treatments according to usual clinical care. Withdrawal from allocated treatment within 3 months was the primary outcome. Secondary outcomes included severity of symptoms on the Brief Psychiatric Rating Scale and antipsychotic subjective tolerability on the Liverpool University Neuroleptic Side Effect Rating Scale. A total of 106 patients with schizophrenia were randomly assigned to treatment. After 3 months, we found no difference in the proportion of patients who discontinued treatment between the aripiprazole and haloperidol groups (13.2% vs 15.1%, P = 0.780). The 3-month change of the Brief Psychiatric Rating Scale total score was similar in the aripiprazole and haloperidol groups (-5.9 vs -4.4 points, P = 0.523), whereas the 3-month decrease of the Liverpool University Neuroleptic Side Effect Rating Scale total score was significantly higher in the aripiprazole group than in the haloperidol group (-7.4 vs -2.0 points, P = 0.006). These results suggest that augmentation of clozapine with aripiprazole offers no benefit with regard to treatment withdrawal and overall symptoms in schizophrenia compared with augmentation with haloperidol. However, an advantage in the perception of adverse effects with aripiprazole treatment may be meaningful for patients.

  7. Olanzapine versus haloperidol in the treatment of acute mania: clinical outcomes, health-related quality of life and work status.

    PubMed

    Shi, L; Namjoshi, M A; Zhang, F; Gandhi, G; Edgell, E T; Tohen, M; Breier, A; Haro, J M

    2002-09-01

    We aimed to compare clinical outcomes, health-related quality of life (HRQOL) and work status associated with olanzapine and haloperidol treatment in patients with bipolar disorder. This double-blind, randomized controlled trial, comparing flexible dosing of olanzapine (5-20 mg/day, n = 234) to haloperidol (3-15 mg/day, n = 219), consisted of a 6-week acute phase, followed by a 6-week continuation phase. Symptomatic remission rates were similar for olanzapine- and haloperidol-treated patients at weeks 6 and 12. At week 6, significant changes in five dimensions of the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) [general health (P = 0.010), physical functioning (P < 0.001), role limitations due to physical problems (P < 0.001), social functioning (P < 0.05) and vitality (P < 0.01)] and the SF-36 physical components summary score were found in favour of olanzapine compared to haloperidol. At week 12, olanzapine treatment maintained the significantly favourable HRQOL changes. At the end of week 12, patients on olanzapine showed significantly greater improvement than haloperidol in work activities impairment and household activities impairment scores on the Streamlined Longitudinal Interview Clinical Evaluation from the Longitudinal Interval Follow-up Evaluation (SLICE/LIFE) activities impairment scores. Subgroup analyses revealed that olanzapine treatment significantly increased a proportion of employed patients and their weekly paid working hours. In conclusion, compared to haloperidol, olanzapine treatment was comparably effective in the remission of bipolar mania and significantly improved HRQOL and work status in patients with bipolar I disorder.

  8. Intranasal haloperidol-loaded miniemulsions for brain targeting: Evaluation of locomotor suppression and in-vivo biodistribution.

    PubMed

    El-Setouhy, Doaa Ahmed; Ibrahim, A B; Amin, Maha M; Khowessah, Omneya M; Elzanfaly, Eman S

    2016-09-20

    Haloperidol is a commonly prescribed antipsychotic drug currently administered as oral and injectable preparations. This study aimed to prepare haloperidol intranasal miniemulsion helpful for psychiatric emergencies and exhibiting lower systemic exposure and side effects associated with non-target site delivery. Haloperidol miniemulsions were successfully prepared by spontaneous emulsification adopting 2(3) factorial design. The effect of three independent variables at two levels each namely; oil type (Capmul®-Capryol™90), lipophilic emulsifier type (Span 20-Span 80) and HLB value (12-14) on globule size, PDI and percent locomotor activity inhibition in mice was evaluated. The optimized formula (F4, Capmul®, Tween 80/Span 20, HLB 14) showed globule size of 209.5±0.98nm, PDI of 0.402±0.03 and locomotor inhibition of 83.89±9.15% with desirability of 0.907. Biodistribution study following intranasal and intravenous administration of the radiolabeled (99m)Tc mucoadhesive F4 revealed that intranasal administration achieved 1.72-fold higher and 6 times faster peak brain levels compared with intravenous administration. Drug targeting efficiency percent and brain/blood exposure ratios remained above 100% and 1 respectively after intranasal instillation compared to a maximum brain/blood exposure ratio of 0.8 post intravenous route. Results suggested the CNS delivery of major fraction of haloperidol via direct transnasal to brain pathway that can be a promising alternative to oral and parenteral routes in chronic and acute situations. Haloperidol concentration of 275.6ng/g brain 8h post intranasal instillation, higher than therapeutic concentration range of haloperidol (0.8 to 5.15ng/ml), suggests possible sustained delivery of the drug through nasal route.

  9. Bauhinia forficata prevents vacuous chewing movements induced by haloperidol in rats and has antioxidant potential in vitro.

    PubMed

    Peroza, Luis Ricardo; Busanello, Alcindo; Leal, Caroline Queiroz; Röpke, Jivago; Boligon, Aline Augusti; Meinerz, Daiane; Libardoni, Milena; Athayde, Margareth Linde; Fachinetto, Roselei

    2013-04-01

    Classical antipsychotics can produce motor disturbances like tardive dyskinesia in humans and orofacial dyskinesia in rodents. These motor side effects have been associated with oxidative stress production in specific brain areas. Thus, some studies have proposed the use of natural compounds with antioxidant properties against involuntary movements induced by antipsychotics. Here, we examined the possible antioxidant activity of Bauhinia forficata (B. forficata), a plant used in folk medicine as a hypoglycemic, on brain lipid peroxidation induced by different pro-oxidants. B. forficata prevented the formation of lipid peroxidation induced by both pro-oxidants tested. However, it was effective against lipid peroxidation induced by sodium nitroprusside (IC50 = 12.08 μg/mL) and Fe(2+)/EDTA (IC50 = 41.19 μg/mL). Moreover, the effects of B. forficata were analyzed on an animal model of orofacial dyskinesia induced by long-term treatment with haloperidol, where rats received haloperidol each 28 days (38 mg/kg) and/or B. forficata decoction daily (2.5 g/L) for 16 weeks. Vacuous chewing movements (VCMs), locomotor and exploratory activities were evaluated. Haloperidol treatment induced VCMs, and co-treatment with B. forficata partially prevented this effect. Haloperidol reduced the locomotor and exploratory activities of animals in the open field test, which was not modified by B. forficata treatment. Our present data showed that B. forficata has antioxidant potential and partially protects against VCMs induced by haloperidol in rats. Taken together, our data suggest the protection by natural compounds against VCMs induced by haloperidol in rats.

  10. Extrapyramidal side effects in a blue and gold macaw (Ara ararauna) treated with haloperidol and clomipramine.

    PubMed

    Starkey, Simon R; Morrisey, James K; Hickam, Hillary D; Albright, Julia D; Lynch, Mary J

    2008-09-01

    A diagnosis of adverse extrapyramidal symptoms (EPS) was reached in a 14-year-old female blue and gold macaw (Ara ararauna) that presented with disseminated dystonia (manifesting as pacing, head bobbing, and circling), intermittent ataxia, and coarse-muscle tremors of 60 hours duration. The patient had been treated 23 days previously with haloperidol decanoate (1.7 mg/kg IM once), and for 3 days before hospitalization with clomipramine HCl at a prescribed dosage of 3.9 mg/kg PO q12h. The patient was treated with supportive care, a gradual reduction in the clomipramine dose, and intramuscular and oral diphenhydramine (2 mg/kg q12h). As commonly observed in human patients with drug-induced EPS, a dramatic resolution of clinical signs was observed within 2 hours after the first intramuscular administration of diphenhydramine. It is recommended that EPS be considered in macaws experiencing neurologic signs secondary to clomipramine administration and, in particular, in those treated concurrently or previously with haloperidol.

  11. Transdermal delivery of haloperidol by proniosomal formulations with non-ionic surfactants.

    PubMed

    Azarbayjani, Anahita Fathi; Tan, En Hui; Chan, Yew Weng; Chan, Sui Yung

    2009-08-01

    Proniosomal formulations with non-ionic surfactant were studied. The effect of hydrophilicity and hydrophobicity of one or two surfactants on drug solubility, proniosome surface structure and stability and skin permeation of haloperidol from different formulations were investigated. Haloperidol (HP) was entrapped in proniosomes with very high efficiency for all formulations. Stability studies performed at 4 degrees C and 25 degrees C for a period of 6 weeks did not reveal any significant drug leakage (p>0.05). Formulations with single surfactants were found to increase the skin permeation of HP more than formulations containing two surfactants. The number of carbons in the alkyl chain of the non-ionic surfactant influenced the in vitro permeation of HP though the epidermis and the skin permeation was increased with increase in hydrophilic-lipophilic balance (HLB) value of the surfactant. Interfacial tension and surfactant hydrophobicity appeared to be useful for elucidating mechanism of skin permeation and for comparing drug fluxes from different proniosomal formulations.

  12. Haloperidol-based irreversible inhibitors of the HIV-1 and HIV-2 proteases.

    PubMed

    De Voss, J J; Sui, Z; DeCamp, D L; Salto, R; Babé, L M; Craik, C S; Ortiz de Montellano, P R

    1994-03-04

    The proteases expressed by the HIV-1 and HIV-2 viruses process the polyproteins encoded by the viral genomes into the mature proteins required for virion replication and assembly. Eight analogs of haloperidol have been synthesized that cause time-dependent inactivation of the HIV-1 protease and, in six cases, HIV-2 protease. The IC50 values for the analogues are comparable to that of haloperidol itself. Enzyme inactivation is due to the presence of an epoxide in two of the analogues and carbonyl-conjugated double or triple bonds in the others. Irreversible inactivation is confirmed by the failure to recover activity when one of the inhibitors is removed from the medium. At pH 8.0, the agents inactivate the HIV-1 protease 4-80 times more rapidly than the HIV-2 protease. Faster inactivation of the HIV-1 protease is consistent with alkylation of cysteine residues because the HIV-1 protease has four such residues whereas the HIV-2 protease has none. Inactivation of the HIV-2 protease requires modification of non-cysteine residues. The similarities in the rates of inactivation of the HIV-2 protease by six agents that have intrinsically different reactivities toward nucleophiles suggest that the rate-limiting step in the inactivation process is not the alkylation reaction itself. At least five of the agents inhibit polyprotein processing in an ex vivo cell assay system, but they are also toxic to the cells.

  13. Sex differences in catalepsy: evidence for hormone-dependent postural mechanisms in haloperidol-treated rats.

    PubMed

    Field, E F; Whishaw, I Q; Pellis, S M

    2000-05-01

    Catalepsy, a symptom of Parkinson's disease and related disorders can be produced in rats and other laboratory animals by the blockade of nigrostriatal dopamine using dopaminergic antagonists such as haloperidol. When haloperidol-induced cataleptic rats are placed facing downward on an inclined plane, they will brace against the resulting downward force by pushing backwards, and if they lose postural stability, or their position on the inclined plane, they will jump forward. Females, however, jump from the inclined plane at a significantly lower angle than do males. Frame-by-frame analysis of the jumping sequences revealed that females and males use a different combination of postural adjustments to maintain their position on the inclined plane prior to jumping. Furthermore, gonadal hormone manipulations at birth and in adulthood reveal that these sex differences in postural adjustments are dependent on the organizational effects of gonadal hormones in the perinatal period. These results provide evidence for sex differences in postural support mechanisms and suggest that the sex of subjects, or their hormonal state, must be considered when studying the behavioral aspects of neurological disorders such as Parkinson's disease which include a postural component.

  14. Combined treatment of quetiapine with haloperidol in animal models of antipsychotic effect and extrapyramidal side effects: comparison with risperidone and chlorpromazine.

    PubMed

    Tada, Miho; Shirakawa, Kiyoharu; Matsuoka, Nobuya; Mutoh, Seitaro

    2004-10-01

    Quetiapine, an atypical neuroleptic, has beneficial antipsychotic effects in schizophrenic patients, but with a lower incidence of extrapyramidal symptoms (EPS) compared with typical antipsychotics. While typical antipsychotics are often switched to atypical agents when adverse effects become limiting, there is little preclinical information to support this strategy, both in terms of efficacy and side effects. The antipsychotic effects and EPS during concomitant administration of quetiapine with haloperidol, a typical antipsychotic agent, were evaluated in mice and compared with chlorpromazine and risperidone. We first investigated the antipsychotic effects and EPS liability of quetiapine, risperidone, chlorpromazine, and haloperidol when administered alone to select optimal doses for subsequent combination studies. The second study was designed to evaluate the antipsychotic efficacy and EPS profile of concomitant administration of quetiapine, risperidone, or chlorpromazine with haloperidol. Antipsychotic effects were evaluated with the methamphetamine-induced hyperlocomotion test, and EPS liability was evaluated in a catalepsy-induction model. Quetiapine, risperidone, chlorpromazine, and haloperidol dose-dependently reduced methamphetamine-induced hyperlocomotion, with ED50 values of 5.6, 0.020, 1.8, 0.035 mg/kg, respectively. In the catalepsy test, quetiapine only weakly induced catalepsy at the highest dose of 100 mg/kg, whereas risperidone, chlorpromazine, and haloperidol dose-dependently induced catalepsy with ED50 values of 0.25, 4.6, and 0.10 mg/kg, respectively. While the combination of quetiapine (6 mg/kg) and haloperidol (0.04 mg/kg) significantly reduced methamphetamine-induced hyperlocomotion in comparison with haloperidol alone, quetiapine (10, 32 mg/kg) plus haloperidol did not potentiate the cataleptogenic activity of haloperidol. In contrast, risperidone (0.1, 0.32 mg/kg) or chlorpromazine (3.2 mg/kg) significantly augmented catalepsy induced by

  15. CYP2D6 *6/*6 genotype and drug interactions as cause of haloperidol-induced extrapyramidal symptoms.

    PubMed

    Šimić, Iveta; Potočnjak, Ines; Kraljičković, Iva; Stanić Benić, Mirjana; Čegec, Ivana; Juričić Nahal, Danica; Ganoci, Lana; Božina, Nada

    2016-08-01

    A 66-year-old male Caucasian, received 1 mg of haloperidol orally and rapidly developed severe iatrogenic extrapyramidal symptoms. Treatment was immediately discontinued, and the side effects resolved. Haloperidol is mainly metabolized by Phase I CYP2D6 and to the lesser extent by CYP3A4 and by Phase II UGT2B7 enzymes. Genotyping was performed revealing CYP2D6*6/*6, CYP3A4*1/*1, and UGT2B7 -161 C/T genotypes, implicating poor, extensive and intermediate metabolism, respectively. Of the CYPs, haloperidol is metabolized by CYP2D6 and CYP3A4 primarily. It was the introduction of ciprofloxacin which was a trigger for the development of adverse drug reaction due to inhibition of CYP3A4, which was in presented patient main metabolic pathway for haloperidol since he was CYP2D6 poor metabolizer. Presented case report highlights the importance of genotyping. Pharmacogenetics testing should be considered when drug toxicity is suspected, polymorphic metabolic pathways used and drugs concomitantly applied.

  16. Antiproliferative activity of phenylbutyrate ester of haloperidol metabolite II [(±)-MRJF4] in prostate cancer cells.

    PubMed

    Marrazzo, Agostino; Fiorito, Jole; Zappalà, Laura; Prezzavento, Orazio; Ronsisvalle, Simone; Pasquinucci, Lorella; Scoto, Giovanna M; Bernardini, Renato; Ronsisvalle, Giuseppe

    2011-01-01

    Complex mechanisms of prostate cancer progression prompt to novel therapeutic strategies concerning a combination of drugs or of single molecules able to interact with more crucial targets. Histone deacetylase inhibitors and sigma ligands with mixed σ(1) antagonist and σ(2) agonist properties were proposed as new potential tools for treatment of prostate cancer. (±)-MRJF4 was synthesized as phenylbutyrate ester of haloperidol metabolite II, which is a molecule consisting of a histone deacetilase inhibitor (4-phenylbutyric acid) and a sigma ligand (haloperidol metabolite II). Antiproliferatives activities of 4-phenylbutyric acid, haloperidol metabolite II, equimolar mixture of both compounds and (±)-MRJF4 were evaluated in vitro on LNCaP and PC3 prostate cancer cells. Preliminary binding studies of (±)-MRJF4 for σ(1), σ(2), D(2) and D(3) receptors and inhibition HDAC activity were reported. MTT cell viability assays highlighted a notable increase of antiproliferative activity of (±)-MRJF4 (IC(50) = 11 and 13 μM for LNCaP and PC3, respectively) compared to 4-phenylbutyric acid, haloperidol metabolite II and the respective equimolar pharmacological association. (±)-MRJF4 was also used in combination with σ(1) agonist (+)-pentazocine and σ(2) antagonist AC927 in order to evaluate the role of σ receptor subtypes in prostate cancer cell death.

  17. Haloperidol impairs auditory filial imprinting and modulates monoaminergic neurotransmission in an imprinting-relevant forebrain area of the domestic chick.

    PubMed

    Gruss, M; Bock, J; Braun, K

    2003-11-01

    In vivo microdialysis and behavioural studies in the domestic chick have shown that glutamatergic as well as monoaminergic neurotransmission in the medio-rostral neostriatum/hyperstriatum ventrale (MNH) is altered after auditory filial imprinting. In the present study, using pharmaco-behavioural and in vivo microdialysis approaches, the role of dopaminergic neurotransmission in this juvenile learning event was further evaluated. The results revealed that: (i) the systemic application of the potent dopamine receptor antagonist haloperidol (7.5 mg/kg) strongly impairs auditory filial imprinting; (ii) systemic haloperidol induces a tetrodotoxin-sensitive increase of extracellular levels of the dopamine metabolite, homovanillic acid, in the MNH, whereas the levels of glutamate, taurine and the serotonin metabolite, 5-hydroxyindole-3-acetic acid, remain unchanged; (iii) haloperidol (0.01, 0.1, 1 mm) infused locally into the MNH increases glutamate, taurine and 5- hydroxyindole-3-acetic acid levels in a dose-dependent manner, whereas homovanillic acid levels remain unchanged; (iv) systemic haloperidol infusion reinforces the N-methyl-d-aspartate receptor-mediated inhibitory modulation of the dopaminergic neurotransmission within the MNH. These results indicate that the modulation of dopaminergic function and its interaction with other neurotransmitter systems in a higher associative forebrain region of the juvenile avian brain displays similar neurochemical characteristics as the adult mammalian prefrontal cortex. Furthermore, we were able to show that the pharmacological manipulation of monoaminergic regulatory mechanisms interferes with learning and memory formation, events which in a similar fashion might occur in young or adult mammals.

  18. Differential effects of clozapine, metoclopramide, haloperidol and risperidone on acquisition and performance of operant responding in rats.

    PubMed

    Baker, Tyson W; Florczynski, Matthew M; Beninger, Richard J

    2015-05-01

    Prior research has not systematically investigated the effects of systemic antipsychotic drugs on operant response acquisition, specifically their behavioural microstructure, reinforcement blunting and relative potency in acquisition compared to performance once operant responding has stabilized. This study aims to systematically investigate the effects of systemically administered clozapine, metoclopramide, haloperidol and risperidone during free operant response acquisition and performance. Following magazine training, food-restricted male Wistar rats lever pressed for food reward in 15 min daily operant conditioning sessions. All drugs suppressed operant response acquisition and performance. Risperidone and metoclopramide, but not clozapine or haloperidol, suppressed operant responding more potently during acquisition than performance. The dopamine D2-like receptor antagonists haloperidol and metoclopramide that affect the ventral and dorsal striatum blunted reinforcement and decreased inactive lever presses in acquisition. In contrast, the atypical antipsychotics clozapine and risperidone that affect the ventral striatum and prefrontal cortex failed to decrease inactive lever presses during acquisition, suggesting a possible decision-making deficit. Haloperidol decreased active lever pressing over performance days. The drugs did not appear to affect rats' sensitivity to active lever press outcome, even though they suppressed active lever pressing. Results suggest that reinforcement impact during operant acquisition is dependent on dopamine D2 receptors while drugs affecting, among other areas, the prefrontal cortex produce a deficit in ability to suppress inactive lever press responses.

  19. Haloperidol Injection

    MedlinePlus

    ... release injection are used to treat schizophrenia (a mental illness that causes disturbed or unusual thinking, loss of ... medications); medications for anxiety, depression, irritable bowel disease, mental illness, motion sickness, Parkinson's disease, seizures, ulcers, or urinary ...

  20. Efficacy of Oral Risperidone, Haloperidol, or Placebo for Symptoms of Delirium Among Patients in Palliative Care: A Randomized Clinical Trial.

    PubMed

    Agar, Meera R; Lawlor, Peter G; Quinn, Stephen; Draper, Brian; Caplan, Gideon A; Rowett, Debra; Sanderson, Christine; Hardy, Janet; Le, Brian; Eckermann, Simon; McCaffrey, Nicola; Devilee, Linda; Fazekas, Belinda; Hill, Mark; Currow, David C

    2017-01-01

    Antipsychotics are widely used for distressing symptoms of delirium, but efficacy has not been established in placebo-controlled trials in palliative care. To determine efficacy of risperidone or haloperidol relative to placebo in relieving target symptoms of delirium associated with distress among patients receiving palliative care. A double-blind, parallel-arm, dose-titrated randomized clinical trial was conducted at 11 Australian inpatient hospice or hospital palliative care services between August 13, 2008, and April 2, 2014, among participants with life-limiting illness, delirium, and a delirium symptoms score (sum of Nursing Delirium Screening Scale behavioral, communication, and perceptual items) of 1 or more. Age-adjusted titrated doses of oral risperidone, haloperidol, or placebo solution were administered every 12 hours for 72 hours, based on symptoms of delirium. Patients also received supportive care, individualized treatment of delirium precipitants, and subcutaneous midazolam hydrochloride as required for severe distress or safety. Improvement in mean group difference of delirium symptom score (severity range, 0-6) between baseline and day 3. Five a priori secondary outcomes: delirium severity, midazolam use, extrapyramidal effects, sedation, and survival. Two hundred forty-seven participants (mean [SD] age, 74.9 [9.8] years; 85 women [34.4%]; 218 with cancer [88.3%]) were included in intention-to-treat analysis (82 receiving risperidone, 81 receiving haloperidol, and 84 receiving placebo). In the primary intention-to-treat analysis, participants in the risperidone arm had delirium symptom scores that were significantly higher than those among participants in the placebo arm (on average 0.48 Units higher; 95% CI, 0.09-0.86; P = .02) at study end. Similarly, for those in the haloperidol arm, delirium symptom scores were on average 0.24 Units higher (95% CI, 0.06-0.42; P = .009) than in the placebo arm. Compared with placebo, patients in both

  1. Effectiveness of Paliperidone Palmitate vs. Haloperidol Decanoate for Maintenance Treatment of Schizophrenia: A Randomized Clinical Trial

    PubMed Central

    McEvoy, Joseph P.; Byerly, Matthew; Hamer, Robert M.; Dominik, Rosalie; Swartz, Marvin S.; Rosenheck, Robert A.; Ray, Neepa; Lamberti, J. Steven; Buckley, Peter F.; Wilkins, Tania M.; Stroup, T. Scott

    2014-01-01

    Importance Long-acting injectable (LAI) antipsychotics are used to reduce medication non-adherence and subsequent relapse in schizophrenia-spectrum disorders. The relative effectiveness of LAI versions of second-generation (atypical) and older antipsychotics has not been assessed. Objective To compare the effectiveness of the second-generation LAI antipsychotic paliperidone palmitate (PP) to the older LAI antipsychotic haloperidol decanoate (HD). Design, Setting, and Participants Multisite, double-blind, randomized clinical trial conducted at 22 clinical research sites in the U.S. The 311 randomized patients (PP=157, HD=154) were adults diagnosed with schizophrenia or schizoaffective disorder who were clinically assessed to be at risk of relapse and likely to benefit from a LAI antipsychotic. Interventions Intramuscular injections of HD 25–200 mg or PP 39–234 mg every month for up to 24 months. Main Outcome Measures Efficacy failure, which reflected inadequate control of psychopathology by the study medication, as determined by a blinded adjudication committee. Key secondary outcomes were common adverse effects of antipsychotic medications. Results There was no statistically significant difference in the rate of efficacy failure for PP compared to HD (adjusted hazard ratio 0.98, 95% confidence interval [CI] 0.65–1.47). On average, patients on PP gained and those on HD lost weight; after six months the least squares mean weight change on PP was +2.17 kg (1.25 to 3.09) and on HD was −0.96 kg (−1.88 to −0.04). Patients taking PP had significantly greater increases in serum prolactin (men 34.56 µg/L (29.75 to 39.37) vs. 15.41 (10.73 to 20.08), p<0.001; women 75.19 (63.03 to 87.36) vs. 26.84 (13.29 to 40.40), p<0.001). Patients taking HD had significantly larger increases in global ratings of akathisia (0.73 [0.59 to 0.87] vs. 0.45 [0.31 to 0.59], p=0.006). Conclusions and Relevance Among adults with schizophrenia or schizoaffective disorder, treatment with

  2. Haloperidol-stomach lesions attenuation by pentadecapeptide BPC 157, omeprazole, bromocriptine, but not atropine, lansoprazole, pantoprazole, ranitidine, cimetidine and misoprostol in mice.

    PubMed

    Bilic, I; Zoricic, I; Anic, T; Separovic, J; Stancic-Rokotov, D; Mikus, D; Buljat, G; Ivankovic, D; Aralica, G; Prkacin, I; Perovic, D; Mise, S; Rotkvic, I; Petek, M; Rucman, R; Seiwerth, S; Sikiric, P

    2001-03-09

    The focus was on haloperidol (central dopamine antagonist)-stomach lesion, a longly described suitable counterpart of dopamine blocker cysteamine-duodenal lesion. In this, the contribution of blockade of central/peripheral dopamine receptors and prostaglandins synthesis, along with influence of antiulcer agents was evaluated in mice. Male NMRI Hannnover mice were sacrificed 24 h after haloperidol (25 mg/kg b.w. i.p., given alone or with saline (haloperidol+saline) (i) or in combination (ii,iii)). Supporting central dopamine predominance for haloperidol stomach lesion induction, co-administration of peripheral dopamine receptor antagonist domperidone (5 mg/kg i.p.) (haloperidol+ domperidone) (ii), or prostaglandin synthesis inhibitor indomethacin (10 mg/kg s.c.) (haloperidol+ indomethacin) (iii) did not aggravate this lesion. (i) In haloperidol+saline challenged mice the lesions were inhibited by co-administration (/kg i.p.) of a gastric pentadecapeptide BPC 157, GlyGluProProProGlyLysProAlaAspAspAlaGlyLeuVal, M.W. 1419 (10 microg, 10 ng, 10 pg, but not 1 pg, 100 fg, 10 fg), bromocriptine (10 mg), omeprazole (10 mg, 100 mg, but not 1 mg). Atropine (10, 100, 200 mg), pirenzepine (10, 100, 200 mg), misoprostol (10, 100, 200 microg), pantoprazole (1, 10, 100 mg), lansoprazole (0.1, 1, 10 mg), cimetidine (10, 100, 200 mg) and ranitidine (10, 100, 200 mg) were not effective. (ii) Dopamine peripheral blockade influence: in haloperidol+domperidone mice, previously effective bromocriptine, pentadecapeptide BPC 157 (10 microg) or omeprazole (10 mg) did not attenuate stomach lesions. (iii) Prostaglandins synthesis blockade effect: in haloperidol+indomethacin mice, previously effective agents, bromocriptine or omeprazole were not active, while BPC 157 effect was only lessened.

  3. Valeriana officinalis does not alter the orofacial dyskinesia induced by haloperidol in rats: role of dopamine transporter.

    PubMed

    Fachinetto, Roselei; Villarinho, Jardel G; Wagner, Caroline; Pereira, Romaiana P; Avila, Daiana Silva; Burger, Marilise E; Calixto, João Batista; Rocha, João B T; Ferreira, Juliano

    2007-10-01

    Chronic treatment with classical neuroleptics in humans can produce a serious side effect, known as tardive dyskinesia (TD). Here, we examined the effects of V. officinalis, a medicinal herb widely used as calming and sleep-promoting, in an animal model of orofacial dyskinesia (OD) induced by long-term treatment with haloperidol. Adult male rats were treated during 12 weeks with haloperidol decanoate (38 mg/kg, i.m., each 28 days) and with V. officinalis (in the drinking water). Vacuous chewing movements (VCMs), locomotor activity and plus maze performance were evaluated. Haloperidol treatment produced VCM in 40% of the treated rats and the concomitant treatment with V. officinalis did not alter either prevalence or intensity of VCMs. The treatment with V. officinalis increased the percentage of the time spent on open arm and the number of entries into open arm in the plus maze test. Furthermore, the treatment with haloperidol and/or V. officinalis decreased the locomotor activity in the open field test. We did not find any difference among the groups when oxidative stress parameters were evaluated. Haloperidol treatment significantly decreased [(3)H]-dopamine uptake in striatal slices and V. officinalis was not able to prevent this effect. Taken together, our data suggest a mechanism involving the reduction of dopamine transport in the maintenance of chronic VCMs in rats. Furthermore, chronic treatment with V. officinalis seems not produce any oxidative damage to central nervous system (CNS), but it also seems to be devoid of action to prevent VCM, at least in the dose used in this study.

  4. Decision analysis model evaluating the cost-effectiveness of risperidone, olanzapine and haloperidol in the treatment of schizophrenia.

    PubMed

    Bounthavong, Mark; Okamoto, Mark P

    2007-06-01

    To evaluate the cost-effectiveness of three antipsychotic medications (olanzapine, risperidone and haloperidol) in the treatment of schizophrenia using the Positive and Negative Symptom Scale. A decision analysis model was created to evaluate the cost-effectiveness of two atypical antipsychotics (risperidone and olanzapine) and haloperidol. Outcome probabilities were determined from published clinical trials. The main dependent variable of interest was to compare the incremental cost-effectiveness ratios (ICER) of the atypical antipsychotic with haloperidol, and also to compare the ICER of olanzapine and risperidone. Sensitivity analyses were conducted for olanzapine and risperidone to determine the effects of altering drug cost, efficacy and re-hospitalization rate on total costs. Risperidone and olanzapine were dominant strategies compared with haloperidol (less costly and more effective). Risperidone was also dominant when compared with olanzapine. A one-way sensitivity analysis for efficacy indicated that the efficacy of risperidone would need to decrease by approximately 3% from the base-case in order for olanzapine and risperidone to have equal total costs. In a two-way sensitivity analysis varying both the cost of olanzapine and risperidone, the difference in drug costs between them would have to increase from $2.12 per day to $4.12 per day in order to have equal total costs. In terms of varying re-hospitalization rates, the re-hospitalization rate for risperidone would have to increase from 3% to 33% greater than the re-hospitalization rate for olanzapine in order to have equal total direct costs. Based on this decision model, atypical antipsychotics were a dominant strategy over haloperidol primarily because of increased efficacy and lower re-hospitalizations. The ICER indicated that risperidone was dominant over olanzapine because of lower drug costs and increased number of responders, which leads to decreased total costs.

  5. Comparing Pharmacological Modulation of Sensory Gating in Healthy Humans and Rats: The Effects of Reboxetine and Haloperidol

    PubMed Central

    Witten, Louise; Bastlund, Jesper Frank; Glenthøj, Birte Y; Bundgaard, Christoffer; Steiniger-Brach, Björn; Mørk, Arne; Oranje, Bob

    2016-01-01

    Sensory gating is the brain's ability to filter out irrelevant information before it reaches high levels of conscious processing. In the current study we aimed to investigate the involvement of the noradrenergic and dopaminergic neurotransmitter systems in sensory gating. Furthermore, we investigated cross-species reliability by comparing effects in both healthy humans and rats, while keeping all experimental conditions as similar as possible between the species. The design of the human experiment (n=21) was a double-blind, placebo-controlled, cross-over study where sensory gating was assessed following a dose of either reboxetine (8 mg), haloperidol (2 mg), their combination or placebo at four separate visits. Similarly in the animal experiment sensory gating was assessed in rats, (n=22) following a dose of reboxetine (2 mg/kg), haloperidol (0.08 mg/kg), their combination or placebo. The sensory gating paradigms in both experiments were identical. In humans, we found significantly reduced P50 suppression following separate administration of reboxetine or haloperidol, while their combined administration did not reach statistical significance compared with placebo. In the rats, we found a similar significant reduction of sensory gating (N40) following treatment with haloperidol and the combination of haloperidol and reboxetine, but not with separate reboxetine treatment, compared with placebo. Our study indicates that even when experimental conditions are kept as similar as possible, direct human to rat cross-species translation of pharmacological effects on sensory gating is challenging, which calls for more focussed research in this important translational area. PMID:26129678

  6. Effects of haloperidol on the behavioral, subjective, cognitive, motor, and neuroendocrine effects of Delta-9-tetrahydrocannabinol in humans.

    PubMed

    D'Souza, Deepak Cyril; Braley, Gabriel; Blaise, Rebecca; Vendetti, Michael; Oliver, Stephen; Pittman, Brian; Ranganathan, Mohini; Bhakta, Savita; Zimolo, Zoran; Cooper, Thomas; Perry, Edward

    2008-07-01

    Cannabinoids produce a spectrum of effects in humans including euphoria, cognitive impairments, psychotomimetic effects, and perceptual alterations. The extent to which dopaminergic systems contribute to the effects of Delta-9-tetrahydrocannabinol (Delta-9-THC) remains unclear. This study evaluated whether pretreatment with a dopamine receptor antagonist altered the effects of Delta-9-THC in humans. In a 2-test-day double-blind study, 28 subjects including healthy subjects (n = 17) and frequent users of cannabis (n = 11) were administered active (0.057 mg/kg) or placebo oral haloperidol in random order followed 90 and 215 min later by fixed order intravenous administration of placebo (vehicle) and active (0.0286 mg/kg) Delta-9-THC, respectively. Consistent with previous reports, intravenous Delta-9-THC produced psychotomimetic effects, perceptual alterations, and subjective effects including "high." Delta-9-THC also impaired verbal recall and attention. Haloperidol pretreatment did not reduce any of the behavioral effects of Delta-9-THC. Haloperidol worsened the immediate free and delayed free and cued recall deficits produced by Delta-9-THC. Haloperidol and Delta-9-THC worsened distractibility and vigilance. Neither drug impaired performance on a motor screening task, the Stockings of Cambridge task, or the delayed match to sample task. Frequent users had lower baseline plasma prolactin levels and blunted Delta-9-THC induced memory impairments. The deleterious effects of haloperidol pretreatment on the cognitive effects of Delta-9-THC are consistent with the preclinical literature in suggesting crosstalk between DAergic and CBergic systems. However, it is unlikely that DA D(2) receptor mechanisms play a major role in mediating the psychotomimetic and perceptual altering effects of Delta-9-THC. Further investigation is warranted to understand the basis of the psychotomimetic effects of Delta-9-THC and to better understand the crosstalk between DAergic and CBergic

  7. Effects of aripiprazole and haloperidol on neural activation during a simple motor task in healthy individuals: A functional MRI study.

    PubMed

    Goozee, Rhianna; O'Daly, Owen; Handley, Rowena; Reis Marques, Tiago; Taylor, Heather; McQueen, Grant; Hubbard, Kathryn; Pariante, Carmine; Mondelli, Valeria; Reinders, Antje A T S; Dazzan, Paola

    2017-04-01

    The dopaminergic system plays a key role in motor function and motor abnormalities have been shown to be a specific feature of psychosis. Due to their dopaminergic action, antipsychotic drugs may be expected to modulate motor function, but the precise effects of these drugs on motor function remain unclear. We carried out a within-subject, double-blind, randomized study of the effects of aripiprazole, haloperidol and placebo on motor function in 20 healthy men. For each condition, motor performance on an auditory-paced task was investigated. We entered maps of neural activation into a random effects general linear regression model to investigate motor function main effects. Whole-brain imaging revealed a significant treatment effect in a distributed network encompassing posterior orbitofrontal/anterior insula cortices, and the inferior temporal and postcentral gyri. Post-hoc comparison of treatments showed neural activation after aripiprazole did not differ significantly from placebo in either voxel-wise or region of interest analyses, with the results above driven primarily by haloperidol. We also observed a simple main effect of haloperidol compared with placebo, with increased task-related recruitment of posterior cingulate and precentral gyri. Furthermore, region of interest analyses revealed greater activation following haloperidol compared with placebo in the precentral and post-central gyri, and the putamen. These diverse modifications in cortical motor activation may relate to the different pharmacological profiles of haloperidol and aripiprazole, although the specific mechanisms underlying these differences remain unclear. Evaluating healthy individuals can allow investigation of the effects of different antipsychotics on cortical activation, independently of either disease-related pathology or previous treatment. Hum Brain Mapp 38:1833-1845, 2017. © 2017 Wiley Periodicals, Inc.

  8. Chlorpromazine, haloperidol, metoclopramide and domperidone release prolactin through dopamine antagonism at low concentrations but paradoxically inhibit prolactin release at high concentrations.

    PubMed Central

    Besser, G. M.; Delitala, G.; Grossman, A.; Stubbs, W. A.; Yeo, T.

    1980-01-01

    1. The effects of chlorpromazine, haloperidol, metoclopramide and domperidone on the release of prolactin from perfused columns of dispersed rat anterior pituitary cells were studied. 2. Chlorpromazine, haloperidol, metoclopramide and domperidone antagonized the dopamine-mediated inhibition of prolactin release at low concentrations. 3. Each dopamine antagonist displaced the dose-response curve for dopamine-induced suppression of prolactin release to the right in a parallel manner. 4. At higher concentrations, the four drugs became less effective as dopamine antagonists. 5. At high concentrations in the absence of dopamine, chlorpromazine, haloperidol, metoclopramide and domperidone paradoxically suppressed prolactin secretion by an unknown mechanism. PMID:6110459

  9. Weak interactions involving organic fluorine: analysis of structural motifs in Flunazirine and Haloperidol

    NASA Astrophysics Data System (ADS)

    Prasanna, M. D.; Row, T. N. Guru

    2001-05-01

    The crystal structure of Flunazirine, an anticonvulsant drug, is analyzed in terms of intermolecular interactions involving fluorine. The structure displays motifs formed by only weak interactions C-H⋯F and C-H⋯π. The motifs thus generated show cavities, which could serve as hosts for complexation. The structure of Flunazirine displays cavities formed by C-H⋯F and C-H⋯π interactions. Haloperidol, an antipsychotic drug, shows F⋯F interactions in the crystalline lattice in lieu of Cl⋯Cl interactions. However, strong O-H⋯N interactions dominate packing. The salient features of the two structures in terms of intermolecular interactions reveal, even though organic fluorine has lower tendency to engage in hydrogen bonding and F⋯F interactions, these interactions could play a significant role in the design of molecular assemblies via crystal engineering.

  10. Nigella sativa Oil Reduces Extrapyramidal Symptoms (EPS)-Like Behavior in Haloperidol-Treated Rats.

    PubMed

    Malik, Tafheem; Hasan, Sheema; Pervez, Shahid; Fatima, Tasneem; Haleem, Darakhshan Jabeen

    2016-12-01

    The symptoms of Parkinsonism and oral dyskinesia have been showing to be induced by neuroleptics that significantly affect its clinical use. In this study, we investigate whether Nigella sativa-oil (NS) (black cumin seeds)-a traditional medicine used for the seizure treatment in eastern country-may reduce the haloperidol (HAL)-induced extrapyramidal symptoms (EPS)-like behavior in rats. After combine treatment with HAL (1 mg/kg) on NS (0.2 ml/rat), rats displayed a significant decreased EPS-like behavior including movement disorders and oral dyskinesia as compared to controls. Immunohistochemical analysis indicates that NS reduced astrogliosis in caudate and accumbens nuclei. These results suggest that NS may consider as an adjunct to antipsychotics to reduce the EPS-like side effect.

  11. In vivo study of the mutagenicity of biperidine, pipotiazine, chlorpromazine, and haloperidol

    SciTech Connect

    de Arruda Cardoso Smith, M.; Valentim de Souza, M.A.; Pugliese, S.; Jesus Mari, J. de

    1996-04-09

    The evaluation of the mutagenic potential of drugs during long-term psychiatric use in schizophrenic patients is of interest considering that the incidence and treatment of this disorder comes in the reproductive age and that there is a close correlation between mutagenic and carcinogenic compounds. We did a case-control study involving 12 patients with schizophrenia diagnosed by DMS III-R, of whom 6 were men and 6 women, with an average age of 33.25 years (s.d. {+-} 7.44) and 12 controls matched for sex and for the same age. This is the first case-controlled study comparing patients under treatment with biperidine, pipotiazine, chlorpromazine, and haloperidol with normal controls in relation to the frequency of chromosomal lesions. 4 refs.

  12. Glucose administration does not modulate prolactin response to exercise, TRH or haloperidol injection.

    PubMed

    Vigas, M; Jezová, D

    1994-01-01

    Glucose was found to exert an In vitro regulatory effect on prolactin secretion. Its role in the modulation of stimulated secretion of prolactin in man is, however, not clear. To evaluate the effect of hyperglycaemia on prolactin release, three stimulatory tests with different mechanisms of stimulation were employed. Healthy male subjects served as volunteers during submaximal exercise, TRH test (0.2 mg i.v.) and administration of haloperidol (2 mg i.v.). Glucose (100 g in 400 ml) or an equal volume of water was given 30 min before the tests. Blood for glucose and prolactin analysis was taken via an indwelling catheter. The plasma prolactin concentration increased in response to each of the stimuli applied. However, the prolactin increase during hyperglycaemia did not differ from values obtained in tests performed in normoglycaemia after water administration. These results indicate that prolactin release in healthy man is not modulated by hyperglycaemia.

  13. (125I)iodoazidococaine, a photoaffinity label for the haloperidol-sensitive sigma receptor.

    PubMed Central

    Kahoun, J R; Ruoho, A E

    1992-01-01

    A carrier-free radioiodinated cocaine photo-affinity label, (-)-3-(125I)iodo-4-azidococaine [(125I)IACoc], has been synthesized and used as a probe for cocaine-binding proteins. Photoaffinity labeling with 0.5 nM (125I)IACoc resulted in selective derivatization of a 26-kDa polypeptide with the pharmacology of a sigma receptor in membranes derived from whole rat brain, rat liver, and human placenta. Covalent labeling of the 26-kDa polypeptide was inhibited by 1 microM haloperidol, di(2-tolyl)guanidine (DTG), 3-(3-hydroxyphenyl)-N-(1-propyl)piperidine (3-PPP), dextromethorphan, and carbetapentane. Stereoselective protection of (125I)IACoc photolabeling by 3-PPP [(+)-3-PPP more potent than (-)-3-PPP] was observed. (125I)IACoc labeling of the 26-kDa polypeptide was also inhibited by 10 microM imipramine, amitriptyline, fluoxetine, benztropine, and tetrabenazine. The size of the (125I)I-ACoc-labeled proteins is consistent with the size of proteins photolabeled in guinea pig brain and liver membranes by using the sigma photolabel azido-[3H]DTG. Kinetic analysis of (125I)IACoc binding to rat liver microsomes revealed two sites with Kd values of 19 and 126 pM, respectively. The presence or absence of proteolytic inhibitors during membrane preparation did not alter the size of the photolabeled sigma receptor, indicating that the 26-kDa polypeptide was not derived from a larger protein. In summary, (125I)IACoc is a potent and highly specific photoaffinity label for the haloperidol-sensitive sigma receptor and will be useful for its biochemical and molecular characterization. Images PMID:1311097

  14. Haloperidol augmentation of fluvoxamine in skin picking disorder: a case report

    PubMed Central

    2012-01-01

    Introduction Compulsive skin picking, being part of the broader category of impulse control disorders, is considered a residual diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. It is characterized by excessive scratching or picking of normal skin, or skin with minor surface irregularities, and occurs in 2% of patients attending dermatology clinics. Despite the clinical relevance of this disorder, no clear guidelines are available yet; clinical management is, therefore, compromised and the day-to-day clinical practice is burdened by difficulties. Studies on selective serotonin reuptake inhibitors and anti-epileptic drugs have provided limited results. The association between anti-depressants and anti-epileptics has been found to be beneficial in some impulse control disorders, but in skin picking no previous studies have been conducted on this pharmacological approach. There are very few reports on the efficacy of anti-psychotics in skin picking. Case presentation The therapeutic path described in this case report produced good results for a 59-year-old Caucasian woman. The first therapeutic approach, with fluvoxamine and oxcarbazepine was partially effective; then, the suspension of oxcarbazepine and haloperidol augmentation of fluvoxamine were adopted. After 10 weeks, a significant improvement of the disease was observed: the clinical picture and the associated symptoms were nearly solved. Conclusions To the best of our knowledge, this is the first article reporting the association of fluvoxamine and haloperidol in skin picking disorder. It might be useful to perform further research regarding the treatment of skin picking disorder: in clinical practice, several variables might limit the choice of certain drugs. Therefore, it would be useful for the clinician to be aware of other therapeutic options. PMID:22834980

  15. Neonatal excitotoxic ventral hippocampal damage alters dopamine response to mild repeated stress and to chronic haloperidol.

    PubMed

    Lipska, B K; Chrapusta, S J; Egan, M F; Weinberger, D R

    1995-06-01

    The effects of neonatal excitotoxic ventral hippocampus (VH) lesions on dopamine release in response to repeated stress (saline injections) and to chronic haloperidol treatment were investigated in Sprague-Dawley rats infused with ibotenic acid or vehicle into the VH on day 7 of postnatal life (PD7). Beginning on PD35, lesioned and sham-operated rats were injected i.p. with saline (INJ) once daily for 3 weeks or were not treated (NO INJ). Another cohort of rats was given haloperidol (HAL, 0.4 mg/kg, i.p.) or vehicle beginning on PD35 and thereafter once daily for 3 weeks. 3-Methoxytyramine (3-MT) was measured by combined gas chromatography/mass spectrometry in the frontal cortex (FC), nucleus accumbens (NAcc), and striatum (STR) at PD56 following MAO inhibition with pargyline. At baseline (NO INJ), 3-MT was reduced in STR of lesioned rats. Repeated saline injections resulted in a further 3-MT reduction in STR, FC, and NAcc of lesioned animals, but had no effect in sham rats. Chronic HAL, compared with vehicle, suppressed locomotor activity, and increased 3-MT accumulation in the FC, NAcc, and STR in sham and lesioned rats. This increase was enhanced in the FC of lesioned rats. These data show that mild repeated stress attenuates dopamine release in FC, NAcc, and STR of lesioned rats, while chronic HAL augments it in FC of lesioned animals versus controls. We conclude that the neonatal excitotoxic lesion of VH alters the functioning of midbrain dopamine systems during environmental and pharmacological challenge.

  16. Haloperidol augmentation of fluvoxamine in skin picking disorder: a case report.

    PubMed

    Luca, Maria; Vecchio, Costanza; Luca, Antonina; Calandra, Carmela

    2012-07-26

    Compulsive skin picking, being part of the broader category of impulse control disorders, is considered a residual diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. It is characterized by excessive scratching or picking of normal skin, or skin with minor surface irregularities, and occurs in 2% of patients attending dermatology clinics. Despite the clinical relevance of this disorder, no clear guidelines are available yet; clinical management is, therefore, compromised and the day-to-day clinical practice is burdened by difficulties. Studies on selective serotonin reuptake inhibitors and anti-epileptic drugs have provided limited results. The association between anti-depressants and anti-epileptics has been found to be beneficial in some impulse control disorders, but in skin picking no previous studies have been conducted on this pharmacological approach. There are very few reports on the efficacy of anti-psychotics in skin picking. The therapeutic path described in this case report produced good results for a 59-year-old Caucasian woman. The first therapeutic approach, with fluvoxamine and oxcarbazepine was partially effective; then, the suspension of oxcarbazepine and haloperidol augmentation of fluvoxamine were adopted. After 10 weeks, a significant improvement of the disease was observed: the clinical picture and the associated symptoms were nearly solved. To the best of our knowledge, this is the first article reporting the association of fluvoxamine and haloperidol in skin picking disorder. It might be useful to perform further research regarding the treatment of skin picking disorder: in clinical practice, several variables might limit the choice of certain drugs. Therefore, it would be useful for the clinician to be aware of other therapeutic options.

  17. CB1 cannabinoid receptor-mediated anandamide signaling mechanisms of the inferior colliculus modulate the haloperidol-induced catalepsy.

    PubMed

    Medeiros, P; de Freitas, R L; Silva, M O; Coimbra, N C; Melo-Thomas, L

    2016-11-19

    The inferior colliculus (IC), a midbrain structure that processes acoustic information of aversive nature, is distinguished from other auditory nuclei in the brainstem by its connections with structures of the motor system. Previous evidence relating the IC to motor behavior shows that glutamatergic and GABAergic mechanisms in the IC exert influence on systemic haloperidol-induced catalepsy. There is substantial evidence supporting a role played by the endocannabinoid system as a modulator of the glutamatergic neurotransmission, as well as the dopaminergic activity in the basal nuclei and therefore it may be considered as a potential pharmacological target for the treatment of movement disorders. The present study evaluated if the endocannabinoid system in the IC plays a role in the elaboration of systemic haloperidol-induced catalepsy. Male Wistar rats received intracollicular microinjection of either the endogenous cannabinoid anandamide (AEA) at different concentrations (5, 50 or 100pmol/0.2μl), the CB1 cannabinoid receptor antagonist AM251 at 50, 100 or 200pmol/0.2μl or vehicle, followed by intraperitoneal (IP) administration of either haloperidol at 0.5 or 1mg/kg or physiological saline. Systemic injection of haloperidol at both doses (0.5 or 1mg/kg, IP) produced a cataleptic state, compared to vehicle/physiological saline-treated group, lasting 30 and 50min after systemic administration of the dopaminergic receptors non-selective antagonist. The midbrain microinjection of AEA at 50pmol/0.2μl increased the latency for stepping down from the horizontal bar after systemic administration of haloperidol. Moreover, the intracollicular administration of AEA at 50pmol/0.2μl was able to increase the duration of catalepsy as compared to AEA at 100pmol/0.2-μl-treated group. Intracollicular pretreatment with AM251 at the intermediate concentration (100pmol/0.2μl) was able to decrease the duration of catalepsy after systemic administration of haloperidol. However

  18. Effects of clozapine, olanzapine and haloperidol on nitric oxide production by lipopolysaccharide-activated N9 cells.

    PubMed

    Hou, Yue; Wu, Chun Fu; Yang, Jing Yu; He, Xiang; Bi, Xiu Li; Yu, Liang; Guo, Tao

    2006-12-30

    Schizophrenia is a devastating illness of unknown etiology and the basis for its treatment rests in the symptomatic response to antipsychotics. It was found that some of the patients with schizophrenia elicited microglia activation. The present study used lipopolysaccharide (LPS)-activated mouse microglial cell line N9 as an in vitro model to mimic microglia activation seen in the patients with schizophrenia. The effects of clozapine, olanzapine and haloperidol on the release of nitric oxide (NO) by LPS-stimulated N9 cells were investigated. The results showed that olanzapine significantly inhibited NO release by LPS-stimulated N9 cells. Clozapine and haloperidol did not show significant effects on this model. The present study suggested that the inhibiting effect of olanzapine on the NO release by LPS-stimulated microglial cells might be a new mechanism through which olanzapine exhibits its therapeutic effect in the treatment of schizophrenia.

  19. Multi-receptor drug design: Haloperidol as a scaffold for the design and synthesis of atypical antipsychotic agents.

    PubMed

    Peprah, Kwakye; Zhu, Xue Y; Eyunni, Suresh V K; Setola, Vincent; Roth, Bryan L; Ablordeppey, Seth Y

    2012-02-01

    Using haloperidol as a scaffold, new agents were designed to investigate the structural contributions of various groups to binding at CNS receptors associated with atypical antipsychotic pharmacology. It is clear that each pharmacophoric group, the butyrophenone, the piperidine and the 4-chlorophenyl moieties contributes to changes in binding to the receptors of interest. This strategy has resulted in the identification of several new agents, compounds 16, 18, 19, 23, 24 and 25, with binding profiles which satisfy our stated criteria for agents to act as potential atypical antipsychotics. This research demonstrates that haloperidol can serve as a useful lead in the identification and design of new agents that target multiple receptors associated with antipsychotic pharmacology.

  20. Low proarrhythmic potential of citalopram and escitalopram in contrast to haloperidol in an experimental whole-heart model.

    PubMed

    Frommeyer, Gerrit; Brücher, Benedict; von der Ahe, Henning; Kaese, Sven; Dechering, Dirk G; Kochhäuser, Simon; Bogossian, Harilaos; Milberg, Peter; Eckardt, Lars

    2016-10-05

    In several case reports proarrhythmic effects of citalopram and escitalopram have been reported. Systematic analyses on prorarrhythmic effects of these drugs are not yet available. The aim of the present study was to investigate if application of citalopram, escitalopram or haloperidol provokes polymorphic ventricular tachycardia in a sensitive model of proarrhythmia. In isolated rabbit hearts monophasic action potentials and ECG showed a significant QT-prolongation after application of citalopram (2µM: +47ms, 4µM: +56ms, P<0.05) accompanied by an increase of action potential duration (APD) but not dispersion of repolarization. Reduced potassium concentration in bradycardic AV-blocked hearts provoked early afterdepolarizations (EAD) in 2 of 12 hearts but no polymorphic ventricular tachycardia (pVT). Application of escitalopram also increased QT-interval (2µM: +3ms, 4µM: +30ms, P<0.05) and APD without effects on dispersion. 3 of 10 hearts showed EAD and pVT in 2 of 10 hearts (32 episodes). The results were compared to 12 rabbits treated with haloperidol which led to an increase in QT-interval (1µM:+62ms; 2µM:+96ms; P<0.01), APD and dispersion (1µM:+15ms, 2µM:+40ms; P<0.01) and induced EAD in all 12 and pVT in 10 of 12 hearts (152 episodes). Citalopram and escitalopram demonstrated a rather safe electrophysiologic profile despite significant QT prolongation. In contrast, haloperidol led to significant increase of dispersion of repolarization while this parameter remained stable under the influence of citalopram or escitalopram. These results imply that application of citalopram or escitalopram is not as proarrhythmic as some case reports might suggest while haloperidol is torsadogenic.

  1. Aripiprazole and Haloperidol Activate GSK3β-Dependent Signalling Pathway Differentially in Various Brain Regions of Rats

    PubMed Central

    Pan, Bo; Huang, Xu-Feng; Deng, Chao

    2016-01-01

    Aripiprazole, a dopamine D2 receptor (D2R) partial agonist, possesses a unique clinical profile. Glycogen synthase kinase 3β (GSK3β)-dependent signalling pathways have been implicated in the pathophysiology of schizophrenia and antipsychotic drug actions. The present study examined whether aripiprazole differentially affects the GSK3β-dependent signalling pathways in the prefrontal cortex (PFC), nucleus accumbens (NAc), and caudate putamen (CPu), in comparison with haloperidol (a D2R antagonist) and bifeprunox (a D2R partial agonist). Rats were orally administrated aripiprazole (0.75 mg/kg), bifeprunox (0.8 mg/kg), haloperidol (0.1 mg/kg) or vehicle three times per day for one week. The levels of protein kinase B (Akt), p-Akt, GSK3β, p-GSK3β, dishevelled (Dvl)-3, and β-catenin were measured by Western Blots. Aripiprazole increased GSK3β phosphorylation in the PFC and NAc, respectively, while haloperidol elevated it in the NAc only. However, Akt activity was not changed by any of these drugs. Additionally, both aripiprazole and haloperidol, but not bifeprunox, increased the expression of Dvl-3 and β-catenin in the NAc. The present study suggests that activation of GSK3β phosphorylation in the PFC and NAc may be involved in the clinical profile of aripiprazole; additionally, aripiprazole can increase GSK3β phosphorylation via the Dvl-GSK3β-β-catenin signalling pathway in the NAc, probably due to its relatively low intrinsic activity at D2Rs. PMID:27043526

  2. Clozapine and olanzapine exhibit an intrinsic anxiolytic property in two conditioned fear paradigms: contrast with haloperidol and chlordiazepoxide.

    PubMed

    Mead, Alexa; Li, Ming; Kapur, Shitij

    2008-10-01

    Psychotic fear and anxiety disturbances are seen at a relatively high frequency in patients with schizophrenia. Atypical anti-psychotics are believed to show superior efficacy in reducing these symptoms. However, clinical and preclinical evidence regarding their anxiolytic efficacy has been mixed. In this study, we evaluated the possible anxiolytic property of two atypicals clozapine and olanzapine and compared them with typical haloperidol and chlordiazepoxide (a prototype of sedative-anxiolytic drug) in two preclinical models of fear. In Experiment 1, we used a fear-induced passive avoidance and conditioned place aversion paradigm and examined the effects of clozapine (20 mg/kg, sc), haloperidol (0.05 mg/kg, sc) and chlordiazepoxide (10 mg/ kg, ip). In Experiments 2 and 3, we used a two-way active avoidance conditioning paradigm and further compared the effects of clozapine (20 mg/kg, sc), haloperidol (0.05 mg/kg, sc), chlordiazepoxide (10 mg/kg, ip) and three doses of olanzapine (0.5, 1.0, and 2.0 mg/kg, sc). Results show that clozapine and chlordiazepoxide, but not haloperidol, significantly attenuated the shock conditioning-induced place aversion, decreased the amount of defecations and the number of the 22-kHz vocalizations. Clozapine also reduced the shock conditioning-induced hyperthermia. Similar to clozapine, olanzapine also significantly decreased the amount of defecations and reduced the shock conditioning-induced hyperthermia, but it did not inhibit the 22-kHz vocalizations. This study demonstrates that clozapine and olanzapine possess an intrinsic anxiolytic property, which is not attributable to its superior anti-"psychotic" effect or its favorable effects on motor functions or learning and memory processes. These findings also suggest that the combined use of passive avoidance and active avoidance conditioning models can be useful in better differentiating typical and atypical anti-psychotics as well as anxiolytics.

  3. A comparison of the neuro-endocrinological and temperature effects of DU 29894, flesinoxan, sulpiride and haloperidol in normal volunteers.

    PubMed Central

    de Koning, P; de Vries, M H

    1995-01-01

    1. Nineteen healthy male volunteers participated in a double-blind, six-way, crossover study. With a separation of 1 week between sessions, volunteers received randomly one oral dose of each of the following compounds: 3 or 10 mg of the dopamine (DA2) receptor antagonist and serotonin (5HT1A) agonist DU 29894, 1 mg flesinoxan, 400 mg sulpiride, 3 mg haloperidol or placebo. 2. To assess the dopamine (DA2) antagonistic activity of the different compounds, plasma levels of prolactin were assessed at pre-dose, 0.5, 1, 2, 3, 4, 6 and 24 h post-dose. To assess the serotonin (5HT1A) agonistic activity, plasma levels of ACTH, cortisol and growth hormone were assessed at the same time-points as well as body temperature; the latter was also assessed 8 h post-dose. Plasma levels of DU 29894 were assessed at pre-dose and 2, 3, 4 and 24 h post-dose. 3. Sulpiride, haloperidol and both doses of 3 mg and 10 mg DU 29894 produced statistically significant increases in prolactin levels. The increase produced by 3 mg was roughly equivalent to that produced by 3 mg haloperidol whereas the increase produced by 10 mg DU 29894 was significantly larger. 4. Only 10 mg DU 29894 and 1 mg flesinoxan produced statistically significant increases in ACTH, cortisol and growth hormone. All compounds either showed a significant attenuation of the normal day time increase of body temperature (3 mg DU 29894, haloperidol and sulpiride) or a true significant decrease in body temperature (10 mg DU 29894 and flesinoxan).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7756102

  4. Fentanyl, but not haloperidol, entrains persisting circadian activity episodes when administered at 24- and 31-hour intervals

    PubMed Central

    Leffel, Joseph K.; Kosobud, Ann E; Timberlake, William

    2009-01-01

    Administration of several drugs of abuse on a 24-hour schedule has been shown to entrain both pre-drug (anticipatory) and post-drug (evoked) circadian activity episodes that persist for several days when the drug is withheld. The present tested the entrainment effects of fentanyl, an opioid agonist with a noted abuse liability, and haloperidol, an antipsychotic dopamine antagonist without apparent abuse liability. Adult female Sprague-Dawley rats housed under constant light in cages with attached running wheels received repeated low, medium, or high doses of either fentanyl or haloperidol on a 24-hour administration schedule followed by a 31-hour schedule (Experiment 1) or solely on a 31-hour schedule (Experiment 2). The results showed that all three doses of fentanyl entrained both pre-drug and post-drug episodes of wheel running when administered every 24░hours, and the combined pre- and post-fentanyl activity episodes persist for at least 3 days when the drug is withheld during test days. On the 31-hour schedule, fentanyl produced an ``ensuing" activity episode approximately 24░hours post-administration, but failed to produce an anticipatory episode 29–31░hours post-administration. In contrast, haloperidol injections failed to produce both pre-drug episodes on the 24-hour schedule and circadian ensuing episodes on the 31-hour schedule, and post-haloperidol suppression of activity appeared to mask the freerunning activity rhythm. Taken together, these results provide additional evidence that drugs of abuse share a common ability to entrain circadian activity episodes. PMID:19595707

  5. Aripiprazole and Haloperidol Activate GSK3β-Dependent Signalling Pathway Differentially in Various Brain Regions of Rats.

    PubMed

    Pan, Bo; Huang, Xu-Feng; Deng, Chao

    2016-03-28

    Aripiprazole, a dopamine D₂ receptor (D₂R) partial agonist, possesses a unique clinical profile. Glycogen synthase kinase 3β (GSK3β)-dependent signalling pathways have been implicated in the pathophysiology of schizophrenia and antipsychotic drug actions. The present study examined whether aripiprazole differentially affects the GSK3β-dependent signalling pathways in the prefrontal cortex (PFC), nucleus accumbens (NAc), and caudate putamen (CPu), in comparison with haloperidol (a D₂R antagonist) and bifeprunox (a D₂R partial agonist). Rats were orally administrated aripiprazole (0.75 mg/kg), bifeprunox (0.8 mg/kg), haloperidol (0.1 mg/kg) or vehicle three times per day for one week. The levels of protein kinase B (Akt), p-Akt, GSK3β, p-GSK3β, dishevelled (Dvl)-3, and β-catenin were measured by Western Blots. Aripiprazole increased GSK3β phosphorylation in the PFC and NAc, respectively, while haloperidol elevated it in the NAc only. However, Akt activity was not changed by any of these drugs. Additionally, both aripiprazole and haloperidol, but not bifeprunox, increased the expression of Dvl-3 and β-catenin in the NAc. The present study suggests that activation of GSK3β phosphorylation in the PFC and NAc may be involved in the clinical profile of aripiprazole; additionally, aripiprazole can increase GSK3β phosphorylation via the Dvl-GSK3β-β-catenin signalling pathway in the NAc, probably due to its relatively low intrinsic activity at D₂Rs.

  6. Clozapine and Olanzapine Exhibit an Intrinsic Anxiolytic Property in Two Conditioned Fear Paradigms: Contrast with Haloperidol and Chlordiazepoxide

    PubMed Central

    Mead, Alexa; Li, Ming; Kapur, Shitij

    2008-01-01

    Psychotic fear and anxiety disturbances are seen at a relatively high frequency in patients with schizophrenia. Atypical antipsychotics are believed to show superior efficacy in reducing these symptoms. However, clinical and preclinical evidence regarding their anxiolytic efficacy has been mixed. In this study, we evaluated the possible anxiolytic property of two atypicals clozapine and olanzapine and compared them with typical haloperidol and chlordiazepoxide (a prototype of sedative-anxiolytic drug) in two preclinical models of fear. In Experiment 1, we used a fear-induced passive avoidance and conditioned place aversion paradigm and examined the effects of clozapine (20 mg/kg, sc), haloperidol (0.05 mg/kg, sc) and chlordiazepoxide (10 mg/kg, ip). In Experiments 2 and 3, we used a two-way active avoidance conditioning paradigm and further compared the effects of clozapine (20 mg/kg, sc), haloperidol (0.05 mg/kg, sc), chlordiazepoxide (10 mg/kg, ip) and three doses of olanzapine (0.5, 1.0, and 2.0 mg/kg, sc). Results show that clozapine and chlordiazepoxide, but not haloperidol, significantly attenuated the shock conditioning-induced place aversion, decreased the amount of defecations and the number of the 22 kHz vocalizations. Clozapine also reduced the shock conditioning-induced hyperthermia. Similar to clozapine, olanzapine also significantly decreased the amount of defecations and reduced the shock conditioning-induced hyperthermia, but it did not inhibit the 22 kHz vocalizations. This study demonstrates that clozapine and olanzapine possess an intrinsic anxiolytic property, which is not attributable to its superior anti-“psychotic” effect or its favorable effects on motor functions or learning and memory processes. These findings also suggest that the combined use of passive avoidance and active avoidance conditioning models can be useful in better differentiating typical and atypical antipsychotics as well as anxiolytics. PMID:18547622

  7. A controlled Nordic multicentre study of zuclopenthixol acetate in oil solution, haloperidol and zuclopenthixol in the treatment of acute psychosis.

    PubMed

    Baastrup, P C; Alhfors, U G; Bjerkenstedt, L; Dencker, S J; Fensbo, C; Gravem, A; Pedersen, V; Elgen, K; Brekke, B; Fredslund-Andersen, K

    1993-01-01

    Zuclopenthixol acetate--a new injectable formulation with a duration of action of 2-3 days--was compared with conventional intramuscular and oral formulations of haloperidol and zuclopenthixol in the initial treatment of acutely disturbed, psychotic patients. The patients were stratified into 3 diagnostic categories: acute psychoses (48 patients), mania (22 patients), and exacerbation of chronic psychoses (73 patients). The patients were rated on the Brief Psychiatric Rating Scale (BPRS), the Bech-Rafaelsen Mania Rating Scale (BRMAS) (only manic patients) and globally on the Clinical Global Impression (CGI). The study was an open, randomized multicentre trial with a 6-day treatment period. The zuclopenthixol acetate patients received 1-4 doses, the haloperidol patients 1-26 and the zuclopenthixol patients 1-22 doses. The assessments on the CGI showed that all 3 treatments caused a clear reduction of the severity of illness scores in all 3 diagnostic categories, with no differences between treatments. The ratings of the acute and chronic psychotic patients on the BPRS also showed significant reductions in scores with no differences between treatments. All 3 treatments caused a rapid remission of symptoms on the BRMAS. Haloperidol induced hypokinesia in significantly more patients than zuclopenthixol acetate after 24 h. Later there were no significant differences between treatments. Zuclopenthixol acetate fulfils many desires for an amended neuroleptic formulation for the initial treatment of acutely disturbed psychotic patients.

  8. Combination of haloperidol, dexamethasone, and ondansetron reduces nausea and pain intensity and morphine consumption after laparoscopic sleeve gastrectomy.

    PubMed

    Benevides, Márcio Luiz; Oliveira, Sérgio de Souza; Aguilar-Nascimento, José Eduardo

    2013-01-01

    Postoperative nausea and vomiting (PONV) occur frequently after laparoscopic bariatric surgery. The combination of haloperidol, dexamethasone, and ondansetron may reduce these undesirable events. The aim of this study was to evaluate the intensity of nausea and pain, the number of vomiting episodes, and morphine consumption in postoperative (PO) obese patients undergoing laparoscopic sleeve gastrectomy (LSG). A clinical, randomized, controlled, double-blind study conducted with 90 patients with body mass index ≥ 35 kg.cm-2. Patients were divided into three groups of 30 individuals to receive ondansetron 8 mg (Group O); ondansetron 8 mg and dexamethasone 8 mg (Group OD); and ondansetron 8 mg, dexamethasone 8 mg, and haloperidol 2 mg (Group HDO). We evaluated the intensity of nausea and pain using the verbal numeric scale, cumulative number of vomiting episodes, and morphine consumption in the period of 0-2, 2-12, 12-24, and 24-36 hours postoperatively. Nausea intensity was lower in Group HDO compared to Group O (p = 0.001), pain intensity was lower in Group HDO compared to Group O (p = 0.046), and morphine consumption was lower in Group HDO compared to Group O (p = 0.037). There was no difference between groups regarding the number of vomiting episodes (p = 0.052). The combination of haloperidol, ondansetron, and dexamethasone reduced nausea and pain intensity and morphine consumption in postoperative obese patients undergoing LSG.

  9. Neuroleptics and learning: effects of haloperidol, molindone, mesoridazine and thioridazine on the behavior of pigeons under a repeated acquisition procedure.

    PubMed

    Poling, A; Cleary, J; Berens, K; Thompson, T

    1990-12-01

    The purpose of the present study was to examine the effects of haloperidol (0.3-10 mg/kg), molindone (0.3-5.6 mg/kg), mesoridazine (0.3-10) and thioridazine (0.3-25 mg/kg) on the behavior of pigeons exposed to a repeated acquisition procedure. At sufficiently high doses, each of these neuroleptics increased error rates (interfered with learning) and reduced rate of responding. When the drugs were compared on the basis of absolute doses administered, haloperidol disrupted behavior at doses considerably lower than the other drugs. If, however, chlorpromazine equivalent doses were examined, haloperidol was the least disruptive of the four drugs. Comparing the degree of behavioral disruption produced by the four drugs with their relative neuroreceptor affinities for dopamine D-2, cholinergic muscarinic, histamine H1, alpha-1 adrenergic and alpha-2 adrenergic receptors suggests that behavioral disruption cannot be attributed in any simple way to dopamine or acetylcholine receptor blockade. The relationship between the behavioral effects of neuroleptics and their simple neuropharmacological actions must be considered as highly tentative.

  10. Positron emission tomography with (18F)methylspiperone demonstrates D2 dopamine receptor binding differences of clozapine and haloperidol.

    PubMed

    Karbe, H; Wienhard, K; Hamacher, K; Huber, M; Herholz, K; Coenen, H H; Stöcklin, G; Lövenich, A; Heiss, W D

    1991-01-01

    Four schizophrenic patients were investigated with dynamic positron emission tomography (PET) using (18F)fluorodeoxyglucose (FDG) and (18F)methylspiperone (MSP) as tracers. Two schizophrenics were on haloperidol therapy at the time of MSP PET. The other two schizophrenics were treated with clozapine, in one of them MSP PET was carried out twice with different daily doses (100 mg and 450 mg respectively). Neuroleptic serum levels were measured in all patients. Results were compared with MSP PET of two drug-free male control subjects and with a previous fluoroethylspiperone (FESP) study of normals. Three hours after tracer injection specific binding of MSP was observed in the striatum in all cases. The striatum to cerebellum ratio was used to estimate the degree of neuroleptic-caused striatal D2 dopamine receptor occupancy. In the haloperidol treated patients MSP binding was significantly decreased, whereas in the clozapine treated patients striatum to cerebellum ratio was normal. Even the increase of clozapine dose in the same patient had no influence on this ratio. Despite the smaller number of patients the study shows for the first time in humans that striatal MSP binding reflects the different D2 dopamine receptor affinities of clozapine and haloperidol.

  11. High estrogen and chronic haloperidol lead to greater amphetamine-induced BOLD activation in awake, amphetamine-sensitized female rats.

    PubMed

    Madularu, Dan; Kulkarni, Praveen; Yee, Jason R; Kenkel, William M; Shams, Waqqas M; Ferris, Craig F; Brake, Wayne G

    2016-06-01

    The ovarian hormone estrogen has been implicated in schizophrenia symptomatology. Low levels of estrogen are associated with an increase in symptom severity, while exogenous estrogen increases the efficacy of antipsychotic medication, pointing at a possible interaction between estrogen and the dopaminergic system. The aim of this study is to further investigate this interaction in an animal model of some aspects of schizophrenia using awake functional magnetic resonance imaging. Animals receiving 17β-estradiol and haloperidol were scanned and BOLD activity was assessed in response to amphetamine. High 17β-estradiol replacement and chronic haloperidol treatment showed increased BOLD activity in regions of interest and neural networks associated with schizophrenia (hippocampal formations, habenula, amygdala, hypothalamus etc.), compared with low, or no 17β-estradiol. These data show that chronic haloperidol treatment has a sensitizing effect, possibly on the dopaminergic system, and this effect is dependent on hormonal status, with high 17β-estradiol showing the greatest BOLD increase. Furthermore, these experiments further support the use of imaging techniques in studying schizophrenia, as modeled in the rat, but can be extended to addiction and other disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomised, double-blind, placebo-controlled trial.

    PubMed

    Page, Valerie J; Ely, E Wesley; Gates, Simon; Zhao, Xiao Bei; Alce, Timothy; Shintani, Ayumi; Jackson, Jim; Perkins, Gavin D; McAuley, Daniel F

    2013-09-01

    Delirium is frequently diagnosed in critically ill patients and is associated with poor clinical outcomes. Haloperidol is the most commonly used drug for delirium despite little evidence of its effectiveness. The aim of this study was to establish whether early treatment with haloperidol would decrease the time that survivors of critical illness spent in delirium or coma. We did this double-blind, placebo-controlled randomised trial in a general adult intensive care unit (ICU). Critically ill patients (≥18 years) needing mechanical ventilation within 72 h of admission were enrolled. Patients were randomised (by an independent nurse, in 1:1 ratio, with permuted block size of four and six, using a centralised, secure web-based randomisation service) to receive haloperidol 2.5 mg or 0.9% saline placebo intravenously every 8 h, irrespective of coma or delirium status. Study drug was discontinued on ICU discharge, once delirium-free and coma-free for 2 consecutive days, or after a maximum of 14 days of treatment, whichever came first. Delirium was assessed using the confusion assessment method for the ICU (CAM-ICU). The primary outcome was delirium-free and coma-free days, defined as the number of days in the first 14 days after randomisation during which the patient was alive without delirium and not in coma from any cause. Patients who died within the 14 day study period were recorded as having 0 days free of delirium and coma. ICU clinical and research staff and patients were masked to treatment throughout the study. Analyses were by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Registry, number ISRCTN83567338. 142 patients were randomised, 141 were included in the final analysis (71 haloperidol, 70 placebo). Patients in the haloperidol group spent about the same number of days alive, without delirium, and without coma as did patients in the placebo group (median 5 days [IQR 0-10] vs 6 days [0-11] days; p=0

  13. Efficacy of Intravenous Haloperidol on the duration of Delirium and Coma in Critically Ill Patients (Hope-ICU): a Randomised, Placebo-Controlled Trial

    PubMed Central

    Page, Valerie J; Ely, E Wesley; Gates, Simon; Zhao, Xiao Bei; Alce, Timothy; Shintani, Ayumi; Jackson, Jim; Perkins, Gavin D; McAuley, Daniel F

    2016-01-01

    Background Delirium is frequently diagnosed in critically ill patients and is associated with poor clinical outcomes. Haloperidol is the most commonly used drug for delirium despite little evidence of its effectiveness. The aim of this study was to establish whether early treatment with haloperidol would decrease the time that survivors of critical illness spent in delirium or in coma. Methods We did this double-blind, placebo-controlled randomised trial in a general adult intensive care unit (ICU). Critically ill patients (≥18 years) needing mechanical ventilation within 72 of admission were enrolled. Patients were randomised (by an independent nurse, in 1:1 ratio, with permuted block size of four and six, using a centralised, secure web-based randomisation service) to receive haloperidol 2·5mgs or 0·9% saline placebo intravenously every 8 h irrespective of coma or delirium status. Study drug was discontinued on ICU discharge, once delirium-free and coma-free for 2 consecutive days, or after a maximum of 14 days treatment, which ever came first. Delirium was assessed using the confusion assessment method - for the ICU (CAM-ICU). The primary outcome was delirium-free and coma-free days, defined as the number of days in the first 14 days after randomisation during which the patient was alive without delirium and not in coma from any cause. Patients who died within the 14-day study period were recorded as having 0 days free of delirium and coma. ICU clinical and research staff and patients were masked to treatment throughout the study. Analyses were by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Registry, number ISRCTN83567338. Findings 142 patients were randomised, 141 were included in the final analysis (71 haloperidol, 70 placebo). Patients in the haloperidol group spent about the same number of days alive, without delirium, and without coma as did patients in the placebo group (median 5 days [IQR 0

  14. Evaluating the Effects and Safety of Intravenous Lipid Emulsion on Haloperidol-Induced Neurotoxicity in Rabbit

    PubMed Central

    Moshiri, Mohammad; Mohammadpour, Amir Hooshang; Vahabzadeh, Maryam; Etemad, Leila; Memar, Bahram; Hosseinzadeh, Hossein

    2014-01-01

    There are many reports on the effect of intravenous lipid emulsion (ILE) as an antidote in drugs related toxicities. We determined the effects of ILE on neurotoxicity of haloperidol (HA), a highly lipophilic antipsychotic, as a model of antipsychotics poisoning. We used six groups of five male rabbits. Two groups received distilled water intravenously followed by infusions of either 18 mL/kg of normal saline or ILE 20%, after 30 minutes. The third group received 18 mL/kg of normal saline after HA (2.6 mg/kg) administration. The three other groups received ILE 20% solution (6, 12, and 18 mL/kg) following HA injection. Catalepsy scores, temperature, pupil size, and mortality rate were measured at 0, 0.5, 1, 2, 3, 4, 8, and 24 hours after HA administration began. Blood and tissue samples were taken from all animals at 24 hours or at death time for biochemical, cell count, and pathological studies. ILE reversed cataleptic scores, miotic pupils, and hypothermia of HA intoxication much faster than normal saline (P < 0.001). Biochemical complications and mortality rate of the animals were significantly higher in the HA + 18 mL/Kg ILE group. ILE reversed sings of HA neurotoxicity; however, synergistic effect of high dose of ILE and HA increased complications and mortality. PMID:24971362

  15. [A case of malignant syndrome triggered by the use of haloperidol and chrorpromazine].

    PubMed

    Konishi, K; Fujimoto, K; Kubota, M; Ogawa, H

    1997-04-01

    Malignant syndrome is a disease characterized by high fever, extrapyramidal syndrome and dysautonomia recognized during or at the time of stopping administration of antipsychotic medication and it is the most severe and lethal side effect of antipsychotic medication. In the present case, triggered by the use of haloperidol and chrorpromazine, lisp of the tongue, trembling of both hands, perspiration on the hands and legs and other symptoms appeared. Later, difficulty of breathing, trembling of whole body and massive perspiration appeared, and disturbance of autonomic nervous system such as mydriasis and perspiration occurred. By blood analysis, CPK showed a high value of 518 U.l-1 and malignant syndrome was suspected. After i.v. administration of dantololene 20 mg, the perspiration was and the trembling were reduced. With this improvement of symptoms the patient was released from the hospital after about one month. These care suggests that a fundamental knowledge of antipsychotic agents must be acquired and attentive care be given when such drugs are administered.

  16. Evaluating the effects and safety of intravenous lipid emulsion on haloperidol-induced neurotoxicity in rabbit.

    PubMed

    Moshiri, Mohammad; Mohammadpour, Amir Hooshang; Vahabzadeh, Maryam; Etemad, Leila; Memar, Bahram; Hosseinzadeh, Hossein

    2014-01-01

    There are many reports on the effect of intravenous lipid emulsion (ILE) as an antidote in drugs related toxicities. We determined the effects of ILE on neurotoxicity of haloperidol (HA), a highly lipophilic antipsychotic, as a model of antipsychotics poisoning. We used six groups of five male rabbits. Two groups received distilled water intravenously followed by infusions of either 18 mL/kg of normal saline or ILE 20%, after 30 minutes. The third group received 18 mL/kg of normal saline after HA (2.6 mg/kg) administration. The three other groups received ILE 20% solution (6, 12, and 18 mL/kg) following HA injection. Catalepsy scores, temperature, pupil size, and mortality rate were measured at 0, 0.5, 1, 2, 3, 4, 8, and 24 hours after HA administration began. Blood and tissue samples were taken from all animals at 24 hours or at death time for biochemical, cell count, and pathological studies. ILE reversed cataleptic scores, miotic pupils, and hypothermia of HA intoxication much faster than normal saline (P < 0.001). Biochemical complications and mortality rate of the animals were significantly higher in the HA + 18 mL/Kg ILE group. ILE reversed sings of HA neurotoxicity; however, synergistic effect of high dose of ILE and HA increased complications and mortality.

  17. Evaluation of intravenous lipid emulsion on haloperidol-induced hypotension in rabbits.

    PubMed

    Moshiri, Mohammad; Vahabzadeh, Maryam; Mohammadpour, Amir Hooshang; Hosseinzadeh, Hossein

    2016-05-01

    There are many reports on the effects of intravenous lipid emulsion (ILE) as an antidote in drug toxicity. Haloperidol (HAL) is a butyrophenone antipsychotic agent which is highly lipophilic. Hypotension is an important adverse effect of HAL administration and overdose. The aim of this study was to investigate the beneficial hemodynamic effects of ILE on acute HAL poisoning. We used six groups of five male rabbits. Two groups received aseptic distilled water intravenously followed by infusion of 18.6 ml/kg normal saline, as negative control group, or ILE 20% after 0.5 h. The third group received 18.6 ml/kg normal saline after HAL infusion (2.6 mg/kg). The other three groups received ILE 20% solution (6, 12, and 18.6 ml/kg) following HAL (2.6 mg/kg) administration. We measured blood pressure at 0, 0.5, 1, 2, 3, 4, 8, and 24 h after starting HAL administration, from left forelimb using a noninvasive method that was carried out automatically with a neonatal intensive care unit bedside monitor. ILE 20% at the dose of 18 ml/kg could return the reduced mean arterial pressure and diastolic blood pressure sooner than the other doses and normal saline. In conclusion, ILE could reverse HAL-induced hypotension same as the other lipophilic drugs. However, the clinical use of ILE for this purpose needs more evaluation to determine its exact indication and safety.

  18. ( sup 125 I)Iodoazidococaine, a photoaffinity label for the haloperidol-sensitive sigma receptor

    SciTech Connect

    Kahoun, J.R.; Ruoho, A.E. )

    1992-02-15

    A carrier-free radioiodinated cocaine photoaffinity label, (-)-3-({sup 125}I)iodo-4-azidococaine (({sup 125}I)IACoc), has been synthesized and used as a probe for cocaine-binding proteins. Photoaffinity labeling with 0.5 nM ({sup 125}I)IACoc resulted in selective derivatization of a 26-kDa polypeptide with the pharmacology of a sigma receptor in membranes derived from whole rat brain, rat liver, and human placenta. ({sup 125}I)IACoc labeling of the 26-kDa polypeptide was also inhibited by 10 {mu}M imipramine, amitriptyline, fluoxetine, benztropine, and tetrabenazine. The size of the ({sup 125}I)I-ACoc-labeled proteins is consistent with the size of proteins photolabeled in guinea pig brain and liver membranes by using the sigma photolabel azido-({sup 3}H)DTG. Kinetic analysis of ({sup 125}I)IACoc binding to rat liver microsomes revealed two sites with K{sub d} values of 19 and 126 pM, respectively. The presence or absence of proteolytic inhibitors during membrane preparation did not alter the size of the photolabeled sigma receptor, indicating that the 26-kDa polypeptide was not derived from a larger protein. In summary, ({sup 125}I)IACoc is a potent and highly specific photoaffinity label for the haloperidol-sensitive sigma receptor and will be useful for its biochemical and molecular characterization.

  19. Enduring behavioural and biochemical effects in the adult rat after prolonged postnatal administration of haloperidol.

    PubMed

    Cuomo, V; Cagiano, R; Coen, E; Mocchetti, I; Cattabeni, F; Racagni, G

    1981-01-01

    Rats were administered 0.5 mg/kg SC of haloperidol (H) or saline (S) daily from day 1 after birth until 20 days of age. At 60 days of age (40 days after the postnatal treatment with H or S was interrupted) the stereotyped behaviour and the effects on locomotor activity elicited by apomorphine in S- and H-pretreated rats were investigated. The intensity of apomorphine (0.5--1 mg/kg, SC)-induced stereotyped behaviour was significantly greater in the H-pretreated group than in S-pretreated animals and this was accompanied by a much more marked reduction of locomotor activity in H-pretreated than in S-pretreated rats. Finally, at 80 days of age (60 days after the postnatal treatment with H or S was interrupted) rats were subjected to a Differential Reinforcement of Low Rates schedule (DRL 15-s). The results indicate that the acquisition of the DRL task performance criterion (Rs/Rf less than or equal to 2.5) was significantly more rapid on S-pretreated rats than in H-pretreated ones. In parallel biochemical experiments, acute H produced smaller increases in dopamine turnover in chronic H-treated rats compared with S-treated controls. These data indicate that H treatment in neonatal rats induces behavioural and biochemical changes which can be observed up to 60 days after H withdrawal.

  20. A comparison of risperidone and haloperidol for the risk of ischemic stroke in the elderly: a propensity score-matched cohort analysis.

    PubMed

    Shin, Ju-Young; Choi, Nam-Kyong; Lee, Joongyub; Park, Mi-Ju; Lee, Shin Haeng; Park, Byung-Joo

    2015-08-01

    With an increase in antipsychotic use in the elderly, the safety profile of antipsychotics has been emphasized. Strong concerns have been raised about whether the risk of ischemic stroke differs between risperidone and haloperidol. This study compared the risk of ischemic stroke between elderly patients taking risperidone and haloperidol. We conducted a retrospective cohort study using the Korea Health Insurance Review and Assessment Service database, applying a propensity-matched analysis. The cohort consisted of elderly patients who were newly prescribed haloperidol or risperidone between January 1, 2006 and December 31, 2009. Patients with prior cerebrovascular diseases (ICD-10, I60-I69), transient ischemic attack (ICD-10, G45), or cerebral tumors (ICD-10, C31) during 365 days prior to the initiation date were excluded. The study subjects were selected by propensity score matching. The outcome was defined as the first hospitalization for ischemic stroke (ICD-10, I63). Cox regression models were used to estimate the hazard ratio (HR) and 95% confidence intervals (95% CI) for ischemic stroke with haloperidol compared with risperidone use. A total of 14,103 patients were included in the propensity-matched cohort for each drug. Overall, the incidence rate was higher for haloperidol users compared to the risperidone users (6.43 per 1000 person-years vs. 2.88 per 1000 person-years). A substantially increased risk was observed in haloperidol users (adjusted HR = 2.02, 95% CI, 1.12-3.62). The evidence showed that haloperidol should be prescribed in the elderly with caution. © The Author(s) 2015.

  1. Beneficial effects of EGb761 and vitamin E on haloperidol-induced vacuous chewing movements in rats: Possible involvement of S100B mechanisms.

    PubMed

    An, Hui Mei; Tan, Yun Long; Shi, Jing; Wang, Zhi Ren; Li, Jia; Wang, Yue Chan; Lv, Meng Han; Zhou, Dong Feng; Soares, Jair C; Kosten, Thoams R; Yang, Fu De; Zhang, Xiang Yang

    2016-01-15

    Tardive dyskinesia (TD) is a serious side effect induced by the long-term administration of typical antipsychotics. The pathophysiology of TD remains unclear, but experimental evidence suggests that neurodegeneration caused by free radicals may play an important role in TD development. S100B is considered a potential biomarker of structural neural and glial damage. This study investigated S100B expression in TD-related brain regions and assessed the effect of antioxidants Gingko biloba leaf extract (EGb761) and vitamin E (VE) on S100B in TD rats. A total of 32 rats were randomly divided into 4 study groups: saline control (saline), haloperidol alone group (Hal), EGb761-haloperidol (EGb-Hal), and vitamin E-haloperidol (VE-Hal). Rats were treated with haloperidol intraperitoneal injections (2mg/kg/day) each day for 5 weeks. EGb761 (50mg/kg/day) and VE (20mg/kg/day) were then administered during a 5-week withdrawal period. We performed behavioral assessments and immunohistochemically analyzed S100B expression in four TD-related brain regions. Our findings demonstrated that haloperidol administration led to a progressive increase in VCMs and in S100B expression in all four brain regions. Both EGb761 and VE reversed these changes, and there were no group differences between the EGb761 and VE groups. Our results indicated that long-term administration of haloperidol may induce VCMs and increase S100B expression in TD-related brain regions, and S100B may be a significant biomarker related to TD pathophysiology. Moreover, the antioxidant capacity of EGb761 and VE coupled with the possible neuroprotective effects of S100B may account for their success in improving the symptoms of haloperidol-induced TD. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. The efficacy and safety of blonanserin compared with haloperidol in acute-phase schizophrenia: a randomized, double-blind, placebo-controlled, multicentre study.

    PubMed

    Garcia, Esther; Robert, Marta; Peris, Francesc; Nakamura, Hiroshi; Sato, Noriko; Terazawa, Yoshikatsu

    2009-01-01

    Blonanserin is a novel atypical antipsychotic agent with potent dopamine D(2) and serotonin 5-HT(2) antagonist properties. It may potentially have a lower incidence of adverse events than other antipsychotic agents. To determine the efficacy and safety of three doses of blonanserin compared with placebo and haloperidol in patients with acute-phase schizophrenia. This was a 6-week, randomized, double-blind, placebo- and haloperidol-controlled, international, multicentre study. Patients with an acute exacerbation of their schizophrenia, with a Positive and Negative Syndrome Scale (PANSS) score >/=70 and a Clinical Global Impression - Severity of Illness (CGI-S) score >/=4 ('moderately ill') [with no decrease >/=20% or >/=1 point, respectively, during the wash-out period] were randomized into one of five treatment groups (blonanserin 2.5, 5 or 10 mg, haloperidol 10 mg or placebo once daily). Patients were assessed weekly for clinical efficacy, adverse events, extrapyramidal symptoms (EPS) and drug compliance, and were assessed biweekly for other safety variables. All 307 randomized patients received at least one dose of study medication and 228 (74.3%) completed the study. The mean reduction in PANSS total score at week 6 was significantly greater with all active treatments compared with placebo (-12.58; p < 0.001); blonanserin 10 mg was significantly superior to blonanserin 2.5 mg (-30.18 vs -20.6; p < 0.001), but blonanserin 5 mg (-27.19) and haloperidol 10 mg (-28.16) were not. All active treatments showed greater efficacy against the positive symptoms of schizophrenia, and blonanserin (5 and 10 mg) was more effective against the negative symptoms than haloperidol. Blonanserin was well tolerated at all doses and there was no evidence of clinically important weight gain, orthostatic hypotension, corrected QT interval prolongation or clinically relevant changes in laboratory test results. Haloperidol caused persistent elevation in prolactin levels, but this was not

  3. A double-blind controlled study of intramuscular zuclopenthixol acetate and liquid oral haloperidol in the treatment of schizophrenic patients with acute exacerbation.

    PubMed

    Chouinard, G; Safadi, G; Beauclair, L

    1994-12-01

    We carried out a 9-day double-blind clinical trial comparing intramuscular zuclopenthixol acetate with liquid oral haloperidol in the treatment of 40 newly admitted schizophrenic patients with acute exacerbation. A parallel-group design was used with stratification by sex. Zuclopenthixol acetate (50 to 150 mg) was given intramuscularly every 3 days, whereas liquid haloperidol (10 to 30 mg daily) was given orally three times a day, with supplementary doses of each medication given under double-blind conditions when needed for agitation. No other sedative drugs, including benzodiazepines, were administered. The mean daily dose was 18.9 mg for haloperidol as compared with a mean dose per 3 days of 117.6 mg for zuclopenthixol. The two treatments were found to be equally efficacious on the Brief Psychiatric Rating Scale and Clinical Global Impression Scale. Both drugs induced similar extrapyramidal side effects. However, more tremors were associated with zuclopenthixol as was a tendency for tardive dyskinesia to be unmasked at the end of the injection interval. Sedation was higher with zuclopenthixol acetate than with haloperidol. Serum creatinine phosphokinase levels were not significantly increased after zuclopenthixol injections. The results of this trial suggest that zuclopenthixol acetate given intramuscularly every second to third day offers an alternative to conventional liquid oral haloperidol in the management of acute schizophrenia.

  4. Effect of d-limonene, alpha-pinene and cineole on in vitro transdermal human skin penetration of chlorpromazine and haloperidol.

    PubMed

    Almirall, M; Montaña, J; Escribano, E; Obach, R; Berrozpe, J D

    1996-07-01

    The aim of this research is to carry out a comparative study of the ability to cross human skin of two neuroleptic drugs: chlorpromazine (CAS 50-53-3) and haloperidol (CAS 52-86-8), in the absence and in the presence of three terpenes (cineole, d-limonene and alpha-pinene) with the purpose of considering the possibility of improving their transdermal penetration profile. Franz diffusion cells were used, in conjunction with human skin as permeation membrane. The permeation parameters calculated were permeability constant (Kp), flux (J) and lag time (Tl) in the presence and in the absence of enhancers. None of the three enhancers assayed improved the penetration profile of chlorpromazine, and d-limonene even reduced the transdermal permeability (enhancement index, EI = 0.67) since its coefficient of relative activity was reduced, (Xr = 0.73). Cineole and d-limonene increased the permeation profile of haloperidol, giving EI values of 1.95 and 4.21, respectively, and leading to a fourfold increase in the flux value for both enhancers. alpha-Pinene did not modify the permeation profile of haloperidol. None of the three terpenes assayed had a significant effect on the lag time of chlorpromazine or haloperidol. In these experimental conditions the concentration values predicted at steady state of chlorpromazine formulated without enhancers are within the therapeutic range. In contrast, therapeutic levels of haloperidol cannot be predicted in the absence of enhancers such as d-limonene or cineole.

  5. Comparison of long-term efficacy and safety of risperidone and haloperidol in children and adolescents with autistic disorder. An open label maintenance study.

    PubMed

    Gencer, Ozlem; Emiroglu, F Neslihan Inal; Miral, Suha; Baykara, Burak; Baykara, Aysen; Dirik, Eray

    2008-06-01

    The aim of the study was to investigate safety, efficacy and tolerability of risperidone in comparison with haloperidol in the long-term treatment of autistic disorder. This was an open-label continuation study of the randomized, double-blind, controlled trial of risperidone and haloperidol study for 12 week in autistic children and adolescents. A total of 28 subjects between 8 and 18 ages with autistic disorder were enrolled to the open label phase of the study. Behavioral rating scales (Clinical Global Impression Scale [CGI-I], Ritvo-Freeman Real Life Rating Scale [RF-RLRS]), Aberrant Behavior Checklist [ABC], Turgay DSM-IV Pervasive Developmental Disorder Rating Scale [TPDDRS]) and safety assessment scales (Extrapyramidal Symptoms Rating Scale [ESRS], UKU-Side Effect Rating Scale) were performed at 12, 16, 20 and 24 weeks, following the 12 week double-blind phase. Risperidone and haloperidol treatments were applied with a once daily dosage regimen as 0.01-0.08 mg/kg/day. Risperidone led to a significant greater reduction on CGI scale. There was significant improvement on RF-RLRS sensory motor and language subscale and ABC scores in risperidone group. Weight gain was observed more frequently in the haloperidol group at week 24. These results demonstrate that risperidone is more efficacious and well tolerated than haloperidol in the long-term maintenance treatment of autistic disorder.

  6. Determination of oxidative stress and activities of antioxidant enzymes in guinea pigs treated with haloperidol

    PubMed Central

    GUMULEC, JAROMIR; RAUDENSKA, MARTINA; HLAVNA, MARIAN; STRACINA, TIBOR; SZTALMACHOVA, MARKETA; TANHAUSEROVA, VERONIKA; PACAL, LUKAS; RUTTKAY-NEDECKY, BRANISLAV; SOCHOR, JIRI; ZITKA, ONDREJ; BABULA, PETR; ADAM, VOJTECH; KIZEK, RENE; NOVAKOVA, MARIE; MASARIK, MICHAL

    2013-01-01

    Guinea pigs (Cavia porcellus) were treated with haloperidol (HP), and free radical (FR) and ferric reducing antioxidant power (FRAP) assays were used to determine oxidative stress levels. Furthermore, the superoxide dismutase (SOD), glutathione reductase (GR) and glutathione-S-transferase (GST) activity levels were detected and glucose levels and the reduced and oxidized glutathione (GSH/GSSG) ratio were measured in HP-treated and untreated guinea pigs. The present study demonstrated that the administration of HP causes significant oxidative stress in guinea pigs (P=0.022). In animals treated with HP, the activity of GST was significantly increased compared with a placebo (P= 0.007). The elevation of SOD and GR activity levels and increase in the levels of glutathione (GSH) in HP-treated animals were not statistically significant. In the HP-untreated animals, a significant positive correlation was observed between oxidative stress detected by the FR method and GST (r=0.88, P=0.008) and SOD (r=0.86, P= 0.01) activity levels, respectively. A significant negative correlation between the levels of plasma glucose and oxidative stress detected by the FRAP method was observed (r=−0.78, P=0.04). Notably, no significant correlations were observed in the treated animals. In the HP-treated group, two subgroups of animals were identified according to their responses to oxidative stress. The group with higher levels of plasma HP had higher enzyme activity and reactive oxygen species production compared with the group with lower plasma levels of HP. The greatest difference in activity (U/μl) between the two groups of animals was for GR. PMID:23403848

  7. Determination of oxidative stress and activities of antioxidant enzymes in guinea pigs treated with haloperidol.

    PubMed

    Gumulec, Jaromir; Raudenska, Martina; Hlavna, Marian; Stracina, Tibor; Sztalmachova, Marketa; Tanhauserova, Veronika; Pacal, Lukas; Ruttkay-Nedecky, Branislav; Sochor, Jiri; Zitka, Ondrej; Babula, Petr; Adam, Vojtech; Kizek, Rene; Novakova, Marie; Masarik, Michal

    2013-02-01

    Guinea pigs (Cavia porcellus) were treated with haloperidol (HP), and free radical (FR) and ferric reducing antioxidant power (FRAP) assays were used to determine oxidative stress levels. Furthermore, the superoxide dismutase (SOD), glutathione reductase (GR) and glutathione-S-transferase (GST) activity levels were detected and glucose levels and the reduced and oxidized glutathione (GSH/GSSG) ratio were measured in HP-treated and untreated guinea pigs. The present study demonstrated that the administration of HP causes significant oxidative stress in guinea pigs (P=0.022). In animals treated with HP, the activity of GST was significantly increased compared with a placebo (P= 0.007). The elevation of SOD and GR activity levels and increase in the levels of glutathione (GSH) in HP-treated animals were not statistically significant. In the HP-untreated animals, a significant positive correlation was observed between oxidative stress detected by the FR method and GST (r=0.88, P=0.008) and SOD (r=0.86, P= 0.01) activity levels, respectively. A significant negative correlation between the levels of plasma glucose and oxidative stress detected by the FRAP method was observed (r=-0.78, P=0.04). Notably, no significant correlations were observed in the treated animals. In the HP-treated group, two subgroups of animals were identified according to their responses to oxidative stress. The group with higher levels of plasma HP had higher enzyme activity and reactive oxygen species production compared with the group with lower plasma levels of HP. The greatest difference in activity (U/μl) between the two groups of animals was for GR.

  8. Haloperidol and clozapine affect social behaviour in rats postnatally lesioned in the ventral hippocampus.

    PubMed

    Becker, Axel; Grecksch, Gisela

    2003-08-01

    Neonatal ibotenic acid lesion of the ventral hippocampus results in altered patterns of social behaviour. After puberty, lesioned animals spent less time in social interaction and the nonaggressive/aggressive behaviour ratio shifted towards increased aggressiveness. In this study, the effects on social behaviour of the neuroleptic drugs haloperidol (HAL) and clozapine (CLO) after acute and subchronic treatment were studied. Seven-day-old rats were lesioned and social behaviour was tested at the age of 13 weeks. Drug effects were tested after acute (HAL 0.025 mg/kg, CLO 1.0 mg/kg) and subchronic (10 injections, HAL 0.075 mg/kg, CLO 5.0 mg/kg) administration. For comparison, diazepam (DZP, 0.5 mg/kg) was used in the acute experiment. After acute administration, DZP had no effect on social behaviour in sham-lesioned rats, but nonaggressive behaviour increased significantly in lesioned animals. CLO and HAL did reduce the time sham-lesioned rats spent in social contact, and CLO also increased % nonaggressive behaviour in lesioned rats. Here, HAL had no effect. Subchronic administration did not alter social behaviour in sham-lesioned animals. However, CLO increased the time lesioned animals spent in social interaction, whereas HAL had an effect on nonaggressive behaviour. The results of this study indicate that the lesion model is sensitive to differentiated effects of classical neuroleptic drugs such as HAL and atypical neuroleptic drugs like CLO. It might be a useful tool in the search for potential neuroleptic drugs.

  9. Extracellular GABA in globus pallidus increases during the induction of oral tremor by haloperidol but not by muscarinic receptor stimulation.

    PubMed

    Collins-Praino, Lyndsey E; Podurgiel, Samantha J; Kovner, Rotem; Randall, Patrick A; Salamone, John D

    2012-09-01

    Tremulous jaw movements in rats can be induced by several conditions associated with parkinsonism and tremorogenesis, including dopamine depletion, dopamine antagonism, and cholinomimetic drugs. Previous research indicates that neostriatal mechanisms are involved in the generation of tremulous jaw movements, but the striatal output pathways involved in these movements remain uncertain. One important pathway for striatal output is the GABAergic striatopallidal system. The present studies were undertaken to determine if extracellular levels of GABA in globus pallidus are associated with the induction of tremulous jaw movements by either a dopamine D2 antagonist (haloperidol) or a cholinomimetic (the muscarinic agonist pilocarpine). The first experiment studied the effects of both acute and repeated (i.e. 8 days) administration of the D2 antagonist haloperidol. In the second experiment, the effect of acute administration of the muscarinic agonist pilocarpine on GABA levels in the globus pallidus was examined. In both experiments, behavioral observations of tremulous jaw movements were conducted in parallel with the collection of microdialysis samples. Acute and repeated haloperidol treatment induced tremulous jaw movements, and significantly elevated extracellular GABA in globus pallidus. Pooling across all treatment groups, there was a significant positive correlation between pallidal GABA levels and the number of tremulous jaw movements induced during the first three samples collected after injection. However, injection of 4.0mg/kg pilocarpine had no effect on pallidal GABA release, despite the robust induction of tremulous jaw movements. These results indicate that the tremulous jaw movements induced by dopamine D2 antagonism and those induced through muscarinic receptor stimulation may be generated via distinct mechanisms.

  10. Low doses of haloperidol combined with ondansetron are not effective for prophylaxis of postoperative nausea and vomiting in susceptible patients.

    PubMed

    Veiga-Gil, Leonor; López-Olaondo, Luis; Pueyo, Javier; Callejas, Raquel; Duque, Paula; Carrascosa, Francisco

    2015-02-01

    In this observational study we reviewed the efficacy and side effects of different antiemetic combinations used in our hospital for postoperative nausea and vomiting (PONV) prophylaxis in high-risk women undergoing highly emetogenic surgery. After reviewing retrospectively the medical records of patients undergoing highly emetogenic elective surgeries under general anaesthesia, we selected 368 women whose Apfel risk score was ≥ 3 and receiving a combination of 2 antiemetics for PONV prophylaxis. We analysed the incidence of PONV at 2, 6, 12 and 24h after surgery, antiemetic rescue requirements, pattern of occurrence of PONV, side effects and level of sedation were also assessed. The main goal was complete response defined as no PONV within 24h after surgery. Ondansetron 4mg i.v. plus dexamethasone 8mg i.v. (O&Dex), haloperidol 1mg i.v. (O&Hal1), haloperidol 2mg i.v. (O&Hal2) or droperidol 1.25mg i.v. (O&Dro) were the combinations most frequently used. The complete response was better in groups O&Dex: 68.5% (CI: 58-78), O&Hal2: 64.1% (CI: 53-74) and O&Dro 63% (CI: 52-73) than in group O&Hal1: 41.3% (CI: 31-52) (p<0,01). Peak incidence of PONV occurred within the 2-6h period. The incidence of side effects was higher in group O&Hal2. In high risk patients for PONV who underwent highly emetogenic surgeries, the efficacy of low-dose haloperidol (1mg) in combination is limited. Higher doses (2mg) are more effective but its use is associated with a high incidence of side effects. Copyright © 2013 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Oral Haloperidol or Risperidone Treatment in Rats: Temporal Effects on Nerve Growth Factor Receptors, Cholinergic Neurons, and Memory Performance

    PubMed Central

    Terry, Alvin V.; Gearhart, Debra A.; Warner, Samantha E.; Zhang, Guodong; Bartlett, Michael G.; Middlemore, Mary-Louise; Beck, Wayne D.; Mahadik, Sahebarao P.; Waller, Jennifer L.

    2007-01-01

    First and second generation antipsychotics (FGAs and SGAs) ameliorate psychotic symptoms of schizophrenia, however, their chronic effects on information processing and memory function (i.e., key determinants of long term functional outcome) are largely unknown. In this rodent study the effects of different time periods (ranging from two weeks to six months) of oral treatment with the FGA, haloperidol (2.0 mg/kg/day), or the SGA, risperidone (2.5 mg/kg/day) on a water maze repeated acquisition procedure, the levels of nerve growth factor receptors, and two important cholinergic proteins, the vesicular acetylcholine transporter and the high affinity choline transporter were evaluated. The effects of the antipsychotics on a spontaneous novel object recognition procedure were also assessed during days 8-14 and 31-38 of treatment. Haloperidol (but not risperidone) was associated with impairments in water maze hidden platform trial performance at each of the time periods evaluated up to 45 days, but not when tested during days 83-90. In contrast, risperidone did not impair water maze task performance at the early time periods and it was actually associated with improved performance during the 83-90 day period. Both antipsychotics, however, were associated with significant water maze impairments during the 174-180 day period. Further, haloperidol was associated with decrements in short delay performance in the spontaneous novel object recognition task during both the 8-14 and 31-38 periods of treatment, while risperidone was associated with short delay impairment during the 31-38 day time period. Both antipsychotics were also associated with time dependent alterations in the vesicular acetylcholine transporter, the high affinity choline transporter, as well as TrkA, and p75 neurotrophin receptors in specific brain regions. These data support the notion that while risperidone may hold some advantages over haloperidol, both antipsychotics can produce time

  12. Genetics of adverse reactions to haloperidol in a mouse diallel: a drug-placebo experiment and Bayesian causal analysis.

    PubMed

    Crowley, James J; Kim, Yunjung; Lenarcic, Alan B; Quackenbush, Corey R; Barrick, Cordelia J; Adkins, Daniel E; Shaw, Ginger S; Miller, Darla R; de Villena, Fernando Pardo-Manuel; Sullivan, Patrick F; Valdar, William

    2014-01-01

    Haloperidol is an efficacious antipsychotic drug that has serious, unpredictable motor side effects that limit its utility and cause noncompliance in many patients. Using a drug-placebo diallel of the eight founder strains of the Collaborative Cross and their F1 hybrids, we characterized aggregate effects of genetics, sex, parent of origin, and their combinations on haloperidol response. Treating matched pairs of both sexes with drug or placebo, we measured changes in the following: open field activity, inclined screen rigidity, orofacial movements, prepulse inhibition of the acoustic startle response, plasma and brain drug level measurements, and body weight. To understand the genetic architecture of haloperidol response we introduce new statistical methodology linking heritable variation with causal effect of drug treatment. Our new estimators, "difference of models" and "multiple-impute matched pairs", are motivated by the Neyman-Rubin potential outcomes framework and extend our existing Bayesian hierarchical model for the diallel (Lenarcic et al. 2012). Drug-induced rigidity after chronic treatment was affected by mainly additive genetics and parent-of-origin effects (accounting for 28% and 14.8% of the variance), with NZO/HILtJ and 129S1/SvlmJ contributions tending to increase this side effect. Locomotor activity after acute treatment, by contrast, was more affected by strain-specific inbreeding (12.8%). In addition to drug response phenotypes, we examined diallel effects on behavior before treatment and found not only effects of additive genetics (10.2-53.2%) but also strong effects of epistasis (10.64-25.2%). In particular: prepulse inhibition showed additivity and epistasis in about equal proportions (26.1% and 23.7%); there was evidence of nonreciprocal epistasis in pretreatment activity and rigidity; and we estimated a range of effects on body weight that replicate those found in our previous work. Our results provide the first quantitative description of

  13. Genetics of Adverse Reactions to Haloperidol in a Mouse Diallel: A Drug–Placebo Experiment and Bayesian Causal Analysis

    PubMed Central

    Crowley, James J.; Kim, Yunjung; Lenarcic, Alan B.; Quackenbush, Corey R.; Barrick, Cordelia J.; Adkins, Daniel E.; Shaw, Ginger S.; Miller, Darla R.; de Villena, Fernando Pardo-Manuel; Sullivan, Patrick F.; Valdar, William

    2014-01-01

    Haloperidol is an efficacious antipsychotic drug that has serious, unpredictable motor side effects that limit its utility and cause noncompliance in many patients. Using a drug–placebo diallel of the eight founder strains of the Collaborative Cross and their F1 hybrids, we characterized aggregate effects of genetics, sex, parent of origin, and their combinations on haloperidol response. Treating matched pairs of both sexes with drug or placebo, we measured changes in the following: open field activity, inclined screen rigidity, orofacial movements, prepulse inhibition of the acoustic startle response, plasma and brain drug level measurements, and body weight. To understand the genetic architecture of haloperidol response we introduce new statistical methodology linking heritable variation with causal effect of drug treatment. Our new estimators, “difference of models” and “multiple-impute matched pairs”, are motivated by the Neyman–Rubin potential outcomes framework and extend our existing Bayesian hierarchical model for the diallel (Lenarcic et al. 2012). Drug-induced rigidity after chronic treatment was affected by mainly additive genetics and parent-of-origin effects (accounting for 28% and 14.8% of the variance), with NZO/HILtJ and 129S1/SvlmJ contributions tending to increase this side effect. Locomotor activity after acute treatment, by contrast, was more affected by strain-specific inbreeding (12.8%). In addition to drug response phenotypes, we examined diallel effects on behavior before treatment and found not only effects of additive genetics (10.2–53.2%) but also strong effects of epistasis (10.64–25.2%). In particular: prepulse inhibition showed additivity and epistasis in about equal proportions (26.1% and 23.7%); there was evidence of nonreciprocal epistasis in pretreatment activity and rigidity; and we estimated a range of effects on body weight that replicate those found in our previous work. Our results provide the first

  14. Antiangiogenic Effect of (±)-Haloperidol Metabolite II Valproate Ester [(±)-MRJF22] in Human Microvascular Retinal Endothelial Cells.

    PubMed

    Olivieri, Melania; Amata, Emanuele; Vinciguerra, Shila; Fiorito, Jole; Giurdanella, Giovanni; Drago, Filippo; Caporarello, Nunzia; Prezzavento, Orazio; Arena, Emanuela; Salerno, Loredana; Rescifina, Antonio; Lupo, Gabriella; Anfuso, Carmelina Daniela; Marrazzo, Agostino

    2016-11-10

    (±)-MRJF22 [(±)-2], a novel prodrug of haloperidol metabolite II (sigma-1 receptor antagonist/sigma-2 receptor agonist ligand) obtained by conjugation to valproic acid (histone deacetylase inhibitor) via an ester bond, exhibits antiangiogenic activity, being able to reduce human retinal endothelial cell (HREC) viability in a comparable manner to bevacizumab. Moreover, (±)-2 was able to significantly reduce viable cells count, endothelial cell migration, and tube formation in vascular endothelial growth factor A (VEGF-A) stimulated HREC cultures.

  15. Preventing ICU Subsyndromal Delirium Conversion to Delirium with Low Dose IV Haloperidol: A Double-Blind, Placebo-Controlled Pilot Study

    PubMed Central

    Al-Qadheeb, Nada S.; Skrobik, Yoanna; Schumaker, Greg; Pacheco, Manuel; Roberts, Russel; Ruthazer, Robin; Devlin, John W

    2016-01-01

    Objective To compare the efficacy and safety of scheduled low-dose, haloperidol vs. placebo for the prevention of delirium [Intensive Care Delirium Screening Checklist (ICDSC) ≥ 4)] administered to critically ill adults with subsyndromal delirium (ICDSC = 1-3). Design Randomized, double-blind, placebo-controlled trial. Setting Three 10-bed ICUs (2 medical; 1 surgical) at an academic medical center in the U.S. Patients Sixty-eight mechanically ventilated patients with subsyndromal delirium without complicating neurologic conditions, cardiac surgery or requiring deep sedation. Interventions Patients were randomly assigned to receive intravenous haloperidol 1 mg or placebo every six hours until either delirium (ICDSC ≥ 4 with psychiatric confirmation), therapy ≥ 10 days or ICU discharge occurred. Measurements and Main Results Baseline characteristics were similar between the haloperidol (n=34) and placebo (n=34) groups. A similar number of patients given haloperidol [12/34 (35%)] and placebo [8/34 (23%)] patients developed delirium (p=0.29). Haloperidol use reduced the hours per study day spent agitated (SAS ≥ 5) (p=0.008), but did not influence the proportion of 12-hour ICU shifts patients’ spent alive without coma (SAS ≤ 2) or delirium (p=0.36), the time to first delirium occurrence (p=0.22) nor delirium duration (p=0.26). Days of mechanical ventilation (p=0.80), ICU mortality (p=0.55) and ICU patient disposition (p=0.22) were similar in the two groups. The proportion of patients who developed QTc-interval prolongation (p=0.16), extrapyramidal symptoms (p=0.31), excessive sedation (p=0.31) or new-onset hypotension (p=1.0) that resulted in study drug discontinuation was comparable between the two groups. Conclusions Low-dose scheduled haloperidol, initiated early in the ICU stay, does not prevent delirium and has little therapeutic advantage in mechanically ventilated, critically ill adults with subsyndromal delirium. PMID:26540397

  16. Differential protection of black-seed oil on econucleotidase, cholinesterases and aminergic catabolizing enzyme in haloperidol-induced neuronal damage of male rats

    PubMed Central

    Akintunde, Jacob K.; Irechukwu, C. Abigail

    2016-01-01

    Background: The antipsychotic, haloperidol, is extremely efficient in the treatment of schizophrenia but its application is constrained because of irreversible adverse drug reactions. Hence, in this study, we investigate the differential effects of black seed oil on cholinesterase [acetylcholinesterase (AChE) and butrylcholinesterase (BuChE), ectonucleotidase (5′-nucleotidase), lactate dehydrogenase (LDH) and monoamine oxidase (MAO)] activities and relevant markers of oxidative stress in the cerebrum of haloperidol-induced neuronal-damaged rats. Methods: The animals were divided into six groups (n = 10): normal control rats; haloperidol-induced rats: induced rats were pre-, co- and post-treated with black-seed oil respectively, while the last group was treated with extract oil only. The treatment was performed via oral administration and the experiment lasted 14 days. Results: The results revealed an increase in 5I nucleotidase, a marker of adenosine triphosphate (ATP) and adenosine monophosphate (AMP) hydrolysis, as well as AChE, BuChE and MAO activities, with concomitant decrease in LDH activity of cerebrum in induced rats when compared with controls. Also, administration of haloperidol caused systemic oxidative damage and adverse histopathological changes in neuronal cells, indications of mental disorder. The differential treatments with black-seed oil prevented these alterations by increasing LDH and decreasing 5I nucleotidase, AChE, BuChE and MAO activities in the cerebrum. Essential oil post-treatment is most efficacious in reversing haloperidol-induced neuronal damage in rat; followed by pre- and cotreatment, respectively. Conclusions: We concluded that essential black-seed oil enhanced the wellness of aminergic, purinergic and cholinergic neurotransmissions of haloperidol-induced neuronal damage in rats. PMID:27493717

  17. Differential protection of black-seed oil on econucleotidase, cholinesterases and aminergic catabolizing enzyme in haloperidol-induced neuronal damage of male rats.

    PubMed

    Akintunde, Jacob K; Irechukwu, C Abigail

    2016-08-01

    The antipsychotic, haloperidol, is extremely efficient in the treatment of schizophrenia but its application is constrained because of irreversible adverse drug reactions. Hence, in this study, we investigate the differential effects of black seed oil on cholinesterase [acetylcholinesterase (AChE) and butrylcholinesterase (BuChE), ectonucleotidase (5'-nucleotidase), lactate dehydrogenase (LDH) and monoamine oxidase (MAO)] activities and relevant markers of oxidative stress in the cerebrum of haloperidol-induced neuronal-damaged rats. The animals were divided into six groups (n = 10): normal control rats; haloperidol-induced rats: induced rats were pre-, co- and post-treated with black-seed oil respectively, while the last group was treated with extract oil only. The treatment was performed via oral administration and the experiment lasted 14 days. The results revealed an increase in 5(I) nucleotidase, a marker of adenosine triphosphate (ATP) and adenosine monophosphate (AMP) hydrolysis, as well as AChE, BuChE and MAO activities, with concomitant decrease in LDH activity of cerebrum in induced rats when compared with controls. Also, administration of haloperidol caused systemic oxidative damage and adverse histopathological changes in neuronal cells, indications of mental disorder. The differential treatments with black-seed oil prevented these alterations by increasing LDH and decreasing 5(I) nucleotidase, AChE, BuChE and MAO activities in the cerebrum. Essential oil post-treatment is most efficacious in reversing haloperidol-induced neuronal damage in rat; followed by pre- and cotreatment, respectively. We concluded that essential black-seed oil enhanced the wellness of aminergic, purinergic and cholinergic neurotransmissions of haloperidol-induced neuronal damage in rats.

  18. High frequency stimulation of the posterior hypothalamic nucleus restores movement and reinstates hippocampal-striatal theta coherence following haloperidol-induced catalepsy.

    PubMed

    Jackson, Jesse; Young, Calvin K; Hu, Bin; Bland, Brian H

    2008-09-01

    Deep brain stimulation (DBS) of the subthalamic nucleus has been used extensively in the treatment of Parkinson's disease. However, the efficacy of such treatments on bradykinesia/akinesia remains low. DBS of the posterior hypothalamic nucleus (PH) elicits spontaneous, non-stereotypical motor behaviours. We tested the hypothesis that PH stimulation could restore movement in animals made cataleptic by the D(2) receptor antagonist haloperidol. We further hypothesized that hippocampal-striatal neural synchrony may be important in the organization of motor behaviours. Animals chronically implanted with hippocampal and striatal recording electrodes and PH stimulating electrode were tested in open field, catalepsy and active avoidance paradigms. The degree of hippocampal-striatal theta (5-10 Hz) field coherence was assessed during baseline avoidance testing and following the administration of haloperidol. Haloperidol abolished movement in open field and active avoidance tasks and increased the latency to respond in the catalepsy test. Stimulation of the PH under haloperidol reversed catalepsy. Hippocampal-striatal theta coherence was high throughout the active avoidance task in control experiments but was greatly reduced under haloperidol. PH stimulation was able to reinstate the hippocampal-striatal theta coherence while restoring task-related behaviours. These results support the hypothesis that DBS of the PH could restore motor behaviours in rats made cataleptic with haloperidol, thus providing strong support for the PH as a promising candidate for DBS in the treatment of Parkinson's disease. Furthermore, the results support the view that hippocampal-striatal theta coherence may be important for the planning and execution of goal-oriented behaviors.

  19. The correlation between CYP2D6 isoenzyme activity and haloperidol efficacy and safety profile in patients with alcohol addiction during the exacerbation of the addiction

    PubMed Central

    Sychev, Dmitry Alekseevich; Zastrozhin, Mikhail Sergeevich; Smirnov, Valery Valerieevich; Grishina, Elena Anatolievna; Savchenko, Ludmila Mikhailovna; Bryun, Evgeny Alekseevich

    2016-01-01

    Background Today, it is proved that isoenzymes CYP2D6 and CYP3A4 are involved in metabolism of haloperidol. In our previous investigation, we found a medium correlation between the efficacy and safety of haloperidol and the activity of CYP3A4 in patients with alcohol abuse. Objective The aim of this study was to evaluate the correlation between the activity of CYP2D6 and the efficacy and safety of haloperidol in patients with diagnosed alcohol abuse. Methods The study involved 70 men (average age: 40.83±9.92 years) with alcohol addiction. A series of psychometric scales were used in the research. The activity of CYP2D6 was evaluated by high-performance liquid chromatography with mass spectrometry using the ratio of 6-hydroxy-1,2,3,4-tetrahydro-beta-carboline to pinoline. Genotyping of CYP2D6 (1846G>A) was performed using real-time polymerase chain reaction. Results According to results of correlation analysis, statistically significant values of Spearman correlation coefficient (rs) between the activity of CYP2D6 and the difference of points in psychometric scale were obtained in patients receiving haloperidol in injection form (Sheehan Clinical Anxiety Rating Scale =−0.721 [P<0.001] and Udvald for Kliniske Undersogelser Side Effect Rating Scale =0.692 [P<0.001]) and in those receiving haloperidol in tablet form (Covi Anxiety Scale =−0.851 [P<0.001] and Udvald for Kliniske Undersogelser Side Effect Rating Scale =0.797 [P<0.001]). Conclusion This study demonstrated the correlations between the activity of CYP2D6 isozyme and the efficacy and safety of haloperidol in patients with alcohol addiction. PMID:27695358

  20. The α2C-adrenoceptor antagonist, ORM-10921, has antipsychotic-like effects in social isolation reared rats and bolsters the response to haloperidol.

    PubMed

    Uys, Madeleine; Shahid, Mohammed; Sallinen, Jukka; Dreyer, Walter; Cockeran, Marike; Harvey, Brian H

    2016-11-03

    Early studies suggest that selective α2C-adrenoceptor (AR)-antagonism has anti-psychotic-like and pro-cognitive properties. However, this has not been demonstrated in an animal model of schizophrenia with a neurodevelopmental construct. The beneficial effects of clozapine in refractory schizophrenia and associated cognitive deficits have, among others, been associated with its α2C-AR modulating activity. Altered brain-derived neurotrophic factor (BDNF) has been linked to schizophrenia and cognitive deficits. We investigated whether the α2C-AR antagonist, ORM-10921, could modulate sensorimotor gating and cognitive deficits, as well as alter striatal BDNF levels in the social isolation reared (SIR) model of schizophrenia, comparing its effects to clozapine and the typical antipsychotic, haloperidol, the latter being devoid of α2C-AR-activity. Moreover, the ability of ORM-10921 to augment the effects of haloperidol on the above parameters was also investigated. Animals received subcutaneous injection of either ORM-10921 (0.01mg/kg), clozapine (5mg/kg), haloperidol (0.2mg/kg), haloperidol (0.2mg/kg)+ORM-10921 (0.01mg/kg) or vehicle once daily for 14days, followed by assessment of novel object recognition (NOR), prepulse inhibition (PPI) of startle response and striatal BDNF levels. SIR significantly attenuated NOR memory as well as PPI, and reduced striatal BDNF levels vs. social controls. Clozapine, ORM-10921 and haloperidol+ORM-10921, but not haloperidol alone, significantly improved SIR-associated deficits in PPI and NOR, with ORM-10921 also significantly improving PPI deficits vs. haloperidol-treated SIR animals. Haloperidol+ORM-10921 significantly reversed reduced striatal BDNF levels in SIR rats. α2C-AR-antagonism improves deficits in cognition and sensorimotor gating in a neurodevelopmental animal model of schizophrenia and bolsters the effects of a typical antipsychotic, supporting a therapeutic role for α2C-AR-antagonism in schizophrenia. Copyright

  1. Supra-therapeutic plasma concentrations of haloperidol induce moderate inhibition of lipopolysaccharide-induced interleukin-8 release in human monocytes

    PubMed Central

    2016-01-01

    Background The clinical use of antipsychotics and mood-stabilizing drugs with proven efficacy is largely determined by the occurrence of treatment-emergent adverse events and routine clinical chemistry and haematology data, which together define the safety and tolerability profile of these psychopharmaceuticals. Whereas the effects of mood-stabilizing drugs on functional properties of blood cells have been poorly investigated, the effects of antipsychotics have received more attention. Such studies have yielded conflicting results. This study examined the effects of the mood-stabilizing drugs carbamazepine and valproic acid and of the antipsychotic drugs olanzapine, risperidone and haloperidol on the production of the pro-inflammatory chemokine interleukin-8 (IL-8), which is released from human monocytes when activated by Gram-negative lipopolysaccharide (LPS). Methods Peripheral human whole blood was diluted with Roswell Park Memorial Institute (RPMI) cell culture medium and stimulated with LPS. Accumulating IL-8 was quantified in the supernatant with an adapted enzyme-linked immunosorbent assay (ELISA) and the results correlated to the number of monocytes at venipuncture. Results At supra-therapeutic concentrations of 100 µM, haloperidol inhibited the LPS-induced release of IL-8 in peripheral human monocytes moderately, whereas olanzapine, risperidone, carbamazepine and valproic acid showed no such effect. Conclusions The results suggest that these mood-stabilizing drugs and antipsychotics are endowed with clinically favorable inertness rather than pro-inflammatory properties. PMID:27867948

  2. Use of haloperidol and risperidone in highly aggressive Swiss Webster mice by applying the model of spontaneous aggression (MSA).

    PubMed

    Fragoso, Viviane Muniz da Silva; Hoppe, Luanda Yanaan; de Araújo-Jorge, Tânia Cremonini; de Azevedo, Marcos José; Campos, Jerônimo Diego de Souza; Cortez, Célia Martins; de Oliveira, Gabriel Melo

    2016-03-15

    Aggression is defined as the act in which an individual intentionally harms or injures another of their own species. Antipsychotics are a form of treatment used in psychiatric routine. They have been used for decades in treatment of patients with aggressive behavior. Haloperidol and risperidone promote the control of psychiatric symptoms, through their respective mechanisms of action. Experimental models are obtained by behavioral, genetic, and pharmacological manipulations, and use a reduced number of animals. In this context, we applied the model of spontaneous aggression (MSA), originating the presence of highly aggressive mice (AgR) when reassembled in adulthood. We administered haloperidol and risperidone in escalating doses, for ten consecutive days. Using positive and negative control groups, we evaluated the effectiveness of these drugs and the reversal of the aggressive behavior, performing the tail suspension test (TST) and open field test (OFT) on 10th day of treatment and 10 days after its discontinuation. The results showed that both antipsychotic drugs were effective in AgR and reversed the aggressive phenotype, reducing the number of attacks by AgR and the extent of lesions in the subordinate mice (AgD) exposed to the pattern of aggressive behavior (PAB) of the aggressors. This conclusion is based on the reduction in the animals' motor and exploratory activity, and on the reversal of patterns of aggressive behavior. The association between the MSA and experiments with other therapeutic protocols and different antipsychotics can be an important methodology in the study of aggressive behavior in psychiatric patients.

  3. The antipsychotic drugs olanzapine and haloperidol modify network connectivity and spontaneous activity of neural networks in vitro.

    PubMed

    Dzyubenko, Egor; Juckel, Georg; Faissner, Andreas

    2017-09-14

    Impaired neural synchronization is a hallmark of psychotic conditions such as schizophrenia. It has been proposed that schizophrenia-related cognitive deficits are caused by an unbalance of reciprocal inhibitory and stimulatory signaling. This supposedly leads to decreased power of induced gamma oscillations during the performance of cognitive tasks. In light of this hypothesis an efficient antipsychotic treatment should modify the connectivity and synchronization of local neural circuits. To address this issue, we investigated a model of hippocampal neuronal networks in vitro. Inhibitory and excitatory innervation of GABAergic and glutamatergic neurons was quantified using immunocytochemical markers and an automated routine to estimate network connectivity. The first generation (FGA) and second generation (SGA) antipsychotic drugs haloperidol and olanzapine, respectively, differentially modified the density of synaptic inputs. Based on the observed synapse density modifications, we developed a computational model that reliably predicted distinct changes in network activity patterns. The results of computational modeling were confirmed by spontaneous network activity measurements using the multiple electrode array (MEA) technique. When the cultures were treated with olanzapine, overall activity and synchronization were increased, whereas haloperidol had the opposite effect. We conclude that FGAs and SGAs differentially affect the balance between inhibition and excitation in hippocampal networks.

  4. Different effects of bifeprunox, aripiprazole, and haloperidol on body weight gain, food and water intake, and locomotor activity in rats.

    PubMed

    De Santis, Michael; Pan, Bo; Lian, Jiamei; Huang, Xu-Feng; Deng, Chao

    2014-09-01

    Following on the success of Aripiprazole with its high clinical efficacy and minimal side effects, further antipsychotic drugs (such as Bifeprunox) have been developed based on the same dopamine D2 partial agonist pharmacological profile as Aripiprazole. However clinical trials of Bifeprunox have found differing results to that of its predecessor, without the same significant clinical efficacy. This study has therefore investigated the different effects of 10 week treatment with Aripiprazole (0.75 mg/kg, 3 times per day), Bifeprunox (0.8 mg/kg, 3 times per day) and Haloperidol (0.1mg/kg, 3 times per day) on body weight gain, food and water intake, white fat mass, and 8 week treatment on locomotor activity. Treatment with Bifeprunox was found to significantly reduce all of the measured parameters except white fat mass compared to the control group. However, Aripiprazole and Haloperidol treatment reduced water intake compared to the control, without any significant effects on the other measured parameters. These findings further demonstrate the potential pharmacological differences between Aripiprazole and Bifeprunox, and identify potential weight loss side effects and increased anxiety behaviour with Bifeprunox treatment.

  5. Comparison of haloperidol and midazolam in restless management of patients referred to the Emergency Department: A double-blinded, randomized clinical trial

    PubMed Central

    Esmailian, Mehrdad; Ahmadi, Omid; Taheri, Mehrsa; Zamani, Majid

    2015-01-01

    Background: Restless and violent behaviors are common in Emergency Departments (EDs), which need therapeutic interventions in most of the times. The first-generation anti-psychotic drugs are one of the most applicable therapeutic agents in the management of such patients, but their use has some limitations. Some studies suggest midazolam as an alternative medicine. Therefore, this study was performed with the aim of comparison of the efficacy and safety of haloperidol and midazolam in the restless management of referring patients to EDs. Materials and Methods: The present double-blinded trial was done on patients needed sedation and referred to the ED of Alzahra Hospital, Isfahan, Iran, in 2014. The patients were categorized into two random groups of haloperidol (5 mg) and midazolam receivers (2.5 mg for those weighing <50 kg and 5 mg in >50 kg), as intramuscular administration. The time to achieve sedation, need for rescue dose, need to resedation within the first 60 min, and adverse effects of drugs were compared among the groups. Results: Forty-eight patients were entered to the study. The mean age in the haloperidol and midazolam groups was 44.8 ± 4.1 years and 45.5 ± 4.7 years, respectively (P = 0.91). The mean time of sedation in the haloperidol and midazolam groups was 5.6 ± 0.3 min and 5.2 ± 0.1 min, respectively (P = 0.31). The mean time of full consciousness after sedation was 36.2 ± 4.5 min and 38.2 ± 3.4 min in the haloperidol and midazolam groups, respectively (P = 0.72). On average, time to arousal in the midazolam group was 10.33 min more than the haloperidol group, but it was not statistically significant. Conclusion: The results of the present study show that administration of midazolam and haloperidol have similar efficacy in the treatment of restless symptoms with the same recovery time from drug effects for referring patients to the ED. In addition, none of the adverse effects were observed in this study. PMID:26759570

  6. Frequency of sexual dysfunction and other reproductive side-effects in patients with schizophrenia treated with risperidone, olanzapine, quetiapine, or haloperidol: the results of the EIRE study.

    PubMed

    Bobes, J; Garc A-Portilla, M P; Rejas, J; Hern Ndez, G; Garcia-Garcia, M; Rico-Villademoros, F; Porras, A

    2003-01-01

    Atypical antipsychotics seem to differ mainly in their tolerability profile. The aim of this cross-sectional study, the Estudio de Investigaci n de Resultados en Esquizofrenia (Outcomes Research Study in Schizophrenia; EIRE study), was to assess in a clinical setting the frequency of several side-effects related to haloperidol, risperidone, olanzapine, and quetiapine. This article addresses sexual dysfunction and other reproductive side-effects (gynecomastia, menorrhage, amenorrhea, and galactorrhea). We recruited outpatients diagnosed with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, 1994) criteria and who had received a single antipsychotic (risperidone, olanzapine, quetiapine, or haloperidol) for at least 4 weeks. During a single visit, we collected data, including demographic and clinical characteristics, current antipsychotic and concomitant treatment, and adverse effects listed in a modified version of the UKU Scale. We used a Chi-squared test to determine pairs comparisons of the frequency of adverse reactions between treatments. To estimate risk of a given adverse reaction with a given treatment, we used a logistic regression method. We assessed 636 evaluable patients out of 669 recruited. Frequency of sexual dysfunction was high with haloperidol (38.1%) and also with olanzapine (35.3%), quetiapine (18.2%), and risperidone (43.2%). We found the frequency of other reproductive side-effects to be relatively low with all four drugs: haloperidol (6.9%), olanzapine (6.4%), quetiapine (2.7%), and risperidone (11.7%). Sexual dysfunction appeared to be dose-related with haloperidol, risperidone, and olanzapine. Risperidone and olanzapine showed a higher risk of sexual dysfunction and other reproductive sideeffects than haloperidol. Quetiapine showed a lower risk of sexual dysfunction during short-term treatment (< 12 weeks). However, data on longer-term treatment (> 12 weeks) are lacking

  7. Systemic administration of MK-801 produces an abnormally persistent latent inhibition which is reversed by clozapine but not haloperidol.

    PubMed

    Gaisler-Salomon, I; Weiner, I

    2003-04-01

    Latent inhibition (LI) refers to retarded conditioning to a stimulus as a consequence of its inconsequential pre-exposure, and disrupted LI in the rat is considered to model an attentional deficit in schizophrenia. Blockade of NMDA receptor transmission, which produces behavioral effects potentially relevant to schizophrenic symptomatology in several animal models, has been reported to spare LI. To show that systemic administration of the non-competitive NMDA antagonist MK-801 will lead to an abnormally persistent LI which will emerge under conditions that disrupt LI in controls, and that this will be reversed by the atypical neuroleptic clozapine but not by the typical neuroleptic haloperidol, as found for other NMDA antagonist-induced models. LI was measured in a thirst-motivated conditioned emotional response (CER) procedure by comparing suppression of drinking in response to a tone in rats which previously received 0 (non-pre-exposed) or 40 tone exposures (pre-exposed) followed by two (experiment 1) or five (experiments 2-5) tone - foot shock pairings. MK-801 at doses of 0.1 and 0.2 mg/kg reduced conditioned suppression while no effect on suppression was seen at the 0.05 mg/kg dose. At the latter dose, intact LI was seen with parameters that produced LI in controls (40 pre-exposures and two conditioning trials). Raising the number of conditioning trials to five disrupted LI in control rats, but MK-801-treated rats continued to show LI, and this abnormally persistent LI was due to the action of MK-801 in the conditioning stage. MK-801-induced LI perseveration was unaffected by both haloperidol (0.1 mg/kg) and clozapine (5 mg/kg) administered in conditioning, and was reversed by clozapine but not by haloperidol administered in pre-exposure. MK-801-induced perseveration of LI is consistent with other reports of perseverative behaviors, suggested to be particularly relevant to negative symptoms of schizophrenia, following NMDA receptor blockade. We suggest that LI

  8. Comparison of intramuscular olanzapine, orally disintegrating olanzapine tablets, oral risperidone solution, and intramuscular haloperidol in the management of acute agitation in an acute care psychiatric ward in Taiwan.

    PubMed

    Hsu, Wen-Yu; Huang, Si-Sheng; Lee, Bo-Shyan; Chiu, Nan-Ying

    2010-06-01

    The purpose of this study was to compare efficacy and safety among intramuscular olanzapine, intramuscular haloperidol, orally disintegrating olanzapine tablets, and oral risperidone solution for agitated patients with psychosis during the first 24 hours of treatment in an acute care psychiatric ward. Forty-two inpatients from an acute care psychiatric ward of a medical center in central Taiwan were enrolled. They were randomly assigned to 1 of the 4 treatment groups (10-mg intramuscular olanzapine, 10-mg olanzapine oral disintegrating tablet, 3-mg oral risperidone solution, or 7.5-mg intramuscular haloperidol). Agitation was measured by using the excited component of the Positive and Negative Syndrome Scale (PANSS-EC), the Agitation-Calmness Evaluation Scale, and the Clinical Global Impression--Severity Scale during the first 24 hours. There were significant differences in the PANSS-EC total scores for the 4 intervention groups at 15, 30, 45, 60, 75, and 90 minutes after the initiation of treatment. More significant differences were found early in the treatment. In the post hoc analysis, the patients who received intramuscular olanzapine or orally disintegrating olanzapine tablets showed significantly greater improvement in PANSS-EC scores than did patients who received intramuscular haloperidol at points 15, 30, 45, 60, 75, and 90 minutes after injection. These findings suggest that intramuscular olanzapine, orally disintegrating olanzapine tablets, and oral risperidone solution are as effective treatments as intramuscular haloperidol for patients with acute agitation. Intramuscular olanzapine and disintegrating olanzapine tablets are more effective than intramuscular haloperidol in the early phase of the intervention. There is no significant difference in effectiveness among intramuscular olanzapine, orally disintegrating olanzapine tablets, and oral risperidone solution.

  9. Acute effects of single-dose aripiprazole and haloperidol on resting cerebral blood flow (rCBF) in the human brain.

    PubMed

    Handley, Rowena; Zelaya, Fernando O; Reinders, A A T Simone; Marques, Tiago Reis; Mehta, Mitul A; O'Gorman, Ruth; Alsop, David C; Taylor, Heather; Johnston, Atholl; Williams, Steve; McGuire, Philip; Pariante, Carmine M; Kapur, Shitij; Dazzan, Paola

    2013-02-01

    Antipsychotic drugs act on the dopaminergic system (first-generation antipsychotics, FGA), but some also directly affect serotonergic function (second-generation antipsychotics, SGA) in the brain. Short and long-term effects of these drugs on brain physiology remain poorly understood. Moreover, it remains unclear whether any physiological effect in the brain may be different for FGAs and SGAs. Immediate (+3.30 h) and different effects of single-dose FGA (haloperidol, 3 mg) and a SGA (aripiprazole, 10 mg) on resting cerebral blood flow (rCBF) were explored in the same 20 healthy volunteers using a pulsed continuous arterial spin labeling (pCASL) sequence (1.5T) in a placebo-controlled, repeated measures design. Both antipsychotics increased striatal rCBF but the effect was greater after haloperidol. Both decreased frontal rCBF, and opposite effects of the drugs were observed in the temporal cortex (haloperidol decreased, aripiprazole increased rCBF) and in the posterior cingulate (haloperidol increased, aripiprazole decreased rCBF). Further increases were evident in the insula, hippocampus, and anterior cingulate after both antipsychotics, in the motor cortex following haloperidol and in the occipital lobe the claustrum and the cerebellum after aripiprazole. Further decreases were observed in the parietal and occipital cortices after aripiprazole. This study suggests that early and different rCBF changes are evident following a single-dose of FGA and SGA. The effects occur in healthy volunteers, thus may be independent from any underlying pathology, and in the same regions identified as structurally and functionally altered in schizophrenia, suggesting a possible relationship between antipsychotic-induced rCBF changes and brain alterations in schizophrenia.

  10. Intramuscular olanzapine versus intramuscular haloperidol plus lorazepam for the treatment of acute schizophrenia with agitation: An open-label, randomized controlled trial.

    PubMed

    Huang, Charles Lung-Cheng; Hwang, Tzung-Jeng; Chen, Yi-Hsing; Huang, Guan-Hua; Hsieh, Ming H; Chen, Hsiu-Hsi; Hwu, Hai-Gwo

    2015-05-01

    To compare the efficacy and safety profile between intramuscular (IM) olanzapine and IM haloperidol plus IM lorazepam in acute schizophrenic patients with moderate to severe agitation. This was a prospective, randomized, open-label study. Acutely agitated patients with schizophrenia or schizoaffective disorder (n = 67) were randomized to receive 10 mg IM olanzapine (n = 37) or 5 mg IM haloperidol plus 2 mg IM lorazepam (n = 30). Agitation was measured with Positive and Negative Syndrome Scale Excited Component (PANSS-EC) and Agitation-Calmness Evaluation Scale (ACES) during the first 2 hours and at 24 hours after the first injection. Safety was assessed using the Simpson-Angus Scale and Barnes Akathisia Rating Scale and by recording adverse events at 24 hours following the first injection. The Clinical Global Impression-Severity scale was also rated. The PANSS-EC scores decreased significantly at 2 hours after the first injection in both groups (olanzapine: -10.2, p < 0.001; haloperidol + lorazepam: -9.9, p < 0.001). Haloperidol plus lorazepam was not inferior to olanzapine in reducing agitation at 2 hours. There were no significant differences in PANSS-EC or ACES scores between the two groups within 2 hours following the first injection. The frequencies of adverse events and changes in Clinical Global Impression-Severity, Simpson-Angus Scale, and Barnes Akathisia Rating Scale scores from baseline to 24 hours showed no significant differences between the groups. The findings suggest that IM haloperidol (5 mg) plus lorazepam (2 mg) is not inferior to IM olanzapine (10 mg) in the treatment of acute schizophrenic patients with moderate to severe agitation (ClinialTrials.gov identifier number NCT00797277). Copyright © 2015. Published by Elsevier B.V.

  11. Ameliorative effect of yokukansan on vacuous chewing movement in haloperidol-induced rat tardive dyskinesia model and involvement of glutamatergic system.

    PubMed

    Sekiguchi, Kyoji; Kanno, Hitomi; Yamaguchi, Takuji; Ikarashi, Yasushi; Kase, Yoshio

    2012-12-01

    Effects of yokukansan (YKS) on vacuous chewing movement (VCM), which is an index for tardive dyskinesia, were investigated in haloperidol decanoate-treated rats. Haloperidol decanoate was injected to a thigh muscle once every four weeks for 18 weeks. The rats which exhibited VCM eight times or more in 3min were selected on the 12th week, and examined. A significant increase in VCM on the 12th week continued until the 18th week. Oral administration of YKS (0.1 and 0.5g/kg) once a day for three weeks (21 days) from the 12th week to 15th week ameliorated the haloperidol decanoate-induced increase in VCM in a dose-dependent manner. The significant ameliorative effect observed in 0.5g/kg YKS-treated rats was abolished by stopping administration for three weeks from the 15th week to the 18th week. The extracellular glutamate concentration and glutamate transporter mRNA expression in the striatum were evaluated by microdialysis and real-time reverse-transcription polymerase chain reaction assays at the 15th week. The striatal glutamate level increased in haloperidol-treated rats, and the increase was inhibited by treatment with YKS. The striatal GLT-1 mRNA level showed a tendency to decrease in the haloperidol-treated rats. The GLT-1 mRNA level after treatment with YKS (0.5g/kg) was greater than the control level. These results suggest the effect of YKS may be involved in the extracellular glutamate level and GLT-1 mRNA expression in the striatum. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Haloperidol disrupts, clozapine reinstates the circadian rest-activity cycle in a patient with early-onset Alzheimer disease.

    PubMed

    Wirz-Justice, A; Werth, E; Savaskan, E; Knoblauch, V; Gasio, P F; Müller-Spahn, F

    2000-01-01

    Measurement of the circadian rest-activity cycle in a patient with early-onset Alzheimer disease for 555 days revealed marked changes in the timing and amount of nocturnal activity. After neuroleptic medication was changed to haloperidol, the rest-activity cycle became completely arrhythmic for two months, concomitant with a marked worsening of cognitive state. Circadian integrity returned together with clinical improvement when the patient was subsequently treated with clozapine. This observation suggests that the known tendency for patients with Alzheimer disease to develop sleep-wake cycle disturbances may be aggravated by a classic neuroleptic; in contrast, the atypical neuroleptic clozapine may consolidate it. Similar observations in schizophrenic patients indicate that this chronobiological finding is drug- and not illness-related.

  13. A randomized, controlled prospective trial of zolpidem and haloperidol for use as sleeping agents in pediatric burn patients.

    PubMed

    Armour, Alexis; Gottschlich, Michele M; Khoury, Jane; Warden, Glenn D; Kagan, Richard J

    2008-01-01

    Children with burn injuries often require hospital treatment where they are subjected to stimuli likely to produce sleep deprivation. Previously demonstrated sleep fragmentation and significantly reduced sleep stage 3/4 and rapid eye movement in this population led to a search for sleep-enhancing interventions. The purpose of this study was to evaluate the effects of selected therapeutic interventions on sleep architecture. Forty patients with a mean (+/-SEM) age of 9.4 +/- 0.7 years, mean total burn surface area of 50.1 +/- 2.9% and full thickness burns of 43.2 +/- 3.6% were randomly assigned to one of two treatment regimens using a blinded crossover design. Continuous polysomnographic recordings were obtained for six study periods. Each patient alternately received zolpidem one week and haloperidol the next, with the first monitored night conducted without medication. Zolpidem minimally increased the proportion of 3/4 and rapid eye movement sleep (0.81 +/- 0.16 vs 0.61 +/- 0.10 hrs, P = .02) but not total sleep time (4.8 +/- 0.3 vs 4.3 +/- 0.3 hrs on control nights, P = .1). Haloperidol significantly increased total sleep (5.3 +/- 0.3 vs 4.3 +/- 0.3 hrs on control nights, P = .02) and stage 2 sleep (3.3 +/- 0.3 vs 2.4 +/- 0.2 hrs, P = .001) compared with control nights. Both drugs slightly improved average sleep and wake period duration compared with control nights. Although sleep was somewhat improved by each test drug, there were no statistically significant differences between the drugs. Additional studies are needed to identify methods for improving restorative sleep postburn.

  14. Changes in brain volume in response to estradiol levels, amphetamine sensitization and haloperidol treatment in awake female rats.

    PubMed

    Madularu, Dan; Kulkarni, Praveen; Ferris, Craig F; Brake, Wayne G

    2015-08-27

    Estrogen has been shown to further ameliorate symptoms when administered in conjunction with antipsychotics in patients with schizophrenia. We have previously shown that chronic haloperidol (HAL) treatment reduces amphetamine (AMPH)-induced locomotor activity in AMPH-sensitized rats, but only when paired with high levels of the estrogen, 17-β estradiol. In addition, we reported estradiol-dependent responses to AMPH in AMPH-sensitized rats as measured by functional magnetic resonance imaging. It is thus clear that estradiol and antipsychotics both affect the rat brain, however the mechanism by which this occurs is unknown. The aim of the current study was to assess this interaction by investigating the effects of estradiol, AMPH and HAL on brain volume changes in awake female rats. Repeated exposure to AMPH resulted in an overall reduction in brain volume, regardless of hormonal status (i.e. no, low or high estradiol). Similarly, chronic HAL treatment further reduced brain volume compared to acute treatment. Hormonal status affected hippocampal volume with rats receiving low estradiol replacement showing larger volume; this difference was no longer significant after repeated exposure to AMPH. Finally, we found changes in volume in response to AMPH throughout hippocampal components (i.e. CA1-CA3 and dentate) as well as components of the mesocortical system. In conclusion, brain volume seems to be influenced by hormonal status, as well as exposure to AMPH and haloperidol treatment. These findings implicate areas where estradiol, amphetamine and antipsychotics may be producing volumetric changes in the brain, pointing the way to where future studies should focus. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Amphetamine-induced disruption and haloperidol-induced potentiation of latent inhibition depend on the nature of the stimulus.

    PubMed

    Ruob, C; Elsner, J; Weiner, I; Feldon, J

    1997-10-01

    If a stimulus (e.g. light) is repeatedly preexposed without consequences, it subsequently develops a weaker association with a reinforcer (e.g. foot shock) than does a non-preexposed stimulus. This retarded conditioning to the preexposed as compared to the non-preexposed stimulus, is latent inhibition (LI). It is well documented that LI is disrupted by low doses of amphetamine and potentiated by neuroleptic drugs, and there is evidence that the action of these agents on LI can be modified by changes in the parameters of preexposure or conditioning. The present experiments tested whether the effects of DA agents on LI are influenced by the nature of the stimulus. In two experiments, LI was assessed using an off-baseline conditioned emotional response (CER) procedure in rats licking for water, consisting of three stages: preexposure, in which the stimulus (a light) to be conditioned, was repeatedly presented without being followed by reinforcement; conditioning, in which the preexposed stimulus was paired with reinforcement (a foot-shock); and test, in which LI was indexed by animals' degree of suppression of licking during stimulus presentation. In both experiments, different groups of animals were preexposed and conditioned with four different preexposed visual stimuli: three steady side-lights, three flashing side-lights, one flashing side-light, and a flashing houselight. Experiment 1 used 40 stimulus preexposures and tested the effects of 1 mg/kg D-amphetamine, whereas experiment 2 used 10 preexposures and tested the effects of 0.1 mg/kg haloperidol. The results showed that of the four stimuli used, both drugs were effective with only one and the same stimulus, namely, flashing houselight. This demonstrates that the disruptive effect of amphetamine and the potentiating effect of haloperidol on LI, are modifiable by manipulating the nature of the preexposed stimulus.

  16. Ginkgo biloba leaf extract and alpha-tocopherol attenuate haloperidol-induced orofacial dyskinesia in rats: Possible implication of antiapoptotic mechanisms by preventing Bcl-2 decrease and Bax elevation.

    PubMed

    An, Hui Mei; Tan, Yun Long; Shi, Jing; Wang, Zhiren; Lv, Meng Han; Soares, Jair C; Zhou, Dongfeng; Yang, Fude; Zhang, Xiang Yang

    2016-12-01

    Tardive dyskinesia (TD) is a serious side effect of long-term administration of typical neuroleptics, such as haloperidol. The pathophysiology of TD remains unclear, but the experimental evidence suggests that free radical-induced neuronal apoptosis in the basal ganglia may play an important role. This study was to investigate changes in Bax and Bcl-2 expression levels in TD-associated brain regions and the effects of the antioxidant EGb761 on Bax and Bcl-2 levels in an animal model of TD. Thirty-two rats were randomly divided into four study groups: saline control (saline), haloperidol-alone (haloperidol), EGb761-haloperidol (EGb), and alpha-tocopherol-haloperidol (vitamin E). Rats were treated with daily intraperitoneal haloperidol injections (2 mg/kg/day) for 5 weeks. EGb761 (50 mg/kg/day) and alpha-tocopherol (20 mg/kg/day) were then administered for another 5 weeks during the withdrawal period. Behavioral assessments were performed, and Bax and Bcl-2 protein expression levels were immunohistochemically analyzed in four brain regions, including the prefrontal cortex, striatum, substantia nigra, and globus pallidum. We found that increased vacuous chewing movements (VCMs) were associated with increased proapoptotic Bax protein expression, decreased antiapoptotic Bcl-2 protein expression, and an increased Bax/Bcl-2 ratio. EGb761 and alpha-tocopherol treatment reversed the increase in VCMs, decreased Bax expression, increased Bcl-2 expression, and decreased the Bax/Bcl-2 ratio. These results demonstrate that long-term haloperidol administration may affect Bcl-2 protein family expression and promote neuronal apoptosis in the basal ganglia. In combination with their antioxidant capacity, EGb761 and alpha-tocopherol's antiapoptotic effects through Bcl-2 might account for the symptom improvement observed in haloperidol-induced TD rats. Copyright © 2016 Elsevier GmbH. All rights reserved.

  17. Effects of ceruletide and haloperidol on the hypothalamo-pituitary beta-endorphin system and brain beta-endorphin contents in the rat: with special reference to effects of ceruletide in chronically haloperidol-treated rats.

    PubMed

    Hagino, Y; Okuwa, M; Moroji, T

    1991-01-01

    Subcutaneous (sc) administration of 200 micrograms/kg ceruletide (CER), a decapeptide chemically related CCK-8, and 5 mg/kg haloperidol (HLP) to rats increased the plasma immunoreactive beta-endorphin (ir-beta-END) level. The combined injection of CER and haloperidol caused higher plasma ir-beta-END levels than either drug alone. High plasma ir-beta-END levels returned to control levels on the 2nd day. Prior intraperitoneal (ip) administration of a CCK receptor antagonist, L-364,718 (3 mg/kg), but not proglumide (400 mg/kg, ip), inhibited CER-induced, but not HLP-induced, elevation in plasma ir-beta-END levels. The dopamine agonist, bromocriptine (1 mg/kg, ip) decreased plasma ir-beta-END levels, but had not effect on CER-induced elevation in plasma ir-beta-END levels, whereas bromocriptine-induced reduction in plasma ir-beta-END levels was antagonised by HLP. CER injection to chronically HLP-treated rats caused a greater elevation of plasma ir-beta-END levels compared to saline-injected rats. In contrast to the acute experiment, plasma ir-beta-END levels remained elevated over a period of 24 h. In the acute experiment, CER, HLP or the combined treatment with these two drugs had no effect on ir-beta-END contents in the pituitary gland and brain. In the chronic experiment, HLP increased the adenohypophyseal and septal ir-beta-END contents and decreased the hippocampal ir-beta-END contents 24 h after the final HLP injection. CER caused a small reduction only in the hippocampal ir-beta-END contents of CER-injected rats 15 min after injection. When determined on the 2nd day, however, the increases in the adenohypophyseal and septal ir-beta-END contents and the decrease in the hippocampal ir-beta-END contents observed in CER-injected rats were of the same magnitude as those of rats not given the CER injection. These findings indicate that CER stimulates the release of ir-beta-END from the adenohypophysis through CCK-A receptors and that elevated plasma ir

  18. Enhanced striatial /sup 3/H-spiroperidol binding induced by chronic haloperidol treatment inhibited by peptides administered during the withdrawal phase

    SciTech Connect

    Bhargava, H.N.

    1984-02-27

    Chronic intragastric administration of haloperidol (1.5 mg/kg/day) for 21 days followed by a 3-day withdrawal period resulted in the development of enhanced locomotor activity response to apomorphine, and an increase in the number of binding sites for /sup 3/H-spiroperidol in the striatal membranes of the rat brain. Subcutaneous administration of Pro-Leu-Gly-NH/sub 2/ or cyclo-(Leu-Gly) in doses of 2 mg/kg/day given for 3-days after termination of haloperidol treatment inhibited the enhanced response to apomorphine, as well as the increases in the number of /sup 3/H-spiroperidol binding sites in the striatum. If indeed, the supersensitivity of striatal dopamine receptors is one of the mechanisms in the development of tardive dyskinesia symptoms, the present results suggest that the above peptides may be helpful in ameliorating some of the symptoms of tardive dyskinesia induced by neuroleptic drugs. 31 references, 3 figures.

  19. Choosing voluntary exercise over sucrose consumption depends upon dopamine transmission: effects of haloperidol in wild type and adenosine A₂AKO mice.

    PubMed

    Correa, Mercè; Pardo, Marta; Bayarri, Pilar; López-Cruz, Laura; San Miguel, Noemí; Valverde, Olga; Ledent, Catherine; Salamone, John D

    2016-02-01

    Mesolimbic dopamine (DA) regulates behavioral activation and effort-related decision-making in motivated behaviors. Mesolimbic DA D2 receptors are co-localized with adenosine A2A receptors, and they interact in an antagonistic manner. A T-maze task was developed to assess dopaminergic involvement in preference between a reinforcer that involves vigorous voluntary activity (running wheel) and a reinforcer that requires minimal behavioral activation (sucrose pellets). Haloperidol (D2 antagonist) was administered to adenosine A2A receptor knockout (A2AKO) and wild-type (WT) littermate controls to assess the involvement of these two receptors in the selection of running wheel activity versus sucrose consumption. Under control conditions, mice spent more time running and less time eating. In WT mice, haloperidol reduced time running but actually increased time-consuming sucrose. However, A2AKO mice did not show the haloperidol-induced shift from running wheel activity to sucrose intake. Prefeeding reduced sucrose consumption in the T-maze in both strains, indicating that this paradigm is sensitive to motivational devaluation. Haloperidol increased c-Fos immunoreactivity in anterior cingulate cortex (ACg) and nucleus accumbens (Acb) core of WT but not KO mice. These results indicate that after DA antagonism, the preference for vigorous physical activity is reduced, while palatable food selection increases. Adenosine A2A receptor deletion provides resistance to these effects of D2 receptor antagonism. These two receptors in Acb core and ACg seem to be involved in the regulation of the intrinsic reinforcing characteristics of voluntary exercise but not in the regulation of the primary reinforcing characteristics of palatable sedentary reinforcers.

  20. Comparison between the efficacies of Risperidone with Haloperidol in the treatment of attention-deficit hyperactivity disorder (ADHD) among preschoolers: a randomized double-blind clinical trial.

    PubMed

    Riahi, Forough; Tashakori, Ashraf; Abdi, Leila

    2016-09-01

    Attention-deficit hyperactivity disorder (ADHD) is a common psychiatric disease with a worldwide pooled prevalence of 5.29%. To compare the efficacy of Risperidone with Haloperidol in the treatment of attention-deficit hyperactivity disorder (ADHD) among 3- to 6-year-old children. In a 6-week double-blind clinical trial, the efficacy of Risperidone 0.5-2 mg with a dose of maximum Haloperidol 0.075 mg/kg was assessed in 39 children aged 3-6 years. This study was conducted at the Golestan Psychiatric Clinic (Ahvaz, Iran). Measurement tools included the Conners' Parent Rating Scale (CPRS-48), Children's Global Assessment Scale (CGAS), and the Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS). Data were analyzed using the Wilcoxon, Mann-Whitney, and Fisher's exact tests in the SPSS 19. During the 6 weeks, the decline in points was seen in Conner's rating scale and in ADHD-RS score in Risperidone and Haloperidol groups (p<0.001). On the CGAS scale, an increase of performance in both groups for six weeks was statistically significant (p<0.001). In the scales of ADHD-RS and CPRS-48, no statistically significant difference was observed between the two treatment groups; i.e., in terms of reducing the rate during weeks of two, four, and six (p>0.05). Haloperidol and Risperidone possibly can be an acceptable treatment choice in the ADHD treatment of 3- to 6-year-old children. The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the Irct ID: IRCT2015082623766N1. This work was financially supported by grant (ref. no.: U-93130) from the vice chancellor for Research Affairs of Ahvaz Jundishapur University of Medical Sciences.

  1. Comparison between the efficacies of Risperidone with Haloperidol in the treatment of attention-deficit hyperactivity disorder (ADHD) among preschoolers: a randomized double-blind clinical trial

    PubMed Central

    Riahi, Forough; Tashakori, Ashraf; Abdi, Leila

    2016-01-01

    Background Attention-deficit hyperactivity disorder (ADHD) is a common psychiatric disease with a worldwide pooled prevalence of 5.29%. Objective To compare the efficacy of Risperidone with Haloperidol in the treatment of attention-deficit hyperactivity disorder (ADHD) among 3- to 6-year-old children. Methods In a 6-week double-blind clinical trial, the efficacy of Risperidone 0.5–2 mg with a dose of maximum Haloperidol 0.075 mg/kg was assessed in 39 children aged 3–6 years. This study was conducted at the Golestan Psychiatric Clinic (Ahvaz, Iran). Measurement tools included the Conners’ Parent Rating Scale (CPRS-48), Children’s Global Assessment Scale (CGAS), and the Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS). Data were analyzed using the Wilcoxon, Mann-Whitney, and Fisher’s exact tests in the SPSS 19. Results During the 6 weeks, the decline in points was seen in Conner’s rating scale and in ADHD-RS score in Risperidone and Haloperidol groups (p<0.001). On the CGAS scale, an increase of performance in both groups for six weeks was statistically significant (p<0.001). In the scales of ADHD-RS and CPRS-48, no statistically significant difference was observed between the two treatment groups; i.e., in terms of reducing the rate during weeks of two, four, and six (p>0.05). Conclusions Haloperidol and Risperidone possibly can be an acceptable treatment choice in the ADHD treatment of 3- to 6-year-old children. Trial registration The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the Irct ID: IRCT2015082623766N1. Funding This work was financially supported by grant (ref. no.: U-93130) from the vice chancellor for Research Affairs of Ahvaz Jundishapur University of Medical Sciences. PMID:27790334

  2. Haloperidol-loaded lipid-core polymeric nanocapsules reduce DNA damage in blood and oxidative stress in liver and kidneys of rats

    NASA Astrophysics Data System (ADS)

    Roversi, Katiane; Benvegnú, Dalila M.; Roversi, Karine; Trevizol, Fabíola; Vey, Luciana T.; Elias, Fabiana; Fracasso, Rafael; Motta, Mariana H.; Ribeiro, Roseane F.; dos S. Hausen, Bruna; Moresco, Rafael N.; Garcia, Solange C.; da Silva, Cristiane B.; Burger, Marilise E.

    2015-04-01

    Haloperidol (HP) nanoencapsulation improves therapeutic efficacy, prolongs the drug action time, and reduces its motor side effects. However, in a view of HP toxicity in organs like liver and kidneys in addition to the lack of knowledge regarding the toxicity of polymeric nanocapsules, our aim was to verify the influence of HP-nanoformulation on toxicity and oxidative stress markers in the liver and kidneys of rats, also observing the damage caused in the blood. For such, 28 adult male Wistar rats were designated in four experimental groups ( n = 7) and treated with vehicle (C group), free haloperidol suspension (FH group), blank nanocapsules suspension (B-Nc group), and haloperidol-loaded lipid-core nanocapsules suspension (H-Nc group). The nanocapsules formulation presented the size of approximately 250 nm. All suspensions were administered to the animals (0.5 mg/kg/day-i.p.) for a period of 28 days. Our results showed that FH caused damage in the liver, evidenced by increased lipid peroxidation, plasma levels of aspartate aminotransferase, and alanine aminotransferase, as well as decreased cellular integrity and vitamin C levels. In kidneys, FH treatment caused damage to a lesser extent, observed by decreased activity of δ-aminolevulinate dehydratase (ALA-D) and levels of VIT C. In addition, FH treatment was also related to a higher DNA damage index in blood. On the other hand, animals treated with H-Nc and B-Nc did not show damage in liver, kidneys, and DNA. Our study indicates that the nanoencapsulation of haloperidol was able to prevent the sub-chronic toxicity commonly observed in liver, kidneys, and DNA, thus reflecting a pharmacological superiority in relation to free drug.

  3. Psychomotor and cognitive effects of a single oral dose of talnetant (SB223412) in healthy volunteers compared with placebo or haloperidol.

    PubMed

    Liem-Moolenaar, M; Gray, F A; de Visser, S J; Franson, K L; Schoemaker, R C; Schmitt, J A J; Cohen, A F; van Gerven, J M A

    2010-01-01

    Central Nervous System (CNS) effects of talnetant, an NK-3 antagonist in development for schizophrenia, were compared to those of haloperidol and placebo. The study was randomised, double-blind, three-way crossover of talnetant 200 mg, haloperidol 3 mg or placebo. Twelve healthy males participated and EEG, saccadic and smooth pursuit eye movements, adaptive tracking, body sway, finger tapping, hormones, visual analogue scales (VAS) for alertness, mood and calmness and psychedelic effects, left/right distraction task, Tower of London and Visual and Verbal Learning Task were assessed. Haloperidol showed (difference to placebo; 95% CI; p-value) decreases in EEG alpha power (-0.87microV; -1.51/-0.22; p = 0.0110), saccadic inaccuracy (2.0%; 0.5/3.6; p = 0.0133), smooth pursuit eye movements (-7.5%; -12.0/-3.0; p = 0.0026), adaptive tracking (-3.5%; -5.4/-1.7; p = 0.0009), alertness (-6.8 mm; -11.1/-2.4; p = 0.0039), negative mood (-4.6 mm; -8.6/-0.6; p = 0.0266), the ability to control thoughts (1.2 mm; 0.2/2.3; p = 0.0214), and an increase of serum prolactin (ratio 4.1; 3.0/5.6; p < 0.0001). Talnetant showed decreased alpha power (-0.69 muV; -1.34/-0.04; p = 0.0390), improved adaptive tracking (1.9%; 0.1/3.7; p = 0.0370) and reduced calmness on VAS Bond and Lader (-4.5 mm; -8.0/-1.0; p = 0.0151). Haloperidol effects were predominantly CNS-depressant, while those of talnetant were slightly stimulatory. The results suggest that talnetant penetrates the brain, but it remains to be established whether this dose is sufficient and whether the observed effect profile is class-specific for NK3-antagonists.

  4. Beacon-like/ubiquitin-5-like immunoreactivity is highly expressed in human hypothalamus and increased in haloperidol-treated schizophrenics and a rat model of schizophrenia.

    PubMed

    Bernstein, Hans-Gert; Lendeckel, Uwe; Dobrowolny, Henrik; Stauch, Renate; Steiner, Johann; Grecksch, Gisela; Becker, Axel; Jirikowski, Gustav F; Bogerts, Bernhard

    2008-04-01

    The beacon gene is involved in the regulation of energy metabolism, food intake, and obesity. We localized its gene product, beacon-/ubiquitin 5-like immunoreactivity in brains of normal-weight, non-psychotic individuals, adipose (BMI over 32), non-psychotic individuals, and haloperidol-treated schizophrenics. The protein was found to be highly expressed in many neurons of the paraventricular and supraoptic hypothalamic nuclei. Besides, it was detected in neurons of other hypothalamic areas (suprachiasmatic, arcuate, and ventromedial nuclei) as well as outside the hypothalamus (Nuc. basalis Meynert, thalamus, hippocampus, and some neocortical areas). A morphometric analysis of beacon-immunoreactive hypothalamic and neocortical neurons revealed that compared to normal-weight controls in haloperidol-treated schizophrenics, there was a significant increase of protein-expressing supraoptic, paraventricular, and orbitofrontal neurons. However, a significant increase in beacon-expressing supraoptic neurons was also seen in adipose, non-psychotic individuals in comparison with normal-weight controls. Haloperidol at different doses has no effect on beacon expression in SHSY5Y neuroblastoma cells, which makes the assumption unlikely that haloperidol per se is responsible for the increased neuronal expression of the peptide in schizophrenics. In rats with a neonatal lesion of the ventral hippocampus (a widely used animal model of schizophrenia), we found an increased neuronal expression of beacon in the paraventricular and supraoptic nuclei. We suppose that elevated hypothalamic expression of beacon-like protein in non-obese schizophrenics is not primarily related to metabolic alterations, but to a certain role in schizophrenia, which is possibly unrelated to aspects of weight gain and obesity. The latter assumption finds some support by data obtained in rats with ventral hippocampus lesion.

  5. Injections of the selective adenosine A2A antagonist MSX-3 into the nucleus accumbens core attenuate the locomotor suppression induced by haloperidol in rats

    PubMed Central

    Ishiwari, Keita; Madson, Lisa J.; Farrar, Andrew M.; Mingote, Susana M.; Valenta, John P.; DiGianvittorio, Michael D.; Frank, Lauren E.; Correa, Merce; Hockemeyer, Jörg; Müller, Christa; Salamone, John D.

    2009-01-01

    There is considerable evidence of interactions between adenosine A2A receptors and dopamine D2 receptors in striatal areas, and antagonists of the A2A receptor have been shown to reverse the motor effects of DA antagonists in animal models. The D2 antagonist haloperidol produces parkinsonism in humans, and also induces motor effects in rats, such as suppression of locomotion. The present experiments were conducted to study the ability of the adenosine A2A antagonist MSX-3 to reverse the locomotor effects of acute or subchronic administration of haloperidol in rats. Systemic (i.p.) injections of MSX-3 (2.5–10.0 mg/kg) were capable of attenuating the suppression of locomotion induced by either acute or repeated (i.e., 14 day) administration of 0.5 mg/kg haloperidol. Bilateral infusions of MSX-3 directly into the nucleus accumbens core (2.5 µg or 5.0 µg in 0.5 µl per side) produced a dose-related increase in locomotor activity in rats treated with 0.5 mg/kg haloperidol either acutely or repeatedly. There were no overall significant effects of MSX-3 infused directly into the dorsomedial nucleus accumbens shell or the ventrolateral neostriatum. These results indicate that antagonism of adenosine A2A receptors can attenuate the locomotor suppression produced by DA antagonism, and that this effect may be at least partially mediated by A2A receptors in the nucleus accumbens core. These studies suggest that adenosine and dopamine systems interact to modulate the locomotor and behavioral activation functions of nucleus accumbens core. PMID:17223207

  6. Ginkgo biloba and vitamin E ameliorate haloperidol-induced vacuous chewingmovement and brain-derived neurotrophic factor expression in a rat tardive dyskinesia model.

    PubMed

    Shi, Jing; Tan, Yun Long; Wang, Zhi Ren; An, Hui Mei; Li, Jia; Wang, Yue Chan; Lv, Meng Han; Yan, Shao Xiao; Wu, Jing Qin; Soares, Jair C; Yang, Fu De; Zhang, Xiang Yang

    2016-09-01

    Neurodegeneration may be involved in the development of tardive dyskinesia (TD), and low levels of brain-derived neurotrophic factor (BDNF) may play a role. Ginkgo biloba (EGb761), a potent antioxidant, may have neuroprotective effects. We hypothesized that there would be decreased BDNF expression in TD, but that treatment with EGb761 would increase BDNF expression and reduce TD manifestations in a rat model. Forty rats were treated with haloperidol (2mg/kg/day via intraperitoneal injections) for 5weeks. EGb761 (50mg/kg/day) and vitamin E (20mg/kg/day) were then administered by oral gavage for another 5weeks, and we compared the effects of treatment with EGb761 or vitamin E on haloperidol-induced vacuous chewing movements (VCMs) and BDNF expression in four brain regions: prefrontal cortex (PFC), striatum (ST), substantia nigra (SNR), and globus pallidus (GP). Our results showed that haloperidol administration led to a progressive increase in VCMs, but both EGb761 and vitamin E significantly decreased VCMs. Haloperidol also decreased BDNF expression in all four brain regions, but both EGb761 and vitamin E administration significantly increased BDNF expression. Our results showed that both EGb761 and VE treatments exerted similar positive effects in a rat model of TD and increased BDNF expression levels in the four tested brain regions, suggesting that both EGb761 and vitamin E improve TD symptoms, possibly by enhancing BDNF in the brain and/or via their free radical-scavenging actions. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. IBZM SPECT imaging of striatal dopamine-2 receptors in psychotic patients treated with the novel antipsychotic substance quetiapine in comparison to clozapine and haloperidol.

    PubMed

    Küfferle, B; Tauscher, J; Asenbaum, S; Vesely, C; Podreka, I; Brücke, T; Kasper, S

    1997-10-01

    We investigated the striatal dopamine-2 (D2) receptor occupancy caused by different antipsychotic substances in 18 psychotic patients (16 with schizophrenic and two with schizoaffective disorder according to DSM-IV) with single photon emission computed tomography (SPECT) using 123I-iodobenzamide (IBZM) as tracer substance. Four patients were treated with the novel antipsychotic compound quetiapine (300-700 mg/day), six with clozapine (300-600 mg/ day) and eight with haloperidol (10-20 mg/day). They were compared with eight healthy controls. Measurement of S/F ratios and consecutive calculation of D2 receptor occupancy revealed a significantly lower striatal D2 occupancy rate with quetiapine and clozapine in comparison to haloperidol. In correspondence with the low striatal D2 receptor occupancy rates and again in contrast to the haloperidol treatment group, there were no extrapyramidal motor side-effects (EPS) in the quetiapine and clozapine treatment groups. Therefore, the reported data support the position that quetiapine can be considered to be an atypical antipsychotic substance due to its relatively weak striatal D2 receptor blocking property and therefore its low propensity to induce EPS.

  8. EL MANEJO DE LA BIODIVERSIDAD EN EL SIGLO XXI

    Treesearch

    ARIEL E. LUGO

    2001-01-01

    ser humano está transformando rápidamente el planeta Tierra (Meyer y Turner, 1994; Vitousek et al., 1997a). Su actividad tiene efectos globales que modifican el ambiente terrícola (Tabla I). Estos cambios, que comenzaron con la revolución industrial del siglo XIX, serán más notables en el siglo XXI en lo que se ha denominado la era Homogeocena donde el efecto...

  9. Prior haloperidol, but not olanzapine, exposure augments the pursuit of reward cues: implications for substance abuse in schizophrenia.

    PubMed

    Bédard, Anne-Marie; Maheux, Jérôme; Lévesque, Daniel; Samaha, Anne-Noël

    2013-05-01

    Drug abuse and addiction are excessively common in schizophrenia. Chronic antipsychotic treatment might contribute to this comorbidity by inducing supersensitivity within the brain's dopamine system. Dopamine supersensitivity can enhance the incentive motivational properties of reward cues, and reward cues contribute to the maintenance and severity of drug addiction. We have shown previously that rats withdrawn from continuous haloperidol (HAL) treatment (via subcutaneous minipump) develop dopamine supersensitivity and pursue reward cues more vigorously than HAL-naive rats following an amphetamine (AMPH) challenge. Atypical antipsychotic drugs are thought to be less likely than typicals to produce dopamine supersensitivity. Thus, we compared the effects of HAL and the atypical antipsychotic olanzapine (OLZ) on the pursuit of reward cues. Rats were trained to associate a light-tone cue with water then treated with HAL or OLZ. Following antipsychotic withdrawal, we assessed AMPH-induced enhancement of lever pressing for the cue. Withdrawal from HAL, but not from OLZ, enhanced this effect. HAL, but not OLZ, also enhanced AMPH-induced psychomotor activation and c-fos mRNA expression in the caudate-putamen. Thus, prior HAL, but not OLZ, enhanced conditioned reward following an AMPH challenge, and this was potentially linked to enhanced behavioral sensitivity to AMPH and AMPH-induced engagement of the caudate-putamen. These findings suggest that HAL, but not an atypical like OLZ, modifies reward circuitry in ways that increase responsiveness to reward cues. Because enhanced responsiveness to reward cues can promote drug-seeking behavior, it should be investigated whether atypical antipsychotics might be a preferential option in schizophrenic patients at risk for drug abuse or addiction.

  10. Comparable impediment of cognitive function in female and male rats subsequent to daily administration of haloperidol after traumatic brain injury.

    PubMed

    Free, Kristin E; Greene, Anna M; Bondi, Corina O; Lajud, Naima; de la Tremblaye, Patricia B; Kline, Anthony E

    2017-10-01

    Antipsychotic drugs, such as haloperidol (HAL), are prescribed in the clinic to manage traumatic brain injury (TBI)-induced agitation. While preclinical studies have consistently shown that once-daily administration of HAL hinders functional recovery after TBI in male rats, its effects in females are unknown. Hence, the objective of this study was to directly compare neurobehavioral and histological outcomes in both sexes to determine whether the reported deleterious effects of HAL extend to females. Anesthetized adult female and male rats received either a controlled cortical impact (CCI) or sham injury and then were randomly assigned to a dosing regimen of HAL (0.5mg/kg, i.p.) or vehicle (VEH; 1mL/kg, i.p.) that was initiated 24h after injury and continued once daily for 19 consecutive days. Motor function was tested using established beam-balance/walk protocols on post-operative days 1-5 and acquisition of spatial learning was assessed with a well-validated Morris water maze task on days 14-19. Cortical lesion volume was quantified at 21days. No statistical differences were revealed between the HAL and VEH-treated sham groups and thus they were pooled for each sex. HAL only impaired motor recovery in males (p<0.05), but significantly diminished spatial learning in both sexes (p<0.05). Females, regardless of treatment, exhibited smaller cortical lesions vs VEH-treated males (p<0.05). Taken together, the data show that daily HAL does not prohibit motor recovery in females, but does negatively impact cognition. These task-dependent differential effects of HAL in female vs male rats may have clinical significance as they can direct therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Solid lipid nanoparticles for nose to brain delivery of haloperidol: in vitro drug release and pharmacokinetics evaluation

    PubMed Central

    Yasir, Mohd; Sara, Udai Vir Singh

    2014-01-01

    In the present study, haloperidol (HP)-loaded solid lipid nanoparticles (SLNs) were prepared to enhance the uptake of HP to brain via intranasal (i.n.) delivery. SLNs were prepared by a modified emulsification–diffusion technique and evaluated for particle size, zeta potential, drug entrapment efficiency, in vitro drug release, and stability. All parameters were found to be in an acceptable range. In vitro drug release was found to be 94.16±4.78% after 24 h and was fitted to the Higuchi model with a very high correlation coefficient (R2=0.9941). Pharmacokinetics studies were performed on albino Wistar rats and the concentration of HP in brain and blood was measured by high performance liquid chromatography. The brain/blood ratio at 0.5 h for HP-SLNs i.n., HP sol. i.n. and HP sol. i.v. was 1.61, 0.17 and 0.031, respectively, indicating direct nose-to-brain transport, bypassing the blood–brain barrier. The maximum concentration (Cmax) in brain achieved from i.n. administration of HP-SLNs (329.17±20.89 ng/mL, Tmax 2 h) was significantly higher than that achieved after i.v. (76.95±7.62 ng/mL, Tmax 1 h), and i.n. (90.13±6.28 ng/mL, Tmax 2 h) administration of HP sol. The highest drug-targeting efficiency (2362.43%) and direct transport percentage (95.77%) was found with HP-SLNs as compared to the other formulations. Higher DTE (%) and DTP (%) suggest that HP-SLNs have better brain targeting efficiency as compared to other formulations. PMID:26579417

  12. Effects of typical (haloperidol) and atypical (risperidone) antipsychotic agents on protein expression in rat neural stem cells.

    PubMed

    Kashem, Mohammed A; Ummehany, Rahnuma; Ukai, Wataru; Hashimoto, Eri; Saito, Toshikazu; Mcgregor, Iain S; Matsumoto, Izuru

    2009-12-01

    Neural stem cells (NSCs) play a crucial role in the development and maturation of the central nervous system. Recently studies suggest that antipsychotic drugs regulate the activities of NSCs. However, the molecular mechanisms underlying antipsychotic-induced changes of the activity of NSCs, particularly protein expression, are still unknown. We studied the growth and protein expression in haloperidol (HD) and risperidone (RS) treated rat NSCs. The treatment with RS (3microM) or HD (3microM) had no effect on morphology of NSCs after 24h, but significantly promotes or inhibits the differentiation of NSCs after a 96h of treatment. 2-DE based proteomics was performed at 24h, a stage before phenotypic expression of NSCs. Gel image analysis revealed that 30 protein spots in HD- and 60 spots in RS-treated groups were differentially regulated in their expression compared to control group (p<0.05; ANOVA). When these spots were compared between the two drug-treated groups, 23 spots overlapped leaving 7 HD-specific and 37 RS-specific spots. Of these 67 spots, 32 different proteins were identified. The majority of the differentially regulated proteins were classified into several functional groups, such as cytoskeletal, calcium regulating protein, metabolism, signal transduction and proteins related to oxidative stress. Our data shows that atypical RS expressed more proteins than typical HD, and these results might explain the molecular mechanisms underlying the different effects of both drugs on NSCs activities as described above. Identified proteins in this experiment may be useful in future studies of NSCs differentiation and/or understanding in molecular mechanisms of different neural diseases including schizophenia.

  13. Solid lipid nanoparticles for nose to brain delivery of haloperidol: in vitro drug release and pharmacokinetics evaluation.

    PubMed

    Yasir, Mohd; Sara, Udai Vir Singh

    2014-12-01

    In the present study, haloperidol (HP)-loaded solid lipid nanoparticles (SLNs) were prepared to enhance the uptake of HP to brain via intranasal (i.n.) delivery. SLNs were prepared by a modified emulsification-diffusion technique and evaluated for particle size, zeta potential, drug entrapment efficiency, in vitro drug release, and stability. All parameters were found to be in an acceptable range. In vitro drug release was found to be 94.16±4.78% after 24 h and was fitted to the Higuchi model with a very high correlation coefficient (R (2)=0.9941). Pharmacokinetics studies were performed on albino Wistar rats and the concentration of HP in brain and blood was measured by high performance liquid chromatography. The brain/blood ratio at 0.5 h for HP-SLNs i.n., HP sol. i.n. and HP sol. i.v. was 1.61, 0.17 and 0.031, respectively, indicating direct nose-to-brain transport, bypassing the blood-brain barrier. The maximum concentration (C max) in brain achieved from i.n. administration of HP-SLNs (329.17±20.89 ng/mL, T max 2 h) was significantly higher than that achieved after i.v. (76.95±7.62 ng/mL, T max 1 h), and i.n. (90.13±6.28 ng/mL, T max 2 h) administration of HP sol. The highest drug-targeting efficiency (2362.43%) and direct transport percentage (95.77%) was found with HP-SLNs as compared to the other formulations. Higher DTE (%) and DTP (%) suggest that HP-SLNs have better brain targeting efficiency as compared to other formulations.

  14. Combining the Antipsychotic Drug Haloperidol and Environmental Enrichment after Traumatic Brain Injury Is a Double-Edged Sword.

    PubMed

    Folweiler, Kaitlin A; Bondi, Corina O; Ogunsanya, Elizabeth A; LaPorte, Megan J; Leary, Jacob B; Radabaugh, Hannah L; Monaco, Christina M; Kline, Anthony E

    2017-01-15

    Environmental enrichment (EE) confers significant benefits after experimental traumatic brain injury (TBI). In contrast, the antipsychotic drug (APD) haloperidol (HAL) exerts deleterious effects on neurobehavioral and cognitive recovery. Neurorehabilitation and management of agitation, however, are integral components of the treatment strategy for patients with TBI. Hence, the goal of this study was to determine how the two therapeutic approaches interact and influence motor and cognitive recovery. Anesthetized adult male rats received a controlled cortical impact (2.8 mm tissue deformation at 4 m/sec) or sham injury and then were provided HAL (0.5 mg/kg; intraperitoneally [IP]) or vehicle (VEH; 1 mL/kg; IP) commencing 24 h after surgery and once daily for 19 days while housed in EE or standard (STD) conditions. Beam balance/walk and Morris water maze performance were assessed on post-injury days 1-5 and 14-19, respectively, followed immediately by quantification of cortical lesion volumes. The data revealed both expected and unexpected findings. It was not surprising that the TBI groups receiving EE performed significantly better than those in STD housing and that the TBI + STD + HAL group performed worse than the TBI + STD + VEH group (p < 0.05). What was surprising was that the therapeutic effects of EE were greatly reduced by concomitant administration of HAL. No differences in cortical lesion volumes were observed among the groups (p > 0.05). The potential clinical implications of these findings suggest that administering HAL to patients undergoing neurorehabilitation may be a double-edged sword because agitation must be controlled before rehabilitation can be safely initiated and executed, but its use may compromise therapeutic efficacy.

  15. Lipoic acid and haloperidol-induced vacuous chewing movements: Implications for prophylactic antioxidant use in tardive dyskinesia.

    PubMed

    Lister, Joshua; Andreazza, Ana C; Navaid, Bushra; Wilson, Virginia S; Teo, Celine; Nesarajah, Yasika; Wilson, Alan A; Nobrega, José N; Fletcher, Paul J; Remington, Gary

    2017-01-04

    Tardive dyskinesia (TD), a potentially irreversible antipsychotic (AP)-related movement disorder, is a risk with all currently available antipsychotics. AP-induced vacuous chewing movements (VCMs) in rats, a preclinical model of TD, can be attenuated by antioxidant-based treatments although there is a shortage of well-designed studies. Lipoic acid (LA) represents a candidate antioxidant for the treatment of oxidative stress-related nervous system disorders; accordingly, its effects on AP-induced VCMs and striatal oxidative stress were examined. Rats treated with haloperidol decanoate (HAL; 21mg/kg every 3weeks, IM) for 12weeks were concurrently treated with LA (10 or 20mg/kg, PO). VCMs were assessed weekly by a blinded rater, and locomotor activity was evaluated as were striatal lipid peroxidation markers and serum HAL levels. VCMs were decreased by the lower dose (nonsignificant), whereas a significant increase was recorded with the higher dose of LA. HAL decreased locomotor activity and this was unaffected by LA. Striatal malondialdehyde (MDA) levels in HAL-treated rats were reduced by both LA doses, while 4-hydroxynonenal (4-HNE) levels were predictive of final VCM scores (averaged across weeks 10-12). Study limitations include differences between antipsychotics in terms of oxidative stress, LA dosing, choice of biomarkers for lipid peroxidation, and generalizability to TD in humans. Collectively, current preclinical evidence does not support a "protective" role for antioxidants in preventing TD or its progression, although clinical evidence offers limited evidence supporting such an approach. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Sigma opiates and certain antipsychotic drugs mutually inhibit (+)-[3H] SKF 10,047 and [3H]haloperidol binding in guinea pig brain membranes.

    PubMed Central

    Tam, S W; Cook, L

    1984-01-01

    The relationship between binding of antipsychotic drugs and sigma psychotomimetic opiates to binding sites for the sigma agonist (+)-[3H]SKF 10,047 (N-allylnormetazocine) and to dopamine D2 sites was investigated. In guinea pig brain membranes, (+)-[3H]SKF 10,047 bound to a single class of sites with a Kd of 4 X 10(-8) M and a Bmax of 333 fmol/mg of protein. This binding was different from mu, kappa, or delta opiate receptor binding. It was inhibited by opiates that produce psychotomimetic activities but not by opiates that lack such activities. Some antipsychotic drugs inhibited (+)-[3H]SKF 10,047 binding with high to moderate affinities in the following order of potency: haloperidol greater than perphenazine greater than fluphenazine greater than acetophenazine greater than trifluoperazine greater than molindone greater than or equal to pimozide greater than or equal to thioridazine greater than or equal to chlorpromazine greater than or equal to triflupromazine. However, there were other antipsychotic drugs such as spiperone and clozapine that showed low affinity for the (+)-[3H]SKF 10,047 binding sites. Affinities of antipsychotic drugs for (+)-[3H]SKF 10,047 binding sites did not correlate with those for [3H]spiperone (dopamine D2) sites. [3H]-Haloperidol binding in whole brain membranes was also inhibited by the sigma opiates pentazocine, cyclazocine, and (+)-SKF 10,047. In the striatum, about half of the saturable [3H]haloperidol binding was to [3H]spiperone (D2) sites and the other half was to sites similar to (+)-[3H]SKF 10,047 binding sites. PMID:6147851

  17. sigma opiates and certain antipsychotic drugs mutually inhibit (+)-(/sup 3/H)SKF 10,047 and (/sup 3/H)haloperidol binding in guinea pig brain membranes

    SciTech Connect

    Tam, S.W.; Cook, L.

    1984-09-01

    The relationship between binding of antipsychotic drugs and sigma psychotomimetic opiates to binding sites for the sigma agonist (+)-(/sup 3/H)SKF 10,047 (N-allylnormetazocine) and to dopamine D/sub 2/ sites was investigated. In guinea pig brain membranes, (+)-(/sup 3/H)SKF 10,047 bound to single class of sites with a K/sub d/ of 4 x 10/sup -8/ M and a B/sub max/ of 333 fmol/mg of protein. This binding was different from ..mu.., kappa, or delta opiate receptor binding. It was inhibited by opiates that produce psychotomimetic activities but not by opiates that lack such activities. Some antipsychotic drugs inhibited (+)-(/sup 3/H)SKF 10,047 binding with high to moderate affinities in the following order of potency: haloperidol > perphenazine > fluphenazine > acetophenazine > trifluoperazine > molindone greater than or equal to pimozide greater than or equal to thioridazine greater than or equal to chlorpromazine greater than or equal to triflupromazine. However, there were other antipsychotic drugs such as spiperone and clozapine that showed low affinity for the (+)-(/sup 3/H)SKF 10,047 binding sites. Affinities of antipsychotic drugs for (+)-(/sup 3/H)SKF 10,047 binding sites did not correlate with those for (/sup 3/H)spiperone (dopamine D/sub 2/) sites. (/sup 3/H)-Haloperidol binding in whole brain membranes was also inhibited by the sigma opiates pentazocine, cyclazocine, and (+)-(/sup 3/H)SKF 10,047. In the striatum, about half of the saturable (/sup 3/H)haloperidol binding was to (/sup 3/H)spiperone (D/sub 2/) sites and the other half was to sites similar to (+)-(/sup 3/H)SKF 10,047 binding sites. 15 references, 4 figures, 1 table.

  18. Distinct effects of haloperidol in the mediation of conditioned fear in the mesolimbic system and processing of unconditioned aversive information in the inferior colliculus.

    PubMed

    Muthuraju, S; Nobre, M J; Saito, V M N; Brandao, M L

    2014-03-07

    Chemical and electrical stimulation of the inferior colliculus (IC) causes defensive behavior. Electrical stimulation of the IC at the escape threshold enhances dopamine (DA) release in the prefrontal cortex. Intra-ventral tegmental area injections of quinpirole at doses that act presynaptically reduce the release of DA in the terminal fields of the mesolimbic system and clearly reduce conditioned fear in several animal models of anxiety. However, little is known about the involvement of DA in the mediation of unconditioned fear, such as the reactivity to acute stressors. The present study investigated the neural substrates mediated by DA transmission associated with emotional changes triggered by the activation or inhibition of D2 receptors during conditioned and unconditioned fear. We examined the effects of systemic or local injections of the DA-receptor antagonist and agonist haloperidol and quinpirole, respectively, into the IC in rats subjected to fear-potentiated startle, a Pavlovian paradigm that uses loud sounds as the unconditioned stimulus and light previously paired with footshock as the conditioned stimulus. We also assessed auditory-evoked potentials (AEPs) recorded from electrodes implanted in the IC. Intraperitoneal haloperidol administration dose-dependently enhanced AEPs induced by loud tones and inhibited fear-potentiated startle. Intra-IC injections of quinpirole left AEPs unchanged, suggesting that an optimal level of postsynaptic D2 receptors in the IC may regulate the transmission of aversive information through the midbrain tectum. These findings provide evidence of opposing DA-mediated mechanisms in fear/anxiety processes that depend on the area under study. The activity of the neural substrates of conditioned fear was attenuated by haloperidol, whereas midbrain neural substrates of unconditioned fear were enhanced. Thus, DA appears to regulate unconditioned fear at the midbrain level, likely by reducing the sensory gating of aversive

  19. The association study of polymorphisms in DAT, DRD2, and COMT genes and acute extrapyramidal adverse effects in male schizophrenic patients treated with haloperidol.

    PubMed

    Zivković, Maja; Mihaljević-Peles, Alma; Bozina, Nada; Sagud, Marina; Nikolac-Perkovic, Matea; Vuksan-Cusa, Bjanka; Muck-Seler, Dorotea

    2013-10-01

    Extrapyramidal symptoms (EPSs) are common adverse effects of antipsychotics. The development of acute EPSs could depend on the activity of dopaminergic system and its gene variants. The aim of this study was to determine the association between dopaminergic type 2 receptor (DRD2) dopamine transporter (SLC6A3) and catechol-O-methyltransferase (COMT) gene polymorphisms and acute EPSs in 240 male schizophrenic patients treated with haloperidol (15-mg/d) over a period of 2 weeks. Acute EPSs were assessed with Simpson-Angus Scale. Three dopaminergic gene polymorphisms, the DRD2 Taq1A, the SLC6A3 VNTR, and the COMT Val158Met, were determined. Extrapyramidal symptoms occurred in 116 (48.3%) of patients. Statistically significant associations were found for SLC6A3 VNTR and COMT Val158Met polymorphisms and EPS susceptibility. Patients with SLC6A3 9/10 genotype had almost twice the odds to develop EPSs compared with those with all other SLC6A3 genotypes (odds ratio, 1.9; 95% confidence interval, 1.13-3.30), and patients with COMT Val/Met genotype had 1.7 times greater odds to develop EPSs than those with all other COMT genotypes (odds ratio, 1.7; 95% confidence interval, 1.01-2.88). There was no statistically significant association between genotype and allele frequencies of DRD2, SLC6A3, or COMT polymorphisms and the development of particular EPSs.In conclusion, the results of the present study showed for the first time the association between acute haloperidol-induced EPSs and SLC6A3 VNTR and COMT Val158Met polymorphisms. Although the precise biological mechanisms underlying these findings are not yet understood, the results suggest that the dopaminergic gene variations could predict the vulnerability to the development of the acute EPSs in haloperidol-treated schizophrenic patients.

  20. Short-term regulation of tyrosine hydroxylase in tonically-active and in tonically-inactive dopamine neurons: effects of haloperidol and protein phosphorylation.

    PubMed

    Iuvone, P M

    1983-09-26

    Dopamine (DA)-containing neurons of retina were employed as an experimental model for studying the short-term regulation of tyrosine hydroxylase (TH) in tonically-active and tonically-inactive neurons. These DA-containing neurons are trans-synaptically activated by light. Two mechanisms have been observed in this system for regulation of TH activity. A short-term activation of TH that is characterized by a decreased apparent Km for pteridine cofactors occurs in response to rapid increases of neuronal activity. A second mechanism occurs in response to prolonged, tonic changes of neuronal activity and is characterized by changes of Vmax. Both the Km changes and Vmax changes represent changes of specific activity of TH rather than enzyme induction. To determine the effects of short-term increases of neuronal activity on TH in tonically-active and tonically-inactive neurons, the effects of acute administration of haloperidol were examined in rats that were continuously light-exposed or light-deprived for 4 days. Haloperidol increased TH activity in both light-exposed and light-deprived retinas. The drug elicited the same percent stimulation in both experimental conditions. However, because the basal activity of TH was higher in the light-exposed than the light-deprived retinas, the absolute increase of TH specific activity was greater in the light-exposed samples. The effect of protein phosphorylation on TH activity in extracts of chronically light-exposed or light-deprived retinas was also examined to determine if the differences in the response to haloperidol might be due to a difference in the amount of TH available for short-term activation. Phosphorylation by endogenous cyclic AMP-dependent protein kinase (APK) or by purified catalytic subunit of APK resulted in larger increases of TH specific activity in extracts of light-exposed retinas than in those of light-deprived retinas. As was observed for haloperidol-induced activation, the percent stimulation elicited

  1. Nefazodone in psychotic unipolar and bipolar depression: a retrospective chart analysis and open prospective study on its efficacy and safety versus combined treatment with amitriptyline and haloperidol.

    PubMed

    Grunze, Heinz; Marcuse, Alain; Schärer, Lars O; Born, Christoph; Walden, Jörg

    2002-01-01

    Although atypical antipsychotics are on the rise, traditional treatment of psychotic (or delusional) depression mostly includes the addition of classical antipsychotics to antidepressants. As there are only few data supporting this approach compared with antidepressant monotherapy, and almost no data comparing it with antidepressants of the latest generation, we conducted a retrospective chart analysis and a prospective, randomized open study on the efficacy and tolerability of nefazodone monotherapy versus combined treatment with amitriptyline and haloperidol in psychotic depression. The results suggest that the addition of classical antipsychotics should be reserved for those with very severe psychotic symptoms, but may not be needed in milder forms. Copyright 2003 S. Karger AG, Basel

  2. Continuous Preparation of 1:1 Haloperidol-Maleic Acid Salt by a Novel Solvent-Free Method Using a Twin Screw Melt Extruder.

    PubMed

    Lee, Hung Lin; Vasoya, Jaydip M; Cirqueira, Marilia de Lima; Yeh, Kuan Lin; Lee, Tu; Serajuddin, Abu T M

    2017-03-10

    Salts are generally prepared by acid-base reaction in relatively large volumes of organic solvents, followed by crystallization. In this study, the potential for preparing a pharmaceutical salt between haloperidol and maleic acid by a novel solvent-free method using a twin-screw melt extruder was investigated. The pH-solubility relationship between haloperidol and maleic acid in aqueous medium was first determined, which demonstrated that 1:1 salt formation between them was feasible (pHmax 4.8; salt solubility 4.7 mg/mL). Extrusion of a 1:1 mixture of haloperidol and maleic acid at the extruder barrel temperature of 60 °C resulted in the formation of a highly crystalline salt. The effects of operating temperature and screw configuration on salt formation were also investigated, and those two were identified as key processing parameters. Salts were also prepared by solution crystallization from ethyl acetate, liquid-assisted grinding, and heat-assisted grinding and compared with those obtained by melt extrusion by using DSC, PXRD, TGA, and optical microscopy. While similar salts were obtained by all methods, both melt extrusion and solution crystallization yielded highly crystalline materials with identical enthalpies of melting. During the pH-solubility study, a salt hydrate form was also identified, which, upon heating, converted to anhydrate similar to that obtained by other methods. There were previous reports of the formation of cocrystals, but not salts, by melt extrusion. (1)H NMR and single-crystal X-ray diffraction confirmed that a salt was indeed formed in the present study. The haloperidol-maleic acid salt obtained was nonhygroscopic in the moisture sorption study and converted to the hydrate form only upon mixing with water. Thus, we are reporting for the first time a relatively simple and solvent-free twin-screw melt extrusion method for the preparation of a pharmaceutical salt that provides material comparable to that obtained by solution

  3. Effect of subtype-selective adenosine receptor antagonists on basal or haloperidol-regulated striatal function: studies of exploratory locomotion and c-Fos immunoreactivity in outbred and A(2A)R KO mice.

    PubMed

    Pardo, M; López-Cruz, L; Valverde, O; Ledent, C; Baqi, Y; Müller, C E; Salamone, J D; Correa, M

    2013-06-15

    Behavioral activation is regulated by dopamine (DA) in striatal areas. At low doses, while typical antipsychotic drugs produce psychomotor slowing, psychostimulants promote exploration. Minor stimulants such as caffeine, which act as adenosine receptor antagonists, can also potentiate behavioral activation. Striatal areas are rich in adenosine and DA receptors, and adenosine A2A receptors are mainly expressed in the striatum where they are co-localized with DA D2 receptors. Adenosine antagonists with different receptor-selectivity profiles were used to study spontaneous or haloperidol-impaired exploration and c-Fos expression in different striatal areas. Because A2A antagonists were expected to be more selective for reversing the effects of the D2 antagonist haloperidol, A2A receptor knockout (A2ARKO) mice were also assessed. CD1 and A2ARKO male mice were tested in an open field and in a running wheel. Only the A1/A2A receptor antagonist theophylline (5.0-15.0 mg/kg) and the A2A antagonist MSX-3 (2.0 mg/kg) increased spontaneous locomotion and rearing. Co-administration of theophylline (10.0-15.0 mg/kg), and MSX-3 (1.0-3.0 mg/kg) reversed haloperidol-induced suppression of locomotion. The A1 antagonist CPT was only marginally effective in reversing the effects of haloperidol. Although adenosine antagonists did not affect c-Fos expression on their own, theophylline and MSX-3, but not CPT, attenuated haloperidol induction of c-Fos expression. A2ARKO mice were resistant to the behavioral effects of haloperidol at intermediate doses (0.1 mg/kg) in the open field and in the running wheel. A2A receptors are important for regulating behavioral activation, and interact with D2 receptors in striatal areas to regulate neural processes involved in exploratory activity.

  4. Therapeutic drug monitoring of haloperidol, perphenazine, and zuclopenthixol in serum by a fully automated sequential solid phase extraction followed by high-performance liquid chromatography.

    PubMed

    Angelo, H R; Petersen, A

    2001-04-01

    In Denmark, haloperidol, perphenazine, and zuclopenthixol are among the most frequently requested antipsychotics for therapeutic drug monitoring. With the number of requests made at the authors' laboratory, the only rational analysis is one that can measure all three drugs simultaneously. The authors therefore decided to develop an automated high-performance liquid chromatography (HPLC) method. Two milliliters serum, 2.0 mL 10 mmol/L sodium phosphate buffer (pH 5.5), and 150 microL internal standard (trifluoperazine) solution were pipetted into HPLC vials and extracted on an ASPEC XL equipped with 1 mL (50 mg) Isolute C2 (EC) extraction columns and acetonitrile-methanol-ammonium acetate buffer (60:34:6) as extracting solution. Three hundred fifty microliters was analyzed by HPLC; a 150 x 4.6-mm S5CN Spherisorb column with a mobile phase of 10 mmol/L ammonium acetate buffer-methanol (1:9), a flow rate of 0.6-1.7 mL/min, and ultraviolet detection at 256 and 245 nm were used. Reproducibility was 5-12% and the lower limit of quantitation was 10, 1, and 5 nmol/L (4, 0.4, and 2 ng/mL) for haloperidol, perphenazine, and zuclopenthixol, respectively. The method was found to be sufficiently selective and robust for routine analysis.

  5. Dependence of the kinetic and thermodynamic parameters on hydrophilic-lipophilic character of alprazolam, clonazepam, diazepam, doxepin and haloperidol in alkaline environment.

    PubMed

    Maślanka, Anna; Krzek, Jan; Szlósarczyk, Marek; Żmudzki, Paweł; Wach, Katarzyna

    2013-10-15

    Examination of the stability of clonazepam, diazepam, alprazolam, haloperidol, and doxepin in basic solutions was performed, together with an assessment of the kinetic (k, t0.1i t0.5) and thermodynamic (Ea, ΔH(++)i ΔS(++)) stability-indicating parameters, which were compared with the lipophilicity (logP) of the studied drugs. It was observed that the calculated values of Ea, ΔH(++) and ΔS(++) for the studied drugs increased from 41.04 kJ/mol to 125.50 kJ/mol, from 37.82 kJ/mol to 122.24 kJ/mol and from -167.09 J/Kmol to 53.02 J/Kmol, respectively, along with an increase of lipophilicity (logP) from 2.12 to 4.30 for the most hydrophilic alprazolam to the most lipophilic haloperidol. The degradation products were identified using UPLC/MS/MS method.

  6. Posterior hypothalamic nucleus deep brain stimulation restores locomotion in rats with haloperidol-induced akinesia but not skilled forelimb use in pellet reaching and lever pressing.

    PubMed

    Young, C K; Whishaw, I Q; Bland, B H

    2011-09-29

    Recent studies have shown that electrical stimulation of the posterior hypothalamic nucleus (PH) facilitates locomotion in control rats, and rats were made akinetic by dopaminergic blockade via haloperidol or dopamine depletion by the neurotoxin 6-hydroxydopamine. These findings suggest that PH stimulation might be a promising treatment for akinesia associated with dopamine loss in Parkinson's disease. The present study further examined the positive effects of PH stimulation on behavior by characterizing its potential facilitatory effects on tasks that require skilled movements. Rats were trained to reach for food pellets with a forelimb (skilled reaching) or press a bar in an operant conditioning task for food. PH stimulation in undrugged rats not only facilitated locomotion in each of the tasks, but also impaired performance of the skilled movement components of the tasks. Haloperidol reduced locomotion and skilled movement, and PH stimulation only restored locomotion. The results are discussed in relation to the idea that PH stimulation selectively facilitates locomotor behavior and may have limited use in restoring impairments in skilled movements and consummatory behavior that results from dopaminergic depletion.

  7. Righting elicited by novel or familiar auditory or vestibular stimulation in the haloperidol-treated rat: rat posturography as a model to study anticipatory motor control.

    PubMed

    Clark, Callie A M; Sacrey, Lori-Ann R; Whishaw, Ian Q

    2009-09-15

    External cues, including familiar music, can release Parkinson's disease patients from catalepsy but the neural basis of the effect is not well understood. In the present study, posturography, the study of posture and its allied reflexes, was used to develop an animal model that could be used to investigate the underlying neural mechanisms of this sound-induced behavioral activation. In the rat, akinetic catalepsy induced by a dopamine D2 receptor antagonist (haloperidol 5mg/kg) can model human catalepsy. Using this model, two experiments examined whether novel versus familiar sound stimuli could interrupt haloperidol-induced catalepsy in the rat. Rats were placed on a variably inclined grid and novel or familiar auditory cues (single key jingle or multiple key jingles) were presented. The dependent variable was movement by the rats to regain equilibrium as assessed with a movement notation score. The sound cues enhanced movements used to regain postural stability and familiar sound stimuli were more effective than unfamiliar sound stimuli. The results are discussed in relation to the idea that nonlemniscal and lemniscal auditory pathways differentially contribute to behavioral activation versus tonotopic processing of sound.

  8. [Effect of a buzepide metiodide-haloperidol combination in treating functional intestinal disorders. Randomized double-blind controlled versus placebo study].

    PubMed

    Barbier, J P; Dorf, G; Gordin, J; Krainik, F; Neveu, D; Parlier, H; Richard, P; Vitaux, J; Fraitag, B

    1989-05-01

    The efficacy and safety of a combination of buzepide metiodide and haloperidol was assessed in a placebo-controlled double-blind trial during 2 months in 224 patients (154 women, 79 men) with the irritable bowel syndrome. The 2 groups were comparable at inclusion. The efficacy was assessed at days 15, 30 and 60. Inclusion and assessment criteria were clinical, abdominal pain being considered as the main assessment criterion. The combination proved statistically better than placebo on the frequency of symptoms at all visits and on the intensity of the most frequent symptoms (abdominal pain and distension) at the final visit. A previously defined global assessment score was found significantly better in favor of the treated group at day 15 and day 30. At the final visit, the score of a visual scale assessing the patient's global impression was also found significantly better on the combination, There was no serious side-effect. In conclusion, this study demonstrates the efficacy and safety of a combination of buzepide metiodide and haloperidol in patients with the irritable bowel syndrome.

  9. The local application of a flavonoid, (-)-epicatechin, increases the spiking of globus pallidus neurons in a dose-dependent manner and diminishes the catalepsy induced by haloperidol.

    PubMed

    Alatorre, Alberto; Oviedo-Chávez, Aldo; Villalobos, Nelson; Ríos, Alain; Barrientos, Rafael; Querejeta, Enrique

    2015-02-01

    Flavonoids are natural substances obtained from plants. Most flavonoids cross the blood-brain barrier and exert a wide range of effects on the central nervous system. These actions have been attributed to the modulation of GABA-A receptors. Although motor systems in the central nervous system express a high density of GABA-A receptors, physiological studies about the effects of flavonoids on motor nuclei are scarce. Among the nuclei of the basal ganglia, the globus pallidus is potentially important for the processing of information related to movement. The electrical activity of globus pallidus neurons depends on the GABAergic fibers coming from the striatum and recurrent collateral fibers. It is known that the basal activity of the globus pallidus is modified by blocking dopaminergic receptors. In the present work, we analyzed the effects of the local application of a flavonoid, (-)-epicatechin, on the spiking of globus pallidus neurons in chloral hydrate-anesthetized rats and determined whether (-)-epicatechin applied bilaterally to the globus pallidus can modify the catalepsy induced by systemic administration of haloperidol. The results showed that (-)-epicatechin increased the basal firing of globus pallidus neurons in a dose-dependent manner and antagonized the inhibitory effect of GABA. Bilateral infusion of (-)-epicatechin to the globus pallidus diminished the catalepsy induced by haloperidol.

  10. Effects of haloperidol, olanzapine, ziprasidone, and PHA-543613 on spatial learning and memory in the Morris water maze test in naïve and MK-801-treated mice.

    PubMed

    Ning, Houxu; Cao, Dong; Wang, Haidong; Kang, Bing; Xie, Shiping; Meng, Yujing

    2017-08-01

    Cognitive impairment is the core symptom of schizophrenia, significantly impacting the functional outcome. Improvement of cognitive function has been an important aspect of the treatment of schizophrenia. Therefore, this study is to demonstrate the effects of first-generation antipsychotic haloperidol, second-generation antipsychotic olanzapine and ziprasidone, and alpha-7 nicotinic acetylcholine receptor agonist PHA-543613 on spatial learning and memory. C57BL/6 mice received intraperitoneal injections of haloperidol (2 mg/kg), olanzapine (2.5 mg/kg), ziprasidone (2 mg/kg), and PHA-543613 (1 mg/kg), and cognitive dysfunctions were induced by MK-801 (0.1 mg/kg). Morris water maze was used for investigating the effects of all agents. Mk-801 significantly increased the mean escape latency to the platform and decreased the number of platform area crossings. Ziprasidone had no effect on the mean escape latency to platform and the number of platform area crossings in naïve mice, but haloperidol, olanzapine, and PHA-543613 did not. Haloperidol and olanzapine significantly increased the mean escape latency to platform and decreased the number of platform area crossings, while ziprasidone and PHA-543613 did not. All the agents had no effect on swimming speed. Ziprasidone and alpha-7 nicotinic acetylcholine receptor agonist PHA-543613 might be helpful in the treatment of CIAS.

  11. Changes in [(3)H]-ouabain and [(3)H]-neurotensin binding to rat cerebral cortex membranes after administration of antipsychotic drugs haloperidol and clozapine.

    PubMed

    Rosin, Carina; López Ordieres, María Graciela; Rodríguez de Lores Arnaiz, Georgina

    2017-03-01

    Evidences indicate the relationship between neurotensinergic and dopaminergic systems. Neurotensin inhibits synaptosomal membrane Na(+), K(+)-ATPase activity, an effect blocked by SR 48692, antagonist for high affinity neurotensin receptor (NTS1) type. Assays of high affinity [(3)H]-ouabain binding (to analyze K(+) site of Na(+), K(+)-ATPase) show that in vitro addition of neurotensin decreases binding. Herein potential interaction between NTS1 receptor, dopaminergic D2 receptor and Na(+), K(+)-ATPase was studied. To test the involvement of dopaminergic D2 receptors in [(3)H]-ouabain binding inhibition by neurotensin, Wistar rats were administered i.p.with antipsychotic drugs haloperidol (2mg/kg) and clozapine (3, 10 and 30mg/kg). Animals were sacrificed 18h later, cerebral cortices harvested, membrane fractions prepared and high affinity [(3)H]-ouabain binding assayed in the absence or presence of neurotensin at a 10 micromolar concentration. No differences versus controls for basal binding or for binding inhibition by neurotensin were recorded, except after 10mg/kg clozapine. Rats were administered with neurotensin (3, 10y 30μg, i.c.v.) and 60min later, animals were sacrificed, cerebral cortices harvested and processed to obtain membrane fractions for high affinity [(3)H]-ouabain binding assays. Results showed a slight but statistically significant decrease in binding with the 30μg neurotensin dose. To analyze the interaction between dopaminergic D2 and NTS1 receptors, [(3)H]-neurotensin binding to cortical membranes from rats injected with haloperidol (2mg/kg, i.p.) or clozapine (10mg/kg) was assayed. Saturation curves and Scatchard transformation showed that the only statistically significant change occurred in Bmax after haloperidol administration. Hill number was close to the unit in all cases. Results indicated that typical and atypical antipsychotic drugs differentially modulate the interaction between neurotensin and Na(+), K(+)-ATPase. At the same time

  12. Genome-wide association study supports the role of the immunological system and of the neurodevelopmental processes in response to haloperidol treatment.

    PubMed

    Drago, Antonio; Giegling, Ina; Schäfer, Martin; Hartmann, Annette M; Konte, Bettina; Friedl, Marion; Serretti, Alessandro; Rujescu, Dan

    2014-06-01

    The aim of the study was to detect the genetic predictors of reseponse to haloperidol. Haloperidol is a benchmark drug for the pharmacological treatment of schizophrenia, but the genetics of its efficacy is yet to be elucidated. A genome-wide association analysis was carried out in a small sample of patients treated with haloperidol (n=96) and the results were replicated in a larger sample of patients treated with second-generation antipsychotics or perphenazine (final n=169, available from the Clinical Antipsychotic Trials for Intervention Effectiveness study). The Positive and Negative Symptom Scale % score decrease was the outcome in both samples. The period of observation was restricted to 1 month in the replication sample and the most severe cases were included to best balance the replication. The quality control (QC) for the investigation and replication sample included a minor allele frequency at least 0.01, call rate at least 0.95, and Hardy-Weinberg equilibrium P at least 0.0001. The source for imputation was the 1000 Genomes Pilot+HapMap 3 dataset. In total 1 080 870 single nucleotide polymorphisms (SNPs) were available after imputation and QC in the investigation sample. After QC of real genotypes, locus-targeted imputations were restricted to windows of 10 kb on either side of the sentinel SNP in the replication sample. Sentinel SNPs were the most significant findings in the investigation sample. Analysis of variance was the test of choice, PLINK, SNPTEST, and GTOOL were used in the analysis. Two SNPs (rs7912580 and rs2412459) were associated with response in both samples, respectively, located in an intergenic region between the AT-rich interactive domain 5B (ARID5B, MRF1-like) gene and rhotekin 2 (RTKN2) gene, an intronic region located in the eukaryotic translation initiation factor 2α kinase 4 (EIF2AK4) gene (P=1.358e-06 and 0.015 for the Positive and Negative Symptom Scale % total score decrease in the investigation and replication samples

  13. Different effects of long-term haloperidol administration on GABA/sub A/ and benzodiazepine receptors in various parts of the brain

    SciTech Connect

    Vasar, Oe.Oe.; Nurk, A.M.; Maimets, M.O.; Soosaar, A.H.; Allikmets, L.H.

    1986-09-01

    The data described in this paper are evidence that long-term administration of haloperidol has an opposite effect on the density of GABA/sub A/ and benzodiazepine receptors in the fore- and hindbrain. These changes are reflected at the molecular level as reversal of behavioral effect of the GABA/sub A/ agonist muscimol and the benzodiazepine agonist Ro15-1788. By means of parallel behavioral tests, binding of /sup 3/H-muscimol in the fore- and hindbrain of rats was investigated in experiments in vitro. /sup 3/H-flunitrazepam binding experiments were carried out in vivo on mice. Parallel with reversal of the behavioral effects of muscimol and Ro15-1788, the number of binding sites both for /sup 3/H-muscimol and for /sup 3/H-flunitrazepam in the forebrain was reduced; in the hindbrain the opposite process took place.

  14. Acoustic tone or medial geniculate stimulation cue training in the rat is associated with neocortical neuroplasticity and reduced akinesia under haloperidol challenge.

    PubMed

    Brown, Andrew R; Hu, Bin; Kolb, Bryan; Teskey, G Campbell

    2010-12-06

    Sensory cues can improve movement deficits in Parkinson's disease, but little is known about the mechanisms involved. To investigate neuroplastic changes following sensorimotor cue training, rats were shaped to respond to acoustic tone or medial geniculate stimulation cues by retrieving a food reward. Neuroplasticity associated with training was assessed by changes in auditory neocortical evoked field potentials and dendritic morphology. Stimulation cue training was associated with changes in dendritic arbour length and complexity in auditory and motor neocortices, but was without effect on evoked electrophysiological responses. Tone cue training was associated with a significant increase in peak height of the evoked auditory response and then under haloperidol challenge, demonstrated reduced akinesia. Results indicate that cue-training induces neuroplastic changes that may be related to improved sensorimotor function under dopaminergic antagonism.

  15. Rationale and design of an independent randomised controlled trial evaluating the effectiveness of aripiprazole or haloperidol in combination with clozapine for treatment-resistant schizophrenia

    PubMed Central

    Nosè, Michela; Accordini, Simone; Artioli, Paola; Barale, Francesco; Barbui, Corrado; Beneduce, Rossella; Berardi, Domenico; Bertolazzi, Gerardo; Biancosino, Bruno; Bisogno, Alfredo; Bivi, Raffaella; Bogetto, Filippo; Boso, Marianna; Bozzani, Alberto; Bucolo, Piera; Casale, Marcello; Cascone, Liliana; Ciammella, Luisa; Cicolini, Alessia; Cipresso, Gabriele; Cipriani, Andrea; Colombo, Paola; Dal Santo, Barbara; De Francesco, Michele; Di Lorenzo, Giorgio; Di Munzio, Walter; Ducci, Giuseppe; Erlicher, Arcadio; Esposito, Eleonora; Ferrannini, Luigi; Ferrato, Farida; Ferro, Antonio; Fragomeno, Nicoletta; Parise, Vincenzo Fricchione; Frova, Maria; Gardellin, Francesco; Garzotto, Nicola; Giambartolomei, Andrea; Giupponi, Giancarlo; Grassi, Luigi; Grazian, Natalia; Grecu, Lorella; Guerrini, Gualtiero; Laddomada, Francesco; Lazzarin, Ermanna; Lintas, Camilla; Malchiodi, Francesca; Malvini, Lara; Marchiaro, Livio; Marsilio, Alessandra; Mauri, Massimo Carlo; Mautone, Antonio; Menchetti, Marco; Migliorini, Giuseppe; Mollica, Marco; Moretti, Daniele; Mulè, Serena; Nicholau, Stylianos; Nosè, Flavio; Occhionero, Guglielmo; Pacilli, Anna Maria; Pecchioli, Stefania; Percudani, Mauro; Piantato, Ennio; Piazza, Carlo; Pontarollo, Francesco; Pycha, Roger; Quartesan, Roberto; Rillosi, Luciana; Risso, Francesco; Rizzo, Raffella; Rocca, Paola; Roma, Stefania; Rossattini, Matteo; Rossi, Giuseppe; Rossi, Giovanni; Sala, Alessandra; Santilli, Claudio; Saraò, Giuseppe; Sarnicola, Antonio; Sartore, Francesca; Scarone, Silvio; Sciarma, Tiziana; Siracusano, Alberto; Strizzolo, Stefania; Tansella, Michele; Targa, Gino; Tasser, Annamarie; Tomasi, Rodolfo; Travaglini, Rossana; Veronese, Antonio; Ziero, Simona

    2009-01-01

    Background One third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study. Methods/Design The principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time. This project is a prospective, multicentre, randomized, parallel-group, superiority trial that follow patients over a period of 12 months. Withdrawal from allocated treatment within 3 months is the primary outcome. Discussion The implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce randomised knowledge. The employed pragmatic attitude allowed to randomly allocate more than 100 individuals, which means that this study is the largest antipsychotic combination trial conducted so far in Western countries. We expect that the current project, by generating evidence on whether it is clinically useful to combine clozapine with aripiprazole rather than with haloperidol

  16. Methamphetamine-induced expression of zif268 mRNA is prevented by haloperidol in mice lacking μ-opioid receptor

    PubMed Central

    Tien, Lu-Tai; Ho, Ing-Kang; Ma, Tangeng

    2010-01-01

    We investigated the role of μ-opioid receptor (μ-OR) and dopamine receptor in the modulation of methamphetamine (METH)-induced expression of zif268 mRNA in the striatum of mice. Four groups of wild-type and μ-OR knockout mice were given a single daily intraperitoneal injection of saline (control; group 1) or METH (10 mg/kg; groups 2–4) for 7 consecutive days. On day 11 (after 4 abstinent days), groups 1 and 2 were challenged with saline, group 3 was challenged with METH (10 mg/kg), and group 4 was challenged with dopamine receptor antagonist haloperidol (0.06 mg/kg, subcutaneous injection) plus METH (10 mg/kg). Two hours after the last saline or METH injection, mouse brain tissues were taken for zif268 mRNA analysis using in situ hybridization histochemistry. In comparison to corresponding saline control group (group 1), striatal zif268 mRNA levels were unchanged in group 2 and increased in group 3 in both wild-type and μ-OR knockout mice and without genotype difference. METH challenge-enhanced expression of zif268 mRNA was completely abolished by pre-administration of haloperidol (group 4) in μ-OR knockout mice but not in wild-type mice. The results suggest a crosstalk of the two neurotransmitter systems in modulation of METH-induced IEG expression, because only in μ-OR knockout mice in which dopamine receptors were blocked were METH-induced zif268 expression abolished. METH-induced zif268 expression was not altered inμ-OR knockout mice without blockade of dopamine receptors or wild-type mice with blockade of dopamine receptors. PMID:20184921

  17. Compatibility of cholecalciferol, haloperidol, imipramine hydrochloride, levodopa/carbidopa, lorazepam, minocycline hydrochloride, tacrolimus monohydrate, terbinafine, tramadol hydrochloride and valsartan in SyrSpend SF PH4 oral suspensions.

    PubMed

    Polonini, H C; Silva, S L; Cunha, C N; Brandão, M A F; Ferreira, A O

    2016-04-01

    A challenge with compounding oral liquid formulations is the limited availability of data to support the physical, chemical and microbiological stability of the formulation. This poses a patient safety concern and a risk for medication errors. The objective of this study was to evaluate the compatibility of the following active pharmaceutical ingredients (APIs) in 10 oral suspensions, using SyrSpend SF PH4 (liquid) as the suspending vehicle: cholecalciferol 50,000 IU/mL, haloperidol 0.5 mg/mL, imipramine hydrochloride 5.0 mg/mL, levodopa/carbidopa 5.0/1.25 mg/mL, lorazepam 1.0 mg/mL, minocycline hydrochloride 10.0 mg/mL, tacrolimus monohydrate 1.0 mg/mL, terbinafine 25.0 mg/mL, tramadol hydrochloride 10.0 mg/mL and valsartan 4.0 mg/mL. The suspensions were stored both refrigerated (2 - 8 degrees C) and at controlled room temperature (20 - 25 degrees C). This is the first stability study for these APIs in SyrSpend SF PH4 (liquid). Further, the stability of haloperidol,ilmipramine hydrochloride, minocycline, and valsartan in oral suspension has not been previously reported in the literature. Compatibility was assessed by measuring percent recovery at varying time points throughout a 90 days period. Quantification of the APIs was performed by high performance liquid chromatography (HPLC-UV). Given the percentage of recovery of the APIs within the suspensions, the beyond-use date of the final preparations was found to be at least 90 days for most suspensions both refrigerated and at room temperature. Exceptions were: Minocycline hydrochloride at both storage temperatures (60 days), levodopa/carbidopa at room temperature (30 days), and lorazepam at room temperature (60 days). This suggests that compounded suspensions of APIs from different pharmacological classes in SyrSpend SF PH4 (liquid) are stable.

  18. ConSCRIPT

    PubMed Central

    Mottarella, Scott E.; Rosa, Mario; Bangura, Abdul; Bernstein, Herbert J.; Craig, Paul A.

    2011-01-01

    The aim of the Structural Biology Extensible Visualization Scripting Language (SBEVSL) project is to allow users who are experts in one scripting language to use that language in a second molecular visualization environment without requiring the user to learn a new scripting language. ConSCRIPT, the first SBEVSL release, is a plug-in for PyMOL that accepts RasMol scripting commands either as premade scripts or as line-by-line entries from PyMOL's own command line. The plug-in is available for download at http://sourceforge.net/projects/sbevsl/files in the ConSCRIPT folder. PMID:21567873

  19. Differential Long-Term Effects of Haloperidol and Risperidone on the Acquisition and Performance of Tasks of Spatial Working and Short-Term Memory and Sustained Attention in Rats

    PubMed Central

    Hutchings, Elizabeth J.; Waller, Jennifer L.

    2013-01-01

    A common feature of the neuropsychiatric disorders for which antipsychotic drugs are prescribed is cognitive dysfunction, yet the effects of long-term antipsychotic treatment on cognition are largely unknown. In the current study, we evaluated the effects of long-term oral treatment with the first-generation antipsychotic haloperidol (1.0 and 2.0 mg/kg daily) and the second-generation antipsychotic risperidone (1.25 and 2.5 mg/kg daily) on the acquisition and performance of two radial-arm maze (RAM) tasks and a five-choice serial reaction-time task (5C-SRTT) in rats during days 15–60 and 84–320 days of treatment, respectively. In the RAM, neither antipsychotic significantly affected the acquisition or performance of a spatial win shift or a delayed non–match-to-position task. Conversely, in the rats administered 5C-SRTT, haloperidol was associated with profound deficits in performance, and the subjects were not able to progress through all stages of task acquisition. Depending on the dose, risperidone was associated with a greater number of trials to meet specific performance criteria during task acquisition compared with vehicle-treated controls; however, most subjects were eventually able to achieve all levels of task acquisition. Both haloperidol and risperidone also increased the number of perseverative and time-out responses during certain stages of task acquisition, and the response and reward latencies were slightly higher than controls during several stages of the study. These results in rats suggest that while long-term treatment with haloperidol or risperidone may not significantly affect spatial working or short-term memory, both antipsychotics can (depending on dose) impair sustained attention, decrease psychomotor speed, increase compulsive-type behaviors, and impair cognitive flexibility. PMID:24042161

  20. Electron spin resonance spectroscopy reveals alpha-phenyl-N-tert-butylnitrone spin-traps free radicals in rat striatum and prevents haloperidol-induced vacuous chewing movements in the rat model of human tardive dyskinesia.

    PubMed

    Rogoza, Raina M; Fairfax, David F; Henry, Paul; N-Marandi, Sevil; Khan, Rao F; Gupta, Suresh K; Mishra, Ram K

    2004-12-01

    The typical antipsychotic drug haloperidol causes vacuous chewing movements (VCM) in rats, which are representative of early-Parkinsonian symptoms or later-onset extrapyramidal side effects of tardive dyskinesia (TD) in humans. Haloperidol (HP) has been hypothesized to potentiate increases in oxidative stress or free radical-mediated levels of toxic metabolites in rat striatum while simultaneous upregulating dopamine (DA)-D2 receptors leading to presumed DA supersensitivity. Alpha(alpha)-Phenyl-N-tert-butylnitrone (PBN) is an antioxidant used to combat oxidative stress and measure increases in PBN spin-adduct activity. Thus, the aim of this study was to investigate whether VCMs are related to upregulation of DA-D2 receptors or to increased levels of free radicals produced during oxidative stress, and whether PBN had any protective effects. Rats received daily chronic (28 day) i.p. injections of saline, haloperidol (2 mg/kg), PBN (150 mg/kg), or haloperidol + PBN. The VCM model was used to measure extrapyramidal side effects of drug treatments. Electron spin resonance (ESR) spectroscopy was performed to compare concentrations of free radical species in rats receiving injections of HP + PBN. To examine the upregulation of DA-D2 receptors, binding assays were carried out to assess the increase in DA-D(2) receptor numbers with respect to VCMs following treatment of rats injected with HP, PBN, and HP + PBN. Results of these experiments show that HP-induced VCMs in rats results from increases in oxidative cellular events and may not be related to increases in striatal DA-D(2) receptors.

  1. A comparison of (/sup 18/F)spiroperidol, (/sup 18/F)benperidol and (/sup 18/F) haloperidol kinetics in baboon brain

    SciTech Connect

    Arnett, C.D.; Shiue, C.Y.; Wolf, A.P.; Fowler, J.S.; Logan, J.

    1984-01-01

    Neuroleptic receptor ligands, spiroperidol, benperidol and haloperidol were labeled with fluorine-18 by a nucleophilic aromatic substitution reaction of p-nitrobenzo-nitrile with /sup 18/F/sup -/ to produce p-(/sup 18/F)fluorobenzonitrile which was converted to p-(/sup 18/F)fluoro-y-chlorobutyrophenone and then alkylated with the appropriate amine to give (/sup 18/F)spiroperidol ((/sup 18/F)SP), (/sup 18/F)benperidol ((/sup 18/F)BEN), or (/sup 18/F)haloperidol ((/sup 18/F)HAL). Specific activity ranged from 3 to 6 Ci/..mu..mol. Anesthetized baboons were injected with 6-17 mCi of (/sup 18/F)-labeled tracer. Kinetic curves (striatum and cerebellum) were obtained from PETT scans up to 4 hr with each drug; (/sup 18/F)SP was studied to 8 hr. (/sup 18/F)SP and (/sup 18/F)BEN exhibited similar kinetics in striatum, with radioactivity concentration plateauing by 30 min after injection and remaining constant for the remainder of the study. These two compounds cleared rapidly from the cerebellum. (/sup 18/F)HAL showed a much different kinetic pattern in the striatum. Although it reached a higher striatal concentration (approx. =0.07% per ml vs. approx. = 0.02% per ml for (/sup 18/F)SP or (/sup 18/F)BEN), a peak occurred at 30 min after injection, followed by a decline almost as rapid as that in the cerebellum. Plasma analyses for (/sup 18/F)SP showed > 90% unchanged drug up to 5 min and approx. = 30% metabolites at 20 min after injection. Pretreatment with (+)-butaclamol abolished the selective distribution of (/sup 18/F)SP to the striatum in the four animals studied. Both (/sup 18/F)SP and (/sup 18/F)BEN may be suitable for PETT studies of neuroleptic receptors, but the in vivo kinetics of these compounds are markedly different from their in vitro receptor binding kinetics.

  2. The Con Test

    ERIC Educational Resources Information Center

    Fletcher, Michael

    2009-01-01

    In this article, the author describes the format of the Con Test, an Australian television game show which followed the same general rules and game play as the UK show PokerFace. At the end of each round a contestant needs to decide whether or not he or she should fold. A contestant needs to know how likely it is that he or she is in last place.…

  3. An in vitro model for assessment of drug-induced torsade de pointes arrhythmia : effects of haloperidol and dofetilide on potential duration, repolarization inhomogeneities, and torsade de pointes arrhythmia.

    PubMed

    Dhein, Stefan; Perlitz, Franziska; Mohr, Friedrich-Wilhelm

    2008-12-01

    Torsade de pointes (TdP) is a serious side effect of many drugs. We aimed to establish an in vitro TdP model for drug testing, which includes typical risk factors, such as female gender, hypokalemia, low magnesium levels, and bradycardia. Isolated, spontaneously beating rabbit hearts (female White New Zealand rabbits) were perfused according to the Langendorff technique and submitted to conditions known as risk factors for TdP, i.e., [K(+)](e) = 2.5 mM and [Mg(++)](e) = 0.5 mM, with 10(-8) M noradrenaline and 10(-7) M carbachol. Thereafter, cumulative concentration-response curves for haloperidol (10, 100, 200, 1,000, and 2,000 nM) and dofetilide (1, 10, 20, 100, and 200 nM) were performed, while cardiac activation and repolarization was measured at 256 ventricular sites (unipolar extracellular potentials). We found in three of six hearts under haloperidol TdP arrhythmias in supratherapeutic concentrations > or =100 nM. Dofetilide also induced TdP (three of seven) in concentrations > or =20 nM. The TdP showed a complex pattern being initiated in one region by an early R-on-T ventricular extrasystole, when in the other regions high activation-recovery interval (ARI) dispersion occurred, then spreading in complex beat-to-beat changing patterns until self-termination. Dofetilide and haloperidol significantly prolonged ARI and QTc. Haloperidol significantly increased dispersion predominantly at the right wall and prolonged basic cycle length. Dofetilide also increased dispersion and slowed basic cycle length. Haloperidol (> or =100 nM) and dofetilide (> or =20 nM) can induce TdP by prolongation of ARI, slowing of heart rate, and increasing repolarization inhomogeneities. The linear combination of the independent variables QTc, BCL and dispersion could highly significantly predict TaP (adjusted R(2): 0.896, p < 0.001) The model seems suitable to identify a pharmacological risk for TdP in vitro within a limited number of animals.

  4. N-n-butyl haloperidol iodide ameliorates hypoxia/reoxygenation injury through modulating the LKB1/AMPK/ROS pathway in cardiac microvascular endothelial cells

    PubMed Central

    Lu, Binger; Wang, Bin; Zhong, Shuping; Zhang, Yanmei; Gao, Fenfei; Chen, Yicun; Zheng, Fuchun; Shi, Ganggang

    2016-01-01

    Endothelial cells are highly sensitive to hypoxia and contribute to myocardial ischemia/reperfusion injury. We have reported that N-n-butyl haloperidol iodide (F2) can attenuate hypoxia/reoxygenation (H/R) injury in cardiac microvascular endothelial cells (CMECs). However, the molecular mechanisms remain unclear. Neonatal rat CMECs were isolated and subjected to H/R. Pretreatment of F2 leads to a reduction in H/R injury, as evidenced by increased cell viability, decreased lactate dehydrogenase (LDH) leakage and apoptosis, together with enhanced AMP-activated protein kinase (AMPK) and liver kinase B1 (LKB1) phosphorylation in H/R ECs. Blockade of AMPK with compound C reversed F2-induced inhibition of H/R injury, as evidenced by decreased cell viability, increased LDH release and apoptosis. Moreover, compound C also blocked the ability of F2 to reduce H/R-induced reactive oxygen species (ROS) generation. Supplementation with the ROS scavenger N-acetyl-L-cysteine (NAC) reduced ROS levels, increased cell survival rate, and decreased both LDH release and apoptosis after H/R. In conclusion, our data indicate that F2 may mitigate H/R injury by stimulating LKB1/AMPK signaling pathway and subsequent suppression of ROS production in CMECs. PMID:27166184

  5. Impact of geographical and cultural factors on clinical trials in acute mania: lessons from a ziprasidone and haloperidol placebo-controlled study.

    PubMed

    Vieta, Eduard; Pappadopulos, Elizabeth; Mandel, Francine S; Lombardo, Ilise

    2011-09-01

    Clinical trials today are conducted in multiple countries to enhance patient recruitment and improve efficiency of trials. However, the demographic and cultural diversity may contribute to variations in study outcomes. Here we conducted post-hoc analyses for a placebo-controlled study with ziprasidone and haloperidol for the treatment of acute mania to address the demographic, dosing, and outcome disparities in India, Russia and the USA. We compared the baseline characteristics, outcomes and discontinuations in patients and explored the relationship between the outcome measures across these countries. We found substantial differences in baseline characteristics of subjects, administered dosage and disease severity in India compared to the USA and Russia. Conversely, US subjects had a higher placebo response compared to subjects in Russia and India. These results are probably due to demographic differences in patient populations and psychiatric clinical practice across countries. While we offer initial ideas to address the disparities identified in this analysis, it is clear that further research to improve our understanding of geographical differences is essential to ensure globally applicable results for clinical trials in psychiatry.

  6. The influence of chronic exposure to antipsychotic medications on brain size before and after tissue fixation: a comparison of haloperidol and olanzapine in macaque monkeys.

    PubMed

    Dorph-Petersen, Karl-Anton; Pierri, Joseph N; Perel, James M; Sun, Zhuoxin; Sampson, Allan R; Lewis, David A

    2005-09-01

    It is unclear to what degree antipsychotic therapy confounds longitudinal imaging studies and post-mortem studies of subjects with schizophrenia. To investigate this problem, we developed a non-human primate model of chronic antipsychotic exposure. Three groups of six macaque monkeys each were exposed to oral haloperidol, olanzapine or sham for a 17-27 month period. The resulting plasma drug levels were comparable to those seen in subjects with schizophrenia treated with these medications. After the exposure, we observed an 8-11% reduction in mean fresh brain weights as well as left cerebrum fresh weights and volumes in both drug-treated groups compared to sham animals. The differences were observed across all major brain regions (frontal, parietal, temporal, occipital, and cerebellum), but appeared most robust in the frontal and parietal regions. Stereological analysis of the parietal region using Cavalieri's principle revealed similar volume reductions in both gray and white matter. In addition, we assessed the subsequent tissue shrinkage due to standard histological processing and found no evidence of differential shrinkage due to drug exposure. However, we observed a pronounced general shrinkage effect of approximately 20% and a highly significant variation in shrinkage across brain regions. In conclusion, chronic exposure of non-human primates to antipsychotics was associated with reduced brain volume. Antipsychotic medication may confound post-mortem studies and longitudinal imaging studies of subjects with schizophrenia that depend upon volumetric measures.

  7. Novel therapeutic approaches of natural oil from black seeds and its underlying mechanisms against kidney dysfunctions in haloperidol-induced male rats.

    PubMed

    Akintunde, Jacob K; Abubakar, Opeyemi K

    2017-05-24

    Antipsychotic drugs could be nephrotoxic in schizophrenia patients. The present study investigated the protective effect of oil from black seed on kidney dysfunctions using several biological approaches in adult rats. The animals were divided into six groups (n=10): normal control rats; haloperidol (HAL)-induced rats: induced rats were pre-, co- and post-treated with black seed oil (BSO), respectively, and the last group was treated with the oil only. The treatment was done through oral administration, and the experiment lasted 14 days. Therapeutic administration of HAL to rats caused reduction in both enzymatic and non-enzymatic proteins mediated by stable OH˙ and DPPH free radicals. K+, Na+ and MDA contents as well as 51 nucleotidase, aldose-reductase activities were increased with corresponding decrease in the activity of lactate dehydrogenase (LDH) in HAL-induced toxicity rats. Contrariwise, differential treatments with BSO prevented and reversed the nephrotoxicity by depleting K+, Na+, MDA contents and aldose-reductase activity, and AMP hydrolysis with increased adenosine triphosphate (ATP) in the PMFs of rat kidney. The cytotoxicity of HAL elicited on both inner renal cortex and outer medulla was equally alleviated by combined active molecules of oil from black seed (OBS). However, pre-, co- and post-treatment demonstrate significant approaches in averting nephrotoxicity of neuroleptic drug (HAL) via several biological mechanisms. This study therefore validates the use of black seed oil as therapy particularly for individuals with renal dysfunctions.

  8. Functional Oil from Black Seed Differentially Inhibits Aldose-reductase and Ectonucleotidase Activities by Up-regulating Cellular Energy in Haloperidol-induced Hepatic Toxicity in Rat Liver.

    PubMed

    Kehinde, Akintunde Jacob

    2017-09-01

    In this study, the effect of rate-limiting enzymes involved in degradation of hepatic adenosine and intracellular sorbitol was investigated in rats exposed to haloperidol (HAL) and treated with functional oil (FO), containing principal active phytochemicals from black seed. Animals were divided into six groups (n=10): Distilled water, HAL 15 mg/kg, pre-administration/HAL 15 mg/kg, co-administration/HAL 15 mg/kg, post-administration/HAL 15 mg/kg, FO 150 mg/kg. The results of this study revealed that the activities of ectonucleotidase and aldose-reductase were significantly increased in HAL-treated rats when compared with the control (p < 0.05). However, differential treatments (pre, co and post) with FO depleted the activities of these enzymes compared with HAL-treated rats. Furthermore, therapeutic HAL administration increased the levels of key hepatic biomarkers (ALT, AST, and ALP) and malondialdehyde level with a concomitant decrease in functional hepatic cellular ATP. However, differential treatment with FO increases hepatic ATP and non-enzymatic antioxidant status, with a concomitant decrease in the levels of malondialdehyde and liver biomarkers. Therefore, results of this finding underlined the importance of aldose-reductase and econucleotidase activities in HAL induced toxicity and suggest some possible mechanisms of action by which FO prevent HAL-induced hepatic toxicity in rats.

  9. Liquid chromatography/tandem mass spectrometry method for the simultaneous determination of olanzapine, risperidone, 9-hydroxyrisperidone, clozapine, haloperidol and ziprasidone in rat plasma.

    PubMed

    Zhang, Guodong; Terry, Alvin V; Bartlett, Michael G

    2007-01-01

    A simple, sensitive and rapid liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) method was developed and validated for simultaneous quantification of olanzapine, clozapine, ziprasidone, haloperidol, risperidone, and its active metabolite 9-hydroxyrisperidone, in rat plasma using midazolam as internal standard (IS). The analytes were extracted from rat plasma using a single step liquid-liquid extraction technique. The compounds were separated on a Waters Atlantis dC-18 (30 mm x 2.1 mm i.d., 3 microm) column using a mobile phase of acetonitrile/5 mM ammonium formate (pH 6.1 adjusted with formic acid) with gradient elution. All of the analytes were detected in positive ion mode using multiple reaction monitoring (MRM). The method was validated and the specificity, linearity, lower limit of quantitation (LLOQ), precision, accuracy, recoveries and stability were determined. LLOQ was 0.1 ng/mL and correlation coefficient (R(2)) values for the linear range of 0.1-100 ng/mL were 0.997 or greater for all the analytes. The intra-day and inter-day precision and accuracy were better than 8.05%. The relative and absolute recovery was above 77% and matrix effects were low for all the analytes except for ziprasidone. This validated method has been successfully used to quantify the plasma concentration of the analytes after chronic treatment with antipsychotic drugs.

  10. Nam Con Son Basin

    SciTech Connect

    Tin, N.T.; Ty, N.D.; Hung, L.T.

    1994-07-01

    The Nam Con Son basin is the largest oil and gas bearing basin in Vietnam, and has a number of producing fields. The history of studies in the basin can be divided into four periods: Pre-1975, 1976-1980, 1981-1989, and 1990-present. A number of oil companies have carried out geological and geophysical studies and conducted drilling activities in the basin. These include ONGC, Enterprise Oil, BP, Shell, Petro-Canada, IPL, Lasmo, etc. Pre-Tertiary formations comprise quartz diorites, granodiorites, and metamorphic rocks of Mesozoic age. Cenozoic rocks include those of the Cau Formation (Oligocene and older), Dua Formation (lower Miocene), Thong-Mang Cau Formation (middle Miocene), Nam Con Son Formation (upper Miocene) and Bien Dong Formation (Pliocene-Quaternary). The basement is composed of pre-Cenozoic formations. Three fault systems are evident in the basin: north-south fault system, northeast-southwest fault system, and east-west fault system. Four tectonic zones can also be distinguished: western differentiated zone, northern differentiated zone, Dua-Natuna high zone, and eastern trough zone.

  11. The potency and efficacy of anticholinergics to inhibit haloperidol-induced catalepsy in rats correlates with their rank order of affinities for the muscarinic receptor subtypes.

    PubMed

    Erosa-Rivero, Helena B; Bata-García, José L; Alvarez-Cervera, Fernando J; Heredia-López, Francisco J; Góngora-Alfaro, José L

    2014-06-01

    Extrapyramidal syndromes (EPS) caused by antipsychotic therapy are currently treated with anticholinergics that lack selectivity for the five muscarinic receptor subtypes. Since these receptors are heterogeneously expressed among the different classes of striatal neurons and their afferents, it can be expected that their simultaneous blockade will cause distinct, sometimes opposed, effects within the striatal circuitry. In order to test the hypothesis that the differential blockade of the muscarinic receptor subtypes would influence their potency and efficacy to prevent EPS, here we tested four anticholinergics with varying order of affinities for the muscarinic receptor subtypes, and compared their dose-response curves to inhibit haloperidol-induced catalepsy in male rats. Drugs were applied into the lateral ventricle 15 min before haloperidol (2 mg/kg, s.c.). Catalepsy was measured in the bar test at 15 min intervals during 5 h. The preferential M1/M4 antagonist pirenzepine (3, 10, 30, 100, and 300 nmol) caused a dose-dependent inhibition of catalepsy intensity: ED50 = 5.6 nmol [95% CI, 3.9-8.1], and latency: ED50 = 5.6 nmol [95% CI, 3.7-8.6]. Pirenzepine had the steepest dose-response curve, producing maximal inhibition (84 ± 5%) at the dose of 10 nmol, while its effect tended to reverse at higher doses (62 ± 11%). The purported M1/M3 antagonist 4-DAMP (30, 100, and 300 nmol) also caused a dose-dependent inhibition of catalepsy intensity: ED50 = 29.5 nmol [95% CI, 7.0 to 123.0], and latency: ED50 = 28.5 nmol [95% CI, 2.2 to 362.0]. However, the curve for 4-DAMP had a less pronounced slope, reaching its maximal effect (63 ± 14%) at the dose of 300 nmol. The M2/M4 antagonist AF-DX 116 (10, 30, and 300 nmol) only caused a partial inhibition of catalepsy (30 ± 11%) at the dose of 30 nmol, but this changed to a non-significant increment (15 ± 10%) at the dose of 100 nmol. The alleged M4 antagonist tropicamide (30, 100, 300, and

  12. N-n-butyl Haloperidol Iodide Protects against Hypoxia/Reoxygenation Injury in Cardiac Microvascular Endothelial Cells by Regulating the ROS/MAPK/Egr-1 Pathway.

    PubMed

    Lu, Shishi; Zhang, Yanmei; Zhong, Shuping; Gao, Fenfei; Chen, Yicun; Li, Weiqiu; Zheng, Fuchun; Shi, Ganggang

    2016-01-01

    Endothelium dysfunction induced by reactive oxygen species (ROS) is an important initial event at the onset of myocardial ischemia/reperfusion in which the Egr-1 transcription factor often serves as a master switch for various damage pathways following reperfusion injury. We hypothesized that an intracellular ROS/MAPK/Egr-1 signaling pathway is activated in cardiac microvascular endothelial cells (CMECs) following hypoxia/reoxygenation (H/R). ROS generation, by either H/R or the ROS donor xanthine oxidase-hypoxanthine (XO/HX) activated all three MAPKs (ERK1/2, JNK, p38), and induced Egr-1 expression and Egr-1 DNA-binding activity in CMECs, whereas ROS scavengers (EDA and NAC) had the opposite effect following H/R. Inhibitors of all three MAPKs individually inhibited induction of Egr-1 expression by H/R in CMECs. Moreover, N-n-butyl haloperidol (F2), previously shown to protect cardiomyocytes subjected to I/R, dose-dependently downregulated H/R-induced ROS generation, MAPK activation, and Egr-1 expression and activity in CMECs, whereas XO/HX and MAPK activators (EGF, anisomycin) antagonized the effects of F2. Inhibition of the ROS/MAPK/Egr-1 signaling pathway, by either F2, NAC, or inhibition of MAPK, increased CMEC viability and the GSH/GSSG ratio, and decreased Egr-1 nuclear translocation. These results show that the ROS/MAPK/Egr-1 signaling pathway mediates H/R injury in CMECs, and F2 blocks this pathway to protect against H/R injury and further alleviate myocardial I/R injury.

  13. Effects of adjunct galantamine to risperidone, or haloperidol, in animal models of antipsychotic activity and extrapyramidal side-effect liability: involvement of the cholinergic muscarinic receptor.

    PubMed

    Wadenberg, Marie-Louise G; Fjällström, Ann-Kristin; Federley, Malin; Persson, Pernilla; Stenqvist, Pia

    2011-06-01

    The acetylcholine esterase inhibitor/cholinergic nicotinic receptor (nAChR) allosteric modulator galantamine (Gal) is used against cognitive impairment in Alzheimer's disease. Negative/cognitive and psychotic symptom improvement in schizophrenia by adjunct Gal to antipsychotic drugs (APDs) has been reported. Cognitive symptoms in schizophrenia may involve brain prefrontal hypo-dopaminergia. Experimental data by others indicate nAChR involvement in animal pro-cognitive effects of Gal. The role of nAChRs in antipsychotic effects by Gal has, however, not been elucidated. Using the conditioned avoidance response (CAR) and the catalepsy tests for antipsychotic activity and extrapyramidal side-effect (EPS) liability, respectively, we here investigated the effects of adjunct Gal (1.25 mg/kg) to the typical APD haloperidol (Hal) (0.05 mg/kg), or the atypical APD risperidone (Ris) (0.2 mg/kg), in rats. Adjunct Gal significantly enhanced APD-like effects by low doses of Hal or Ris, but showed a safe EPS liability profile only in combination with Ris. Pretreatment with the muscarinic receptor (mAChR) antagonist scopolamine, but not the nAChR antagonist mecamylamine, completely reversed the enhancing effects of adjunct Gal to Hal treatment, in the CAR test. While the nAChR-modulating properties of Gal probably contribute to pro-cognitive activity, as shown by others, the present data suggest that any contribution to antipsychotic activity by Gal is mediated primarily via mAChRs. This property combination of Gal may offer a unique, favourable therapeutic profile for schizophrenia treatment.

  14. Charge transfer complex of some nervous and brain drugs - Part 1: Synthesis, spectroscopic, analytical and biological studies on the reaction between haloperidol antipsychotic drugs with π-acceptors

    NASA Astrophysics Data System (ADS)

    El-Habeeb, Abeer A.; Al-Saif, Foziah A.; Refat, Moamen S.

    2013-02-01

    Donor-acceptor interactions between the electron donor haloperidol (HPL) and π-acceptors like 7,7,8,8-tetracyanoquinodimethane (TCNQ) and picric acid (PA) have been studied spectrophotometrically in CH3OH solvent. The donor-acceptor (charge transfer complexes) were discussed in terms of formation constant (KCT), molar extinction coefficient (ɛCT), standard free energy (ΔGo), oscillator strength (ƒ), transition dipole moment (μ), resonance energy (RN) and ionization potential (ID). The stoichiometry of these complexes was found to be 1:1 M ratio and having the formulas [(HPL)(TCNQ)] and [(HPL)(PA)], respectively. The charge transfer interaction was successfully applied to determine of HPL drug using mentioned common π-acceptors also, the results obtained herein are satisfactory for estimation of HPL compound in the pharmaceutical form. The formed solid charge-transfer complexes were also isolated and characterized using elemental analysis, conductivity, (infrared, Raman, and 1H NMR) spectra and X-ray powder diffraction (XRD). The experimental data of elemental analyses are in agreement with calculated data. The infrared spectra of both HPL complexes are confirming the participation of sbnd OH of 4-hydroxy-1-piperidyl moiety in the donor-acceptor chelation. The morphological surface of the resulted charge transfer complexes were investigated using scanning electron microscopy (SEM). The thermogravimetric analysis (TG/DTG) and differential scanning calorimetry (DSC) techniques were performed to give knowledge about the thermal stability behavior of the synthesized charge transfer complexes. Thermodynamic parameters were computed from the thermal decomposition data. These complexes were also tested for their antimicrobial activity against six different microorganisms, and the results were compared with the parent drug.

  15. N-n-butyl Haloperidol Iodide Protects against Hypoxia/Reoxygenation Injury in Cardiac Microvascular Endothelial Cells by Regulating the ROS/MAPK/Egr-1 Pathway

    PubMed Central

    Lu, Shishi; Zhang, Yanmei; Zhong, Shuping; Gao, Fenfei; Chen, Yicun; Li, Weiqiu; Zheng, Fuchun; Shi, Ganggang

    2017-01-01

    Endothelium dysfunction induced by reactive oxygen species (ROS) is an important initial event at the onset of myocardial ischemia/reperfusion in which the Egr-1 transcription factor often serves as a master switch for various damage pathways following reperfusion injury. We hypothesized that an intracellular ROS/MAPK/Egr-1 signaling pathway is activated in cardiac microvascular endothelial cells (CMECs) following hypoxia/reoxygenation (H/R). ROS generation, by either H/R or the ROS donor xanthine oxidase-hypoxanthine (XO/HX) activated all three MAPKs (ERK1/2, JNK, p38), and induced Egr-1 expression and Egr-1 DNA-binding activity in CMECs, whereas ROS scavengers (EDA and NAC) had the opposite effect following H/R. Inhibitors of all three MAPKs individually inhibited induction of Egr-1 expression by H/R in CMECs. Moreover, N-n-butyl haloperidol (F2), previously shown to protect cardiomyocytes subjected to I/R, dose-dependently downregulated H/R-induced ROS generation, MAPK activation, and Egr-1 expression and activity in CMECs, whereas XO/HX and MAPK activators (EGF, anisomycin) antagonized the effects of F2. Inhibition of the ROS/MAPK/Egr-1 signaling pathway, by either F2, NAC, or inhibition of MAPK, increased CMEC viability and the GSH/GSSG ratio, and decreased Egr-1 nuclear translocation. These results show that the ROS/MAPK/Egr-1 signaling pathway mediates H/R injury in CMECs, and F2 blocks this pathway to protect against H/R injury and further alleviate myocardial I/R injury. PMID:28111550

  16. Divergent long-term consequences of chronic treatment with haloperidol, risperidone, and bromocriptine on traumatic brain injury-induced cognitive deficits.

    PubMed

    Phelps, Thomas I; Bondi, Corina O; Ahmed, Rashid H; Olugbade, Yewande T; Kline, Anthony E

    2015-04-15

    Antipsychotic drugs (APDs) are provided in the clinic to manage traumatic brain injury (TBI)-induced agitation and aggression. Experimental TBI studies consistently show that daily administration of the APDs, haloperidol (HAL) and risperidone (RISP), hinder recovery. However, it is unknown how long the adverse effects remain after cessation of treatment. To elucidate this clinically relevant issue, anesthetized male rats were randomly assigned to four TBI (controlled cortical impact) and four sham groups administered HAL (0.5 mg/kg), RISP (0.45 mg/kg), bromocriptine (BRO; 5.0 mg/kg, included as a control for D2 receptor action), or vehicle (VEH; 1 mL/kg) 24 h after surgery and once-daily for 19 days. Motor and cognitive recovery was assessed on days 1-5 and 14-19, respectively, and again at 1 and 3 months after drug withdrawal. No overall group differences were observed for motor function among the TBI groups, although the HAL group showed a greater beam-walk deficit on day 5 versus the VEH and BRO groups. Cognitive recovery was significantly impaired in the HAL and RISP groups during the treatment phase versus VEH and BRO. Further, BRO was superior to VEH (p=0.0042). At 1 month, both groups that received APDs continued to exhibit significant cognitive impairment versus VEH and BRO; at 3 months, only the HAL group was impaired. Moreover, the HAL, RISP, and VEH groups continued to be cognitively deficient versus BRO, which also reduced cortical damage. These data replicate previous reports that HAL and RISP impede cognitive recovery after TBI and expand the literature by revealing that the deleterious effects persist for 3 months after drug discontinuation. BRO conferred cognitive benefits when administered concomitantly with behavioral testing, thus replicating previous findings, and also after cessation demonstrating enduring efficacy.

  17. Effects of SKF-83566 and haloperidol on performance on progressive ratio schedules maintained by sucrose and corn oil reinforcement: quantitative analysis using a new model derived from the Mathematical Principles of Reinforcement (MPR).

    PubMed

    Olarte-Sánchez, C M; Valencia-Torres, L; Cassaday, H J; Bradshaw, C M; Szabadi, E

    2013-12-01

    Mathematical models can assist the interpretation of the effects of interventions on schedule-controlled behaviour and help to differentiate between processes that may be confounded in traditional performance measures such as response rate and the breakpoint in progressive ratio (PR) schedules. The effects of a D1-like dopamine receptor antagonist, 8-bromo-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol hydrobromide (SKF-83566), and a D2-like receptor antagonist, haloperidol, on rats' performance on PR schedules maintained by sucrose and corn oil reinforcers were assessed using a new model derived from Killeen's (Behav Brain Sci 17:105-172, 1994) Mathematical Principles of Reinforcement. Separate groups of rats were trained under a PR schedule using sucrose or corn oil reinforcers. SKF-83566 (0.015 and 0.03 mg kg(-1)) and haloperidol (0.05 and 0.1 mg kg(-1)) were administered intraperitoneally (five administrations of each treatment). Running and overall response rates in successive ratios were analysed using the new model, and estimates of the model's parameters were compared between treatments. Haloperidol reduced a (the parameter expressing incentive value) in the case of both reinforcers, but did not affect the parameters related to response time and post-reinforcement pausing. SKF-83566 reduced a and k (the parameter expressing sensitivity of post-reinforcement pausing to the prior inter-reinforcement interval) in the case of sucrose, but did not affect any of the parameters in the case of corn oil. The results are consistent with the hypothesis that blockade of both D1-like and D2-like receptors reduces the incentive value of sucrose, whereas the incentive value of corn oil is more sensitive to blockade of D2-like than D1-like receptors.

  18. The pharmacology of impulsive behaviour in rats II: the effects of amphetamine, haloperidol, imipramine, chlordiazepoxide and other drugs on fixed consecutive number schedules (FCN 8 and FCN 32).

    PubMed

    Evenden, J L

    1998-08-01

    The effects of drugs on one aspect of impulsive behaviour were evaluated using a schedule in which rats were trained to complete a fixed consecutive number of responses on one of two levers before pressing the second to obtain a reinforcer (FCN). Terminating the chain before completing the FCN resulted in the omission of the food, and can be considered an impulsive decision. Two groups of food-deprived rats were trained to press either 8 or 32 times on the left lever (FCN lever) of a two lever operant chamber before pressing the right lever (Reinforcement lever) to deliver a food pellet. Responding on the Reinforcement lever before completion of the sequence resulted in a short time-out and the rat had to begin the sequence again. After responding had stabilised, the rats were treated with a range of doses of a number of drugs. Impulsivity was assessed by several measures, including the mean chain length and the proportion of chains terminating in food delivery, and the distribution of chain lengths was analysed. The efficiency of the rats was similar under both FCN 8 and FCN 32, although it was more difficult to maintain a consistent baseline under FCN 32. Under the FCN 8 schedule, significant decreases in chain length were obtained with d-amphetamine (0.8-2.4 mg/kg), haloperidol (0.1 mg/kg), ethanol (1 and 3 g/kg) and chlordiazepoxide (10.0 mg/kg), and there were alterations in other measures consistent with an increase in impulsivity. Imipramine (1-10 mg/kg), citalopram (1-10 mg/kg) and metergoline (0.3-3.0 mg/kg) had no effect on mean chain length, although the first two drugs shifted the chain length distribution to the left. d-Amphetamine (0.4-1.2 mg/kg) and PCPA (100 mg/kg) reduced chain length and had other effects consistent with increased impulsivity under FCN 32 schedule, whereas imipramine had little, and citalopram no, effect. Taken generally, effect of the active drugs was relatively non-specific, including both a reduction in response rate and

  19. Potentiation of latent inhibition by haloperidol and clozapine is attenuated in Dopamine D2 receptor (Drd-2)-deficient mice: do antipsychotics influence learning to ignore irrelevant stimuli via both Drd-2 and non-Drd-2 mechanisms?

    PubMed

    O'Callaghan, Matthew J; Bay-Richter, Cecilie; O'Tuathaigh, Colm Mp; Heery, David M; Waddington, John L; Moran, Paula M

    2014-10-01

    Whether the dopamine Drd-2 receptor is necessary for the behavioural action of antipsychotic drugs is an important question, as Drd-2 antagonism is responsible for their debilitating motor side effects. Using Drd-2 null mice (Drd2 -/-) it has previously been shown that Drd-2 is not necessary for antipsychotic drugs to reverse D-amphetamine disruption of latent inhibition (LI), a behavioural measure of learning to ignore irrelevant stimuli. Weiner's 'two-headed' model indicates that antipsychotics not only reverse LI disruption, 'disrupted LI', but also potentiate LI when low/absent in controls, 'persistent' LI. We investigated whether antipsychotic drugs haloperidol or clozapine potentiated LI in wild-type controls or Drd2 -/-. Both drugs potentiated LI in wild-type but not in Drd2 -/- mice, suggesting moderation of this effect of antipsychotics in the absence of Drd-2. Haloperidol potentiated LI similarly in both Drd1 -/- and wild-type mice, indicating no such moderation in Drd1 -/-. These data suggest that antipsychotic drugs can have either Drd-2 or non-Drd-2 effects on learning to ignore irrelevant stimuli, depending on how the abnormality is produced. Identification of the non-Drd-2 mechanism may help to identify novel non-Drd2 based therapeutic strategies for psychosis.

  20. In silico study of naphtha [1, 2-d] thiazol-2-amine with adenosine A 2A receptor and its role in antagonism of haloperidol-induced motor impairments in mice.

    PubMed

    Luthra, Pratibha Mehta; Prakash, Amresh; Barodia, Sandeep Kumar; Kumari, Rita; Mishra, Chandra Bhushan; Kumar, J B Senthil

    2009-10-09

    Loss of dopaminergic nigrostriatal neurons in the substantia nigra leads to Parkinson's disease (PD). Adenosine A(2A) receptors (A(2A)Rs) have been anticipated as novel therapeutic target for PD. A(2A)Rs potentiate locomotor behavior and are predominantly expressed in striatum. Naphtha [1, 2-d] thiazol-2-amine (NATA), a tricyclic thiazole have been studied as new anti-Parkinsonian compound. AutoDock analysis and pharmacophore study of NATA with known A(2A)R antagonists explicit its efficacy as a possible adenosine receptor antagonist. In vivo pharmacology of NATA showed reduction of haloperidol (HAL)-induced motor impairments in Swiss albino male mice. Relatively elevated levels of dopamine in NATA pre-treated mice are suggestive of its possible role as neuromodulator in PD.

  1. Clozapine, ziprasidone and aripiprazole but not haloperidol protect against kainic acid-induced lesion of the striatum in mice, in vivo: role of 5-HT1A receptor activation.

    PubMed

    Cosi, Cristina; Waget, Aurelie; Rollet, Karin; Tesori, Valentina; Newman-Tancredi, Adrian

    2005-05-10

    Excessive activation of non-NMDA receptors, AMPA and kainate, contributes to neuronal degeneration in acute and progressive pathologies, possibly including schizophrenia. Because 5-HT(1A) receptor agonists have neuroprotective properties (e.g., against NMDA-induced neurotoxicity), we compared the effects of the antipsychotics, clozapine, ziprasidone and aripiprazole, that are partial agonists at 5-HT(1A) receptor, with those of haloperidol, which is devoid of 5-HT(1A) agonist properties, on kainic acid (KA)-induced striatal lesion volumes, in C57Bl/6N mice. The involvement of 5-HT(1A) receptors was determined by antagonist studies with WAY100635, and data were compared with those obtained using the potent and high efficacy 5-HT(1A) receptor agonist, F13714. Intra-striatal KA lesioning and measurement of lesion volumes using cresyl violet staining were carried out at 48 h after surgery. F13714, antipsychotics or vehicle were administered ip twice, 30 min before and 3 1/2 h after KA injection. WAY100635 (0.63 mg/kg) or vehicle were given sc 30 min before each drug injection. Clozapine (2 x 10 mg/kg), ziprasidone (2 x 20 mg/kg) and aripiprazole (2 x 10 mg/kg) decreased lesion volume by 61%, 59% and 73%, respectively. WAY100635 antagonized the effect of ziprasidone and of aripiprazole but only slightly attenuated that of clozapine. In contrast, haloperidol (2 x 0.16 mg/kg) did not affect KA-induced lesion volume. F13714 dose-dependently decreased lesion volume. The 61% decrease of lesion volume obtained with F13714 (2 x 0.63 mg/kg) was antagonized by WAY100635. WAY100635 alone did not affect lesion volume. These results show that 5-HT(1A) receptor activation protects against KA-induced striatal lesions and indicate that some atypical antipsychotic agents with 5-HT(1A) agonist properties may protect against excitotoxic injury, in vivo.

  2. Simultaneous RP-HPLC-DAD quantification of bromocriptine, haloperidol and its diazepane structural analog in rat plasma with droperidol as internal standard for application to drug-interaction pharmacokinetics

    PubMed Central

    Billups, Johnique; Jones, Cynthia; Jackson, Tanise L.; Ablordeppey, Seth Y.; Spencer, Shawn D.

    2010-01-01

    A simple and rapid RP-HPLC-DAD method was developed and validated for simultaneous determination of the dopamine antagonists haloperidol, its diazepane analog, and the dopamine agonist bromocriptine in rat plasma, to perform pharmacokinetic drug-interaction studies. Samples were prepared for analysis by acetonitrile (22.0 μg/mL) plasma protein precipitation with droperidol as an internal standard, followed by a double-step liquid-liquid extraction with hexane:chloroform (70:30) prior to C-18 separation. Isocratic elution was achieved using a 0.1% (v/v) trifluoroacetic acid in deionized water, methanol and acetonitrile (45/27.5/27.5, v/v/v). Triple-wavelength diode-array detection at the λmax of 245 nm for haloperidol, 254 nm for the diazepane analog and droperidol, and 240 nm for bromocriptine was carried out. The LLOQ of DAL, HAL, and BCT were 45.0, 56.1, and 150 ng/mL, respectively. In rats, the estimated pharmacokinetic parameters (i.e., t1/2, CL, and Vss) of HAL when administered with DAL and BCT were t1/2 = 16.4 min, Vss = 0.541 L/kg for HAL, t1/2 = 28.0 min, Vss = 2.00 L/kg for DAL, and t1/2 = 24.0 min, Vss = 0.106 L/kg for BCT. The PK parameters for HAL differed significantly from those previously reported, which may be an indication of a drug-drug interaction. PMID:19908205

  3. RETOS EN LA INTERVENCIÓN CON ADOLESCENTES PUERTORRIQUEÑOS/AS QUE MANIFIESTAN COMPORTAMIENTO SUICIDA*

    PubMed Central

    Vélez, Yovanska Duarté; Dávila, Paloma Torres; Hernández, Samariz Laboy

    2015-01-01

    Presentamos un estudio de caso de una adolescente puertorriqueña con comportamiento suicida. Esta comenzó una Terapia Socio Cognitivo-Conductual para el Comportamiento Suicida (TSCC-CS) de tipo ambulatorio luego de una hospitalización por intento suicida. La TSCC-CS incorpora una perspectiva ecológica y de desarrollo a la terapia cognitivo-conductual. Inicialmente mostró baja autoestima y severos síntomas depresivos y de ansiedad. Al finalizar el tratamiento, manifestó un cambio significativo en su sintomatología clínica y evidenció una mejoría en sus destrezas de manejo. No presentó ideas suicidas durante meses previos, ni durante el seguimiento. El análisis de este caso permitió realizar cambios en el protocolo de tratamiento, particularmente en las sesiones de familia y de comunicación con el fin de aumentar la viabilidad del tratamiento. PMID:26702337

  4. Actitudes Éticas de los estudiantes y egresados en carrera de medicina con metodologías activas

    PubMed Central

    Novaes, Maria Rita Carvalho Garbi; Novaes, Luiz Carlos Garcez; Guilhem, Dirce; Stepke, Fernando Lolas; Silveira, Carla Cristina Costa; Komatsu, Ricardo Shoiti; Trindade, Eliane Mendonça Vilar; Guiotti, Murilo Galvão

    2010-01-01

    El presente estudio tiene por objeto desarrollar un diagnostico de la inserción integrada de la ética en la carrera de medicina brasileña con una metodología de aprendizaje basada en problemas y describir las percepciones de actitudes éticas de los estudiantes y egresados. El diseño metodológico es un estudio de caso, descriptivo y documental, con abordaje cualitativo y cuantitativo. La muestra de esta investigación ha sido constituida por 120 estudiantes y 40 egresados de dos promociones del Curso de Medicina de la ESCS. Este proyecto fue aprobado por el Comité de Ética en Investigación - SES/DF. Los estudiantes y egresados de la ESCS demostraron un buen manejo en el abordaje de los conflictos éticos y respeto a los pacientes. Sin embargo, el análisis de sensibilidad ética mostró una fragilidad en las percepciones y aptitudes inapropiadas de los estudiantes de la carrera de medicina, identificada básicamente en los años iniciales, que necesitan más discusiones sistematizadas sobre los aspectos éticos y bioéticos integrados a las actividades prácticas para estimular y fortalecer la reflexión ética de los estudiantes. PMID:20981242

  5. Comparison of the anti-dopamine D₂ and anti-serotonin 5-HT(2A) activities of chlorpromazine, bromperidol, haloperidol and second-generation antipsychotics parent compounds and metabolites thereof.

    PubMed

    Suzuki, Hidenobu; Gen, Keishi; Inoue, Yuichi

    2013-04-01

    Second-generation antipsychotics, which have become the standard drug therapies for schizophrenia, are known to have a serotonin 5-HT(2A) receptor blocking effect in addition to a dopamine D₂ receptor blocking effect. However, although chlorpromazine (CPZ) has a 5-HT(2A) receptor blocking effect and has the profile of a second-generation antipsychotic in vitro, it loses this pharmacological profile in vivo. In order to elucidate the differences between the in vivo and in vitro pharmacological characteristics of CPZ, we used a radioreceptor assay to measure the anti-D₂ activity and the anti-5-HT(2A) activity of CPZ and five major metabolites of CPZ, and compared the results to the anti-D₂ activity and anti-5-HT(2A) activity of risperidone, zotepine, perospirone, the major metabolites of each of these drugs, and olanzapine, bromperidol, and haloperidol. The subjects were 182 patients who had received diagnoses of schizophrenia based on the DSM-IV criteria. The results revealed that CPZ exhibited little anti-5-HT(2A) activity, regardless of the anti-D₂ activity level, and that none of the metabolites possessed anti-5-HT(2A) activity. However, both the parent compounds and the metabolites of each of the second-generation antipsychotics possessed both anti-D₂ activity and anti-5-HT(2A) activity. This clarified that, unlike second-generation antipsychotics, the reason CPZ loses its second-generation antipsychotic profiles in vivo is because it does not have any metabolites that possess anti-5-HT(2A) activity.

  6. Mincle Signaling Promotes Con A Hepatitis.

    PubMed

    Greco, Stephanie H; Torres-Hernandez, Alejandro; Kalabin, Aleksandr; Whiteman, Clint; Rokosh, Rae; Ravirala, Sushma; Ochi, Atsuo; Gutierrez, Johana; Salyana, Muhammad Atif; Mani, Vishnu R; Nagaraj, Savitha V; Deutsch, Michael; Seifert, Lena; Daley, Donnele; Barilla, Rocky; Hundeyin, Mautin; Nikifrov, Yuriy; Tejada, Karla; Gelb, Bruce E; Katz, Steven C; Miller, George

    2016-10-01

    Con A hepatitis is regarded as a T cell-mediated model of acute liver injury. Mincle is a C-type lectin receptor that is critical in the immune response to mycobacteria and fungi but does not have a well-defined role in preclinical models of non-pathogen-mediated inflammation. Because Mincle can ligate the cell death ligand SAP130, we postulated that Mincle signaling drives intrahepatic inflammation and liver injury in Con A hepatitis. Acute liver injury was assessed in the murine Con A hepatitis model using C57BL/6, Mincle(-/-), and Dectin-1(-/-) mice. The role of C/EBPβ and hypoxia-inducible factor-1α (HIF-1α) signaling was assessed using selective inhibitors. We found that Mincle was highly expressed in hepatic innate inflammatory cells and endothelial cells in both mice and humans. Furthermore, sterile Mincle ligands and Mincle signaling intermediates were increased in the murine liver in Con A hepatitis. Most significantly, Mincle deletion or blockade protected against Con A hepatitis, whereas Mincle ligation exacerbated disease. Bone marrow chimeric and adoptive transfer experiments suggested that Mincle signaling in infiltrating myeloid cells dictates disease phenotype. Conversely, signaling via other C-type lectin receptors did not alter disease course. Mechanistically, we found that Mincle blockade decreased the NF-κβ-related signaling intermediates C/EBPβ and HIF-1α, both of which are necessary in macrophage-mediated inflammatory responses. Accordingly, Mincle deletion lowered production of nitrites in Con A hepatitis and inhibition of both C/EBPβ and HIF-1α reduced the severity of liver disease. Our work implicates a novel innate immune driver of Con A hepatitis and, more broadly, suggests a potential role for Mincle in diseases governed by sterile inflammation.

  7. Mincle Signaling Promotes Con-A Hepatitis

    PubMed Central

    Greco, Stephanie H.; Torres-Hernandez, Alejandro; Kalabin, Aleksandr; Whiteman, Clint; Rokosh, Rae; Ravirala, Sushma; Ochi, Atsuo; Gutierrez, Johana; Salyana, Muhammad Atif; Mani, Vishnu R.; Nagaraj, Savitha V.; Deutsch, Michael; Seifert, Lena; Daley, Donnele; Barilla, Rocky; Hundeyin, Mautin; Nikifrov, Yuriy; Tejada, Karla; Gelb, Bruce E.; Katz, Steven C.; Miller, George

    2016-01-01

    Concanavalin-A (Con-A) hepatitis is regarded as a T cell-mediated model of acute liver injury. Mincle is a C-type lectin receptor (CLR) that is critical in the immune response to mycobacteria and fungi, but does not have a well-defined role in pre-clinical models of non-pathogen mediated inflammation. Since Mincle can ligate the cell death ligand SAP130, we postulated that Mincle signaling drives intrahepatic inflammation and liver injury in Con-A hepatitis. Acute liver injury was assessed in the murine Con-A hepatitis model using C57BL/6, Mincle−/−, and Dectin-1−/− mice. The role of C/EBPβ and HIF-1α signaling was assessed using selective inhibitors. We found that Mincle was highly expressed in hepatic innate inflammatory cells and endothelial cells in both mice and humans. Furthermore, sterile Mincle ligands and Mincle signaling intermediates were increased in the murine liver in Con-A hepatitis. Most significantly, Mincle deletion or blockade protected against Con-A hepatitis whereas Mincle ligation exacerbated disease. Bone marrow chimeric and adoptive transfer experiments suggested that Mincle signaling in infiltrating myeloid cells dictates disease phenotype. Conversely, signaling via other CLRs did not alter disease course. Mechanistically, we found that Mincle blockade decreased the NF-κβ related signaling intermediates, C/EBPβ and HIF-1α, both of which are necessary in macrophage-mediated inflammatory responses. Accordingly, Mincle deletion lowered production of nitrites in Con-A hepatitis and inhibition of both C/EBPβ and HIF1-α reduced the severity of liver disease. Our work implicates a novel innate immune driver of Con-A hepatitis and, more broadly, suggests a potential role for Mincle in diseases governed by sterile inflammation. PMID:27559045

  8. Galaxias australes con núcleo doble

    NASA Astrophysics Data System (ADS)

    Gimeno, G.; Díaz, R.; Carranza, G.

    Se estudia una muestra de galaxias australes con núcleo doble a partir de una búsqueda extensiva en la literatura. Se analizan las características morfológicas, fotométricas y espectroscópicas de la muestra. Para algunas galaxias se han realizado observaciones con el espectrógrafo multifunción (EMF) de la Estación Astrofísica de Bosque Alegre a partir de las cuales se determinaron parámetros cinemáticos.

  9. GeConT: gene context analysis.

    PubMed

    Ciria, R; Abreu-Goodger, C; Morett, E; Merino, E

    2004-09-22

    The fact that adjacent genes in bacteria are often functionally related is widely known. GeConT (Gene Context Tool) is a web interface designed to visualize genome context of a gene or a group of genes and their orthologs in all the completely sequenced genomes. The graphical information of GeConT can be used to analyze genome annotation, functional ortholog identification or to verify the genomic context congruence of any set of genes that share a common property. http://www.ibt.unam.mx/biocomputo/gecont.html

  10. Medición de placas astrométricas obtenidas con el telescopio Astrográfico de La Plata

    NASA Astrophysics Data System (ADS)

    di Sisto, R. P.; Orellana, R.

    El Observatorio de La Plata cuenta con un gran número de placas de asteroides y cometas obtenidas con el telescopio astrográfico, que cubren gran parte del cielo del hemisferio sur. En 1996 se recopilaron y clasificaron 2187 placas (Beca para estudiantes de la AAA 1996) de las cuales 2031 corresponden a asteroides. Los datos de cada placa se volcaron en una base de datos creada para facilitar su manejo y preservar la información. A partir de este trabajo se revisaron los MPC electrónicos y se identificaron aquellas placas de asteroides pertenecientes a nuestra base de datos cuyos resultados no fueron publicados en los mismos. De un total de 400 placas que no aparecían publicadas sobresalía un paquete constituído por 40 placas obtenidas en 1977. Estas últimas fueron reducidas utilizando las posiciones y movimientos propios de las estrellas de referencia obtenidas del catálogo SAO 2000 dadas para el sistema FK5. Las posiciones calculadas fueron enviadas y publicadas en los Minor Planet Circulars (MPC).

  11. InterCon Travel Health: Case B

    ERIC Educational Resources Information Center

    Truman, Gregory E.; Pachamanova, Dessislava A.; Goldstein, Michael A.

    2010-01-01

    InterCon provides services to health insurers of foreign tourists who travel to the United States and Canada. Management wants to implement a new information system that will deal with several operational problems, but it is having difficulty securing the capital resources to fund the system's development. After an initial failure, the chief…

  12. InterCon Travel Health: Case B

    ERIC Educational Resources Information Center

    Truman, Gregory E.; Pachamanova, Dessislava A.; Goldstein, Michael A.

    2010-01-01

    InterCon provides services to health insurers of foreign tourists who travel to the United States and Canada. Management wants to implement a new information system that will deal with several operational problems, but it is having difficulty securing the capital resources to fund the system's development. After an initial failure, the chief…

  13. Ependimoma myxopapilar sacro gigante con osteolisis

    PubMed Central

    Ajler, Pablo; Landriel, Federico; Goldschmidt, Ezequiel; Campero, Álvaro; Yampolsky, Claudio

    2014-01-01

    Objetivo: la presentación de un caso de una paciente con un ependimoma sacro con extensa infiltración y destrucción ósea local. Descripción del caso: una mujer de 53 años acudió a la consulta por dolor lumbosacro y alteraciones sensitivas perineales y esfinterianas. La imágenes por Resonancia Magnética (IRM) y la Tomografía Axial Computada (TAC) mostraron una lesión expansiva gigante a nivel S2-S4 con extensa osteólisis e invasión de tejidos adyacentes. Se realizó una exéresis tumoral completa con mejoría del estatus funcional. La anatomía patológica informó ependimoma mixopapilar. Discusión: la extensión de la resección quirúrgica es el mejor predictor de buen pronóstico. El tratamiento radiante se reserva como opción adyuvante para las resecciones incompletas y recidiva tumoral. La quimioterapia sólo debería utilizarse en casos en que la cirugía y la radioterapia estén contraindicadas. Conclusión: Los ependimomas mixopapilares sacros con destrucción ósea y presentación intra y extradural son muy infrecuentes y deben ser tenidos en cuenta entre los diagnósticos diferenciales preoperatorios. Su resección total, siempre que sea posible, es la mejor alternativa terapéutica. PMID:25165615

  14. Conserva a Puerto Rico con bosques maderables

    Treesearch

    Frank H. Wadsworth

    2009-01-01

    [article in Spanish] Puerto Rico consume muchos productos forestales costosos de importar. También tiene bosques extensos con maderas explotables. Además, existen condiciones físicas favorables para la producción de madera útil. No obstante, hoy día no se utiliza la madera de los bosques actuales ocurre la deforestación para cualquier fin. Los Bosques productivos de...

  15. Somatic cell nuclear transfer: pros and cons.

    PubMed

    Sumer, Huseyin; Liu, Jun; Tat, Pollyanna; Heffernan, Corey; Jones, Karen L; Verma, Paul J

    2009-01-01

    Even though the technique of mammalian SCNT is just over a decade old it has already resulted in numerous significant advances. Despite the recent advances in the reprogramming field, SCNT remains the bench-mark for the generation of both genetically unmodified autologous pluripotent stem cells for transplantation and for the production of cloned animals. In this review we will discuss the pros and cons of SCNT, drawing comparisons with other reprogramming methods.

  16. S18327 (1-[2-[4-(6-fluoro-1, 2-benzisoxazol-3-yl)piperid-1-yl]ethyl]3-phenyl imidazolin-2-one), a novel, potential antipsychotic displaying marked antagonist properties at alpha(1)- and alpha(2)-adrenergic receptors: II. Functional profile and a multiparametric comparison with haloperidol, clozapine, and 11 other antipsychotic agents.

    PubMed

    Millan, M J; Brocco, M; Rivet, J M; Audinot, V; Newman-Tancredi, A; Maiofiss, L; Queriaux, S; Despaux, N; Peglion, J L; Dekeyne, A

    2000-01-01

    S18327 was dose-dependently active in several models of potential antipsychotic activity involving dopaminergic hyperactivity: inhibition of apomorphine-induced climbing in mice, of cocaine- and amphetamine-induced hyperlocomotion in rats, and of conditioned avoidance responses in rats. Furthermore, reflecting its high affinity at serotonin(2A) sites, S18327 potently blocked phencyclidine-induced locomotion and 1-[2, 5-dimethoxy-4-iodophenyl]-2-aminopropane-induced head-twitches in rats. In models of glutamatergic hypoactivity, S18327 blocked hyperlocomotion and spontaneous tail-flicks elicited by the N-methyl-D-aspartate antagonist dizocilpine. The actions of S18327, together with its binding profile at multiple monoaminergic receptors (15 parameters in total), were compared with those of clozapine, haloperidol, and 11 other antipsychotics by multiparametric analysis, and the resulting dendrogram positioned S18327 close to clozapine. Consistent with a clopazine-like profile, S18327 generalized to a clozapine discriminative stimulus and evoked latent inhibition in rats, blocked aggression in isolated mice, and displayed anxiolytic properties in the ultrasonic vocalization and Vogel procedures in rats. Relative to the above paradigms, only markedly (>20-fold) higher doses of S18327 were active in models predictive of potential extrapyramidal side effects: induction of catalepsy and prolactin secretion, and inhibition of methylphenidate-induced gnawing in rats. S18327 showed only modest affinity for histaminic and muscarinic receptors. Multiparametric analysis of these data distinguished S18327 from both haloperidol (high extrapyramidal potential) and clozapine (high histaminic and muscarinic affinity). In conclusion, S18327 displays a broad-based pattern of potential antipsychotic activity at doses appreciably lower than those eliciting extrapyramidal side effects. In this respect, S18327 closely resembles clozapine, but it is chemically distinct and displays weak

  17. 9 CFR 319.301 - Chili con carne with beans.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Chili con carne with beans. 319.301 Section 319.301 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Dehydrated Meat Food Products § 319.301 Chili con carne with beans. Chili con carne with beans shall contain...

  18. 9 CFR 319.301 - Chili con carne with beans.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Chili con carne with beans. 319.301 Section 319.301 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Dehydrated Meat Food Products § 319.301 Chili con carne with beans. Chili con carne with beans shall contain...

  19. 9 CFR 319.301 - Chili con carne with beans.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Chili con carne with beans. 319.301 Section 319.301 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Dehydrated Meat Food Products § 319.301 Chili con carne with beans. Chili con carne with beans shall contain...

  20. 9 CFR 319.301 - Chili con carne with beans.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Chili con carne with beans. 319.301 Section 319.301 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Dehydrated Meat Food Products § 319.301 Chili con carne with beans. Chili con carne with beans shall contain...

  1. 9 CFR 319.300 - Chili con carne.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Chili con carne. 319.300 Section 319.300 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... Products § 319.300 Chili con carne. “Chili con carne” shall contain not less than 40 percent of meat...

  2. 9 CFR 319.301 - Chili con carne with beans.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Chili con carne with beans. 319.301 Section 319.301 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Dehydrated Meat Food Products § 319.301 Chili con carne with beans. Chili con carne with beans shall...

  3. 9 CFR 319.300 - Chili con carne.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Chili con carne. 319.300 Section 319.300 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... Products § 319.300 Chili con carne. “Chili con carne” shall contain not less than 40 percent of...

  4. 9 CFR 319.300 - Chili con carne.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Chili con carne. 319.300 Section 319.300 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... Products § 319.300 Chili con carne. “Chili con carne” shall contain not less than 40 percent of...

  5. 9 CFR 319.300 - Chili con carne.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Chili con carne. 319.300 Section 319.300 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... Products § 319.300 Chili con carne. “Chili con carne” shall contain not less than 40 percent of...

  6. 9 CFR 319.300 - Chili con carne.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Chili con carne. 319.300 Section 319.300 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... Products § 319.300 Chili con carne. “Chili con carne” shall contain not less than 40 percent of...

  7. Energy Star program benefits Con Edison

    SciTech Connect

    1995-05-01

    Impressed with savings in energy costs achieved after upgrading the lighting and air conditioning systems at its Manhattan headquarters, Home Box Office (HBO) wanted to do more, James Flock, vice president for computer and office systems, contacted Con Edison Co. of New York in March 1991 to determine what the company could do to save money by reducing energy consumed by personal computers. Arthur Kressner, Con Edison Research and Development manager contacted industry organizations and manufacturers for advice, but was told only to shut off computers at night and on weekends. Kressner arranged a series of meetings with IBM and the Electric Power Research Institute (EPRI) to discuss the issue, then approached the U.S. Environmental Protection Agency (EPA), which was designing a program to promote the introduction and use of energy-efficient office equipment. In 1992, the EPA announced the Energy Star program for PCs, enabling manufacturers to display the Energy Star logo on machines meeting program criteria, including the ability to enter a sleep mode in which neither the computer nor monitor consume more than 30 W or electricity. Industry experts estimate national energy consumption by office equipment could double by the year 2000, but Energy Star equipment is expected to improve efficiency and help maintain electric loads.

  8. Cervical disc arthroplasty: Pros and cons

    PubMed Central

    Moatz, Bradley; Tortolani, P. Justin

    2012-01-01

    Background: Cervical disc arthroplasty has emerged as a promising potential alternative to anterior cervical discectomy and fusion (ACDF) in appropriately selected patients. Despite a history of excellent outcomes after ACDF, the question as to whether a fusion leads to adjacent segment degeneration remains unanswered. Numerous US investigational device exemption trials comparing cervical arthroplasty to fusion have been conducted to answer this question. Methods: This study reviews the current research regarding cervical athroplasty, and emphasizes both the pros and cons of arthroplasty as compared with ACDF. Results: Early clinical outcomes show that cervical arthroplasty is as effective as the standard ACDF. However, this new technology is also associated with an expanding list of novel complications. Conclusion: Although there is no definitive evidence that cervical disc replacement reduces the incidence of adjacent segment degeneration, it does show other advantages; for example, faster return to work, and reduced need for postoperative bracing. PMID:22905327

  9. Pros and cons of phage therapy

    PubMed Central

    Loc-Carrillo, Catherine

    2011-01-01

    Many publications list advantages and disadvantages associated with phage therapy, which is the use of bacterial viruses to combat populations of nuisance or pathogenic bacteria. The goal of this commentary is to discuss many of those issues in a single location. In terms of “Pros,” for example, phages can be bactericidal, can increase in number over the course of treatment, tend to only minimally disrupt normal flora, are equally effective against antibiotic-sensitive and antibiotic-resistant bacteria, often are easily discovered, seem to be capable of disrupting bacterial biofilms, and can have low inherent toxicities. In addition to these assets, we consider aspects of phage therapy that can contribute to its safety, economics, or convenience, but in ways that are perhaps less essential to the phage potential to combat bacteria. For example, autonomous phage transfer between animals during veterinary application could provide convenience or economic advantages by decreasing the need for repeated phage application, but is not necessarily crucial to therapeutic success. We also consider possible disadvantages to phage use as antibacterial agents. These “Cons,” however, tend to be relatively minor. PMID:22334867

  10. Games Con Men Play: The Semiosis of Deceptive Interaction.

    ERIC Educational Resources Information Center

    Hankiss, Agnes

    1980-01-01

    Analyzes some of the most frequent deceptive interactions as rendered through case histories of male con artists and their victims taken from police records. Discusses the recurrent elements in both the con-games strategies and victims' way of interpreting those strategies. (JMF)

  11. Breath Analysis Science at PittCon 2012, Orlando, Florida

    EPA Science Inventory

    Breath analysis science was featured in three organized sessions at this year’s Pittsburgh Conference and Exposition, or ‘PittCon 2012’ (http://www.pittcon.org/). As described in previous meeting reports, PittCon is one of the largest international conferences for analytical chem...

  12. Trazando la materia oscura con cúmulos globulares

    NASA Astrophysics Data System (ADS)

    Forte, J. C.

    Se describe la estrategia adoptada para mapear la distribución de materia oscura y bariónica en galaxias elípticas cuyos cúmulos globulares están siendo observados con los telescopios VLT y Gemini. Se ejemplifican los resultados con los datos obtenidos en el cúmulo de Fornax.

  13. Breath Analysis Science at PittCon 2012, Orlando, Florida

    EPA Science Inventory

    Breath analysis science was featured in three organized sessions at this year’s Pittsburgh Conference and Exposition, or ‘PittCon 2012’ (http://www.pittcon.org/). As described in previous meeting reports, PittCon is one of the largest international conferences for analytical chem...

  14. RoboCon: A general purpose telerobotic control center

    SciTech Connect

    Draper, J.V.; Noakes, M.W.; Schempf, H.; Blair, L.M.

    1997-02-01

    This report describes human factors issues involved in the design of RoboCon, a multi-purpose control center for use in US Department of Energy remote handling applications. RoboCon is intended to be a flexible, modular control center capable of supporting a wide variety of robotic devices.

  15. Pro/con a precessional geodynamo

    NASA Astrophysics Data System (ADS)

    Vanyo, J.

    2003-04-01

    The modest amount of research that exists on the ability, or lack of ability, of mantle precession to power a geodynamo developed mostly during the last half of the 1900s. Papers by Roberts and Stewartson (1965) and by Busse (1968) studied precession generally without a pro/con conclusion. Malkus in the late 1960s attempted to advance a positive role for precession through experiments and analysis. His experiments have survived criticism, but his analyses were discounted, especially by Rochester, Jacobs, Smylie, and Chong (1975) and by Loper (1975). Rochester, et al. critiqued existing analyses of precession, including those of Malkus, but did not reach a strong position either pro or con a precessional geodynamo. Loper argued emphatically that precession was not capable of powering the geodynamo. Explicit analyses that either critique or support Loper’s arguments have yet to appear in the literature. During the 1970s, Vanyo and associates studied energy dissipation during precession of satellite liquid fuels and its effect on satellite attitude stability. Engineers and scientists in every country that has launched satellites completed similar research. Some is published in the aerospace literature, more is available in company and government reports. Beginning in 1981, Vanyo and associates applied this knowledge to the very similar problem of energy dissipation and flow patterns in precessing mechanical models scaled geometrically and dynamically to the Earth’s liquid core. Energy experiments indicate massive amounts of mechanical energy are dissipated at the CMB, and flow experiments show complex motions within the boundary layer and axial flows with helicity throughout the interior. Analysis of Earth core precession also advanced, especially in several papers by Kerswell and by Tilgner in the late 1990s. Detail numerical models have yet to appear. Although progress in understanding the role of precession in Earth core motions has advanced, there remains a

  16. [Cement augmentation of pedicle screws : Pros and cons].

    PubMed

    Schnake, K J; Blattert, T R; Liljenqvist, U

    2016-09-01

    Cement augmentation of pedicle screws biomechanically increases screw purchase in the bone. However, clinical complications may occur. The pros and cons of the technique are discussed from different clinical perspectives.

  17. Planificación Neuroquirúrgica con Software Osirix

    PubMed Central

    Jaimovich, Sebastián Gastón; Guevara, Martin; Pampin, Sergio; Jaimovich, Roberto; Gardella, Javier Luis

    2014-01-01

    Introducción: La individualidad anatómica es clave para reducir el trauma quirúrgico y obtener un mejor resultado. Actualmente, el avance en las neuroimágenes ha permitido objetivar esa individualidad anatómica, permitiendo planificar la intervención quirúrgica. Con este objetivo, presentamos nuestra experiencia con el software Osirix. Descripción de la técnica: Se presentan 3 casos ejemplificadores de 40 realizados. Caso 1: Paciente con meningioma de la convexidad parasagital izquierda en área premotora; Caso 2: Paciente con macroadenoma hipofisario, operada previamente por vía transeptoesfenoidal en otra institución con una resección parcial; Caso 3: Paciente con lesiones en pedúnculo cerebeloso medio bilateral. Se realizó la planificación prequirúrgica con el software OsiriX, fusionando y reconstruyendo en 3D las imágenes de TC e IRM, para analizar relaciones anatómicas, medir distancias, coordenadas y trayectorias, entre otras funciones. Discusión: El software OsiriX de acceso libre y gratuito permite al cirujano, mediante la fusión y reconstrucción en 3D de imágenes, analizar la anatomía individual del paciente y planificar de forma rápida, simple, segura y económica cirugías de alta complejidad. En el Caso 1 se pudo analizar las relaciones del tumor con las estructuras adyacentes para minimizar el abordaje. En el Caso 2 permitió comprender la anatomía post-operatoria previa del paciente, para determinar la trayectoria del abordaje transnasal endoscópico y la necesidad de ampliar su exposición, logrando la resección tumoral completa. En el Caso 3 permitió obtener las coordenadas estereotáxicas y trayectoria de una lesión sin representación tomográfica. Conclusión: En casos de no contar con costosos sistemas de neuronavegación o estereotáxia el software OsiriX es una alternativa a la hora de planificar la cirugía, con el objetivo de disminuir el trauma y la morbilidad operatoria. PMID:25165617

  18. Remodelar Correctamente: Guía de Prácticas Acreditadas Seguras Para Trabajar Con Plomo

    EPA Pesticide Factsheets

    Información general sobre los requisitos legales de las prácticas relacionadas al manejo seguro del plomo para dueños de hogares, inquilinos, proveedores de cuido infantil, y padres durante las actividades de remodelación

  19. Detail of conning tower atop the submarine. Note the wire ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Detail of conning tower atop the submarine. Note the wire rope wrapped around the base of the tower, which may have been used in an attempt to pull the submarine offshore. - Sub Marine Explorer, Located along the beach of Isla San Telmo, Pearl Islands, Isla San Telmo, Former Panama Canal Zone, CZ

  20. Canceling Some d-CON Mouse and Rat Control Products

    EPA Pesticide Factsheets

    EPA has reached agreement with the manufacturer, to cancel 12 d-CON products that do not meet our testing protocols that better protect children, pets and non-target wildlife from accidental exposure to the pesticide. These products will be phased out.

  1. Providers debate pros and cons of pneumonia vaccination at discharge.

    PubMed

    2001-02-01

    When to vaccinate against pneumonia? Does it makes sense when patients are in the hospital? Or should patients wait for the first post-op visit with the PCP? Office-based and hospital-based physicians weigh the pros and cons of each.

  2. Three dimensional boundary layers on submarine conning towers and rudders

    NASA Astrophysics Data System (ADS)

    Gleyzes, C.

    1988-01-01

    Solutions for the definition of grids adapted to the calculation of three-dimensional boundary layers on submarine conning towers and on submarine rudders and fins are described. The particular geometry of such bodies (oblique shaped hull, curved fins) required special adaptations. The grids were verified on examples from a test basin.

  3. Utilice en forma segura los productos con cebo para roedores

    EPA Pesticide Factsheets

    Si se usan de manera inadecuada, los productos con veneno para ratas y ratones podrían hacerle daño a usted, a sus hijos o a sus mascotas. Siempre que use pesticidas lea la etiqueta del producto y siga todas las indicaciones.

  4. Teaching after Retirement: The Pros and the Cons

    ERIC Educational Resources Information Center

    Sommer, Robert

    2014-01-01

    Having enjoyed teaching during my active career, I continued to teach summer school following retirement. Self-observed sensory and cognitive impairments, although not mentioned by students in their evaluations, induced me to consider the pros and cons of continuing to teach. My hope is that this list of benefits and problems will be of assistance…

  5. Opioid analgesics in the substance abuser: pros and cons.

    PubMed

    Ineck, Joseph R; Rule, Ann M

    2006-01-01

    The pros and cons of using opioid analgesics to help manage pain in patient with a history of substance abuse are presented. Topics discussed include ethical constructs, efficacy, and safety relating to the use of opioids in patients with substance abuse histories.

  6. Teaching after Retirement: The Pros and the Cons

    ERIC Educational Resources Information Center

    Sommer, Robert

    2014-01-01

    Having enjoyed teaching during my active career, I continued to teach summer school following retirement. Self-observed sensory and cognitive impairments, although not mentioned by students in their evaluations, induced me to consider the pros and cons of continuing to teach. My hope is that this list of benefits and problems will be of assistance…

  7. LunGradCon: The Lunar Graduate Conference

    NASA Astrophysics Data System (ADS)

    Dove, A.; Poppe, A.; Neish, C.; Fagan, A.; Fuqua, H.; Kramer, G. Y.; Horanyi, M.

    2011-12-01

    Members of the Colorado Center for Lunar Dust and Atmospheric Studies (CCLDAS) initiated the Lunar Graduate Conference (LunGradCon), modeled after the highly successful Astrobiology Graduate Conference (AbGradCon). The purpose of this conference is to enhance the professional development of graduate students and early postdoctoral researchers by providing an opportunity to present and discuss scientific research in an environment of their peers. For the first two years, LunGradCon has been held as a one-day conference in conjunction with the NASA Lunar Science Institue's (NLSI) Lunar Science Forum at the NASA Ames Research Center. Activities include an invited overview talk on each of the NASA Lunar Science Institute's three main research areas (OF the Moon, ON the Moon, and FROM the Moon), submitted oral presentations from graduate students and postdoctoral researchers, and networking opportunities with established member of the lunar science community and the NLSI. In each of the first two years of LunGradCon, there have been 20-25 attendees, with about 15 of those presenting submitted talks. Each speaker received feedback forms from the other participants in order to improve on their presentation techniques. Participants also provided feedback on the conference as a whole in order to evaluate the content and provide suggestions for improvement in following years. Overall, the feedback has been extremely positive. This talk will summarize the achievements of past LunGradCons and plans for expansion of the conference to ensure a long-term positive impact on the early careers of future lunar, planetary and space science researchers.

  8. ConStrains identifies microbial strains in metagenomic datasets.

    PubMed

    Luo, Chengwei; Knight, Rob; Siljander, Heli; Knip, Mikael; Xavier, Ramnik J; Gevers, Dirk

    2015-10-01

    An important fraction of microbial diversity is harbored in strain individuality, so identification of conspecific bacterial strains is imperative for improved understanding of microbial community functions. Limitations in bioinformatics and sequencing technologies have to date precluded strain identification owing to difficulties in phasing short reads to faithfully recover the original strain-level genotypes, which have highly similar sequences. We present ConStrains, an open-source algorithm that identifies conspecific strains from metagenomic sequence data and reconstructs the phylogeny of these strains in microbial communities. The algorithm uses single-nucleotide polymorphism (SNP) patterns in a set of universal genes to infer within-species structures that represent strains. Applying ConStrains to simulated and host-derived datasets provides insights into microbial community dynamics.

  9. Tailoring a ConOps for NASA LSP Integrated Operations

    NASA Technical Reports Server (NTRS)

    Owens, Skip Clark V., III

    2017-01-01

    An integral part of the Systems Engineering process is the creation of a Concept of Operations (ConOps) for a given system, with the ConOps initially established early in the system design process and evolved as the system definition and design matures. As Integration Engineers in NASA's Launch Services Program (LSP) at Kennedy Space Center (KSC), our job is to manage the interface requirements for all the robotic space missions that come to our Program for a Launch Service. LSP procures and manages a launch service from one of our many commercial Launch Vehicle Contractors (LVCs) and these commercial companies are then responsible for developing the Interface Control Document (ICD), the verification of the requirements in that document, and all the services pertaining to integrating the spacecraft and launching it into orbit. However, one of the systems engineering tools that have not been employed within LSP to date is a Concept of Operations. The goal of this paper is to research the format and content that goes into these various aerospace industry ConOps and tailor the format and content into template form, so the template may be used as an engineering tool for spacecraft integration with future LSP procured launch services. This tailoring effort was performed as the authors final Masters Project in the Spring of 2016 for the Stevens Institute of Technology and modified for publication with INCOSE (Owens, 2016).

  10. A complex photoreceptor system mediates the regulation by light of the conidiation genes con-10 and con-6 in Neurospora crassa.

    PubMed

    Olmedo, María; Ruger-Herreros, Carmen; Luque, Eva M; Corrochano, Luis M

    2010-04-01

    Genes con-10 and con-6 in Neurospora crassa are activated during conidiation or after illumination of vegetative mycelia. Light activation requires the white-collar complex (WCC), a transcription factor complex composed of the photoreceptor WC-1 and its partner WC-2. We have characterized the photoactivation of con-10 and con-6, and we have identified 300bp required for photoactivation in the con-10 promoter. A complex stimulus-response relationship for con-10 and con-6 photoactivation suggested the activity of a complex photoreceptor system. The WCC is the key element for con-10 activation by light, but we suggest that other photoreceptors, the cryptochrome CRY-1, the rhodopsin NOP-1, and the phytochrome PHY-2, modify the activity of the WCC for con-10 photoactivation, presumably through a repressor. In addition we show that the regulatory protein VE-1 is required for full photocarotenogenesis. We propose that these proteins may modulate the WCC in a gene-specific way.

  11. Molecular diagnostics: Molecular Med Tri-Con 2013.

    PubMed

    Klein, Roger D

    2013-07-01

    The 20th annual Molecular Med Tri-Con conference, sponsored by Cambridge Health Institute (MA, USA), consisted of over 250 presentations within five parallel 'channels': 'Diagnostics, Therapeutics, Clinical, Informatics and Cancer', along with five preliminary symposia, 15 short courses, a plenary keynote session entitled 'Personalized Oncology - Fulfilling the Promise for Today's Patients' and a keynote panel entitled, 'Emerging Technologies and Industry Perspectives'. Over 3000 individuals from academia, clinical laboratories and industry were in attendance. This article will focus on the Keynote Session of 'Molecular Diagnostics' track within the Diagnostics Channel.

  12. Apoyo a Estudios Geodinamicos con GPS en Guatemala

    NASA Astrophysics Data System (ADS)

    Robles, V. R.

    2013-05-01

    El Instituto Geografico Nacional de Guatemala implemento 17 estaciones GNSS en el año 2009, como un proyecto de credito mixto de donacion de equipamiento del Gobierno de Suiza, el cual, este equipamiento de estaciones CORS GNSS es un sistema de recepción y transmisión de datos crudos GPS RInex que utiliza la tecnologia Spider Web de Leica, asi mismo este sistema esta sirviendo para el espablecimiento de un marco geodesico nacional de coordenadas geodesicas oficiales, el cual se calculan u obtienen las velocidades en tiempos temporales programados de las 17 Estaciones CORS. La infraestructura del marco geodesico de Guatemala esta sirviendo de base para las aplicaciones de estudios geodinamicos como el monitoreo de del desplazamiento de las placas tectonicas por medio de un estudio que se inicio en el año de 1999, llamado medicion con GPS el sistema de Fallas de los rios Polochic Motagua de Guatemala, tambien para un estudio que se implemento para deformación de corteza terrestre local en un Volcan Activo de Guatemala llamado Pacaya. Para el estudio de medicion con GPS en el sistema de falla de los Rios del polochic Motagua se implementaron 16 puntos para medir con GPS de dos frecuencias en el año de 1999, el cual, tres puntos son estaciones geodesicas CORS IGS llamados GUAT, ELEN y HUEH, despues en el año de 2003 se hizo otra medicion en un total de 20 puntos, que permitió calcular las velocidades de desplazamieinto de los puntos en mención, usando como referencia el modelo NUVEL 1A de DeMets de la placa de Norteamerica. Este estudio fue en cooperación internacional por la universidad de Nice de Francia y el IGNde Francia. Para el estudio del monitoreo con GPS del volcan activo de Guatemala, se implementaron cuatro puntos al rededor del volcan, el cual, se realizan cuatro mediciones al año, que permiten determinar axialmente la distancias entre los puntos, y rebisar estadisticamente cual es el comportamiento de las distancias en funcion del tiempo, si

  13. Caffe con Troll: Shallow Ideas to Speed Up Deep Learning.

    PubMed

    Hadjis, Stefan; Abuzaid, Firas; Zhang, Ce; Ré, Christopher

    2015-01-01

    We present Caffe con Troll (CcT), a fully compatible end-to-end version of the popular framework Caffe with rebuilt internals. We built CcT to examine the performance characteristics of training and deploying general-purpose convolutional neural networks across different hardware architectures. We find that, by employing standard batching optimizations for CPU training, we achieve a 4.5× throughput improvement over Caffe on popular networks like CaffeNet. Moreover, with these improvements, the end-to-end training time for CNNs is directly proportional to the FLOPS delivered by the CPU, which enables us to efficiently train hybrid CPU-GPU systems for CNNs.

  14. Conning the conmen: Intelligence and female desire in Dedh Ishqiya.

    PubMed

    Singh, Shailendra Kumar

    2017-04-11

    This article investigates the ostensibly paradoxical relationship that exists between the theme of excessive love, as suggested by the title of Abhishek Chaubey's film Dedh Ishqiya (2014), and the actual representation of it in the movie, which is not only restrained and disproportionate, but is also looked at with suspicion and contempt. It examines the logic of this seeming contradiction through the other two related themes that Chaubey's chef-d'œuvre foregrounds, namely that of intelligence and female desire. The quest for financial autonomy that the female protagonists of the movie are involved in-a necessary pre-condition for leading independent lives-is so inextricably intertwined with manipulation, dexterity, and subterfuge, that any overt expression of homoerotic female desire can only jeopardize their existing possibilities of self-aggrandizement. The heteronormative arrangements of Begum Para's palace thus constitute the elaborate mise en scène, behind which female desire is enacted through a politics of intelligence, resourcefulness, discretion, and anonymity. Through this strategic negotiation, which is also a tactical necessity, the female protagonists are not only able to con the con men in the movie, but also imagine alternative subject positions that recognize the need for both pragmatism and expediency as well as deconstructing heteropatriarchal economies of desire.

  15. Cannabinoids and cancer: pros and cons of an antitumour strategy

    PubMed Central

    Bifulco, Maurizio; Laezza, Chiara; Pisanti, Simona; Gazzerro, Patrizia

    2006-01-01

    In the last two decades, research has dramatically increased the knowledge of cannabinoids biology and pharmacology. In mammals, compounds with properties similar to active components of Cannabis sativa, the so called ‘endocannabinoids', have been shown to modulate key cell-signalling pathways involved in cancer cell growth, invasion and metastasis. To date, cannabinoids have been licensed for clinical use as palliative treatment of chemotherapy, but increased evidences showed direct antiproliferative actions of cannabinoid agonists on several tumour cells in vitro and in animal models. In this article, we will review the principal molecular pathways modulated by cannabinoids on cancer and summarize pros and cons evidence on the possible future use of endocannabinoid-based drugs in cancer therapy. PMID:16501583

  16. Balancing Ethical Pros and Cons of Stem Cell Derived Gametes.

    PubMed

    Segers, Seppe; Mertes, Heidi; de Wert, Guido; Dondorp, Wybo; Pennings, Guido

    2017-07-01

    In this review we aim to provide an overview of the most important ethical pros and cons of stem cell derived gametes (SCD-gametes), as a contribution to the debate about reproductive tissue engineering. Derivation of gametes from stem cells holds promising applications both for research and for clinical use in assisted reproduction. We explore the ethical issues connected to gametes derived from embryonic stem cells (both patient specific and non-patient specific) as well as those related to gametes derived from induced pluripotent stem cells. The technology of SCD-gametes raises moral concerns of how reproductive autonomy relates to issues of embryo destruction, safety, access, and applications beyond clinical infertility.

  17. Endoscopic scoring systems for inflammatory bowel disease: pros and cons.

    PubMed

    Tontini, Gian Eugenio; Bisschops, Raf; Neumann, Helmut

    2014-07-01

    Endoscopy plays a pivotal role for diagnosis and assessment of disease activity and extent in patients with inflammatory bowel diseases. International guidelines recommend the use of endoscopic scoring systems for evaluation of the prognosis and efficacy of medical treatments. Ideal scoring systems are easy to use, reproducible, reliable, responsive to changes, and validated in different clinical settings in order to guide therapeutic strategies. However, currently available endoscopic scoring systems often appear as complex for routine endoscopy and suffer from insufficient interobserver agreement and lack of formal validation which often limit their use in clinical trials. Here, we describe the role of endoscopic scoring systems in inflammatory bowel diseases focusing on pros and cons in the era of advanced endoscopic imaging and mucosal healing.

  18. Gradient Optimization for Analytic conTrols - GOAT

    NASA Astrophysics Data System (ADS)

    Assémat, Elie; Machnes, Shai; Tannor, David; Wilhelm-Mauch, Frank

    Quantum optimal control becomes a necessary step in a number of studies in the quantum realm. Recent experimental advances showed that superconducting qubits can be controlled with an impressive accuracy. However, most of the standard optimal control algorithms are not designed to manage such high accuracy. To tackle this issue, a novel quantum optimal control algorithm have been introduced: the Gradient Optimization for Analytic conTrols (GOAT). It avoids the piecewise constant approximation of the control pulse used by standard algorithms. This allows an efficient implementation of very high accuracy optimization. It also includes a novel method to compute the gradient that provides many advantages, e.g. the absence of backpropagation or the natural route to optimize the robustness of the control pulses. This talk will present the GOAT algorithm and a few applications to transmons systems.

  19. RoboCon: Operator interface for robotic applications

    SciTech Connect

    Schempf, H.; Warwick, J.; Fung, M.; Chemel, B.; Blackwell, M.

    1996-12-31

    Carnegie Mellon U. and ORNL`s Robotics and Process Systems Division are developing a state-of-the-art robot operator control station (RoboCon) with standardized hardware and software control interfaces to be adaptable to a variety of remote and robotic equipment currently funded by DOE`s Office of Science & Technology Robotics Technology Development Program. The human operation and telerobotic and supervisory control of sophisticated and remote and robotic systems is a complex, tiring, and non-intuitive activity. Since decontamination & decommissioning, selective equipment removal, mixed waste operations, and in-tank cleanup are going to be a major future activity in DOE environmental restoration and waste management cleanup agenda, it seems necessary to utilize an operator control station and interface which maximizes operator comfort and productivity.

  20. Caffe con Troll: Shallow Ideas to Speed Up Deep Learning

    PubMed Central

    Hadjis, Stefan; Abuzaid, Firas; Zhang, Ce; Ré, Christopher

    2016-01-01

    We present Caffe con Troll (CcT), a fully compatible end-to-end version of the popular framework Caffe with rebuilt internals. We built CcT to examine the performance characteristics of training and deploying general-purpose convolutional neural networks across different hardware architectures. We find that, by employing standard batching optimizations for CPU training, we achieve a 4.5× throughput improvement over Caffe on popular networks like CaffeNet. Moreover, with these improvements, the end-to-end training time for CNNs is directly proportional to the FLOPS delivered by the CPU, which enables us to efficiently train hybrid CPU-GPU systems for CNNs. PMID:27314106

  1. [Modern tribology in total hip arthroplasty: pros and cons].

    PubMed

    Gómez-García, F

    2014-01-01

    The wear products and adverse reactions that occur on bearing surfaces represent one of the greatest challenges in prosthetic replacements, as the latter experience increasing demands due to the large number of young and older adult patients that have a long life expectancy and remarkable activity. The purpose of this review is to analyze the pros and cons of the new advances in the bearing components of the articular surfaces of current total hip arthroplasties. We also discuss the strategies used historically, their problems, results and the surgeon's role in prescribing the tribologic couple that best fits each patient's needs. We conclude with practical recommendations for the prescription and management of the latest articular couples for total hip arthroplasty.

  2. Cannabinoids and cancer: pros and cons of an antitumour strategy.

    PubMed

    Bifulco, Maurizio; Laezza, Chiara; Pisanti, Simona; Gazzerro, Patrizia

    2006-05-01

    In the last two decades, research has dramatically increased the knowledge of cannabinoids biology and pharmacology. In mammals, compounds with properties similar to active components of Cannabis sativa, the so called 'endocannabinoids', have been shown to modulate key cell-signalling pathways involved in cancer cell growth, invasion and metastasis. To date, cannabinoids have been licensed for clinical use as palliative treatment of chemotherapy, but increased evidences showed direct antiproliferative actions of cannabinoid agonists on several tumour cells in vitro and in animal models. In this article, we will review the principal molecular pathways modulated by cannabinoids on cancer and summarize pros and cons evidence on the possible future use of endocannabinoid-based drugs in cancer therapy.

  3. Neogene sequence stratigraphy, Nam Con Son Basin, offshore Vietnam

    SciTech Connect

    McMillen, K.J. ); Do Van Luu; Lee, E.K.; Hong, S.S. )

    1996-01-01

    An integrated well log, biostratigraphic, and seismic stratigraphic study of Miocene to Recent deltaic sediments deposited in the Nam Con Son Basin offshore from southern Vietnam shows the influence of eustacy and tectonics on sequence development. Sediments consist of Oligocene non-marine rift-basin fill (Cau Formation), early to middle Miocene tide-dominated delta plain to delta front sediments (TB 1.5 to TB 2.5, Due and Thong Formations), and late Miocene to Recent marine shelf sediments (TB. 2.6 to TB 3.1 0, Mang Cau, Nam Con Son, and Bien Dong Formations). Eustacy controlled the timing of key surfaces and sand distribution in the tectonically-quiet early Miocene. Tectonic effects on middle to late Miocene sequence development consist of thick transgressive systems tracts due to basin-wide subsidence and transgression, sand distribution in the basin center, and carbonate sedimentation on isolated fault blocks within the basin. Third-order sequence boundaries (SB) are identified by spore peaks, sand stacking patterns, and channel incision. In the basin center, widespread shale beds with coal occur above sequence boundaries followed by transgressive sandstone units. These TST sandstones merge toward the basin margin where they lie on older HST sandstones. Maximum flooding surfaces (MFS) have abundant marine microfossils and mangrove pollen, a change in sand stacking pattern, and often a strong seismic reflection with downlap. Fourth-order genetic-type sequences are also interpreted. The MFS is the easiest marker to identify and correlate on well logs. Fourth-order SB occur within these genetic units but are harder to identify and correlate.

  4. Neogene sequence stratigraphy, Nam Con Son Basin, offshore Vietnam

    SciTech Connect

    McMillen, K.J.; Do Van Luu; Lee, E.K.; Hong, S.S.

    1996-12-31

    An integrated well log, biostratigraphic, and seismic stratigraphic study of Miocene to Recent deltaic sediments deposited in the Nam Con Son Basin offshore from southern Vietnam shows the influence of eustacy and tectonics on sequence development. Sediments consist of Oligocene non-marine rift-basin fill (Cau Formation), early to middle Miocene tide-dominated delta plain to delta front sediments (TB 1.5 to TB 2.5, Due and Thong Formations), and late Miocene to Recent marine shelf sediments (TB. 2.6 to TB 3.1 0, Mang Cau, Nam Con Son, and Bien Dong Formations). Eustacy controlled the timing of key surfaces and sand distribution in the tectonically-quiet early Miocene. Tectonic effects on middle to late Miocene sequence development consist of thick transgressive systems tracts due to basin-wide subsidence and transgression, sand distribution in the basin center, and carbonate sedimentation on isolated fault blocks within the basin. Third-order sequence boundaries (SB) are identified by spore peaks, sand stacking patterns, and channel incision. In the basin center, widespread shale beds with coal occur above sequence boundaries followed by transgressive sandstone units. These TST sandstones merge toward the basin margin where they lie on older HST sandstones. Maximum flooding surfaces (MFS) have abundant marine microfossils and mangrove pollen, a change in sand stacking pattern, and often a strong seismic reflection with downlap. Fourth-order genetic-type sequences are also interpreted. The MFS is the easiest marker to identify and correlate on well logs. Fourth-order SB occur within these genetic units but are harder to identify and correlate.

  5. Modulation of ConA-induced inflammatory ascites by histamine - short communication.

    PubMed

    Baintner, Károly

    2015-03-01

    The early phase of the ConA-induced inflammatory ascites was studied, with special reference to histamine. Concanavalin A (ConA), a cell-surface binding lectin was injected i.p. (25 mg/kg bw) to mice. After 1 h the animals were killed, the ascitic fluid collected and measured. Other agents were injected s.c., 10 min before the ConA-challenge. Exogenous histamine markedly inhibited the ConA-induced ascites. Release of endogenous vasoactive agents from the mast cells by Compound 48/80 had a similar, but slight effect. Cromolyn, a mast cell stabilizing agent, and chloropyramine, a histamine H1 receptor antagonist was ineffective. Although histamine increases endothelial permeability, it did not enhance the formation of ascitic fluid, on the contrary, it inhibited the ConA-induced ascites, presumably due to its known hypotonic effect. It is concluded that ConA-induced ascites is not mediated by mast cell histamine.

  6. Cardiac CON Regulations and the Availability and Use of Revascularization Services

    PubMed Central

    Ho, Vivian; Ross, Joseph S.; Nallamothu, Brahmajee K.; Krumholz, Harlan M.

    2007-01-01

    Background Many states enforce Certificate of Need (CON) regulations for cardiac procedures, but little is known about how CON affects utilization. We assessed the association between cardiac CON regulations, availability of revascularization facilities, and revascularization rates. Methods We determined when state cardiac CON regulations were active and obtained data for Medicare beneficiaries ages 65 and older who received coronary artery bypass graft surgery (CABG) or a percutaneous coronary intervention (PCI) between 1989 and 2002. We compared the number of hospitals performing revascularization and patient utilization in states with and without CON regulations, and in states which discontinued CON regulations during 1989-2002. Results Each year, the per capita number of hospitals performing CABG and PCI was higher in states without CON (3.7 per 100,000 elderly for CABG, 4.5 for PCI in 2002), compared with CON states (2.5 for CABG, 3.0 for PCI in 2002). Multivariate regressions that adjusted for market and population characteristics found no difference in CABG utilization rates between states with and without CON (p=.7). However, CON was associated with 19.2 percent fewer PCIs per 1,000 elderly (p=.01), equivalent to 322,526 fewer PCIs for 1989-2002. Among most states that discontinued CON, the number of hospitals performing PCI rose in the mid 1990s, but there were no consistent trends in the number of hospitals performing CABG or in PCIs or CABGs per capita. Conclusions CON restricts the number of cardiac facilities, but its effect on utilization rates may vary by procedure. PMID:17893007

  7. Laparoscopy for inflammatory bowel disease: pros and cons.

    PubMed

    Sardinha, T C; Wexner, S D

    1998-04-01

    The role of laparoscopic surgery in the treatment of colorectal malignancies is still under investigation, although it can offer significant benefits to many patients with inflammatory bowel disease (IBD). The aim of this study was to assess the pros and cons of the laparoscopic management of IBD. Data were obtained from a review of the literature published since 1992, when the first report of laparoscopic surgery for IBD appeared in print. From 1992 to 1997 several series of laparoscopic colorectal surgery for the management of IBD have been reported. A close evaluation of these studies revealed that laparoscopy in patients with terminal ileal Crohn's disease or anal Crohn's disease in need of fecal diversion offers significant advantages compared to laparotomy, including decreased pain, length of hospitalization, and disability. An additional bonus is improved cosmesis and a reduction in symptomatic postoperative adhesions. These many benefits can be achieved without any increase in morbidity or expense. Conversely, the use of this technology for restorative proctocolectomy in patients with mucosal ulcerative colitis is associated with a longer operative time and an increased incidence of both intra- and postoperative complications compared to laparotomy. Laparoscopic colorectal surgery can thus be advantageous for treatment of terminal ileal Crohn's disease but cannot be routinely justified for the treatment of mucosal ulcerative colitis.

  8. Pros and cons of circumcision: an evidence-based overview.

    PubMed

    Friedman, B; Khoury, J; Petersiel, N; Yahalomi, T; Paul, M; Neuberger, A

    2016-09-01

    Based on three large randomized controlled trials (RCTs) conducted in Africa, it can clearly be stated that circumcision lowers the risk of infection with the human immunodeficiency virus (HIV) and some sexually transmitted infections (STIs) among males in settings of high HIV and STI endemicity. Similar effects on STI risk may exist for females, although this may result from an indirect effect of decreasing risk of infection among male partners. It is unknown whether circumcision prevents HIV acquisition in men who have sex with men (MSM), although there might be a protective effect for men who engage mainly in insertive anal intercourse. When the effects of adult circumcision on sexual function and satisfaction of men are examined, high-quality evidence strongly supports lack of harm. Whether circumcision alters sexual satisfaction of female partners is not known as fewer and smaller studies reported conflicting results. Circumcision rarely causes serious complications if practiced by trained practitioners, in a sterile setting, and with a proper follow-up. These conclusions are limited by the lack of high-quality data from areas outside of Africa. RCTs have not been conducted to assess the effects of circumcising infants or MSM. Circumcision has well-proven benefits for people residing in areas with high prevalence of STIs, including HIV, and is not unethical for those who choose to be circumcised or have their children circumcised on religious, social, or cultural grounds. For many others, a definite pro or con recommendation, based on a risk-benefit ratio, cannot be made.

  9. Percutaneous coronary intervention in nonagenarians: pros and cons

    PubMed Central

    Biondi Zoccai, Giuseppe; Abbate, Antonio; D'Ascenzo, Fabrizio; Presutti, Davide; Peruzzi, Mariangela; Cavarretta, Elena; Marullo, Antonino G.M.; Lotrionte, Marzia; Frati, Giacomo

    2013-01-01

    Percutaneous coronary intervention is a mainstay in the management of symptomatic or high-risk coronary artery disease. The bulk of clinical evidence and experience underlying this fact relies, however, on relatively young patients. Indeed, few data of very limited quality are available which adequately define the risk-benefit and cost-benefit profile of coronary angioplasty and stenting in very old subjects, such as those of 90 years of age or older (i.e., nonagenarians). The aim of this review is to provide a concise, yet practical, synthesis of the available evidence on percutaneous coronary revascularization in the very elderly. The main arguments elaborated upon are to what extent we can extrapolate findings from studies including younger patients to nonagenarians, whether we should provide higher priority to prognosis or quality of life in such patients, and whether we can afford to allocate vast resources to care for such subjects in an era of financial constraints. Our review of 18 studies and 1082 patients suggest that percutaneous coronary intervention is feasible and associated with acceptable short- and long-term results in this population, which is nonetheless fraught with a high mortality risk irrespective of the revascularization procedure. Accordingly, the pros and cons of percutaneous coronary intervention should be carefully weighed when considering this treatment in nonagenarians. PMID:23610578

  10. Immune cascades in human intervertebral disc: the pros and cons

    PubMed Central

    Sun, Zhen; Zhang, Ming; Zhao, Xu-Hong; Liu, Zhi-Heng; Gao, Yang; Samartzis, Dino; Wang, Hai-Qiang; Luo, Zhuo-Jing

    2013-01-01

    The unique structural hallmark of the intervertebral disc has made its central composition, the nucleus pulposus (NP), excluded from the immunologic tolerance. Consequently, the intervertebral disc is identified as an immune-privileged organ. Traditionally, local detrimental immune activities caused by NP at the lesion sites of the disc are noted as a significant factor contributing to disc degeneration. However, given the beneficial activities of immune cells in other immune-privileged sites on basis of current evidence, the degenerate disc might need the assistance of a subpopulation of immune cells to restore its structure and lessen inflammation. In addition, the beneficial impact of immune cells can be seen in the absorption of the herniated NP, which is an important factor causes the mechanical compression of nerve roots. Consequently, a modulated immune network in degenerate disc is essential for the restoration of this immune-privileged organ. Until now, the understandings of immune response in disc degeneration still rest on the harmful aspect. Further studies are needed to explore its beneficial influence. Accordingly, there are no absolutely the pros and cons in terms of immune reactions caused by NP. PMID:23696917

  11. Immune cascades in human intervertebral disc: the pros and cons.

    PubMed

    Sun, Zhen; Zhang, Ming; Zhao, Xu-Hong; Liu, Zhi-Heng; Gao, Yang; Samartzis, Dino; Wang, Hai-Qiang; Luo, Zhuo-Jing

    2013-01-01

    The unique structural hallmark of the intervertebral disc has made its central composition, the nucleus pulposus (NP), excluded from the immunologic tolerance. Consequently, the intervertebral disc is identified as an immune-privileged organ. Traditionally, local detrimental immune activities caused by NP at the lesion sites of the disc are noted as a significant factor contributing to disc degeneration. However, given the beneficial activities of immune cells in other immune-privileged sites on basis of current evidence, the degenerate disc might need the assistance of a subpopulation of immune cells to restore its structure and lessen inflammation. In addition, the beneficial impact of immune cells can be seen in the absorption of the herniated NP, which is an important factor causes the mechanical compression of nerve roots. Consequently, a modulated immune network in degenerate disc is essential for the restoration of this immune-privileged organ. Until now, the understandings of immune response in disc degeneration still rest on the harmful aspect. Further studies are needed to explore its beneficial influence. Accordingly, there are no absolutely the pros and cons in terms of immune reactions caused by NP.

  12. Pros and cons of screening for occult Cushing syndrome.

    PubMed

    Tabarin, Antoine; Perez, Paul

    2011-03-22

    Systematic screening studies performed mainly in patients with diabetes mellitus have revealed an unexpectedly high prevalence of occult Cushing syndrome. Such studies may provide a rationale for systematically screening obese patients with type 2 diabetes mellitus. However, a screening strategy is only justified if it is supported by enough evidence of its efficacy and if the benefits will outweigh drawbacks. To date, the natural history of occult Cushing syndrome and its possible effect on long-term morbidity are unknown. The clinical spectrum of occult Cushing syndrome and its relatively low prevalence may potentially negatively affect the performance of endocrine tests used to diagnose overt Cushing syndrome and generate false positives. Whether the cure of occult Cushing syndrome favorably influences clinical outcomes and is more beneficial than treatment of diabetes mellitus and cardiovascular risk factors with currently available pharmacological tools remains to be demonstrated. Last, the acceptability of a screening program by professionals and the health-care system in terms of workload and costs is highly questionable. Thus, an assessment of the indications for and against screening for occult Cushing syndrome on the basis of currently available data suggests that, to date, the cons surpass the pros.

  13. Pros and Cons of Medical Management of Ulcerative Colitis

    PubMed Central

    Navaneethan, Udayakumar; Shen, Bo

    2010-01-01

    Ulcerative colitis (UC) is a chronic inflammatory disease characterized by diffuse mucosal inflammation limited to the colon and rectum. Although a complete medical cure may not be possible, UC can be treated with medications that induce and maintain remission. The medical management of this disease continues to evolve with a goal to avoid colectomy and ultimately alter the natural history of UC. Emergence of antitumor necrosis factor-α (TNF-α) agents has expanded the medical armamentarium. 5-Aminosalicylates continue to be used in mild to moderate UC and corticosteroids are mainly used for induction of remission with immunomodulators (6-mercaptopurine/azathiopurine/methotrexate) being applied as steroid-sparing agents for maintenance therapy. Infliximab has been approved by the U.S. Food and Drug Administration and used in the treatment of moderate to severe UC; nevertheless, its use may be associated with significant adverse effects and have a negative impact on the postoperative course should the patients undergo restorative proctocolectomy. In addition, there is always a concern about patients' compliance to medical therapy, cost of medications, and risk for UC-associated dysplasia. The authors discuss the pros and cons of medications used in the treatment of UC. PMID:22131893

  14. Pros, Cons, and Alternatives to Weight Based Cost Estimating

    NASA Technical Reports Server (NTRS)

    Joyner, Claude R.; Lauriem, Jonathan R.; Levack, Daniel H.; Zapata, Edgar

    2011-01-01

    Many cost estimating tools use weight as a major parameter in projecting the cost. This is often combined with modifying factors such as complexity, technical maturity of design, environment of operation, etc. to increase the fidelity of the estimate. For a set of conceptual designs, all meeting the same requirements, increased weight can be a major driver in increased cost. However, once a design is fixed, increased weight generally decreases cost, while decreased weight generally increases cost - and the relationship is not linear. Alternative approaches to estimating cost without using weight (except perhaps for materials costs) have been attempted to try to produce a tool usable throughout the design process - from concept studies through development. This paper will address the pros and cons of using weight based models for cost estimating, using liquid rocket engines as the example. It will then examine approaches that minimize the impct of weight based cost estimating. The Rocket Engine- Cost Model (RECM) is an attribute based model developed internally by Pratt & Whitney Rocketdyne for NASA. RECM will be presented primarily to show a successful method to use design and programmatic parameters instead of weight to estimate both design and development costs and production costs. An operations model developed by KSC, the Launch and Landing Effects Ground Operations model (LLEGO), will also be discussed.

  15. Meeting Report: Breath Biomarkers Networking Sessions at PittCon 2010, Orlando, Florida

    EPA Science Inventory

    The Pittsburgh Conference and Exposition, or "PittCon" (www.pittcon.org/), is one of the largest international conferences for analytical chemistry and instrumentation typically attracting about 25,000 attendees and 1,000 commercial exhibitors. PittCon began in 1950 as a small sp...

  16. Gestational surrogacy: could be a way to be a way to reproduction? Pros and cons.

    PubMed

    Clementina, Peris

    2011-06-01

    The aim of this article was to address pros and cons of gestational surrogacy, the social and psychological issues involved in surrogate motherhood triads. Pros and cons of surrogacy, the possible insurgence of a hematologic disease in the fetus, hemolytic disease of the newborn, naturally acquired microchimerism in surrogacy cases, ethical, medical, psychologic, legal and religious issues of a problem are discussed.

  17. Meeting Report: Breath Biomarkers Networking Sessions at PittCon 2010, Orlando, Florida

    EPA Science Inventory

    The Pittsburgh Conference and Exposition, or "PittCon" (www.pittcon.org/), is one of the largest international conferences for analytical chemistry and instrumentation typically attracting about 25,000 attendees and 1,000 commercial exhibitors. PittCon began in 1950 as a small sp...

  18. ConSearch: An Electronic Document Research and Retrieval Utility for Windows from Management Information Technologies.

    ERIC Educational Resources Information Center

    Combs, Joseph, Jr.

    1995-01-01

    Reviews ConSearch 3.0, a product that provides flexible searching of electronic files, allowing the location of related meanings as well as exact matches. ConSearch 3.0 differs from other file retrieval approaches by relating words in search phrases of questions to the "meaning" of the words, which are stored in a "conceptual…

  19. Self-Exfoliated Guanidinium-Based Ionic Covalent Organic Nanosheets (iCONs).

    PubMed

    Mitra, Shouvik; Kandambeth, Sharath; Biswal, Bishnu P; Khayum M, Abdul; Choudhury, Chandan K; Mehta, Mihir; Kaur, Gagandeep; Banerjee, Subhrashis; Prabhune, Asmita; Verma, Sandeep; Roy, Sudip; Kharul, Ulhas K; Banerjee, Rahul

    2016-03-02

    Covalent organic nanosheets (CONs) have emerged as functional two-dimensional materials for versatile applications. Although π-π stacking between layers, hydrolytic instability, possible restacking prevents their exfoliation on to few thin layered CONs from crystalline porous polymers. We anticipated rational designing of a structure by intrinsic ionic linker could be the solution to produce self-exfoliated CONs without external stimuli. In an attempt to address this issue, we have synthesized three self-exfoliated guanidinium halide based ionic covalent organic nanosheets (iCONs) with antimicrobial property. Self-exfoliation phenomenon has been supported by molecular dynamics (MD) simulation as well. Intrinsic ionic guanidinium unit plays the pivotal role for both self-exfoliation and antibacterial property against both Gram-positive and Gram-negative bacteria. Using such iCONs, we have devised a mixed matrix membrane which could be useful for antimicrobial coatings with plausible medical benefits.

  20. Surgical animal models of neuropathic pain: Pros and Cons.

    PubMed

    Challa, Siva Reddy

    2015-03-01

    One of the biggest challenges for discovering more efficacious drugs for the control of neuropathic pain has been the diversity of chronic pain states in humans. It is now acceptable that different mechanisms contribute to normal physiologic pain, pain arising from tissue damage and pain arising from injury to the nervous system. To study pain transmission, spot novel pain targets and characterize the potential analgesic profile of new chemical entities, numerous experimental animal pain models have been developed that attempt to simulate the many human pain conditions. Among the neuropathic pain models, surgical models have paramount importance in the induction of pain states. Many surgical animal models exist, like the chronic constriction injury (CCI) to the sciatic nerve, partial sciatic nerve ligation (pSNL), spinal nerve ligation (SNL), spared nerve injury (SNI), brachial plexus avulsion (BPA), sciatic nerve transaction (SNT) and sciatic nerve trisection. Most of these models induce responses similar to those found in causalgia, a syndrome of sustained burning pain often seen in the distal extremity after partial peripheral nerve injury in humans. Researchers most commonly use these surgical models in both rats and mice during drug discovery to screen new chemical entities for efficacy in the area of neuropathic pain. However, there is scant literature that provides a comparative discussion of all these surgical models. Each surgical model has its own benefits and limitations. It is very difficult for a researcher to choose a suitable surgical animal model to suit their experimental set-up. Therefore, particular attention has been given in this review to comparatively provide the pros and cons of each model of surgically induced neuropathic pain.

  1. Synergistic hemolysins of coagulase-negative staphylococci (CoNS).

    PubMed

    Różalska, Małgorzata; Derczyńska, Anna; Maszewska, Agnieszka

    2015-01-01

    A total of 104 coagulase negative staphylococci, belonging to S. capitis, S. hominis, S. haemolyticus and S. warneri, originating from the collection of the Department of Pharmaceutical Microbiology (ZMF), Medical University of Lodz, Poland, were tested for their synergistic hemolytic activity. 83% of strains produced δ-hemolysin, however, the percentage of positive strains of S. haemolyticus, S. warneri, S. capitis and S. hominis was different - 98%, 78%, 75% and 68%, respectively. Highly pure hemolysins were obtained from culture supernatants by protein precipitation with ammonium sulphate (0-70% of saturation) and extraction by using a mixture of organic solvents. The purity and molecular mass of hemolysins was determined by TRIS/Tricine PAGE. All CoNS hemolysins were small peptides with a molar mass of about 3.5 kDa; they possessed cytotoxic activity against the line of human foreskin fibroblasts ATCC Hs27 and lysed red cells from different mammalian species, however, the highest activity was observed when guinea pig, dog and human red blood cells were used. The cytotoxic effect on fibroblasts occurred within 30 minutes. The S. cohnii ssp. urealyticus strain was used as a control. The antimicrobial activity was examined using hemolysins of S. capitis, S. hominis, S. cohnii ssp. cohnii and S. cohnii ssp. urealyticus. Hemolysins of the two S. cohnii subspecies did not demonstrate antimicrobial activity. Cytolysins of S. capitis and S. hominis had a very narrow spectrum of action; out of 37 examined strains, the growth of only Micrococcus luteus, Corynebacterium diphtheriae and Pasteurella multocida was inhibited.

  2. Antibiotic susceptibility of coagulase-negative staphylococci (CoNS): emergence of teicoplanin-non-susceptible CoNS strains with inducible resistance to vancomycin.

    PubMed

    Ma, Xiao Xue; Wang, En Hua; Liu, Yong; Luo, En Jie

    2011-11-01

    Coagulase-negative staphylococci (CoNS) have become increasingly recognized as important agents of nosocomial infection. One of the characteristics of CoNS is their resistance to multiple antimicrobial agents commonly used for the treatment of staphylococcal infections. CoNS strains (n = 745) isolated from a university teaching hospital in China between 2004 and 2009 were tested for antibiotic resistance. The antibiotics were placed into three categories based on resistance levels of the CoNS strains to these antibiotics: high resistance (resistance rate >70 %), including penicillin G, oxacillin and erythromycin; medium resistance (resistance rate between 30 and 70 %), including tetracycline, clindamycin, ciprofloxacin, trimethoprim/sulfamethoxazole and chloramphenicol; and low resistance (resistance rate <30 %), including rifampicin, ceftizoxime and gentamicin. We also found that the prevalence of strains non-susceptible to teicoplanin increased from 4.5 to 6.7 % between 2008 and 2009. A one-step vancomycin agar selection experiment and subsequent population analysis revealed potentially vancomycin-resistant subpopulations that have been selected from the teicoplanin-non-susceptible strains. Vigilant surveillance of nosocomial isolates of CoNS is needed to determine their resistance to glycopeptides.

  3. Project "Convective Wind Gusts" (ConWinG)

    NASA Astrophysics Data System (ADS)

    Mohr, Susanna; Richter, Alexandra; Kunz, Michael; Ruck, Bodo

    2017-04-01

    Convectively-driven strong winds usually associated with thunderstorms frequently cause substantial damage to buildings and other structures in many parts of the world. Decisive for the high damage potential are the short-term wind speed maxima with duration of a few seconds, termed as gusts. Several studies have shown that convectively-driven gusts can reach even higher wind speeds compared to turbulent gusts associated with synoptic-scale weather systems. Due to the small-scale and non-stationary nature of convective wind gusts, there is a considerable lack of knowledge regarding their characteristics and statistics. Furthermore, their interaction with urban structures and their influence on buildings is not yet fully understood. For these two reasons, convective wind events are not included in the present wind load standards of buildings and structures, which so far have been based solely on the characteristics of synoptically-driven wind gusts in the near-surface boundary layer (e. g., DIN EN 1991-1-4:2010-12; ASCE7). However, convective and turbulent gusts differ considerably, e.g. concerning vertical wind-speed profiles, gust factors (i.e., maximum to mean wind speed), or exceedance probability curves. In an effort to remedy this situation, the overarching objective of the DFG-project "Convective Wind Gusts" (ConWinG) is to investigate the characteristics and statistics of convective gusts as well as their interaction with urban structures. Based on a set of 110 climate stations of the German Weather Service (DWD) between 1992 and 2014, we analyzed the temporal and spatial distribution, intensity, and occurrence probability of convective gusts. Similar to thunderstorm activity, the frequency of convective gusts decreases gradually from South to North Germany. A relation between gust intensity/probability to orography or climate conditions cannot be identified. Rather, high wind speeds, e.g., above 30 m/s, can be expected everywhere in Germany with almost

  4. Targeted Drug Delivery in Covalent Organic Nanosheets (CONs) via Sequential Postsynthetic Modification.

    PubMed

    Mitra, Shouvik; Sasmal, Himadri Sekhar; Kundu, Tanay; Kandambeth, Sharath; Illath, Kavya; Díaz Díaz, David; Banerjee, Rahul

    2017-03-29

    Covalent organic nanosheets (CONs) have emerged as a new class of functional two-dimensional (2D) porous organic polymeric materials with a high accessible surface, diverse functionality, and chemical stability. They could become versatile candidates for targeted drug delivery. Despite their many advantages, there are limitations to their use for target specific drug delivery. We anticipated that these drawbacks could be overturned by judicious postsynthetic modification steps to use CONs for targeted drug delivery. The postsynthetic modification would not only produce the desired functionality, it would also help to exfoliate to CONs as well. In order to meet this requirement, we have developed a facile, salt-mediated synthesis of covalent organic frameworks (COFs) in the presence of p-toluenesulfonic acid (PTSA). The COFs were subjected to sequential postsynthetic modifications to yield functionalized targeted CONs for targeted delivery of 5-fluorouracil to breast cancer cells. This postsynthetic modification resulted in simultaneous chemical delamination and functionalization to targeted CONs. Targeted CONs showed sustained release of the drug to the cancer cells through receptor-mediated endocytosis, which led to cancer cell death via apoptosis. Considering the easy and facile COF synthesis, functionality based postsynthetic modifications, and chemical delamination to CONs for potential advantageous targeted drug delivery, this process can have a significant impact in biomedical applications.

  5. Analyses of muscular dystrophy and Con A deficiency traits in testcross progeny of chickens.

    PubMed

    Kline, K; Sanders, B G

    1984-01-01

    Hereditary muscular dystrophic chickens of the Storrs strain possess two genetic disorders, muscular dystrophy (MD) and a deficient concanavalin A (Con A), a T-cell mitogen, mediated splenic lymphocyte blastogenic response. A possible amelioration of the MD phenotype in MD chickens expressing normal Con A was postulated on the basis of progeny segregating for these two traits in F2 genetic analyses. To test this possibility, testcross progeny were examined for segregation of MD and Con A deficiency traits, and for the degree of muscle destruction and Con A deficiency. The data show both traits to be inherited independently as autosomal recessive traits, and do not support any phenotypic modifications occurring in chickens expressing MD with normal Con A. In the testcross progeny, the Con A deficiency disorder is equally deficient in normal and MD progeny, and the degree of muscle destruction as measured by serum creatine phosphokinase levels is equally great in MD chickens with or without the Con A deficiency trait. The reduced numbers of MD chickens in the testcross progeny can be accounted for by chance and probably reflect losses during in ovo development.

  6. Abundancias químicas de estrellas de Mercurio-Manganeso obtenidas con espectros EBASIM

    NASA Astrophysics Data System (ADS)

    Pintado, O. I.; Adelman, S. J.

    Se determinan las abundancias químicas de estrellas de HgMn usando espectros obtenidos con EBASIM en CASLEO en un rango de longitud de onda comprendido entre los 400 y 890 nm. Los valores iniciales de temperatura efectiva y gravedad superficial se calculan con la fotometría uvbyβ. Las abundancias se calculan usando WIDTH9 y SYNTHE. Los resultados se comparan análisis realizados por los autores usando espectros obtenidos con el espectrógrado REOSC del CASLEO, el espectrógrafo echelle del Telescopio Anglo-Australiano y el espectrógrafo Coudé del Dominion Astrophysical Observatory.

  7. Manejo de riesgo (Risk Management). ERIC Digest.

    ERIC Educational Resources Information Center

    Gaustad, Joan

    The ordinary conduct of school business is accompanied today by risks that were rare or unknown a few decades ago. This ERIC Digest in Spanish discusses how risk management, a concept long used by corporate decision makers, can help school boards and administrators conserve their districts' assets. Risk management is a coordinated effort to…

  8. Photoelectron spectroscopy and density functional theory study of ConO- (n = 1-3)

    NASA Astrophysics Data System (ADS)

    Li, Ren-Zhong; Liang, Jun; Xu, Xi-Ling; Xu, Hong-Guang; Zheng, Wei-Jun

    2013-06-01

    ConO- (n = 1-3) clusters were investigated with photoelectron spectroscopy and density functional calculations. The vertical detachment energies (VDEs) of ConO- (n = 1-3) were measured to be 1.54 ± 0.04, 1.43 ± 0.08, and 1.42 ± 0.08 eV respectively from their photoelectron spectra. The electron affinity and term energy of CoO were determined to be 1.54 ± 0.04 eV and 0.31 ± 0.04 eV respectively based on the vibrationally resolved photoelectron spectrum of CoO- and theoretical calculations. The structures of ConO- (n = 1-3) were determined by comparison of photoelectron experiments and calculations. The analysis of molecular orbitals shows that the HOMOs of ConO- (n = 1-3) cluster anions are mainly localized on the Co atoms.

  9. The International Consortium for the Investigation of Renal Malignancies (I-ConFIRM)

    Cancer.gov

    The International Consortium for the Investigation of Renal Malignancies (I-ConFIRM) was formed to promote international, multidisciplinary collaborations to advance our understanding of the etiology and outcomes of kidney cancer.

  10. iCon-TMA for control and quantitation of immunohistochemistry and in situ molecular pathology analysis.

    PubMed

    Petersen, Iver; Blind, Christiane; Koepenik, Axel; Dietel, Manfred; Krenn, Veit

    2007-01-01

    Reliable assessment of in situ pathology analyses like immunohistochemistry, RNA in situ hybridization, and FISH are critically important in diagnosis and treatment decisions. We describe the development of small tissue microarrays (TMA) for the internal control and quantitation of these techniques, the iCon-TMA. In its simple variant, these iCon-TMA (abbreviated from internal control TMA) consist of 2 tissue cylinders, one being clearly positive and the other clearly negative for a specific marker. In its more elaborate format, the iCon-TMAs carry additional tissue spots providing a scale for quantitatively assessable markers, e.g. representing scores of negative, weak, moderate, or strong positivity. The specimen with the yet unknown reactivity is then applied to the iCon-TMA section, and both are simultaneously processed and analyzed, thus providing a convenient measure for in situ quality control and quantitation.

  11. Characterization of the effector cells in Con A-induced cytotoxicity against HEp 2 tumour targets.

    PubMed

    Pócsik, E; González-Cabello, R; Benedek, K; Perl, A; Láng, I; Gergely, P

    1983-01-01

    Con A-induced cytotoxic activity of human lymphocyte subpopulations obtained by cell fractionation procedures was studied in a test system using human epipharynx carcinoma cells (HEp 2) as targets. Only T lymphocytes were cytotoxic, non-T cells exerted no cytotoxic activity, but enhanced the adherence of the tumour cells. Tnon-G lymphocytes (Fc-receptor negative T cells) were more active than TG cells (Fc-receptor-positive T cells) in mediating the Con A-induced cytotoxic reaction.

  12. SLUDGE PARTICLE SEPAPATION EFFICIENCIES DURING SETTLER TANK RETRIEVAL INTO SCS-CON-230

    SciTech Connect

    DEARING JI; EPSTEIN M; PLYS MG

    2009-07-16

    The purpose of this document is to release, into the Hanford Document Control System, FA1/0991, Sludge Particle Separation Efficiencies for the Rectangular SCS-CON-230 Container, by M. Epstein and M. G. Plys, Fauske & Associates, LLC, June 2009. The Sludge Treatment Project (STP) will retrieve sludge from the 105-K West Integrated Water Treatment System (IWTS) Settler Tanks and transfer it to container SCS-CON-230 using the Settler Tank Retrieval System (STRS). The sludge will enter the container through two distributors. The container will have a filtration system that is designed to minimize the overflow of sludge fines from the container to the basin. FAI/09-91 was performed to quantify the effect of the STRS on sludge distribution inside of and overflow out of SCS-CON-230. Selected results of the analysis and a system description are discussed. The principal result of the analysis is that the STRS filtration system reduces the overflow of sludge from SCS-CON-230 to the basin by roughly a factor of 10. Some turbidity can be expected in the center bay where the container is located. The exact amount of overflow and subsequent turbidity is dependent on the density of the sludge (which will vary with location in the Settler Tanks) and the thermal gradient between the SCS-CON-230 and the basin. Attachment A presents the full analytical results. These results are applicable specifically to SCS-CON-230 and the STRS filtration system's expected operating duty cycles.

  13. Sport Concussion Management Using Facebook: A Feasibility Study of an Innovative Adjunct "iCon".

    PubMed

    Ahmed, Osman Hassan; Schneiders, Anthony G; McCrory, Paul R; Sullivan, S John

    2017-04-01

      Sport concussion is currently the focus of much international attention. Innovative methods to assist athletic trainers in facilitating management after this injury need to be investigated.   To investigate the feasibility of using a Facebook concussion-management program termed iCon (interactive concussion management) to facilitate the safe return to play (RTP) of young persons after sport concussion.   Observational study.   Facebook group containing interactive elements, with moderation and support from trained health care professionals.   Eleven participants (n = 9 men, n = 2 women; range, 18 to 28 years old) completed the study.   The study was conducted over a 3-month period, with participant questionnaires administered preintervention and postintervention. The primary focus was on the qualitative experiences of the participants and the effect of iCon on their RTP. Usage data were also collected.   At the completion of the study, all participants (100%) stated that they would recommend an intervention such as iCon to others. Their supporting quotes all indicated that iCon has the potential to improve the management of concussion among this cohort. Most participants (n = 9, 82%) stated they were better informed with regard to their RTP due to participating in iCon.   This interactive adjunct to traditional concussion management was appreciated among this participant group, which indicates the feasibility of a future, larger study of iCon. Athletic trainers should consider the role that multimedia technologies may play in assisting with the management of sport concussion.

  14. Pros and cons: prospective predictors of marijuana use on a college campus.

    PubMed

    Elliott, Jennifer C; Carey, Kate B

    2013-03-01

    Marijuana use on college campuses is prevalent and associated with high rates of abuse and dependence. The Marijuana Decisional Balance (MDB) scales measure perceived pros and cons toward marijuana use. Evidence supports reliability and concurrent validity of these scales, but the predictive validity has not yet been assessed. The current study evaluated the prospective predictive validity of pros and cons scales for marijuana use, as well as explored predictive validity for marijuana problem indicators. Secondary analyses included test-retest reliability and internal consistency, to provide additional evidence of psychometric properties. A total of 149 college students (57% recent marijuana users, 77% lifetime users) participated in a baseline survey, then completed a second survey one month later. All provided data on marijuana pros and cons, as well as use status in the past month. Users at each time point reported on use frequency, problems, and disorder symptoms. In the month between assessments, 55% of the students used marijuana. Both pros and cons subscales prospectively predicted use status in the subsequent month, but not use frequency. Pros prospectively predicted marijuana problems and dependence symptoms at follow-up, and remained a significant predictor of later dependence symptoms even after controlling for baseline dependence symptoms. In contrast, pros only marginally predicted abuse. Cons did not predict problems, abuse, or dependence symptoms. Pros and cons showed strong test-retest reliability (rs = 0.80-0.85) and internal consistency (alphas = 0.92-0.95). In a college sample, pros and cons of marijuana use demonstrated stability over one month, and prospectively predicted use. Pros may also have utility in predicting problems and dependence potential on college campuses.

  15. SubCons: a new ensemble method for improved human subcellular localization predictions.

    PubMed

    Salvatore, M; Warholm, P; Shu, N; Basile, W; Elofsson, A

    2017-08-15

    Knowledge of the correct protein subcellular localization is necessary for understanding the function of a protein. Unfortunately large-scale experimental studies are limited in their accuracy. Therefore, the development of prediction methods has been limited by the amount of accurate experimental data. However, recently large-scale experimental studies have provided new data that can be used to evaluate the accuracy of subcellular predictions in human cells. Using this data we examined the performance of state of the art methods and developed SubCons, an ensemble method that combines four predictors using a Random Forest classifier. SubCons outperforms earlier methods in a dataset of proteins where two independent methods confirm the subcellular localization. Given nine subcellular localizations, SubCons achieves an F1-Score of 0.79 compared to 0.70 of the second best method. Furthermore, at a FPR of 1% the true positive rate (TPR) is over 58% for SubCons compared to less than 50% for the best individual predictor. SubCons is freely available as a webserver (http://subcons.bioinfo.se) and source code from https://bitbucket.org/salvatore_marco/subcons-web-server. The golden dataset as well is available from http://subcons.bioinfo.se/pred/download. arne@bioinfo.se. Supplementary data are available at Bioinformatics online.

  16. ConA-based glucose sensing using the long-lifetime azadioxatriangulenium fluorophore

    NASA Astrophysics Data System (ADS)

    Cummins, Brian; Simpson, Jonathan; Gryczynski, Zygmunt; Sørensen, Thomas Just; Laursen, Bo W.; Graham, Duncan; Birch, David; Coté, Gerard

    2014-02-01

    Fluorescent glucose sensing technologies have been identified as possible alternatives to current continuous glucose monitoring approaches. We have recently introduced a new, smart fluorescent ligand to overcome the traditional problems of ConA-based glucose sensors. For this assay to be translated into a continuous glucose monitoring device where both components are free in solution, the molecular weight of the smart fluorescent ligand must be increased. We have identified ovalbumin as a naturally-occurring glycoprotein that could serve as the core-component of a 2nd generation smart fluorescent ligand. It has a single asparagine residue that is capable of displaying an N-linked glycan and a similar isoelectric point to ConA. Thus, binding between ConA and ovalbumin can potentially be monovalent and sugar specific. This work is the preliminary implementation of fluorescently-labeled ovalbumin in the ConA-based assay. We conjugate the red-emitting, long-lifetime azadioxatriangulenium (ADOTA+) dye to ovalbumin, as ADOTA have many advantageous properties to track the equilibrium binding of the assay. The ADOTA-labeled ovalbumin is paired with Alexa Fluor 647-labeled ConA to create a Förster Resonance Energy Transfer (FRET) assay that is glucose dependent. The assay responds across the physiologically relevant glucose range (0-500 mg/dL) with increasing intensity from the ADOTA-ovalbumin, showing that the strategy may allow for the translation of the smart fluorescent ligand concept into a continuous glucose monitoring device.

  17. ConsPred: a rule-based (re-)annotation framework for prokaryotic genomes.

    PubMed

    Weinmaier, Thomas; Platzer, Alexander; Frank, Jeroen; Hellinger, Hans-Jörg; Tischler, Patrick; Rattei, Thomas

    2016-11-01

    The rapidly growing number of available prokaryotic genome sequences requires fully automated and high-quality software solutions for their initial and re-annotation. Here we present ConsPred, a prokaryotic genome annotation framework that performs intrinsic gene predictions, homology searches, predictions of non-coding genes as well as CRISPR repeats and integrates all evidence into a consensus annotation. ConsPred achieves comprehensive, high-quality annotations based on rules and priorities, similar to decision-making in manual curation and avoids conflicting predictions. Parameters controlling the annotation process are configurable by the user. ConsPred has been used in the institutions of the authors for longer than 5 years and can easily be extended and adapted to specific needs. The ConsPred algorithm for producing a consensus from the varying scores of multiple gene prediction programs approaches manual curation in accuracy. Its rule-based approach for choosing final predictions avoids overriding previous manual curations. ConsPred is implemented in Java, Perl and Shell and is freely available under the Creative Commons license as a stand-alone in-house pipeline or as an Amazon Machine Image for cloud computing, see https://sourceforge.net/projects/conspred/. thomas.rattei@univie.ac.atSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. ConTour: Data-Driven Exploration of Multi-Relational Datasets for Drug Discovery.

    PubMed

    Partl, Christian; Lex, Alexander; Streit, Marc; Strobelt, Hendrik; Wassermann, Anne-Mai; Pfister, Hanspeter; Schmalstieg, Dieter

    2014-12-01

    Large scale data analysis is nowadays a crucial part of drug discovery. Biologists and chemists need to quickly explore and evaluate potentially effective yet safe compounds based on many datasets that are in relationship with each other. However, there is a lack of tools that support them in these processes. To remedy this, we developed ConTour, an interactive visual analytics technique that enables the exploration of these complex, multi-relational datasets. At its core ConTour lists all items of each dataset in a column. Relationships between the columns are revealed through interaction: selecting one or multiple items in one column highlights and re-sorts the items in other columns. Filters based on relationships enable drilling down into the large data space. To identify interesting items in the first place, ConTour employs advanced sorting strategies, including strategies based on connectivity strength and uniqueness, as well as sorting based on item attributes. ConTour also introduces interactive nesting of columns, a powerful method to show the related items of a child column for each item in the parent column. Within the columns, ConTour shows rich attribute data about the items as well as information about the connection strengths to other datasets. Finally, ConTour provides a number of detail views, which can show items from multiple datasets and their associated data at the same time. We demonstrate the utility of our system in case studies conducted with a team of chemical biologists, who investigate the effects of chemical compounds on cells and need to understand the underlying mechanisms.

  19. A Con A- purified hydatid glycoprotein fraction effectively diagnoses human hydatidosis.

    PubMed

    Kamel, Manal M; Maher, Kesmat M; Rabia, Ibrahim; Helmy, Ahmed H; El-Adawi, Azza I; Mousa, Mousa A; Mahgoub, Abeer M

    2006-12-01

    Diagnosis and quantification of Echinococcus granulosus infection in man and animal hosts are centralized to feasible control. This study included 93 serum samples, 25 sure positive hydatid cases confirmed surgically, 7 suspected cases diagnosed by indirect haemagglutination IHA and 41 cases other parasitic infections (15 S. mansoni, 8 Fasciola, 7 Ascaris, 5 H. nana & 6 Ancylostoma) diagnosed by microscopic examination and were negative by ELISA and/or IHA for anti-hydatid antibody. Twenty negative serum samples served as healthy controls. Six types of hydatid fluid antigens (crude, host-free & Con-A purified) of human and camel origin were subjected to electrophoretic separation (SDS-PAGE) and immunoblotting (EITB). The anti-hydatid IgG was detected in sera of the different groups for evaluation of sensitivity, specificity and diagnostic efficacy of each type of antigens. Detection of circulating hydatid antigen (CAg) was performed using anti rabbit hyperimmune sera raised against Con-A purified either human or camel hydatid antigen. SDS-PAGE revealed several bands ranging from 55-185 kDa with 10 kDa band shared by all antigens. The specific bands revealed by EITB for Con-A purified camel and human antigens were at 80, 110 & 55, 110 kDa respectively. ELISA highest sensitivity (96.9%) was by using host-free Con-A purified glycoprotein fraction of human hydatid antigen. Highest specificity (98.4%) was recorded upon use of either Con-A purified camel or human antigen with 94.5% & 97.7% diagnostic efficacy respectively. Detection of circulating antigen by polyclonal antibodies against Con-A purified human hydatid antigen revealed 91.8% specificity.

  20. Physician Preparation for the American Board of Emergency Medicine ConCert Examination.

    PubMed

    Marco, Catherine A; Wahl, Robert P; Counselman, Francis L; Heller, Barry N; Kowalenko, Terry; Harvey, Anne L; Joldersma, Kevin B; Reisdorff, Earl J

    2016-02-01

    To maintain certification by the American Board of Emergency Medicine (ABEM), physicians are required to pass the Continuous Certification (ConCert) examination at least every 10 years. On the 2014 ConCert postexamination survey, ABEM sought to understand the manner in which ABEM diplomates prepared for the test and to identify associations between test preparation approaches and performance on the ConCert examination. This was a cross-sectional survey study. The survey was administered at the end of the 2014 ConCert examination. Analyses included chi-square and linear regression to determine the association of preparation methods with performance. Of the 2,431 on-time test-takers, 2,338 (96.2%) were included. The most commonly used study approach was the review of written materials designed for test preparation (1,585; 67.8%), followed by an online training course (1,006; 43.0%). There were 758 (32.4%) physicians who took a single onsite board review course, while 41 (1.8%) took two or more onsite courses. Most physicians (1,611; 68.9%) spent over 35 hours preparing for the ConCert examination. The study method that was most associated with favorable test scores was the review of written materials designed for test preparation (p < 0.001). Attending an onsite preparation course was associated with poorer performance (p < 0.001). There was a significant association between no additional preparation and failing the examination (chi-square with Yates correction; p = 0.001). A substantial majority (97.8%) of physicians taking the 2014 ABEM ConCert examination prepared for it. The majority of physicians used written materials specifically designed for test preparation. Reviewing written materials designed for test preparation was associated with the highest performance. © 2016 by the Society for Academic Emergency Medicine.

  1. Soluciones analiticas AL problema de jets con velocidad de eyeccion variable EN EL tiempo.

    NASA Astrophysics Data System (ADS)

    Canto, J.; Raga, A. C.; D'Alessio, P.

    1998-11-01

    Se presenta un nuevo metodo que permite resolver de manera exacta y analitica las ecuaciones que describen un jet hipersonico con velocidad de eyeccion variable en el tiempo. El metodo se basa en consideraciones sencillas de conservacion de momento para las superficies de trabajo que se forman en el interior del jet. Como ejemplo, se presentan soluciones para jets con variacion sinusoidal en la velocidad de eyeccion, y tambien para el caso de un incremento lineal en el tiempo. Estas soluciones analiticas tienen una clara aplicacion en la interpretacion de las observaciones de jets asociados a objetos Herbig-Haro.

  2. GeConT 2: gene context analysis for orthologous proteins, conserved domains and metabolic pathways.

    PubMed

    Martinez-Guerrero, C E; Ciria, R; Abreu-Goodger, C; Moreno-Hagelsieb, G; Merino, E

    2008-07-01

    The Gene Context Tool (GeConT) allows users to visualize the genomic context of a gene or a group of genes and their orthologous relationships within fully sequenced bacterial genomes. The new version of the server incorporates information from the COG, Pfam and KEGG databases, allowing users to have an integrated graphical representation of the function of genes at multiple levels, their phylogenetic distribution and their genomic context. The sequence of any of the genes can be easily retrieved, as well as the 5' or 3' regulatory regions, greatly facilitating further types of analysis. GeConT 2 is available at: http://bioinfo.ibt.unam.mx/gecont.

  3. Reversible hydrogen adsorption on Co/N4 cluster embedded in graphene: The role of charge manipulation

    NASA Astrophysics Data System (ADS)

    Omidvar, Akbar

    2017-08-01

    Electrical charging of Co/N4 cluster embedded in graphene (Co/N4/G) is proposed as an approach for electrocatalytically switchable hydrogen adsorption. Using density functional theory, we found that the H2 molecule is weakly adsorbed on the uncharged Co/N4/G cluster. Our results show that the adsorption energy of hydrogen molecule on Co/N4/G cluster is significantly increased by introducing extra positive charges into the cluster. Once the charges are removed, H2 molecule spontaneously desorb from the Co/N4/G absorbent. Therefore, this approach promises both facile reversibility and tunable kinetics without the need of specific catalysts. Our study indicates that the Co/N4/G nanomaterial is excellent absorbent for controllable and reversible adsorption and release of H2.

  4. Impact of the ConRed program on different cyberbulling roles.

    PubMed

    Del Rey, Rosario; Casas, José A; Ortega, Rosario

    2016-01-01

    This article presents results from an evaluation of the ConRed cyberbullying intervention program. The program's impacts were separately determined for the different roles within cyberbullying that students can take, i.e., cyber-victims, cyber-bullies, cyber-bully/victims, and bystanders. The ConRed program is a theory-driven program designed to prevent cyberbullying and improve cyberbullying coping skills. It involves students, teachers, and families. During a 3-month period, external experts conducted eight training sessions with students, two with teachers and one with families. ConRed was evaluated through a quasi-experimental design, in which students from three secondary schools were separated into experimental and control groups. The sample comprised 875 students, aged between 11 and 19 years. More students (n = 586) were allocated to the experimental groups at the specific insistence of the management of all schools; the remainder (n = 289) formed the control. Repeated measures MANOVA showed that cyber victims, cyber aggressors and cyberbully/victims reduced their involvement in cyberbullying. Moreover, cyber-victims and bystanders adjusted their perceptions about their control of personal information on the Internet, and cyber aggressors and bystanders reduced their Internet dependence. The ConRed program had stronger effects on male participants, especially in heightening their affective empathy. © 2015 Wiley Periodicals, Inc.

  5. Mandated Mental Health Insurance: A Complex Case of Pros and Cons. Human Resources Series.

    ERIC Educational Resources Information Center

    Paterson, Andrea

    1986-01-01

    The pros and cons of state laws mandating mental health insurance are discussed in this report. The history of a 1985 Supreme Court case which held that states could mandate mental health benefits introduces the report. In an overview of the issue, the long-standing argument between the insurance industry and the mental health establishment is…

  6. [(Con)natal teeth: a role for maternity care and dental care].

    PubMed

    Gambon, D L

    2014-02-01

    A baby was referred to a dentist by an obstetrician 18 days after birth in connection with the presence of 2 teeth in the mandibula which resembled incisors. It appeared to be a case of 2 (con)natal teeth with a high degree of mobility. Dental treatment in the form of 2 extractions was necessary.

  7. Non Invasive Biomedical Analysis - Breath Networking Session at PittCon 2011, Atlanta, Georgia

    EPA Science Inventory

    This was the second year that our breath colleagues organized a networking session at the Pittsburgh Conference and Exposition or ''PittCon'' (http://www.pincon.org/).This time it was called "Non-invasive Biomedical Analysis" to broaden the scope a bit, but the primary focus rema...

  8. Silence, Metaperformance, and Communication in Pedro Almodóvar's "Hable con ella"

    ERIC Educational Resources Information Center

    Fellie, Maria C.

    2016-01-01

    Many scenes in Pedro Almodóvar's "Hable con ella" (2002) include shots of metaperformances such as silent films, dances, television shows, concerts, and bullfights. Spectators often observe passive characters who are in turn observing. By presenting these performances within cinematic performance, Almodóvar highlights our role as viewers…

  9. Wilderness for science: pros and cons of using wilderness areas for biological research

    Treesearch

    Diana L. Six; Paul Alaback; Robert A. Winfree; Delia Snyder; Anne Hagele

    2000-01-01

    Research is one of the intended purposes of wilderness. The Wilderness Act states that “wilderness may contain ecological, geological, or other features of scientific, educational, scenic, or historical value.” This session specifically focuses on the pros and cons of conducting research in wilderness.

  10. Are You Ready to Go Digital?: The Pros and Cons of Electronic Portfolio Development

    ERIC Educational Resources Information Center

    Heath, Marilyn

    2005-01-01

    There is an increasing need for educators to have professional portfolios, which are considered to be authentic tools for evaluating the knowledge, skill, beliefs and attitudes of prospective educators. Electronic portfolios are gaining in popularity and their relative pros and cons are examined.

  11. Silence, Metaperformance, and Communication in Pedro Almodóvar's "Hable con ella"

    ERIC Educational Resources Information Center

    Fellie, Maria C.

    2016-01-01

    Many scenes in Pedro Almodóvar's "Hable con ella" (2002) include shots of metaperformances such as silent films, dances, television shows, concerts, and bullfights. Spectators often observe passive characters who are in turn observing. By presenting these performances within cinematic performance, Almodóvar highlights our role as viewers…

  12. Non Invasive Biomedical Analysis - Breath Networking Session at PittCon 2011, Atlanta, Georgia

    EPA Science Inventory

    This was the second year that our breath colleagues organized a networking session at the Pittsburgh Conference and Exposition or ''PittCon'' (http://www.pincon.org/).This time it was called "Non-invasive Biomedical Analysis" to broaden the scope a bit, but the primary focus rema...

  13. End-User Use of Data Base Query Language: Pros and Cons.

    ERIC Educational Resources Information Center

    Nicholes, Walter

    1988-01-01

    Man-machine interface, the concept of a computer "query," a review of database technology, and a description of the use of query languages at Brigham Young University are discussed. The pros and cons of end-user use of database query languages are explored. (Author/MLW)

  14. Mandated Mental Health Insurance: A Complex Case of Pros and Cons. Human Resources Series.

    ERIC Educational Resources Information Center

    Paterson, Andrea

    1986-01-01

    The pros and cons of state laws mandating mental health insurance are discussed in this report. The history of a 1985 Supreme Court case which held that states could mandate mental health benefits introduces the report. In an overview of the issue, the long-standing argument between the insurance industry and the mental health establishment is…

  15. Are You Ready to Go Digital?: The Pros and Cons of Electronic Portfolio Development

    ERIC Educational Resources Information Center

    Heath, Marilyn

    2005-01-01

    There is an increasing need for educators to have professional portfolios, which are considered to be authentic tools for evaluating the knowledge, skill, beliefs and attitudes of prospective educators. Electronic portfolios are gaining in popularity and their relative pros and cons are examined.

  16. CHILES Con Pol: An ultra-deep JVLA survey probing galaxy evolution and cosmic magnetism

    NASA Astrophysics Data System (ADS)

    Hales, Christopher A.; Momjian, Emmanuel; van Gorkom, Jacqueline; Rupen, Michael P.; Greiner, Maksim; Ensslin, Torsten A.; Bonzini, Margherita; Padovani, Paolo; Harrison, Ian; Brown, Michael L.; Gim, Hansung; Yun, Min S.; Maddox, Natasha; Stewart, Adam; Fender, Rob P.; Tremou, Evangelia; Chomiuk, Laura; Peters, Charee; Wilcots, Eric M.; Lazio, Joseph

    2015-08-01

    We are undertaking a 1000 hour campaign with the Karl G. Jansky VLA to survey 0.2 square degrees of the COSMOS field in full polarization continuum at 1.4 GHz. Our observations are part of a joint program with the spectral line COSMOS HI Large Extragalactic Survey (CHILES). When complete, we expect our CHILES Continuum Polarization (CHILES Con Pol) survey to reach an SKA-era sensitivity of 500 nJy per 4 arcsecond resolving beam, the deepest view of the radio sky yet. CHILES Con Pol will open new and fertile parameter space, with sensitivity to star formation rates of 10 Msun per year out to an unprecedented redshift of z=2, and ultra-luminous infrared galaxies and sub-millimeter galaxies out to redshifts of z=8 and beyond. This rich resource will extend the utility of radio band studies beyond the usual radio quasar and radio galaxy populations, opening sensitivity to the starforming and radio-quiet AGN populations that form the bulk of extragalactic sources detected in the optical, X-ray, and infrared bands. In this talk I will outline the key science of CHILES Con Pol, including galaxy evolution and novel measurements of intergalactic magnetic fields. I will present initial results from the first 180 hours of the survey and describe our forthcoming Data Release 1. I invite the astronomical community to consider unique science that can be pursued with CHILES Con Pol radio data.

  17. Pros & Cons of Using Blackboard Collaborate for Blended Learning on Students' Learning Outcomes

    ERIC Educational Resources Information Center

    Hamad, Mona M.

    2017-01-01

    Blackboard Collaborate was introduced to King Khalid University recently in the last decade; instructors and students were trained to use it in an effective way. The objective of this study is to find pros and cons of using Blackboard Collaborate for Blended Learning and its effect on students' learning outcomes. The researcher used the…

  18. "Con todo mi corazón": Mentoring Latinas in Educational Leadership Doctoral Programs

    ERIC Educational Resources Information Center

    Rodríguez, Mariela A.

    2016-01-01

    Personal narrative essays were used to analyze the experiences of four Latina doctoral students who completed their first year in an educational leadership doctoral program in a Hispanic-Serving Institution (HSI) in the southwestern U.S. Four themes emerged from their "testimonios" 1) "Con todo el corazón"; 2) "Somos como…

  19. "Con todo mi corazón": Mentoring Latinas in Educational Leadership Doctoral Programs

    ERIC Educational Resources Information Center

    Rodríguez, Mariela A.

    2016-01-01

    Personal narrative essays were used to analyze the experiences of four Latina doctoral students who completed their first year in an educational leadership doctoral program in a Hispanic-Serving Institution (HSI) in the southwestern U.S. Four themes emerged from their "testimonios" 1) "Con todo el corazón"; 2) "Somos como…

  20. The Con Edison Emergency Child Care Plan for Management Employees: Summary Plan Description.

    ERIC Educational Resources Information Center

    Consolidated Edison Co., Brooklyn, NY.

    This summary plan description offers guidelines for participation in a pilot program that provides short-term emergency care for children of Con Edison managers who are under 13 years old. The plan offers professional, in-home child care that can be used when usual arrangements have collapsed. The summary plan description addresses the following…

  1. ConMap: Investigating New Computer-Based Approaches to Assessing Conceptual Knowledge Structure in Physics.

    ERIC Educational Resources Information Center

    Beatty, Ian D.

    There is a growing consensus among educational researchers that traditional problem-based assessments are not effective tools for diagnosing a student's knowledge state and for guiding pedagogical intervention, and that new tools grounded in the results of cognitive science research are needed. The ConMap ("Conceptual Mapping") project, described…

  2. Optimizing Electrospray Interfaces Using Slowly Diverging Conical Duct (ConDuct) Electrodes

    PubMed Central

    Krutchinsky, Andrew N.; Padovan, Júlio C.; Cohen, Herbert; Chait, Brian T.

    2015-01-01

    We demonstrate that the efficiency of ion transmission from atmosphere to vacuum through stainless steel electrodes that contain slowly divergent conical duct (ConDuct) channels can be close to 100%. Here, we explore the properties of 2.5 cm long electrodes with angles of divergence of 0°, 1°, 2°, 3°, 5°, 8°, 13°, and 21°, respectively. The ion transmission efficiency was observed to jump from 10–20% for the 0° (straight) channels to 90–95% for channels with an angle of divergence as small as 1°. Furthermore, the 2–3° ConDuct electrodes produced extraordinarily low divergence ion beams that propagated in a laser-like fashion over long distances in vacuum. To take advantage of these newly discovered properties, we constructed a novel atmosphere-to-vacuum ion interface utilizing a 2° ConDuct as an inlet electrode and compared its ion transmission efficiency with that of the interface used in the commercial (Thermo) Velos Orbitrap and Q Exactive mass spectrometers. We observed that the ConDuct interface transmitted up to 17 times more ions than the commercial reference interface and also yielded improved signal-to-noise mass spectra of peptides. We infer from these results that the performance of many current atmosphere-tovacuum interfaces utilizing metal capillaries can be substantially improved by replacing them with 1° or 2° metal ConDuct electrodes, which should preserve the convenience of supplying ion desolvation energy by heating the electrode while greatly increasing the efficiency of ion transmission into the mass spectrometer. PMID:25667060

  3. Optimizing Electrospray Interfaces Using Slowly Diverging Conical Duct (ConDuct) Electrodes

    NASA Astrophysics Data System (ADS)

    Krutchinsky, Andrew N.; Padovan, Júlio C.; Cohen, Herbert; Chait, Brian T.

    2015-04-01

    We demonstrate that the efficiency of ion transmission from atmosphere to vacuum through stainless steel electrodes that contain slowly divergent conical duct (ConDuct) channels can be close to 100%. Here, we explore the properties of 2.5-cm-long electrodes with angles of divergence of 0°, 1°, 2°, 3°, 5°, 8°, 13°, and 21°, respectively. The ion transmission efficiency was observed to jump from 10-20% for the 0° (straight) channels to 90-95% for channels with an angle of divergence as small as 1°. Furthermore, the 2-3° ConDuct electrodes produced extraordinarily low divergence ion beams that propagated in a laser-like fashion over long distances in vacuum. To take advantage of these newly discovered properties, we constructed a novel atmosphere-to-vacuum ion interface utilizing a 2° ConDuct as an inlet electrode and compared its ion transmission efficiency with that of the interface used in the commercial (Thermo Fisher Scientific, San Jose, CA, USA) Velos Orbitrap and Q Exactive mass spectrometers. We observed that the ConDuct interface transmitted up to 17 times more ions than the commercial reference interface and also yielded improved signal-to-noise mass spectra of peptides. We infer from these results that the performance of many current atmosphere-to-vacuum interfaces utilizing metal capillaries can be substantially improved by replacing them with 1° or 2° metal ConDuct electrodes, which should preserve the convenience of supplying ion desolvation energy by heating the electrode while greatly increasing the efficiency of ion transmission into the mass spectrometer.

  4. ConMap - a new spatial data mining framework for terrain based digital soil mapping

    NASA Astrophysics Data System (ADS)

    Behrens, T.; Schmidt, K.; Scholten, T.

    2009-04-01

    In this talk, we present a new digital terrain analysis framework for digital soil mapping based on spatial data mining, referred to as the contextual elevation mapping (ConMap). Aiming at integrating different scales, which can be important at landscape scale level due to interrelations of topo- and climofunctions, it comprises local surface function approximations in terms of standard local terrain attributes as well as the incorporation of geomorphic arrangements within larger neighborhoods. In contrast to common digital terrain analysis of deriving multiple terrain attributes, ConMap is based on elevation differences from the center pixel to each pixel in a local neighborhood. These differences are then used as predictors in machine learning approaches such as Random Forests. Thus, it is not necessary to choose a specific set of terrain attributes. Additionally, possibly unknown surface functions can be taken into account, as well as larger geomorphic settings. We applied and validated the framework by predicting topsoil silt content for an area of 1150 km2 in Rhineland-Palatinate and Hesse, Germany, based on 342 samples, a 20 m resolution DEM, and neighborhood sizes up to 12 km. Cross-validation R2 values increase from 0.15 for standard digital terrain analysis to 0.61 using ConMap. This effect is due to a spatial trend in the data. As ConMap is able to map this trend and as it is based on the pedological concept of integrating scales it can be seen as a new entry to spatial prediction approaches such as Kriging or Geographically Weighted Regression. We conclude that ConMap shows a great potential for future digital soil mapping studies.

  5. BeadCons: detection of nucleic acid sequences by flow cytometry.

    PubMed

    Horejsh, Douglas; Martini, Federico; Capobianchi, Maria Rosaria

    2005-11-01

    Molecular beacons are single-stranded nucleic acid structures with a terminal fluorophore and a distal, terminal quencher. These molecules are typically used in real-time PCR assays, but have also been conjugated with solid matrices. This unit describes protocols related to molecular beacon-conjugated beads (BeadCons), whose specific hybridization with complementary target sequences can be resolved by cytometry. Assay sensitivity is achieved through the concentration of fluorescence signal on discrete particles. By using molecular beacons with different fluorophores and microspheres of different sizes, it is possible to construct a fluid array system with each bead corresponding to a specific target nucleic acid. Methods are presented for the design, construction, and use of BeadCons for the specific, multiplexed detection of unlabeled nucleic acids in solution. The use of bead-based detection methods will likely lead to the design of new multiplex molecular diagnostic tools.

  6. GenomeCons: a web server for manipulating multiple genome sequence alignments and their consensus sequences.

    PubMed

    Sato, Tetsuya; Suyama, Mikita

    2015-04-15

    Genome sequence alignments provide valuable information on many aspects of molecular biological processes. In this study, we developed a web server, GenomeCons, for manipulating multiple genome sequence alignments and their consensus sequences for high-throughput genome sequence analyses. This server facilitates the visual inspection of multiple genome sequence alignments for a set of genomic intervals at a time. This allows the user to examine how these sites are evolutionarily conserved over time for their functional importance. The server also reports consensus sequences for the input genomic intervals, which can be applied to downstream analyses such as the identification of common motifs in the regions determined by ChIP-seq experiments. GenomeCons is freely accessible at http://bioinfo.sls.kyushu-u.ac.jp/genomecons/ mikita@bioreg.kyushu-u.ac.jp. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  7. Air Traffic Management Technology Demonstration-1 Concept of Operations (ATD-1 ConOps)

    NASA Technical Reports Server (NTRS)

    Baxley, Brian T.; Johnson, William C.; Swenson, Harry; Robinson, John E.; Prevot, Thomas; Callantine, Todd; Scardina, John; Greene, Michael

    2012-01-01

    The operational goal of the ATD-1 ConOps is to enable aircraft, using their onboard FMS capabilities, to fly Optimized Profile Descents (OPDs) from cruise to the runway threshold at a high-density airport, at a high throughput rate, using primarily speed control to maintain in-trail separation and the arrival schedule. The three technologies in the ATD-1 ConOps achieve this by calculating a precise arrival schedule, using controller decision support tools to provide terminal controllers with speeds for aircraft to fly to meet times at a particular meter points, and onboard software providing flight crews with speeds for the aircraft to fly to achieve a particular spacing behind preceding aircraft.

  8. GeConT 2: gene context analysis for orthologous proteins, conserved domains and metabolic pathways

    PubMed Central

    Martinez-Guerrero, C. E.; Ciria, R.; Abreu-Goodger, C.; Moreno-Hagelsieb, G.; Merino, E.

    2008-01-01

    The Gene Context Tool (GeConT) allows users to visualize the genomic context of a gene or a group of genes and their orthologous relationships within fully sequenced bacterial genomes. The new version of the server incorporates information from the COG, Pfam and KEGG databases, allowing users to have an integrated graphical representation of the function of genes at multiple levels, their phylogenetic distribution and their genomic context. The sequence of any of the genes can be easily retrieved, as well as the 5′ or 3′ regulatory regions, greatly facilitating further types of analysis. GeConT 2 is available at: http://bioinfo.ibt.unam.mx/gecont. PMID:18511460

  9. Propiedades biomecánicas de la membrana limitante interna tras recibir tratamiento intravítreo con ocriplasmina.

    PubMed

    Vielmuth, Franziska; Schumann, Ricarda G; Spindler, Volker; Wolf, Armin; Scheler, Renate; Mayer, Wolfgang J; Henrich, Paul B; Haritoglou, Christos

    2017-01-01

    Objetivo: Evaluar la rigidez de la membrana limitante interna (MLI) humana y evaluar los posibles cambios de las propiedades mecánicas tras administrar una inyección intravítrea de ocriplasmina para tratar la tracción vitreomacular. Métodos: Este estudio se compone de una serie de casos intervencionales y comparativos de 12 muestras de MLI extraídas mediante cirugía y obtenidas de forma consecutiva de 9 ojos de 9 pacientes después de someterse sin éxito a vitreólisis farmacológica con ocriplasmina. Durante el mismo periodo de tiempo, 16 muestras de otros 13 ojos sin tratamiento con ocriplasmina se obtuvieron mediante vitrectomía y sirvieron como controles. Todos los pacientes presentaron agujeros maculares o tracción vitreomacular y se sometieron a vitrectomía con disección de la MLI tanto con tinción con azul brillante (AB) como sin ella. Todas las muestras se analizaron con un microscopio de fuerza atómica con imágenes de las regiones de 25 × 25 μm. En todas las muestras, se analizaron tanto la parte de la retina como la del vítreo de la MLI. Resultados: La microscopia de fuerza atómica no reveló diferencias significativas en cuanto a elasticidad de las muestras de MLI extraídas de ojos con o sin tratamiento con ocriplasmina. Las áreas onduladas de la parte de la retina presentaron una mayor rigidez que la parte del vítreo de la MLI. La cartografía topográfica tanto de la parte del vítreo como de la retina de la MLI no mostró ninguna alteración aparente de la morfología en ojos tratados con ocriplasmina en comparación con los ojos no tratados. La tinción con azul brillante conllevó un aumento de la rigidez tisular. Conclusiones: Las inyecciones intravítreas de ocriplasmina no varían las propiedades biomecánicas de la MLI humana. No existen pruebas de un posible efecto enzimático que interfiera con la rigidez de esta membrana basal. © 2017 S. Karger AG, Basel.

  10. Extreme lateral lumbar interbody fusion: Do the cons outweigh the pros?

    PubMed Central

    Epstein, Nancy E.

    2016-01-01

    Background: Major factors prompted the development of minimally invasive (MIS) extreme lateral interbody fusion (XLIF; NuVasive Inc., San Diego, CA, USE) for the thoracic/lumbar spine. These include providing interbody stabilization and indirect neural decompression while avoiding major visceral/vessel injury as seen with anterior lumbar interbody fusion (ALIF), and to avert trauma to paraspinal muscles/facet joints found with transforaminal lumbar interbody fusion (TLIF), posterior lumbar interbody fusion (PLIF), and posterior-lateral fusion techniques (PLF). Although anticipated pros of MIS XLIF included reduced blood loss, operative time, and length of stay (LOS), they also included, higher fusion, and lower infection rates. Unanticipated cons, however, included increased morbidity/mortality rates. Methods: We assessed the pros and cons (e.g., risks, complications, comparable value/superiority/inferiority, morbidity/mortality) of MIS XLIF vs. ALIF, TLIF, PLIF, and PLF. Results: Pros of XLIF included various biomechanical and technical surgical advantages, along with multiple cons vs. ALIF, TLIF, PLIF, and PLF. For example, XLIF correlated with a considerably higher frequency of major neurological deficits vs. other constructs; plexus injuries 13.28%, sensory deficits 0–75% (permanent in 62.5%), motor deficits 0.7–33.6%, and anterior thigh pain 12.5–25%. XLIF also disproportionately contributed to other major morbidity/mortality; sympathectomy, major vascular injuries (some life-ending others life-threatening), bowel perforations, and seromas. Furthermore, multiple studies documented no superiority, and the potential inferiority of XLIF vs. ALIF, TLIF, PLIF, and PLF. Conclusion: Reviewing the pros of XLIF (e.g. radiographic, technical, biomechanical) vs. the cons (inferiority, increased morbidity/mortality) vs. ALIF, TLIF, PLIF, and PLF, we question whether XLIF should remain part of the lumbar spinal surgical armamentarium. PMID:27843688

  11. Simulaciones numéricas hidrodinámicas con formación estelar

    NASA Astrophysics Data System (ADS)

    Volpe, M. G.; Merchan, M.; García Lambas, D.

    Se realizan simulaciones numéricas cosmológicas utilizando el código HYDRA modificado para incluir formación estelar. A partir de éstas, se estiman diferentes parámetros observacionales como la relación Tully- Fisher, función de luminosidad y la tasa de formación estelar en función del redshift. Estos resultados son comparados con datos observacionales de diferentes autores.

  12. The pros and cons of endovascular and open surgical treatments for patients with acute limb ischemia.

    PubMed

    Branco, B C; Montero-Baker, M F; Mills, J L

    2015-06-01

    The present review addresses the pros and cons of the current, wide variety of therapeutic options available for the treatment of acute limb ischemia (ALI). Despite five prospective randomized controlled trials comparing catheter directed thrombolysis and open surgical revascularization, no single treatment strategy can yet be considered optimal for patients with ALI. This report includes 20 years of published data to evaluate the efficacy and safety profile of thrombolytic agents and adjunctive endovascular techniques when compared to open surgical revascularization.

  13. Precisión de las velocidades radiales obtenidas con el REOSC

    NASA Astrophysics Data System (ADS)

    González, J. F.; Lapasset, E.

    Complementando una línea de trabajo iniciada con anterioridad discutimos la estabilidad del espectrógrafo REOSC de CASLEO en DC para la medición de velocidades radiales en base al análisis de observaciones realizadas en enero y abril de 1997. En esas oportunidades obtuvimos 26 espectros de estrellas patrones y 27 espectros de 3 estrellas usadas como estrellas de referencia en nuestro programa de cúmulos abiertos. Además tomamos 26 espectros de crepúsculo con el telescopio en posiciones cubriendo el rango H=-4,+4 y δ =-90,+30. Mediante correlaciones cruzadas derivamos la velocidad de 19 órdenes en cada uno de estos espectros. En base a un análisis estadístico de los datos obtenidos discutimos la contribución de los distintos factores que afectan a la dispersión de lectura observada. En particular, la flexión del instrumento no introduciría errores significativos cuando se observa con masas de aire menores que 2.0. La dispersión de los valores de velocidad medidos para espectros de alta relación S/N de una misma estrella resultó del orden de 0.5 km/s. La comparación con los valores de velocidad publicados por distintos autores para las estrellas patrones no permite distinguir ninguna diferencia sistemática apreciable de las velocidades de CASLEO, siendo la media cuadrática de los residuos del orden de 1.0 km/s.

  14. NASA KSC/AFRL Reusable Booster System (RBS) Concept of Operations (ConOps)

    NASA Technical Reports Server (NTRS)

    Zeno, Dnany; Mosteller, Ted; McCleskey, Carey; Jhnson, Robert; Hopkins, Jason; Miller, Thomas

    2010-01-01

    This slide presentation reviews the study and findings of the study on the Concept of Operations (ConOps) for Reusable Booster System (RBS) centering on rapid turnaround and launch of a two-stage partially reusable payload delivery system (i.e., 8 hours between launches). The study was to develop rapid ground processing (aircraft like concepts) and identify areas for follow-on study, technology needs, and proof-of-concept demonstrations.

  15. Nuevas observaciones de 3C10 con el VLA*: estudio de la expansión

    NASA Astrophysics Data System (ADS)

    Reynoso, E. M.; Moffett, D. A.:; Dubner, G. M.; Giacani, E. B.; Reynolds, S. P.; Goss, W. M.; Dickel, J.

    Se presentan nuevos resultados sobre la expansión del remanente de la supernova de Tycho a lo largo de un intervalo de 10.9 años, comparando nuevas observaciones tomadas con el VLA a 1375 y 1635 MHz durante 1994 y 1995, con observaciones previas realizadas entre 1983 y 1984 (Dickel y col. ~1991 AJ 101, 2151), usando las mismas configuraciones, anchos de banda, calibradores y tiempos de integración. El coeficiente de expansión se calcula para sectores radiales de 4o de ancho cada uno, ajustando la correlación cruzada de las derivadas de los perfiles promedio para cada época. A partir de la expansión medida, se estima el índice (parámetro de expansión) de la ley potencial R∝ tm como m≡ d ln R/d ln t . Este valor se compara con coeficientes teóricos para diferentes fases evolutivas de remanentes de supernova.

  16. ConTrack: Finding the most likely pathways between brain regions using diffusion tractography

    PubMed Central

    Sherbondy, Anthony J.; Dougherty, Robert F.; Ben-Shachar, Michal; Napel, Sandy; Wandell, Brian A.

    2009-01-01

    Magnetic resonance diffusion-weighted imaging coupled with fiber tractography (DFT) is the only non-invasive method for measuring white matter pathways in the living human brain. DFT is often used to discover new pathways. But there are also many applications, particularly in visual neuroscience, in which we are confident that two brain regions are connected, and we wish to find the most likely pathway forming the connection. In several cases, current DFT algorithms fail to find these candidate pathways. To overcome this limitation, we have developed a probabilistic DFT algorithm (ConTrack) that identifies the most likely pathways between two regions. We introduce the algorithm in three parts: a sampler to generate a large set of potential pathways, a scoring algorithm that measures the likelihood of a pathway, and an inferential step to identify the most likely pathways connecting two regions. In a series of experiments using human data, we show that ConTrack estimates known pathways at positions that are consistent with those found using a high quality deterministic algorithm. Further we show that separating sampling and scoring enables ConTrack to identify valid pathways, known to exist, that are missed by other deterministic and probabilistic DFT algorithms. PMID:18831651

  17. ConSurf 2016: an improved methodology to estimate and visualize evolutionary conservation in macromolecules.

    PubMed

    Ashkenazy, Haim; Abadi, Shiran; Martz, Eric; Chay, Ofer; Mayrose, Itay; Pupko, Tal; Ben-Tal, Nir

    2016-07-08

    The degree of evolutionary conservation of an amino acid in a protein or a nucleic acid in DNA/RNA reflects a balance between its natural tendency to mutate and the overall need to retain the structural integrity and function of the macromolecule. The ConSurf web server (http://consurf.tau.ac.il), established over 15 years ago, analyses the evolutionary pattern of the amino/nucleic acids of the macromolecule to reveal regions that are important for structure and/or function. Starting from a query sequence or structure, the server automatically collects homologues, infers their multiple sequence alignment and reconstructs a phylogenetic tree that reflects their evolutionary relations. These data are then used, within a probabilistic framework, to estimate the evolutionary rates of each sequence position. Here we introduce several new features into ConSurf, including automatic selection of the best evolutionary model used to infer the rates, the ability to homology-model query proteins, prediction of the secondary structure of query RNA molecules from sequence, the ability to view the biological assembly of a query (in addition to the single chain), mapping of the conservation grades onto 2D RNA models and an advanced view of the phylogenetic tree that enables interactively rerunning ConSurf with the taxa of a sub-tree. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  18. What are the pros and cons of electronically monitoring inhaler use in asthma? A multistakeholder perspective

    PubMed Central

    Howard, Sam; Lang, Alexandra; Sharples, Sarah; Shaw, Dominick

    2016-01-01

    Introduction Electronic monitoring devices (EMDs) are the optimal method for collecting objective data on inhaler use in asthma. Recent research has investigated the attitudes of patients with asthma towards these devices. However, no research to date has formally considered the opinions of stakeholders and decision-makers in asthma care. These individuals have important clinical requirements that need to be taken into account if EMDs are to be successfully provisioned, making collecting their opinions on the key barriers facing these devices a valuable process. Methods Three rounds of surveys in a Delphi format were used to assess the most important pros and cons of EMDs for asthma care in a sample of 31 stakeholders which included healthcare professionals and members of clinical commissioning groups. Results The respondents identified 29 pros and 32 cons. Pros that were rated as most important included new visual evidence to aid clinical discussions with a patient and an increase in patient involvement and motivation. The cons that were rated as most important included a need for more clinical evidence of the effectiveness of EMDs, as well as better clarity over who has responsibilities in managing, interpreting and discussing data with a patient. Conclusions The research provides a guide for EMD developers by highlighting where these devices may provide the most benefit as well as prioritising the key issues that need addressing if they are to be used effectively in everyday asthma care. PMID:27933181

  19. Mound-ACT*DE*CON{sup SM} feasibility study. Phase 2: Final report

    SciTech Connect

    1994-12-01

    A portion of the abandoned Miami-Erie Canal paralleling the Greater Miami River receives the runoff and storm-water discharge from Mound Laboratory. In 1969, a low-level plutonium leak contaminated sediment as far away as 1.5 mi from the Mound site along the old canal system. An estimated one million cubic feet of sediment requires remediation. The technology being evaluated for the remediation of the low-level plutonium-238 contamination of the sediment involves two processes: washing the sediments with ACT*DE*CON{sup SM} solution to dissolve the contaminant, followed by extraction of the solution and processing with the MAG*SEP{sup SM} process to concentrate the contaminant and allow reuse of the ACT*DE*CON{sup SM} solution. The processes are being optimized for pilot-scale and field demonstration. Phase 2 of the project primarily involved identification at the laboratory scale of the optimal ACT*DE*CON{sup SM} formulation, identification of the ion-exchanger and MAG*SEP{sup SM} particles, verification of the plutonium mobility in the treated soil, and evaluation of other process parameters according to a series of tasks.

  20. ConA and UEA-I lectin histochemistry of parotid gland mucoepidermoid carcinoma.

    PubMed

    Sobral, Ana Paula V; Rego, Moacyr J B M; Cavalacanti, Carmelita L B; Carvalho, Luiz B; Beltrão, Eduardo I C

    2010-03-01

    Mucoepidermoid carcinoma (MEC) corresponds to 5-12% of all salivary gland tumours, and is classified as low, intermediate or high grade. Traditionally, immunohistochemistry was considered as the complementary tool for diagnosis of salivary gland neoplasia. Lectin histochemistry has also been increasingly used in recent years. In this work, lectins were used as histochemical markers for normal and transformed parotid glands. Biopsy specimens of 15 cases diagnosed as MEC (low, intermediate and high grade) of the parotid gland were trypsin- and methanol-H(2)O(2)-treated and incubated with horseradish peroxidase (HRP)-conjugated lectins, Concanavalin A (Con A-HRP) and Ulex europeus I (UEA-I-HRP). Con A stained the neoplasic cells of MEC (all grades). In high and intermediate cases, ductal cells were weakly stained by Con A. UEA-I weakly stained normal cells of the excretory duct and neoplasic cells in high grade. Neoplasic cells in intermediate grade were moderately stained and in low grade, the cell membrane was intensely stained with UEA-I. Stroma presented a direct relation between malignancy and staining intensity for UEA-I. The results indicated that lectin histochemistry distinguished the cell biology among histological grades of MEC.

  1. Salud mental en desastres naturales: estrategias interventivas con adultos mayores en sectores rurales de Chile.

    PubMed

    Osorio-Parraguez, Paulina; Espinoza, Adriana

    2016-06-01

    En el presente artículo se da a conocer una estrategia de intervención llevada a cabo con adultos mayores en la comuna de Paredones, sexta región de Chile, con posterioridad al terremoto y tsunami del 27 de febrero 2010 en Chile, en el contexto de una investigación sobre fortalezas y vulnerabilidades desplegadas por este grupo etario, con posterioridad a un desastre natural. Se presenta una descripción del desarrollo metodológico de la intervención y de los sustentos teóricos y conceptuales en los que se basa. Como resultado de este proceso, se propone una estrategia que trabaje a través de la identificación de las propias experiencias y fortalezas de los sujetos. De tal forma se minimizan los efectos negativos de los determinantes sociales de la salud (como la edad y el lugar de residencia) en contexto de crisis; permitiendo a los adultos mayores fortalecer sus recursos individuales y colectivos, en pro de su bienestar psicosocial.

  2. Structure, stratigraphy and petroleum geology of the south east Nam Con Son Basin, offshore Vietnam

    SciTech Connect

    Fraser, A.J.; Matthews, S.J.; Lowe, S.; Todd, S.P.; Simon, P. Peel, F.J. )

    1996-01-01

    Recent exploration of the south east Nam Con Son Basin, offshore Vietnam, by BP in alliance with Statoil has involved acquisition of new seismic and well data. These new data have allowed re-evaluation of the tectono-stratigraphic development and petroleum geology, and have provided additional constraints on the regional tectonic evolution. The offshore Vietnamese basins have evolved in response to the complex relative motions of Indochina, Peninsular Malaysia, Borneo and the South China Sea during the Cenozoic. On the regional scale these motions have been accommodated by strike-slip fault development, rifting and contraction. In the Nam Con Son Basin these motions have interacted in different ways from the Palaeogene to recent. Two rifting episodes are recognized; a Palaeogene phase dominated by E-W trending extensional faults, and a Miocene phase dominated by N-S to NE-SW trending faults. The structural evolution is complicated by a pulse of mild contraction during the Middle Miocene. The sedimentary fill of the basin evolves from continental fluvio-lacustrine in the Palaeogene through to fully marine following the second phase of rifting in the Miocene. This pulsed structural and stratigraphic evolution has resulted in basinwide deposition of source, reservoir and seal facies, and produced a variety of potential trapping styles. This paper describes the hydrocarbon habitat of the south east Nam Con Son Basin within the context of the regional tectono-stratigraphic model.

  3. Structure, stratigraphy and petroleum geology of the south east Nam Con Son Basin, offshore Vietnam

    SciTech Connect

    Fraser, A.J.; Matthews, S.J.; Lowe, S.; Todd, S.P.; Simon, P. Peel, F.J.

    1996-12-31

    Recent exploration of the south east Nam Con Son Basin, offshore Vietnam, by BP in alliance with Statoil has involved acquisition of new seismic and well data. These new data have allowed re-evaluation of the tectono-stratigraphic development and petroleum geology, and have provided additional constraints on the regional tectonic evolution. The offshore Vietnamese basins have evolved in response to the complex relative motions of Indochina, Peninsular Malaysia, Borneo and the South China Sea during the Cenozoic. On the regional scale these motions have been accommodated by strike-slip fault development, rifting and contraction. In the Nam Con Son Basin these motions have interacted in different ways from the Palaeogene to recent. Two rifting episodes are recognized; a Palaeogene phase dominated by E-W trending extensional faults, and a Miocene phase dominated by N-S to NE-SW trending faults. The structural evolution is complicated by a pulse of mild contraction during the Middle Miocene. The sedimentary fill of the basin evolves from continental fluvio-lacustrine in the Palaeogene through to fully marine following the second phase of rifting in the Miocene. This pulsed structural and stratigraphic evolution has resulted in basinwide deposition of source, reservoir and seal facies, and produced a variety of potential trapping styles. This paper describes the hydrocarbon habitat of the south east Nam Con Son Basin within the context of the regional tectono-stratigraphic model.

  4. Equilibrium geometries, electronic structure and magnetic properties of ConSn (n = 1-12) clusters from density functional calculations

    NASA Astrophysics Data System (ADS)

    Zhang, Jing Ya; Lv, Jin

    2017-05-01

    Equilibrium geometries, relative stabilities, electronic stabilities and magnetic properties of ConSn (n = 1-12) clusters have been systematically investigated by using relativistic all-electron density functional theory with generalized gradient approximation. The results indicated that the lowest-energy structures of ConSn (n = 1-5, 7, 9 and 10) clusters are similar to those of corresponding Con+1 clusters. As for Co6Sn, Co8Sn, Co11Sn and Co12Sn clusters, the most stable structures give rise to a geometry reconstruction. In the low-lying structures of ConSn (n = 1-12) clusters, tin impurity prefers to occupy the external site. The second-order difference energy of the ground-state ConSn (n = 1-12) clusters shows a pronounced odd-even oscillation with the number of Co atoms, and the clusters exhibit higher stability at n = 5. Compared with corresponding pure Con+1 clusters, the total magnetic moment of the ConSn clusters reduces with 1, 3 and 5 μB, respectively. The different magnetic changes of the tin doped Co clusters are analyzed in detail based on the magnetism coupling, density of state and hybridization between cobalt and tin atoms.

  5. The Transcription Factor Con7-1 Is a Master Regulator of Morphogenesis and Virulence in Fusarium oxysporum.

    PubMed

    Ruiz-Roldán, Carmen; Pareja-Jaime, Yolanda; González-Reyes, José Antonio; Roncero, M Isabel G

    2015-01-01

    Previous studies have demonstrated the essential role of morphogenetic regulation in Fusarium oxysporum pathogenesis, including processes such as cell-wall biogenesis, cell division, and differentiation of infection-like structures. We identified three F. oxysporum genes encoding predicted transcription factors showing significant identities to Magnaporthe oryzae Con7p, Con7-1, plus two identical copies of Con7-2. Targeted deletion of con7-1 produced nonpathogenic mutants with altered morphogenesis, including defects in cell wall structure, polar growth, hyphal branching, and conidiation. By contrast, simultaneous inactivation of both con7-2 copies caused no detectable defects in the resulting mutants. Comparative microarray-based gene expression analysis indicated that Con7-1 modulates the expression of a large number of genes involved in different biological functions, including host-pathogen interactions, morphogenesis and development, signal perception and transduction, transcriptional regulation, and primary and secondary metabolism. Taken together, our results point to Con7-1 as general regulator of morphogenesis and virulence in F. oxysporum.

  6. Con_A-carbone nanotube conjugate with short wave near-infrared laser ablation for tumor therapy

    NASA Astrophysics Data System (ADS)

    Lei, Huan-Yao; Peng, Ching-An; Tang, Ming-Jer; Reindhart, Kit; Szu, Harold H.

    2009-04-01

    Using the characteristics of T cell mitogen called lectin protein from the jack-beam Canavalia ensiformis Concanavalin A (Con_A) with dual activities, cytotoxicity and immunomodulation, we have shown it has a therapeutic effect on hepatoma. Injection of Con_A can eradicate the established malign tumor, because Con_A can induce tumor cell autophagic, cell-programmed death, as well as activate the effector T cells. Combined, in this paper, with the absorption exceeding the Carbon NanoTube (CNT) band-gap (ɛbg=~1/CNT diameter) with an active short wave near-infrared (SWIR) (1.2~1.5 micron wavelengths), which happened to be translucent to the irradiation upon animal skin, similar to that used in hospital fingertip-clamped Pulse Oxymetry. Once the Con_ACNT is guided to hepatoma cells, it is bonded and internalized into the mitochondria (MC) compartment, the cellular energy factory. Con_A has the higher specificity for tumor cells useful for targeting because of the abnormal glycosylation on tumor cells. When CNT hitch hike with Con_A, they can t together like a laser-denotable chemical missile surgically targeting at the tumor cells precisely by Con_A-guidance. We switch on SWIR laser, when the Con_A-CNT conjugated complex has been bonded and internalized to MC of malign cells and already commenced cellular programmed death. Thus, it might appear to casual readers that we have initiated an overkill, chemical drugged autophage followed with physical laser ablation, but what if we can eradicate hepatoma totally if no blue print is left behind inadvertently in case of a partial failure. We conclude that using Con_A-CNT conjugated complex targeting specifically at malign tumor cells is a novel targeted-laser-radiation therapy for tumors in mice.

  7. Wildland Fire Induced Heating of Dome 375 Perma-Con®

    SciTech Connect

    Flores, Eugene Michael

    2016-08-09

    AET-1 was tasked by ADEM with determining the temperature rise in the drum contents of drums stored in the Dome 375 Perma-Con® at TA-54 given a wildland fire. The wildland fire causes radiative and convective heating on the Perma-Con® exterior. The wildland fire time histories for the radiative and convective heating environment were provided to AET-1 by EES-16. If the calculated temperature rise results in a drum content temperature over 40 °C, then ADEM desires a design solution to ensure the peak temperature remains below 40 °C. An axi-symmetric FE simulation was completed to determine the peak temperature of the contents of a drum stored in the Dome 375 Perma-Con® during a wildland fire event. Three wildland fire time histories for the radiative and convective heat transfer were provided by EES-16 and were inputs for the FE simulation. The maximum drum content temperature reached was found to be 110 °C while using inputs from the SiteG_2ms_4ign_wind_from_west.xlsx time history input and not including the SWB in the model. Including the SWB in the results in a peak drum content temperature of 61 °C for the SiteG_2ms_4ign_wind_from_west.xlsx inputs. EES-16 decided that by using fuel mitigation efforts, such as mowing the grass and shrubs near the Perma-Con® they could reduce the shrub/grass fuel loading near the Perma-Con® from 1.46 kg/m2 to 0.146 kg/m2 and by using a less conservative fuel loading for the debris field inside the Dome 375 perimeter, reducing it from 0.58 kg/m2 to 0.058 kg/m2 in their model. They also greatly increased the resolution of their radiation model and increased the accuracy of their model’s required convergence value. Using this refined input the maximum drum content temperature was found to be 28 °C with no SWB present in the model. Additionally, this refined input model was modified to include worst case emissivity values for the concrete, drum and Perma-Con® interior, along with adding a

  8. El efecto de la panfotocoagulación con láser en edema macular diabético con el fotocoagulador Pascal® versus el láser de argón convencional.

    PubMed

    Mahgoub, Mohamed M; Macky, Tamer A

    2017-07-11

    Objetivo: El objetivo de este estudio fue comparar el efecto de la panfotocoagulación (PFC) en el edema macular diabético (EMD) en pacientes con retinopatía diabética proliferativa (RDP) con el fotocoagulador Pascal® (FP) vs. un fotocoagulador con láser de argón convencional (FLAC). Métodos: Se aleatorizó el uso de FP o FLAC en ochenta ojos con RDP y EMD con afectación central de la mácula. Ambos grupos tuvieron una evaluación de base de mejor agudeza visual corregida y fueron examinados con tomografía de coherencia óptica y angiografía con fluoresceína. Resultados: El número medio de disparos de láser en los grupos de FP y FLAC fue 1.726,10 y 752,00 en la sesión 1 y 1.589,00 y 830,00 (p < 0,001) en la sesión 2, respectivamente. El grosor foveal central (GFC) medio antes de comenzar el estudio fue 306 ± 100 y 314 ± 98 en los grupos de FP y FLAC, respectivamente. A las 8 semanas, el GFC medio fue 332 ± 116 y 347 ± 111 en los grupos de FP y FLAC, respectivamente (p > 0,05). La MAVC media fue similar durante el periodo de estudio y no hubo ninguna diferencia significativa entre los grupos (p > 0,05). Conclusiones: El FP y el FLAC mostraron efectos similares en el EMD en ojos con RDP y fueron igualmente seguros sin un aumento significativo del GFC. © 2017 S. Karger AG, Basel.

  9. Lectin-dependent cell-mediated cytotoxicity in an invertebrate model: Con A does not act as a bridge.

    PubMed Central

    Boswell, C A; Bayne, C J

    1986-01-01

    The plant lectin concanavalin A (Con A) has been used in an invertebrate model of lectin-dependent cell-mediated cytotoxicity (LDCC). Macrophage-like cells from the susceptible host snail Biomphalaria glabrata become cytotoxic effectors when they encounter sporocysts of the parasitic trematode Schistosoma mansoni that have been treated with Con A. The sugar alpha-methyl mannoside and rabbit anti-Con A antibodies fail to block this LDCC. Con A is effective only when the target, not the effector cell, has been exposed to it. These results constitute evidence against the molecular bridging hypothesis and support the notion that surface modulation of the target may be the stimulus that provokes cytotoxicity. Results from this invertebrate model are discussed in the context of murine T lymphocyte LDCC. PMID:3949370

  10. A phase 2 trial of long-acting TransCon growth hormone in adult GH deficiency.

    PubMed

    Höybye, Charlotte; Pfeiffer, Andreas F H; Ferone, Diego; Christiansen, Jens Sandahl; Gilfoyle, David; Christoffersen, Eva Dam; Mortensen, Eva; Leff, Jonathan A; Beckert, Michael

    2017-04-01

    TransCon growth hormone is a sustained-release human growth hormone prodrug under development in which unmodified growth hormone is transiently linked to a carrier molecule. It is intended as an alternative to daily growth hormone in the treatment of growth hormone deficiency. This was a multi-center, randomized, open-label, active-controlled trial designed to compare the safety (including tolerability and immunogenicity), pharmacokinetics and pharmacodynamics of three doses of weekly TransCon GH to daily growth hormone (Omnitrope). Thirty-seven adult males and females diagnosed with adult growth hormone deficiency and stable on growth hormone replacement therapy for at least 3 months were, following a wash-out period, randomized (regardless of their pre-study dose) to one of three TransCon GH doses (0.02, 0.04 and 0.08 mg GH/kg/week) or Omnitrope 0.04 mg GH/kg/week (divided into 7 equal daily doses) for 4 weeks. Main outcomes evaluated were adverse events, immunogenicity and growth hormone and insulin-like growth factor 1 levels. TransCon GH was well tolerated; fatigue and headache were the most frequent drug-related adverse events and reported in all groups. No lipoatrophy or nodule formation was reported. No anti-growth hormone-binding antibodies were detected. TransCon GH demonstrated a linear, dose-dependent increase in growth hormone exposure without accumulation. Growth hormone maximum serum concentration and insulin-like growth factor 1 exposure were similar after TransCon GH or Omnitrope administered at comparable doses. The results suggest that long-acting TransCon GH has a profile similar to daily growth hormone but with a more convenient dosing regimen. These findings support further TransCon GH development. © 2017 The authors.

  11. Segundo Catálogo Estelar del Hemisferio Sur con Astrolabio Fotoeléctrico PAII

    NASA Astrophysics Data System (ADS)

    Manrique, W. T.; Podestá, R. C.; Alonso, E.; Actis, E. V.; Pacheco, A. M.; Bustos, G.; Lizhi, L.; Zezhi, W.; Fanmiao, Z.; Hongqi, W.; Perdomo, R.

    Recordamos que entre el Observatorio Astronómico ``Félix Aguilar'', el Observatorio Astronómico de Beijing y el Observatorio Astronómico de La Plata, se ha convenido en desarrollar un Proyecto de Investigación conjunto, para la observación sistemática de estrellas en el Hemisferio Sur, con el objeto de la elaboración de un Catálogo Estelar Global utilizando un Astrolabio Fotoeléctrico PAII del Observatorio de Beijing, que ha sido usado con éxito en la República de China. En este trabajo se presenta el Segundo Catálogo Estelar del Hemisferio Sur, derivado de las observaciones realizadas con el PAII instalado en el OAFA, durante el períiodo Febrero de 1992 a Marzo de 1997. En este lapso se han observado mas de 400000 pasajes estelares, obteniéndose las correcciones Δ α y Δ δ de 5241 estrellas del FK4, FK5, FK5 Ext., SRS, CAMC y GC. Las precisiones medias son del orden de ± 3,2 ms en ascensión recta y ±0."057 en declinación. Rango de magnitudes : 2,0 a 11,5 Rango de declinaciones : -3o a -60o Epoca Media : 1994.9 Se analizan los residuos en función de la magnitud y tipo espectral, correcciones de grupo y frecuencia de distribución Δ α y Δ δ.

  12. Soy-Based Therapeutic Baby Formulas: Testable Hypotheses Regarding the Pros and Cons

    PubMed Central

    Westmark, Cara J.

    2017-01-01

    Soy-based infant formulas have been consumed in the United States since 1909, and currently constitute a significant portion of the infant formula market. There are efforts underway to generate genetically modified soybeans that produce therapeutic agents of interest with the intent to deliver those agents in a soy-based infant formula platform. The threefold purpose of this review article is to first discuss the pros and cons of soy-based infant formulas, then present testable hypotheses to discern the suitability of a soy platform for drug delivery in babies, and finally start a discussion to inform public policy on this important area of infant nutrition. PMID:28149839

  13. Confrontando teorías físicas con la Cosmología

    NASA Astrophysics Data System (ADS)

    Vucetich, H.

    Hay numerosas teorías físicas que no pueden contrastarse con el experimento en laboratorio y eso las hace poco interesantes como descripción de la naturaleza. Sin embargo, algunas de estas teorías tienen consecuencias cosmológicas observables y se abre la posibilidad de contrastación a través de la observación. Se discuten las observaciones capaces de poner a prueba tales teorías y se examinan ejemplos de teorías limitadas por la observación.

  14. On application of optimal control to SEIR normalized models: Pros and cons.

    PubMed

    de Pinho, Maria do Rosario; Nogueira, Filipa Nunes

    2017-02-01

    In this work we normalize a SEIR model that incorporates exponential natural birth and death, as well as disease-caused death. We use optimal control to control by vaccination the spread of a generic infectious disease described by a normalized model with L1 cost. We discuss the pros and cons of SEIR normalized models when compared with classical models when optimal control with L1 costs are considered. Our discussion highlights the role of the cost. Additionally, we partially validate our numerical solutions for our optimal control problem with normalized models using the Maximum Principle.

  15. Soy-Based Therapeutic Baby Formulas: Testable Hypotheses Regarding the Pros and Cons.

    PubMed

    Westmark, Cara J

    2016-01-01

    Soy-based infant formulas have been consumed in the United States since 1909, and currently constitute a significant portion of the infant formula market. There are efforts underway to generate genetically modified soybeans that produce therapeutic agents of interest with the intent to deliver those agents in a soy-based infant formula platform. The threefold purpose of this review article is to first discuss the pros and cons of soy-based infant formulas, then present testable hypotheses to discern the suitability of a soy platform for drug delivery in babies, and finally start a discussion to inform public policy on this important area of infant nutrition.

  16. The pros and cons about the digital recording of Intangible Cultural Heritage and some strategies

    NASA Astrophysics Data System (ADS)

    Yang, H.

    2015-08-01

    Intangible Cultural Heritage (referred to as ICH), whose fundamental nature different from the tangible cultural heritage is "Intangible", and the related physical presence of the heritage is not the core content. Digital means have irreplaceable advantages in recording intangible and dynamic ICH resources, while it also needs flexible and rigorous recording means as a support, thus striving to maximize resources recording and protection. This article will focus on the pros and cons about the digital recording of ICH, and preliminarily discuss some strategies used in the process of recording.

  17. La interacción de estrellas WN con el medio circundante

    NASA Astrophysics Data System (ADS)

    Arnal, M.; Cappa, C.; Rizzo, J. R.; Cichovolski, S.

    Se presentan resultados preliminares de un estudio de la distribución del hidrógeno neutro en los alrededores de estrellas WR de la serie del nitrógeno. Los datos observacionales de la línea de 21 cm provienen de un relevamineto de baja resolución angular (36'), así como de observaciones de resolución angular intermedia (9') tomadas con el radiotelescopio de Effelsberg. Este análisis ha permitido detectar cavidades y envolturas de H I en expansión vinculadas a las estrellas que componen la muestra.

  18. Nano anti-cancer drugs: pros and cons and future perspectives.

    PubMed

    Ali, Imran

    2011-02-01

    For last one decade, scientists are working for developing nano anti-cancer drugs with claim of ideal ones due to their targeted chemotherapic nature. These drugs have many beneficial properties such as targeted drug delivery and gene therapy modalities with minimum side effects. This article describes pros and cons and future perspectives of nano anti-cancer drugs. Efforts have been made to address importance, special features, toxicities (general, blood identities, immune system and environmental) and future perspectives of nano anti-cancer drugs. It was concluded that nano anti-cancer drugs may be magic bullet drugs for cancer treatment leading to bright future of the whole world.

  19. Perceived pros and cons of smoking and quitting in hard-core smokers: a focus group study.

    PubMed

    Bommelé, Jeroen; Schoenmakers, Tim M; Kleinjan, Marloes; van Straaten, Barbara; Wits, Elske; Snelleman, Michelle; van de Mheen, Dike

    2014-02-18

    In the last decade, so-called hard-core smokers have received increasing interest in research literature. For smokers in general, the study of perceived costs and benefits (or 'pros and cons') of smoking and quitting is of particular importance in predicting motivation to quit and actual quitting attempts. Therefore, this study aims to gain insight into the perceived pros and cons of smoking and quitting in hard-core smokers. We conducted 11 focus group interviews among current hard-core smokers (n = 32) and former hard-core smokers (n = 31) in the Netherlands. Subsequently, each participant listed his or her main pros and cons in a questionnaire. We used a structural procedure to analyse the data obtained from the group interviews and from the questionnaires. Using the qualitative data of both the questionnaires and the transcripts, the perceived pros and cons of smoking and smoking cessation were grouped into 6 main categories: Finance, Health, Intrapersonal Processes, Social Environment, Physical Environment and Food and Weight. Although the perceived pros and cons of smoking in hard-core smokers largely mirror the perceived pros and cons of quitting, there are some major differences with respect to weight, social integration, health of children and stress reduction, that should be taken into account in clinical settings and when developing interventions. Based on these findings we propose the 'Distorted Mirror Hypothesis'.

  20. Establishing confidence in the output of qualitative research synthesis: the ConQual approach.

    PubMed

    Munn, Zachary; Porritt, Kylie; Lockwood, Craig; Aromataris, Edoardo; Pearson, Alan

    2014-09-20

    The importance of findings derived from syntheses of qualitative research has been increasingly acknowledged. Findings that arise from qualitative syntheses inform questions of practice and policy in their own right and are commonly used to complement findings from quantitative research syntheses. The GRADE approach has been widely adopted by international organisations to rate the quality and confidence of the findings of quantitative systematic reviews. To date, there has been no widely accepted corresponding approach to assist health care professionals and policy makers in establishing confidence in the synthesised findings of qualitative systematic reviews. A methodological group was formed develop a process to assess the confidence in synthesised qualitative research findings and develop a Summary of Findings tables for meta-aggregative qualitative systematic reviews. Dependability and credibility are two elements considered by the methodological group to influence the confidence of qualitative synthesised findings. A set of critical appraisal questions are proposed to establish dependability, whilst credibility can be ranked according to the goodness of fit between the author's interpretation and the original data. By following the processes outlined in this article, an overall ranking can be assigned to rate the confidence of synthesised qualitative findings, a system we have labelled ConQual. The development and use of the ConQual approach will assist users of qualitative systematic reviews to establish confidence in the evidence produced in these types of reviews and can serve as a practical tool to assist in decision making.

  1. Avoided costs associated with cogeneration: a case study of Con Ed

    SciTech Connect

    Bright, R.; Davitian, H.; Martorella, J.

    1980-08-01

    The potential impact of cogeneration in office and apartment buildings in New York City on the Consolidated Edison Company (Con Ed) has been investigated using a method of utility cost and fuel use analysis developed at Brookhaven National Laboratory. This method computes a utility's long run marginal costs and long run marginal fuel consumption associated with load modifications due to the introduction of on-site energy producing technologies. The principal findings of this study show that Con Ed's long run average cost is more likely to go down than up due to cogeneration in office and apartment building; the utility's avoided costs (i.e., its long run marginal savings) associated with the gross power output of the cogeneration systems are 10.5 cents/KWh for the office building and 6.4 cents/KWh for the apartment buildings; the utility's marginal savings include a component for avoided capacity costs; and there are net savings in the use of oil due to cogeneration (assuming the building used oil for its boilers before it switched and diesel fuel in its cogenerators afterwards).

  2. Reliability of knee extension and flexion measurements using the Con-Trex isokinetic dynamometer.

    PubMed

    Maffiuletti, Nicola A; Bizzini, Mario; Desbrosses, Kevin; Babault, Nicolas; Munzinger, Urs

    2007-11-01

    The aim of this study was to evaluate the reliability of isokinetic and isometric assessments of the knee extensor and the flexor muscle function using the Con-Trex isokinetic dynamometer. Thirty healthy subjects (15 males, 15 females) were tested and retested 7 days later for maximal strength (isokinetic peak torque, work, power and angle of peak torque as well as isometric maximal voluntary contraction torque and rate of torque development) and fatigue (per cent loss and linear slope of torque and work across a series of 20 contractions). For both the knee extensor and the flexor muscle groups, all strength data - except angle of peak torque - demonstrated moderate-to-high reliability, with intraclass correlation coefficients (ICC) higher than 0.86. The highest reliability was observed for concentric peak torque of the knee extensor muscles (ICC = 0.99). Test-retest reliability of fatigue variables was moderate for the knee extensor (ICC range 0.84-0.89) and insufficient-to-moderate for the knee flexor muscles (ICC range 0.78-0.81). The more reliable index of muscle fatigue was the linear slope of the decline in work output. These findings establish the reliability of isokinetic and isometric measurements using the Con-Trex machine.

  3. Quick fix or long-term cure? Pros and cons of bariatric surgery

    PubMed Central

    Madura, James A.

    2012-01-01

    The past decade has seen an enormous increase in the number of bariatric, or weight loss, operations performed. This trend is likely to continue, mirroring the epidemic of obesity around the world and its rising prevalence among children. Bariatric surgery is considered by many to be the most effective treatment for obesity in terms of maintenance of long-term weight loss and improvement in obesity-related comorbid conditions. Although overly simplified, the primary mechanisms of the surgical interventions currently utilized to treat obesity are the creation of a restrictive or malabsorptive bowel anatomy. Operations based on these mechanisms include the laparoscopic adjustable gastric band and laparoscopic vertical sleeve gastrectomy (considered primarily restrictive operations), the laparoscopic biliopancreatic diversion with or without a duodenal switch (primarily malabsorptive operation), and the laparoscopic Roux-en-Y gastric bypass (considered a combination restrictive and selective malabsorptive procedure). Each operation has pros and cons. Important considerations, for the patient and surgeon alike, in the decision to proceed with bariatric surgery include the technical aspects of the operation, postoperative complications including long-term nutritional problems, magnitude of initial and sustained weight loss desired, and correction of obesity-related comorbidities. Herein, the pros and cons of the contemporary laparoscopic bariatric operations are reviewed and ongoing controversies relating to bariatric surgery are discussed: appropriate patient selection, appropriate operation selection for an individual patient, surgeon selection, and how to measure success after surgery. PMID:23091563

  4. Uso de Sustancias en Mujeres con Desventaja Social: Riesgo para el Contagio de VIH/SIDA

    PubMed Central

    Cianelli, R.; Ferrer, L; Bernales, M.; Miner, S.; Irarrázabal, L.; Molina, Y.

    2009-01-01

    Antecedentes La caracterización epidemiológica en Chile apunta a feminización, pauperización y heterosexualización de la epidemia del VIH, lo que implica un mayor riesgo para las mujeres en desventaja social. Si a esto se suma la utilización de sustancias, la vulnerabilidad de este grupo frente al VIH/SIDA aumenta. Objetivo Describir el uso de sustancias en mujeres con desventaja social e identificar factores de riesgo de contagio de VIH, asociados a este consumo. Material y Método 52 mujeres fueron entrevistadas como parte del proyecto “Testeando una intervención en prevención de VIH/SIDA en mujeres chilenas” GRANT # RO1 TW 006977. Se describen variables sociodemográficas y de consumo de sustancias a través de estadísticas descriptivas y se analiza la relación entre variables a través de pruebas de correlación. Resultados Los resultados indican un perfil sociodemográfico que sitúa a las mujeres en situación de vulnerabilidad frente al contagio de VIH/SIDA, con alto índice de uso de sustancias que acentúa el riesgo. Conclusiones Los hallazgos apuntan a la necesidad de considerar intervenciones que se enfoquen en la prevención de VIH en mujeres, abordando los riesgos asociados al consumo de sustancias. PMID:21197380

  5. Targeting of proConA to the plant vacuole depends on its nine amino-acid C-terminal propeptide.

    PubMed

    Saint-Jore-Dupas, Claude; Claude, Saint-Jore-Dupas; Gilbert, Marie-Agnès; Marie-Agnès, Gilbert; Ramis, Catalina; Catalina, Ramis; Paris, Nadine; Nadine, Paris; Kiefer-Meyer, Marie-Christine; Marie-Christine, Kiefer-Meyer; Neuhaus, Jean-Marc; Jean-Marc, Neuhaus; Faye, Loïc; Loïc, Faye; Gomord, Véronique; Véronique, Gomord

    2005-10-01

    Concanavalin A (ConA) is a well characterized and extensively used lectin accumulated in the protein bodies of jack bean cotyledons. ConA is synthesized as an inactive precursor proConA. The maturation of inactive proConA into biologically active ConA is a complex process including the removal of an internal glycopeptide and a C-terminal propeptide (CTPP), followed by a head-to-tail ligation of the two largest polypeptides. The cDNA encoding proConA was cloned and expressed in tobacco BY-2 cells. ProConA was slowly transported to the vacuole where its maturation into ConA was similar to that in jack bean cotyledons, apart from an incomplete final ligation. To investigate the role of the nine amino acid CTPP, a truncated form lacking the propeptide (proConADelta9) was expressed in BY-2 cells. In contrast to proConA, proConADelta9 was rapidly chased out of the endoplasmic reticulum (ER) and secreted into the culture medium. The CTPP was then fused to the C-terminal end of a secreted form of green fluorescent protein (secGFP). When expressed in tobacco BY-2 cells and leaf protoplasts, the chimaeric protein was located in the vacuole whereas secGFP was located in the culture medium and in the vacuole. Altogether, our results show we have isolated a new C-terminal vacuolar sorting determinant.

  6. Deficits in latent inhibition induced by estradiol replacement are ameliorated by haloperidol treatment

    PubMed Central

    Almey, Anne; Hafez, Nada M.; Hantson, Arne; Brake, Wayne G.

    2013-01-01

    There are sex differences in the symptomatology of schizophrenia, and in the response to antipsychotic treatments. One hallmark symptom of schizophrenia is a deficit in selective attention. Selective attention can be measured using a latent inhibition (LI) paradigm in humans; LI can be measured in rodents, and is used as an animal model of the selective attention deficits observed in schizophrenia. In the current experiments LI was used to clarify whether selective attention differs between male rats and ovariectomized (OVX) female rats receiving different estradiol (E2) replacement regimens. An additional aim was to determine whether haloperidol’s (HAL) facilitation of LI is enhanced by E2. Males and OVX female rats were trained in a conditioned emotional response LI paradigm. Females received no E2 replacement, a chronic low dose of E2 via silastic capsule, or a high phasic dose of E2 via silastic capsule accompanied by E2 (10 µg/kg subcutaneous (SC)) injections every 4th day. Actual plasma levels of E2 were determined using an enzyme linked immunosorbent assay. Rats were also administered a vehicle treatment, a 0.05 mg/kg, or a 0.1 mg/kg IP injection of HAL. Males and OVX females that did not receive E2 replacement both exhibited LI, but LI was not observed in the low and high E2 replacement groups. HAL restored LI at a lower dose in the females receiving high E2 replacement compared to females receiving low E2 replacement, indicating that E2 replacement facilitates HAL in restoring LI. PMID:24101897

  7. Overcoming the aggregation problem: A new type of fluorescent ligand for ConA-based glucose sensing

    PubMed Central

    Cummins, Brian M.; Li, Mingchien; Locke, Andrea K.; Birch, David J.S.; Vigh, Gyula; Coté, Gerard L.

    2016-01-01

    Competitive binding assays based on the lectin Concanavalin A (ConA) have displayed significant potential to serve in continuous glucose monitoring applications. However, to date, this type of fluorescent, affinity-based assay has yet to show the stable, glucose predictive capabilities that are required for such an application. This instability has been associated with the extensive crosslinking between traditionally-used fluorescent ligands (presenting multiple low-affinity moieties) and ConA (presenting multiple binding sites) in free solution. The work herein introduces the design and synthesis of a new type of fluorescent ligand that can avoid this aggregation and allow the assay to be sensitive across the physiologically relevant glucose concentration range. This fluorescent ligand (APTS–MT) presents a single high-affinity trimannose moiety that is recognized by ConA’s full binding site and a fluorophore that can effectively track the ligand’s equilibrium binding via fluorescent anisotropy. This is confirmed by comparing its measured fluorescent lifetime to experimentally-determined rotational correlation lifetimes of the free and bound populations. Using an assay comprised of 200 nM APTS–MT and 1 μM ConA, the fluorescence anisotropy capably tracks the concentration of monosaccharides that are known to bind to ConA’s primary binding site, and the assay displays a MARD of 6.5% across physiologically relevant glucose concentrations. Ultimately, this rationally-designed fluorescent ligand can facilitate the realization of the full potential of ConA-based glucose sensing assays and provide the basis for a new set of competing ligands to be paired with ConA. PMID:25058939

  8. Cue-based assertion classification for Swedish clinical text--developing a lexicon for pyConTextSwe.

    PubMed

    Velupillai, Sumithra; Skeppstedt, Maria; Kvist, Maria; Mowery, Danielle; Chapman, Brian E; Dalianis, Hercules; Chapman, Wendy W

    2014-07-01

    The ability of a cue-based system to accurately assert whether a disorder is affirmed, negated, or uncertain is dependent, in part, on its cue lexicon. In this paper, we continue our study of porting an assertion system (pyConTextNLP) from English to Swedish (pyConTextSwe) by creating an optimized assertion lexicon for clinical Swedish. We integrated cues from four external lexicons, along with generated inflections and combinations. We used subsets of a clinical corpus in Swedish. We applied four assertion classes (definite existence, probable existence, probable negated existence and definite negated existence) and two binary classes (existence yes/no and uncertainty yes/no) to pyConTextSwe. We compared pyConTextSwe's performance with and without the added cues on a development set, and improved the lexicon further after an error analysis. On a separate evaluation set, we calculated the system's final performance. Following integration steps, we added 454 cues to pyConTextSwe. The optimized lexicon developed after an error analysis resulted in statistically significant improvements on the development set (83% F-score, overall). The system's final F-scores on an evaluation set were 81% (overall). For the individual assertion classes, F-score results were 88% (definite existence), 81% (probable existence), 55% (probable negated existence), and 63% (definite negated existence). For the binary classifications existence yes/no and uncertainty yes/no, final system performance was 97%/87% and 78%/86% F-score, respectively. We have successfully ported pyConTextNLP to Swedish (pyConTextSwe). We have created an extensive and useful assertion lexicon for Swedish clinical text, which could form a valuable resource for similar studies, and which is publicly available. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Overcoming the aggregation problem: a new type of fluorescent ligand for ConA-based glucose sensing.

    PubMed

    Cummins, Brian M; Li, Mingchien; Locke, Andrea K; Birch, David J S; Vigh, Gyula; Coté, Gerard L

    2015-01-15

    Competitive binding assays based on the lectin Concanavalin A (ConA) have displayed significant potential to serve in continuous glucose monitoring applications. However, to date, this type of fluorescent, affinity-based assay has yet to show the stable, glucose predictive capabilities that are required for such an application. This instability has been associated with the extensive crosslinking between traditionally-used fluorescent ligands (presenting multiple low-affinity moieties) and ConA (presenting multiple binding sites) in free solution. The work herein introduces the design and synthesis of a new type of fluorescent ligand that can avoid this aggregation and allow the assay to be sensitive across the physiologically relevant glucose concentration range. This fluorescent ligand (APTS-MT) presents a single high-affinity trimannose moiety that is recognized by ConA's full binding site and a fluorophore that can effectively track the ligand's equilibrium binding via fluorescent anisotropy. This is confirmed by comparing its measured fluorescent lifetime to experimentally-determined rotational correlation lifetimes of the free and bound populations. Using an assay comprised of 200 nM APTS-MT and 1 µM ConA, the fluorescence anisotropy capably tracks the concentration of monosaccharides that are known to bind to ConA's primary binding site, and the assay displays a MARD of 6.5% across physiologically relevant glucose concentrations. Ultimately, this rationally-designed fluorescent ligand can facilitate the realization of the full potential of ConA-based glucose sensing assays and provide the basis for a new set of competing ligands to be paired with ConA.

  10. Comparison of phenotypic methods in predicting methicillin resistance in coagulase-negative Staphylococcus (CoNS) from animals.

    PubMed

    Zhang, Yifan; Wang, Xiaogang; LeJeune, Jeffrey T; Zervos, Marcus; Bhargava, Kanika

    2011-02-01

    Phenotypic detection of methicillin resistance in coagulase-negative Staphylococcus (CoNS) of animal origin has been challenging due to the heterogeneous expression of mecA. To compare different phenotypic methods in predicting the mecA presence in CoNS, a total of 87 CoNS isolates from agricultural animals were analyzed in this study by agar dilution, disk diffusion, and broth microdilution. mecA was present in 81 CoNS isolates. Broth microdilution demonstrated the highest sensitivity of 100% in predicting the mecA presence, followed by 72.8% by agar dilution and 70.4% by disk diffusion. The results indicate that broth microdilution may be more suitable for predicting the presence of mecA in CoNS from animals than the other two methods, although staphylococcal species may also be a factor affecting the sensitivities of the methods as the top three staphylococcal species in this study were Staphylococcus lentus, Staphylococcus sciuri, and Staphylococcus xylosus (a total of 75 of 87).

  11. Contribution of the Kallikrein/Kinin System to the Mediation of ConA-Induced Inflammatory Ascites.

    PubMed

    Baintner, Károly

    2016-03-01

    Intraperitoneal administration of concanavalin A (ConA, 25 mg/kg b.w.), a cell-binding plant lectin was used for inducing inflammatory ascites, and potential inhibitors were tested in 1 h and 2.5 h experiments, i.e. still before the major influx of leucocytes. At the end of the experiment the peritoneal fluid was collected and measured. The ConA-induced ascites was significantly (p<0.01) and dose-dependently inhibited by icatibant (HOE-140), a synthetic polypeptide antagonist of bradykinin receptors. Aprotinin, a kallikrein inhibitor protein also had significant (p<0.01), but less marked inhibitory effect. L-NAME, an inhibitor of NO synthesis, and atropine methylnitrate, an anticholinergic compound, were ineffective. It is concluded, that the kallikrein/kinin system contributes to the mediation of the ConA-induced ascites by increasing subperitoneal vascular permeability, independent of the eventual vasodilation produced by NO. It is known, that membrane glycoproteins are aggregated by the tetravalent ConA and the resulting distortion of membrane structure may explain the activation of the labile prekallikrein. Complete inhibition of the ConA-induced ascites could not be achieved by aprotinin or icatibant, which indicates the involvement of additional mediators.

  12. Is ACPA positivity the main driver for rheumatoid arthritis treatment? Pros and cons.

    PubMed

    Alivernini, Stefano; Galeazzi, Mauro; Peleg, Hagit; Tolusso, Barbara; Gremese, Elisa; Ferraccioli, Gianfranco; Naparstek, Yaakov

    2017-09-09

    Rheumatoid Arthritis (RA) is an autoimmune chronic disease that is characterized by the positivity of various antibodies, the most specific being autoantibodies against citrullinated antigens (ACPA). Despite ACPA are not arthritogenic by themselves, ACPA positive individuals have high risk of RA development and ACPA positivity is associated with severe erosive phenotype and higher mortality rate compared to seronegative RA. Moreover, ACPA status is associated with favorable response to biologics targeting pathways involving autoantibody producing cells as B lymphocytes. In the current review we have discussed the pros and cons on the available scientific evidences, regarding the diagnostic, prognostic and management implications of ACPAs in RA. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. The new human papillomavirus (HPV) vaccine: pros and cons for pediatric and adolescent health.

    PubMed

    Thomas, Tami L

    2008-01-01

    The new human papillomavirus (HPV) vaccine is a research breakthrough for pediatric/adolescent health to prevent cervical cancer and related morbidity. The annual heath care cost for the treatment of cervical cancer and genital warts is estimated to be more than three billion dollars a year. The new HPV vaccine has incredible potential to improve reproductive health promotion, reduce health care costs, and close health care disparity gaps. However, issues both for and against the new HPV vaccine, including mandating vaccination, high cost of the vaccine, the short duration of protection offered, and the perceived promotion of sexual activity, cause confusion. Pediatric nurses, including those in advanced practice, benefit by understanding the pros and cons of these issues in advocating for their patients.

  14. Multipotent (adult) and pluripotent stem cells for heart regeneration: what are the pros and cons?

    PubMed

    Liao, Song-Yan; Tse, Hung-Fat

    2013-12-24

    Heart failure after myocardial infarction is the leading cause of mortality and morbidity worldwide. Existing medical and interventional therapies can only reduce the loss of cardiomyocytes during myocardial infarction but are unable to replenish the permanent loss of cardiomyocytes after the insult, which contributes to progressive pathological left ventricular remodeling and progressive heart failure. As a result, cell-based therapies using multipotent (adult) stem cells and pluripotent stem cells (embryonic stem cells or induced pluripotent stem cells) have been explored as potential therapeutic approaches to restore cardiac function in heart failure. Nevertheless, the optimal cell type with the best therapeutic efficacy and safety for heart regeneration is still unknown. In this review, the potential pros and cons of different types of multipotent (adult) stem cells and pluripotent stem cells that have been investigated in preclinical and clinical studies are reviewed, and the future perspective of stem cell-based therapy for heart regeneration is discussed.

  15. From in vitro Experiments to in vivo and Clinical Studies; Pros and Cons.

    PubMed

    Saeidnia, Soodabeh; Manayi, Azadeh; Abdollahi, Mohammad

    2015-01-01

    Biomedical investigators use different methods including experimental animals, tissue, and cell cultures as well as computational simulations and clinical studies finding the ways to treat human diseases and disorders. All the mentioned procedures have their own advantages and disadvantages. For instance although animal models provide some drawbacks like difference in biokinetics parameters or extrapolation of results to human, they are more reliable than in vitro tests. The disadvantage of the in vitro procedures is that they are mostly performed on cancerous cell lines that have a substantially abnormal function. Furthermore, although in vitro models are fruitfully used in biological fields, finding an end point, the initial aim of chemical attack, and extrapolation of the effects to the human are some real weaknesses. Absence of biokinetics in in vitro methods may lead to a misinterpretation of the data. The present review has criticized the pros and cons of both methods, especially in the fields of pharmacology, toxicology, and medical sciences.

  16. What to consider when regulating electronic cigarettes: Pros, cons and unintended consequences.

    PubMed

    Caponnetto, Pasquale; Saitta, Daniela; Sweanor, David; Polosa, Riccardo

    2015-06-01

    Many public health experts, medical research societies, large health organizations and policy makers have expressed concerns about the increased popularity of electronic cigarettes and have pushed for more restrictive measures ranging from complete bans to tight regulations of these products either as medicines or as tobacco products. But these concerns have never been adequately qualified nor quantified. Without judicious assessment and thorough evaluation, regulations may have unintended consequences that can do more damage than good in public health terms. In this article, we will appraise the existing prominent regulatory frameworks for e-cigarettes, namely, general consumer product, medicinal product and tobacco product regulation, to highlight their pros and cons. Moreover, we provide concrete examples of the unintended consequences which may arise from inappropriate regulatory action.

  17. Multipotent (adult) and pluripotent stem cells for heart regeneration: what are the pros and cons?

    PubMed Central

    2013-01-01

    Heart failure after myocardial infarction is the leading cause of mortality and morbidity worldwide. Existing medical and interventional therapies can only reduce the loss of cardiomyocytes during myocardial infarction but are unable to replenish the permanent loss of cardiomyocytes after the insult, which contributes to progressive pathological left ventricular remodeling and progressive heart failure. As a result, cell-based therapies using multipotent (adult) stem cells and pluripotent stem cells (embryonic stem cells or induced pluripotent stem cells) have been explored as potential therapeutic approaches to restore cardiac function in heart failure. Nevertheless, the optimal cell type with the best therapeutic efficacy and safety for heart regeneration is still unknown. In this review, the potential pros and cons of different types of multipotent (adult) stem cells and pluripotent stem cells that have been investigated in preclinical and clinical studies are reviewed, and the future perspective of stem cell-based therapy for heart regeneration is discussed. PMID:24476362

  18. Pros and cons of healthcare information technology implementation: the pros win.

    PubMed

    Maffei, Roxana

    2006-01-01

    Countless studies and investigations have been performed siding either for or against the implementation of technology in the healthcare setting. This article presents both sides of this debate, with an obvious conclusion that the pros of this debate win. The practice of information technology in the medical domain lags behind its knowledge and discovery by at least 7 years. The key to closing this gap is to show, through various studies, how information technology systems provide decision support to users at the point in time when decisions are needed. What the reader will obtain from this article is that the pros for information technology implementation in healthcare settings weigh much more and have a greater effect than the cons.

  19. Space and terrestrial media for military communications - Technical pros and cons

    NASA Astrophysics Data System (ADS)

    Dharamsi, Manoj T.; Reilly, James F.; Hawrylko, Warren P.

    Technical pros and cons are presented for space and terrestrial media for defense-wide long-haul military communications. Defense-wide military space communications include use of leased commercial satellite capability in addition to the government-owned Defense Satellite Communications System (DSCS). The terrestrial communications include use of troposcatter, HF radios, line-of-sight microwave, and metallic and fiber-optic cables. The current usage, capacity, cost, and other attributes of these media are examined. Current trends and future uses of the space and terrestrial media for military communications are discussed. It is concluded that military communications can continue best by using a mix of both space and terrestrial media.

  20. DESAFÍOS ÉTICOS DE LA INVESTIGACIÓN CON ANIMALES, MANIPULACIÓN GENÉTICA

    PubMed Central

    Yunta, Eduardo Rodríguez

    2012-01-01

    En la investigación con animales existen cuestionamientos éticos tanto en el uso como modelos de enfermedades humanas y requisito previo para ensayos en humanos como en la introducción de modificaciones genéticas. Algunos de estos cuestionamientos son: no representar exactamente la condición humana como modelos, realizar pruebas de toxicidad con grave daño para los animales, alterar su naturaleza mediante modificaciones genéticas, riesgos de la introducción de organismos genéticamente modificados. El uso de animales en investigación para beneficio humano, impone al ser humano la responsabilidad moral de respetarlo, no haciéndoles sufrir innecesariamente, al estar trabajando con seres vivientes y sentientes. PMID:23338641

  1. Formación estelar en NGC 6357: viendo a través del polvo con Gemini

    NASA Astrophysics Data System (ADS)

    Bosch, G.; Morrell, N.; Barbá, R.

    Presentamos aquí los primeros resultados de fotometría JHKs obtenidos con Flamingos I en el telescopio Gemini Sur. El mosaico comprendido por tres posiciones adyacentes tomadas a lo largo de varios semestres nos permite caracterizar la población estelar en la zona que presenta una interacción más importante entre las estrellas masivas y la nube molecular que les dió origen. Los diagramas color-magnitud nos permiten identificar numerosas fuentes con exceso infrarrojo, la mayoría de ellas imposible de detectarse en el rango óptico debido a la fuerte absorción del polvo presente en la región. Es altamente probable que la mayoría de estas fuentes con exceso sean protoestrellas, aunque es necesario realizar espectroscopía infrarroja de las mismas para confirmar su naturaleza.

  2. La salud en personas con discapacidad intelectual en España: estudio europeo POMONA-II

    PubMed Central

    Martínez-Leal, Rafael; Salvador-Carulla, Luis; Gutiérrez-Colosía, Mencía Ruiz; Nadal, Margarida; Novell-Alsina, Ramón; Martorell, Almudena; González-Gordón, Rodrigo G.; Mérida-Gutiérrez, M. Reyes; Ángel, Silvia; Milagrosa-Tejonero, Luisa; Rodríguez, Alicia; García-Gutiérrez, Juan C.; Pérez-Vicente, Amado; García-Ibáñez, José; Aguilera-Inés, Francisco

    2011-01-01

    Introducción Estudios internacionales demuestran que existe un patrón diferenciado de salud y una disparidad en la atención sanitaria entre personas con discapacidad intelectual (DI) y población general. Objetivo Obtener datos sobre el estado de salud de las personas con DI y compararlos con datos de población general. Pacientes y métodos Se utilizó el conjunto de indicadores de salud P15 en una muestra de 111 sujetos con DI. Los datos de salud encontrados se compararon según el tipo de residencia de los sujetos y se utilizó la Encuesta Nacional de Salud 2006 para comparar estos datos con los de la población general. Resultados La muestra con DI presentó 25 veces más casos de epilepsia y el doble de obesidad. Un 20% presentó dolor bucal, y existió una alta presencia de problemas sensoriales, de movilidad y psicosis. Sin embargo, encontramos una baja presencia de patologías como la diabetes, la hipertensión, la osteoartritis y la osteoporosis. También presentaron una menor participación en programas de prevención y promoción de la salud, un mayor número de ingresos hospitalarios y un uso menor de los servicios de urgencia. Conclusiones El patrón de salud de las personas con DI difiere del de la población general, y éstas realizan un uso distinto de los servicios sanitarios. Es importante el desarrollo de programas de promoción de salud y de formación profesional específicamente diseñados para la atención de personas con DI, así como la implementación de encuestas de salud que incluyan datos sobre esta población. PMID:21948011

  3. Self-efficacy, pros, and cons as variables associated with adjacent stages of change for regular exercise in Japanese college students.

    PubMed

    Horiuchi, Satoshi; Tsuda, Akira; Kobayashi, Hisanori; Fallon, Elizabeth A; Sakano, Yuji

    2016-01-18

    This study examined self-efficacy (confidence to exercise), pros (exercise's advantages), and cons (exercise's disadvantages) as variables associated across the transtheoretical model's six stages of change in 403 Japanese college students. A series of logistic regression analyses were conducted. Results showed that higher pros and lower cons were associated with being in contemplation compared to precontemplation. Lower cons were associated with being in preparation compared to contemplation. Higher self-efficacy was associated with being in action compared to preparation as well as being in maintenance compared to action. Lower cons were associated with being in termination compared to maintenance.

  4. Prevalence and antimicrobial susceptibility pattern of coagulase-negative staphylococci (CoNS) isolated from clinical specimens in Northern of Jordan.

    PubMed

    Al Tayyar, Ibrahim Ali; Al-Zoubi, Mazhar Salim; Hussein, Emad; Khudairat, Salih; Sarosiekf, Konrad

    2015-12-01

    Coagulase negative Staphylococci (CoNS) are one of the most common bacteria found on human skin and on mucous membranes as a component of normal flora. The presence of CoNS in clinical specimens is frequently associated with an infectious aetiology or contamination. We aimed to evaluate CoNS species distribution and susceptibility patterns in specimens obtained from clinics and hospitals in the Northern area of Jordan. Standard identification methods showed the presence of CoNS in 223 specimens at different local hospitals. Susceptibility testing was performed using 18 antibiotics in accordance with the Clinical and Laboratory Standards Institute (CLSI) recommendations. Staphylococcus epidermidis and S. haemolyticus were found to be the most common species isolated from all specimens representing 122 (54.7%) and 52 (23.4%) of all CoNS species, respectively. Antibiotic susceptibility testing of CoNS species revealed their sensitivity to vancomycin, linozolid, rifampin and nitrofurantin, while showing a highly resistant pattern to ampicillin, penicillin, ceftriaxone, cefazolin, amoxicillin-clavulanic acid and erythromycin. Some variation of the susceptibility pattern of CoNS species were identified in specimens isolated from the ICU and paediatric hospital wards as well as from clinical specimens of urine, blood and catheter tips. The most common CoNS isolates were found to be S. epidermidis and S. haemolyticus with variable percentages according to the specimen source. Moreover, a high susceptibility CoNS to vancomycin, rifampin, and linezolid showed resistance to amoxicillin and penicillin.

  5. Economic and Ethical Consequences of Natural Hazards in Alpine Valleys (EE-Con)

    NASA Astrophysics Data System (ADS)

    Ortner, Florian; Brantl, Dirk; Meyer, Lukas; Steininger, Karl; Sass, Oliver

    2015-04-01

    The Alps and their population are particularly vulnerable to geomorphological and hydrological hazards and this problem might be amplified by ongoing climate change. Natural disasters cause severe monetary damage which often leads to the difficult question whether it socially pays to protect settlements at high costs or whether alternatively settlement areas should better be abandoned. By investigations in the Johnsbachtal and the Kleinsölktal (Styria), the interdisciplinary project "Economic and Ethical Consequences of Natural Hazards in Alpine Valleys" (EE-Con), funded by the Austrian Academy of Sciences, seeks to answer the following questions: (1) Are natural hazards and associated damages in fact increasing, and is this due to meteorological triggers, to anthropogenic factors or to internal process dynamics? (2) What is the perception and knowledge of local people, how is risk and risk prevention communicated? (3) What is the respective cost ratio between protection infrastructure, soft measures of adaptation and other options (e.g. reduction of settlement area)? (4) What legitimate claims to compensation do people have, how far does societal responsibility go and where does individual responsibility start if parts of the settlement area had to be abandoned? These questions will be tackled in an interdisciplinary cooperation between geography, economics and normative theory (philosophy). EE-Con will follow broadly the path of risk analysis and risk assessment, focusing on the temporal dimension (past - present - future) with the aim to unravel the history of natural hazards in the areas and to analyse the economic values involved. In the following, natural hazard scenarios for the future (2050 and 2100) will be developed considering the economic consequences. Besides this, the project deals with local knowledge, risk perception and risk communication, which will be investigated via group interviews and stakeholder workshops and be integrated into a human

  6. Future of clip-on weapon sights: pros and cons from an applications perspective

    NASA Astrophysics Data System (ADS)

    Knight, C. Reed; Greenslade, Ken; Francisco, Glen

    2015-05-01

    US Domestic, International, allied Foreign National Warfighters and Para-Military First Responders (Police, SWAT, Special Operations, Law Enforcement, Government, Security and more) are put in harm's way all the time. To successfully complete their missions and return home safely are the primary goals of these professionals. Tactical product improvements that affect mission effectiveness and solider survivability are pivotal to understanding the past, present and future of Clip-On in-line weapon sights. Clip-On Weapon Sight (WS) technology was deemed an interim solution by the US Government for use until integrated and fused (day/night multi-sensor) Weapon Sights (WSs) were developed/fielded. Clip-On has now become the solution of choice by Users, Warriors, Soldiers and the US Government. SWaP-C (size, weight and power -cost) has been improved through progressive advances in Clip-On Image Intensified (I2), passive thermal, LL-CMOS and fused technology. Clip-On Weapon Sights are now no longer mounting position sensitive. Now they maintain aim point boresight, so they can be used for longer ranges with increased capabilities while utilizing the existing zeroed weapon and daysight optic. Active illuminated low-light level (both analog I2 and digital LL-CMOS) imaging is rightfully a real-world technology, proven to deliver daytime and low-light level identification confidence. Passive thermal imaging is also a real-world technology, proven to deliver daytime, nighttime and all-weather (including dirty battlefield) target detection confidence. Image processing detection algorithms with intelligent analytics provide documented promise to improve confidence by reducing Users, Warriors and Soldiers' work-loads and improving overall system engagement solution outcomes. In order to understand the future of Clip-On in-line weapon sights, addressing pros and cons, this paper starts with an overview of historical weapon sight applications, technologies and stakeholder decisions

  7. iPathCons and iPathDB: an improved insect pathway construction tool and the database

    PubMed Central

    Zhang, Zan; Yin, Chuanlin; Liu, Ying; Jie, Wencai; Lei, Wenjie; Li, Fei

    2014-01-01

    Insects are one of the most successful animal groups on earth. Some insects, such as the silkworm and honeybee, are beneficial to humans, whereas others are notorious pests of crops. At present, the genomes of 38 insects have been sequenced and made publically available. In addition, the transcriptomes of dozens of insects have been sequenced. As gene data rapidly accumulate, constructing the pathway of molecular interactions becomes increasingly important for entomological research. Here, we developed an improved tool, iPathCons, for knowledge-based construction of pathways from the transcriptomes or the official gene sets of genom