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Sample records for chlorpromazine

  1. Pharm GKB: chlorpromazine [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available tine carvedilol chlorpheniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan...ne citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan...ipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine fluvoxami...tine carvedilol chlorpheniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan...lorpheniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan

  2. Chlorpromazine induced ocular myasthenia gravis

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    Nitya S

    2013-10-01

    Full Text Available Drug induced bilateral ptosis is a very rare adverse drug reaction. Here we report a case of ten year old male child with chlorpromazine induced bilateral ptosis due to ocular myasthenia. [Int J Basic Clin Pharmacol 2013; 2(5.000: 653-654

  3. Compound list: chlorpromazine [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available chlorpromazine CPZ 00016 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/chlorproma...zine.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/chlorproma.../in_vivo/Liver/Single/chlorpromazine.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosc...iencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/chlorpromazine.Rat.in_vivo.Liver.Repeat.zip ...

  4. Chlorpromazine

    Science.gov (United States)

    ... of interest in life, and strong or inappropriate emotions) and other psychotic disorders (conditions that cause difficulty ... menstrual periods decreased sexual ability changes in skin color dry mouth stuffed nose difficulty urinating widening or ...

  5. Chlorpromazine inhibits mitosis of mammalian cells.

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    Boder, G B; Paul, D C; Williams, D C

    1983-09-01

    Chlorpromazine (CPZ) at minimally effective concentrations accumulates mammalian cells in mitosis without lethal effects on the cells. Star-metaphase morphology similar to effects seen with classical antimitotic compounds probably results from the preferential action of CPZ on a specific class of microtubules--the pole-to-pole microtubules of the mitotic spindle. At CPZ concentrations of 8 X 10(-6) M, flow cytometry indicates no effect of CPZ on the progress of cells through phases of the cell cycle other than mitosis (M). These results suggest a possible mechanism for toxic side effects of CPZ in man such as granulocytopenia and light sensitization.

  6. Neurotrophic corneal ulcer after retrobulbar injection of chlorpromazine.

    Science.gov (United States)

    Hauck, Matthew J; Lee, Hb Harold; Timoney, Peter J; Shoshani, Yochai; Nunery, William R

    2012-01-01

    An 80-year-old woman with a painful, poorly seeing right eye underwent retrobulbar chlorpromazine injection for pain control. After the injection, the patient's symptoms improved; however, a neurotrophic ulcer developed within 2 weeks after the procedure. It is postulated that chlorpromazine may lead to sensory denervation to the cornea with the subsequent development of neurotrophic keratopathy, as observed in this case. Awareness of this potential adverse effect is important for proper patient safety, education, and postinjection management.

  7. Effect of chlorpromazine on rat arterial lipid synthesis, in vitro

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    Bell, F.P.; Hubert, E.V.

    1982-10-01

    The effect of chlorpromazine, a major tranquilizer, on arterial lipid metabolism was studied in vitro in rat aortas incubated with (/sup 14/C)acetate and (/sup 14/C)mevalonate as lipid precursors. Chlorpromazine at a level of 0.25 mM in the incubation medium significantly reduced the incorporation of (/sup 14/C)acetate into free fatty acids (p less than 0.01) and total phospholipids (p less than 0.001) but not triglycerides. Chlorpromazine also altered the pattern of arterial phospholipids synthesized from (/sup 14/C)acetate by significantly increasing the relative proportion of phosphatidylinositol plus phosphatidylserine (p less than 0.02) and reducing the relative proportion of sphingomyelin (p less than 0.001). (/sup 14/C) Acetate incorporation into the combined fractions of steryl esters plus hydrocarbons and sterols plus diglycerides was also significantly reduced (p less than 0.001) by 0.25 mM chlorpromazine. Studies with (/sup 14/C)mevalonate showed that chlorpromazine is also an inhibitor of sterol biosynthesis in arterial tissues as evidenced by 35-40% reductions (p less than 0.05) in the formation of /sup 14/C-labeled squalene and C27 sterols.

  8. A case of tinnitus induced by chlorpromazine in a pediatric patient

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    Carla Carnovale

    2014-01-01

    Full Text Available Chlorpromazine is a well-known antipsychotic agent that binds with a variety of receptors in the central nervous system. To date, chlorpromazine has never been associated with onset of hearing disorders and tinnitus. We report on an unexpected suspect adverse reaction to chlorpromazine that occurred in a 12-year-old boy, affected by severe generalized anxiety disorder. After treatment with chlorpromazine, the patient experienced an enhanced sensitivity to sounds accompanied by perception of noises of the buzzing or ringing type. This clinical case is of great clinical interest as chlorpromazine is not currently included among potentially ototoxic drugs.

  9. Priapisme induit par la chlorpromazine: A propos de deux cas

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    I. Marrag

    2016-06-01

    Le priapisme veineux est une urgence urologique. Il constitue un des effets secondaires des neuroleptiques parmi les quels la chlorpromazine. Cet effet iatrogène, qui est rare mais grave, doit être connu par les cliniciens afin d’être mieux prévenu pour éviter les séquelles érectiles.

  10. Chlorpromazine-induced status epilepticus: A case report

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    Momčilović-Kostadinović Dragana

    2013-01-01

    Full Text Available Introduction. It is largely known that some antipsychotic agents could have proconvulsive and proepileptogenic effects in some patients and could induce EEG abnormalities as well. However, the association of status epilepticus with certain antipsychotic drugs has been very rarely reported. Case Report. A case of an 18-year-old adolescent girl, with chlorpromazine therapy started for anxiety-phobic disorder was reported. Her personal history disclosed delayed psychomotor development. Shortly after the introduction of the neuroleptic chlorpromazine therapy in minimal daily dose (37.5 mg, she developed myoclonic status epilepticus, confirmed by the EEG records. Frequent, symmetrical bilateral myoclonic jerks and altered behavior were associated with bilateral epileptiform discharges of polyspikes and spike-wave complexes. This epileptic event lasted 3.5 hours and it was stopped by the parenteral administration of valproate and lorazepam; she was EEG monitored until stable remission. Status epilepticus as initial epileptic event induced by neuroleptic agent was not previously reported in our national literature. Conclusion. Introduction of chlorpromazine to a patient without history of seizures is associated with the evolution of an epileptic activity, including the occurrence of status epilepticus. Clinical evaluation of the risk factors possibly related to chlorpromazine-induced seizure is recommended in individual patients before administering this drug.

  11. [Photodegradation of chlorpromazine, a drug-related adverse event].

    Science.gov (United States)

    Chabi, Yossounon; Brahim, Kheira; Da Costa, Maryline; Caffin, Anne-Gaëlle; Camus, Gisèle; Paillet, Michel; Bohand, Xavier

    2016-04-01

    The photodegradation of an active substance during treatment is a rare drug-related adverse event which can sometimes have serious consequences. Health professionals must be aware of the specific storage and administration instructions with regard to chlorpromazine and ensure that they are respected.

  12. [A difficult stabilisation. Chlorpromazine in the fifties in Belgium].

    Science.gov (United States)

    Majerus, Benoît

    2010-01-01

    Through a Belgian case study the article tries to trace the gradual stabilisation of chlorpromazine as an antipsychotic in the 1950s. By varying ranges and angles of approach it shows the heterogeneity of actors involved and the semantic bricolage that accompany the marketing of the first antipsychotic. Far from being a revolution, the presence of Largactil in psychiatric practice is rather characterised by integration into a wider range of medicines and sinuous searching to give sense to this new drug.

  13. Voltammetric Determination of Captopril Using Chlorpromazine as a Homogeneous Mediator

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    Hossein Bahramipur

    2011-01-01

    Full Text Available Chlorpromazine was used as a homogeneous electrocatalyst in the oxidation of captopril. The anodic peak current of chlorpromazine was increased substantially in the presence of low concentrations of captopril (pH 4. Cyclic voltammetry and chronoamperometry were used to study the kinetics of the catalytic electron transfer reaction. The values of electron transfer coefficient ( and catalytic rate constant (cat were estimated to be 0.34 and 8.48×102M−1sec−1, respectively. Linear sweep voltammetry was used for the determination of captopril in the presence of chlorpromazine. A linear calibration curve was obtained in the concentration range of captopril of 10.0–300.0 μM, with a limit of detection of 3.65 μM. The relative standard deviation (RSD% for 5 replicate measurements of captopril (100 μM was 1.96%. The method was applied to the determination of captopril in pharmaceutical formulations and blood serum samples with satisfactory results.

  14. Clinical evaluation of sulpiride in schizophrenic patients--a double-blind comparison with chlorpromazine.

    Science.gov (United States)

    Härnryd, C; Bjerkenstedt, L; Björk, K; Gullberg, B; Oxenstierna, G; Sedvall, G; Wiesel, F A; Wik, G; Aberg-Wistedt, A

    1984-01-01

    To evaluate the clinical potential of sulpiride for the treatment of schizophrenic patients, a double-blind study was performed comparing fixed doses of sulpiride (800 mg daily) and chlorpromazine (400 mg daily). Twenty-five schizophrenic (RDC) patients participated in each treatment group. Antipsychotic effects were evaluated by CPRS and NOSIE ratings before and after 1, 2, 4 and 8 weeks of treatment. Interrater reliabilities for CPRS items and subscales were satisfactory. Treatment with sulpiride or chlorpromazine resulted in a significant reduction of psychotic morbidity as estimated by CPRS and global ratings. CPRS scores reflecting autism were significantly reduced in all ratings of sulpiride-treated patients, but only after four weeks in the chlorpromazine group. Total NOSIE scores indicated improvement in both treatment groups. A significant difference in favour of sulpiride was obtained for the NOSIE subscale "retardation". Extrapyramidal side effects occurred at a similar frequency in both treatment groups. Autonomic side effects occurred to a greater extent in chlorpromazine-treated patients. Lactation was reported only in four sulpiride-treated patients. Liver transaminase enzymes in serum were markedly elevated only in chlorpromazine-treated patients. The results indicate that sulpiride has a marked antipsychotic effect which is at least not inferior to that of chlorpromazine. A better effect on autistic components of behaviour was demonstrated for sulpiride. The results indicate a higher risk of lactation but a lower risk of anticholinergic side effects and liver toxicity for treatment with sulpiride than with chlorpromazine.

  15. Melanogenesis and antioxidant defense system in normal human melanocytes cultured in the presence of chlorpromazine.

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    Otreba, Michał; Wrześniok, Dorota; Beberok, Artur; Rok, Jakub; Buszman, Ewa

    2015-02-01

    Chlorpromazine is used in the treatment of schizophrenia and psychotic disorders and belongs to phenothiazine class of neuroleptic drugs. It shows severe side effects such as extrapyramidal symptoms as well as ocular and skin disorders, but the mechanism is still not fully established. The aim of this study was to examine the effect of chlorpromazine on cell viability, melanogenesis and antioxidant defense system in normal human melanocytes. It has been demonstrated that chlorpromazine induces concentration dependent loss in cell viability. The value of EC(50) was calculated to be 2.53 μM. Chlorpromazine in lower concentrations (0.0001, 0.001 and 0.01 μM) increased the melanin and microphthalmia-associated transcription factor (MITF) content and tyrosinase activity, while changes of antioxidant enzymes activity were not observed. It suggests that long-term chlorpromazine therapy, even with low drug doses, may lead to hyperpigmentation disorders in skin and/or eye. The use of the analyzed drug in higher concentrations (0.1 and 1.0 μM) caused significant alterations of antioxidant enzymes activity in normal melanocytes, what may explain a potential role of chlorpromazine in the depletion of cellular antioxidant status leading to other adverse effects associated with the high-dose and/or long-term therapy.

  16. Molecular cytotoxic mechanisms of chlorpromazine in isolated rat hepatocytes.

    Science.gov (United States)

    MacAllister, Stephanie L; Young, Cheryl; Guzdek, Anna; Zhidkov, Nickholas; O'Brien, Peter J

    2013-01-01

    Chlorpromazine (CPZ), a member of the largest class of first-generation antipsychotic agents, is known to cause hepatotoxicity in the form of cholestasis and hepatocellular necrosis in some patients. The mechanism of CPZ hepatotoxicity is unclear, but is thought to result from reactive metabolite formation. The goal of this research was to assess potential cytotoxic mechanisms of CPZ using the accelerated cytotoxicity mechanism screening (ACMS) technique with freshly isolated rat hepatocytes. This study identified CPZ cytotoxicity and inhibition of mitochondrial membrane potential (MMP) to be concentration-dependent. Furthermore, inhibition of cytochrome P450s (CYPs), including CYP2D1 and 1A2, delayed CPZ cytotoxicity, suggesting a role for CYP activation of CPZ to a toxic metabolite(s) in this model. Metabolism studies also demonstrated glucuronide and glutathione (GSH) requirement for CPZ detoxification in hepatocytes. Inactivating the 2-electron reduction pathway, NAD(P)H quinone oxidoreductase (NQO1), caused a significant increase in hepatocyte susceptibility to CPZ, indicating quinoneimine contribution to CPZ cytotoxicity. Nontoxic concentrations of peroxidase/H(2)O(2) (inflammatory model) increased cytotoxicity in CPZ-treated hepatocytes and caused additional mitochondrial toxicity. Inflammation further depleted GSH and increased oxidized glutathione (GSSG) levels. Results suggest activation of CPZ to reactive metabolites by 2 pathways in hepatocytes: (i) a CYP-catalyzed quinoneimine pathway, and (ii) a peroxidase-catalyzed oxidation of CPZ to CPZ radicals.

  17. The effect of anti-parkinsonian drugs on chlorpromazine-induced depression of operant behaviour.

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    Székely, J I; Dunai-Kovács, Z; Borsy, J

    1976-01-01

    Rats were conditioned in automatic Skinner boxes on a discrete trial avoidance-escape schedule. The chlorpromazine-induced conditioned reflex inhibition could be reversed by apomorphine and amantadine, but not by atropine, trihexyphenidyl and diethazine. These findings seem to provide an additional tool for differentiating the atropine-like and dopaminergic anti-parkinsonian drugs.

  18. The novel combination of chlorpromazine and pentamidine exerts synergistic antiproliferative effects through dual mitotic action.

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    Lee, Margaret S; Johansen, Lisa; Zhang, Yanzhen; Wilson, Amy; Keegan, Mitchell; Avery, William; Elliott, Peter; Borisy, Alexis A; Keith, Curtis T

    2007-12-01

    Combination therapy has proven successful in treating a wide variety of aggressive human cancers. Historically, combination treatments have been discovered through serendipity or lengthy trials using known anticancer agents with similar indications. We have used combination high-throughput screening to discover the unexpected synergistic combination of an antiparasitic agent, pentamidine, and a phenothiazine antipsychotic, chlorpromazine. This combination, CRx-026, inhibits the growth of tumor cell lines in vivo more effectively than either pentamidine or chlorpromazine alone. Here, we report that CRx-026 exerts its antiproliferative effect through synergistic dual mitotic action. Chlorpromazine is a potent and specific inhibitor of the mitotic kinesin KSP/Eg5 and inhibits tumor cell proliferation through mitotic arrest and accumulation of monopolar spindles. Pentamidine treatment results in chromosomal segregation defects and delayed progression through mitosis, consistent with inhibition of the phosphatase of regenerating liver family of phosphatases. We also show that CRx-026 synergizes in vitro and in vivo with the microtubule-binding agents paclitaxel and vinorelbine. These data support a model where dual action of pentamidine and chlorpromazine in mitosis results in synergistic antitumor effects and show the importance of systematic screening for combinations of targeted agents.

  19. Chlorpromazine as permeabilizer and reagent for detection of microbial peroxidase and peroxidaselike activities.

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    Galeazzi, L; Turchetti, G; Grilli, G; Groppa, G; Giunta, S

    1986-01-01

    Chlorpromazine was used to perform a test for the detection of microbial peroxidase activities. The compound acts as both a cell permeabilizer and a reagent in the procedure developed which allows the detection of peroxidase and peroxidase like reactions both semiquantitatively in whole cell determinations and quantitatively in cell-free supernatants. PMID:3539020

  20. Inactivation of the Scrapie agent by ultraviolet irradiation in the presence of chlorpromazine

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    Dees, C.; Wade, W.F.; German, T.L.; Marsh, R.F. (Wisconsin Univ., Madison (USA). Dept. of Veterinary Science)

    1985-04-01

    The sensitivity of the scrapie agent to u.v. inactivation was found to be related to the purity of the tissue preparation. Scrapie infectivity associated with membrane vesicles was unaffected when irradiated with 10/sup 4/ J/m/sup 2/. Irradiation of more highly purified preparations from detergent-extracted CsCl gradient fractions reduced scrapie infectivity from 10sup(7.8) log/sub 10/ LD/sub 50/ per ml to as low as 10sup(4.5). Sensitivity of membrane-associated scrapie infectivity to inactivation by u.v. irradiation could be increased by addition of chlorpromazine, a phenthiazine antipsychotic which penetrates lipid bilayers and induces single-strand breaks in nucleic acids under irradiation. Chlorpromazine without irradiation, and a semiquinone protein-binding radical of chlorpromazine, failed to decrease scrapie infectivity by themselves. A closely related phenthiazine antipsychotic, trifluoperazine, which does not bind to nucleic acids, did not reduce scapie infectivity. These findings suggest that the target of u.v. radiation for inactivation of scrapie infectivity in the presence of chlorpromazine is an essential nucleic acid.

  1. Chlorpromazine equivalents versus defined daily doses : How to compare antipsychotic drug doses?

    NARCIS (Netherlands)

    Rijcken, CAW; Monster, TBM; Brouwers, JRBJ; de Jong-van den Berg, LTW

    2003-01-01

    Classic chlorpromazine (CPZ) equivalents can be used to chart relative antipsychotic potencies of antipsychotic drugs. Values of CPZ equivalents per drug are ambiguous in literature. In drug use evaluation studies, antipsychotic doses are frequently compared by use of the defined daily dose (DDD). T

  2. Response of Ehrlich carcinoma and the small intestine of mouse to combined treatment with chlorpromazine and X-rays

    Energy Technology Data Exchange (ETDEWEB)

    Rao, K.R. (Zurich Univ. (Switzerland). Strahlenbiologisches Inst.)

    1991-05-01

    The effect of combined treatment with chlorpromazine (20 mg/kg body weight) and X-rays at different dose levels was tested on the growth of Ehrlich carcinoma tumor in solid or ascites form in mice. The radiation response of murine gut was also examined separately but under similar experimental conditions. The results obtained indicate that chlorpromazine did not influence the radiation response of all the test systems used in this study. The relevant literature, reviewed in short, shows that the interaction between chlorpromazine and X-rays can result in enhanced radiation response, non-interference or increased radiation tolerance. Therefore any combined effect of chlorpromazine and X-ray observed cannot be generalised. (orig.).

  3. The effect of 4% Lignocaine gel, 5% Amiloride HCl and 10% Chlorpromazine on E.faecalis

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    Udayakumar Jayasimha Raj

    2011-01-01

    Full Text Available Introduction : Thorough disinfection of the root canal system is essential for the success of root canal therapy. Enterococcus faecalis is the most frequently found species in persistent/secondary intracanal infection associated endodontic treatment failure. The aim of this study was to evaluate the disinfection of dentinal tubules using 10% Chlorpromazine, 4% Lignocaine gel, 5% Amiloride hydrochloride in comparison with 2% chlorhexidine gel. Materials and Methods : The antibacterial efficacy of the four medicaments against Enterococcus faecalis was assessed in vitro using extracted human first and second mandibular premolar teeth at the depths of 200 ΅m and 400 ΅m. Results : The overall percentage inhibition of bacterial growth was 100% with 2% chlorhexidine gel followed by 10% chlorpromazine (88.8%, 4% lignocaine gel (76.4% and 5% amiloride hydrochloride (71.4%. Conclusion : 2% chlorhexidine gel was most effective against E. faecalis followed by the newer non- antibiotic medicament 10% chlorpromazine when compared to the other medicaments tested.

  4. Severe Agranulocytosis following Simultaneous Administration of Chlorpromazine and Trimethoprim-Sulfamethoxazole in a Patient with Sepsis: A Possible Toxic Combination

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    Anil Jha

    2016-01-01

    Full Text Available Background. Chlorpromazine and trimethoprim-sulfamethoxazole (TMP/SMX are two commonly prescribed medications by physicians. Either of those medications could cause fatal drug-induced agranulocytosis, with an unclear underlying mechanism. The likelihood of simultaneous prescription of both medications is high and could hypothetically result in severe agranulocytosis that is resistant to treatment. Case Presentation. We are presenting a case of a patient with psychosis on chlorpromazine who was prescribed TMP/SMX for a urinary tract infection. Consequently, the patient developed severe agranulocytosis and septicemia. Patient was managed by granulocyte colony-stimulating factor; however, the time to neutrophil recovery was delayed when compared to the average reported time published by previous studies. Conclusions. Simultaneous use of chlorpromazine and TMP/SMX is a possible toxic combination that could induce severe agranulocytosis. Further reports are needed to confirm this observation.

  5. Randomised clinical trial of Levonantradol and Chlorpromazine in the prevention of radiotherapy-induced vomiting

    Energy Technology Data Exchange (ETDEWEB)

    Lucraft, H.H.; Palmer, M.K. (Christie Hospital and Holt Radium Inst., Manchester (UK))

    1982-11-01

    Levonantradol is a cannabis derivative. Cannabinoid anti-emetics are being assessed in cancer chemotherapy but have been little used in radiotherapy to date. A pilot study and randomised trial compared the anti-emetic effect of a standard drug (Chlorpromazine 25 mg) with Levonantradol at two doses (0.5 and 0.75 mg) in patients receiving palliative single fraction radiotherapy to sites likely to cause nausea and vomiting. Most patients were out-patients. Both drugs were well tolerated. The frequency of vomiting was similar in all three groups in both the pilot study and randomised trial.

  6. Abnormal dissolutions of chlorpromazine hydrochloride tablets in water by paddle method under a high agitation condition.

    Science.gov (United States)

    Aoyagi, Nobuo; Rimando, Annie Policarpio; Izutsu, Kenichi; Katori, Noriko; Kojima, Shigeo

    2003-09-01

    All sugar-coated tablets of chlorpromazine hydrochloride except for those produced by one manufacture showed concave dissolution profiles in water by paddle method at 100 rpm but not at 50 rpm. The study was undertaken to clarify the agitation-dependent abnormal dissolutions. The strange dissolutions were also observed in water at different ionic strengths but not in buffer solutions of pH 1.2, 4.0 and 6.8. When monitored, the pH's of water in dissolution vessels for the abnormal tablets increased with time at 100 rpm and some of them exceeded pH 8 but did not at 50 rpm. The solubility of chlorpromazine hydrochloride decreased with the increase of pH which was too low to dissolve the whole amount of drug contained in a tablet at pH 8. The elevation of pH seemed to be mainly brought about by dissolution of calcium carbonate popularly used for sugar-coated tablets, because larger amount of calcium ion was dissolved out from the abnormal tablets at 100 rpm than from a normal tablet and from them at 50 rpm. These findings indicate that the concave dissolution profiles should be caused by the decrease of drug solubility with increase in pH of water, probably because of dissolution of calcium carbonate. We should pay attention to the change in pH of water which may differ depending on the agitation speed of dissolution tests.

  7. Short-Term Effects of Chlorpromazine on Oxidative Stress in Erythrocyte Functionality: Activation of Metabolism and Membrane Perturbation

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    Silvana Ficarra

    2016-01-01

    Full Text Available The purpose of this paper is to focus on the short-term effects of chlorpromazine on erythrocytes because it is reported that the drug, unstable in plasma but more stable in erythrocytes, interacts with erythrocyte membranes, membrane lipids, and hemoglobin. There is a rich literature about the side and therapeutic effects or complications due to chlorpromazine, but most of these studies explore the influence of long-term treatment. We think that evaluating the short-term effects of the drug may help to clarify the sequence of chlorpromazine molecular targets from which some long-term effects derive. Our results indicate that although the drug is primarily intercalated in the innermost side of the membrane, it does not influence band 3 anionic flux, lipid peroxidation, and protein carbonylation processes. On the other hand, it destabilizes and increases the autooxidation of haemoglobin, induces activation of caspase 3, and, markedly, influences the ATP and reduced glutathione levels, with subsequent exposure of phosphatidylserine at the erythrocyte surface. Overall our observations on the early stage of chlorpromazine influence on erythrocytes may contribute to better understanding of new and interesting characteristics of this compound improving knowledge of erythrocyte metabolism.

  8. The antipsychotic drug chlorpromazine enhances the cytotoxic effect of tamoxifen in tamoxifen-sensitive and tamoxifen-resistant human breast cancer cells

    DEFF Research Database (Denmark)

    Yde, Christina Westmose; Clausen, Mathias Porsmose; Bennetzen, Martin

    2009-01-01

    -glycoprotein in cancer cells. In this study, we have investigated the effect of chlorpromazine on tamoxifen response of human breast cancer cells. We found that chlorpromazine worked synergistically together with tamoxifen with respect to reduction of cell growth and metabolic activity, both in the antiestrogen......-sensitive breast cancer cell line, MCF-7, and in a tamoxifen-resistant cell line, established from the MCF-7 cells. Tamoxifen-sensitive and tamoxifen-resistant cells were killed equally well by combined treatment with chlorpromazine and tamoxifen. This synergistic effect could be prevented by addition of estrogen...

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

    Science.gov (United States)

    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

  10. Chlorpromazine increases the lowered response to antidiuretic hormone in rats with lithium-induced diabetes insipidus.

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    Kristensen, A R; Hammer, M; Christensen, S

    1985-01-01

    The interaction between chlorpromazine (CPZ) and lithium on renal concentrating ability was studied in rats fed a Li-containing diet for 8 weeks (plasma-Li 0.6-0.7 mmol/l). CPZ (15 mg/kg daily orally) reduced the polydipsia and increased the ability to concentrate the urine upon water deprivation in rats treated with lithium. CPZ also reduced systolic blood pressure, but had no effect on the glomerular filtration rate or plasma levels of arginine vasopressin (AVP) in hydrated rats treated with lithium. However, CPZ prevented the rise in plasma AVP levels observed in lithium-polyuric rats in response to dehydration. During anaesthesia CPZ partially restored the impaired anti-diuretic response to exogenous AVP in rats treated with lithium. CPZ had no influence on plasma-Li levels in rats treated with lithium. It is suggested that CPZ by unknown mechanisms interferes with the effects of lithium on the water permeability response to AVP.

  11. Association of DRD2 polymorphisms and chlorpromazine-induced extrapyramidal syndrome in Chinese schizophrenic patients

    Institute of Scientific and Technical Information of China (English)

    Sheng-nan WU; Rui GAO; Qing-he XING; Hua-fang LI; Yi-feng SHEN; Niu-fan GU; Guo-yin FENG; Lin HE

    2006-01-01

    Aim: Extrapyramidal syndrome (EPS) is most commonly affected by typical antipsychotic drugs that have a high affinity with the D2 receptor. Recently, many research groups have reported on the positive relationship between the genetic variations in the DRD2 gene and the therapeutic response in schizophrenia patients as a result of the role of variations in the receptor in modulating receptor expression. In this study, we evaluate the role DRD2 plays in chlorpromazineinduced EPS in schizophrenic patients. Methods: We identified seven SNP(single nucleotide polymorphism) (-141Cins>del, TaqIB, TaqID, Ser311Cys, rs6275, rs6277 and TaqIA) in the DRD2 gene in 146 schizophrenic inpatients (59 with EPS and 87 without EPS according to the Simpson-Angus Scale) treated with chlorpromazine after 8 weeks. The alleles of all loci were determined by PCR (polymerase chain reaction). Results: Polymorphisms TaqID, Ser311 Cys and rs6277 were not polymorphic in the population recruited in the present study. No statistical significance was found in the allele distribution of -141Cins>del, TaqIB, rs6275 and TaqIA. or in the estimated haplotypes (constituted by TaqIB, rs6275 and TaqIA) in linkage disequilibrium between the two groups. Conclusion: Our results did not lend strong support to the view that the genetic variation of the DRD2 gene plays a major role in the individually variable adverse effect induced by chlorpromazine, at least in Chinese patients with schizophrenia. Our results confirmed a previous study on the relationship between DRD2 and EPS in Caucasians.

  12. [Effect of chlorpromazine and amphetamine on incidental memory and its relation to the introvert-extravert structure of personality].

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    Zaimov, K; Kokoshkarova, A

    1978-10-01

    A total of fifty-four test subjects divided into one control group and two experimental groups were used to study the effects of chlorpromazine and amphetamine upon the incidental memory, its accuracy, and possible dependence on the introversive or extroversive personality structure, respectively. It has been found that chlorpromazine tends to lessen the incidental memory in extent and increase the number of allomnesias or instances of inaccurate remembrance, whereas amphetamine has the effects of increasing the extent of the incidental memory and reducing the number of allomnesias. A comparison of the extent of the incidental memory with the structure of personality in respect of introversion or extroversion in the control group also showed significant differences, the incidental memory being of smaller extent in the case of introversion and greater extent in the case of extroversion.

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

    Science.gov (United States)

    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

  14. Effect of chlorpromazine or sulpiride and alcohol on psychomotor skills related to driving.

    Science.gov (United States)

    Seppälä, T

    1976-10-01

    A double-blind cross-over trial was conducted with 20 healthy paid volunteers for the evaluation of the subacute effects of chlorpromazine (CPZ) and sulpiride, in oral doses used for anxious outpatients, on psychomotor skills related to driving. Psychomotor performance was measured on the 7th and 14th days of treatment at 30, 90 and 150 min after the intake of 0.5 g/kg of an alcoholic or placebo drink. After the neuroleptics alone, reaction and coordination skills, but not attention, were slightly impaired, CPZ differing significantly from the placebo on the 14th day. Both drugs interacted additively with alcohol. The combined administration of CPZ and alcohol led to inaccuracy, a slowing of reactions and impaired proprioception and coordination. The combination of sulpiride and alcohol increased the error rate in the choice reaction test and impaired coordination in the coordination test driven at a free speed. It is concluded that the psychomotor decrement that occurs after 2 weeks of treatment with small doses of CPZ may effect the ability to control a motor vehicle. The concurrent administration of alcohol during treatment with CPZ or sulpiride may cause some extra risk in traffic or occupational life.

  15. PLGA biodegradable nanoparticles containing perphenazine or chlorpromazine hydrochloride: effect of formulation and release.

    Science.gov (United States)

    Halayqa, Mohammed; Domańska, Urszula

    2014-12-22

    In our study, poly(dl-lactide-co-glycolide) (PLGA) nanoparticles loaded with perphenazine (PPH) and chlorpromazine hydrochloride (CPZ-HCl) were formulated by emulsion solvent evaporation technique. The effect of various processing variables, including PLGA concentration, theoretical drug loading, poly(vinyl alcohol) (PVA) concentration and the power of sonication were assessed systematically to obtain higher encapsulation efficiency and to minimize the nanoparticles size. By the optimization formulation process, the nanoparticles were obtained in submicron size from 325.5 ± 32.4 to 374.3 ± 10.1 nm for nanoparticles loaded with PPH and CPZ-HCl, respectively. Nanoparticles observed by scanning electron microscopy (SEM) presented smooth surface and spherical shape. The encapsulation efficiency of nanoparticles loaded with PPH and CPZ-HCl were 83.9% and 71.0%, respectively. The drug loading were 51.1% and 39.4% for PPH and CPZ-HCl, respectively. Lyophilized nanoparticles with different PLGA concentration 0.8%, 1.3% and 1.6% (w/v) in formulation process were evaluated for in vitro release in phosphate buffered saline (pH = 7.4) by using dialysis bags. The release profile for both drugs have shown that the rate of PPH and CPZ-HCl release were dependent on a size and amount of drugs in the nanoparticles.

  16. PLGA Biodegradable Nanoparticles Containing Perphenazine or Chlorpromazine Hydrochloride: Effect of Formulation and Release

    Directory of Open Access Journals (Sweden)

    Mohammed Halayqa

    2014-12-01

    Full Text Available In our study, poly(dl-lactide-co-glycolide (PLGA nanoparticles loaded with perphenazine (PPH and chlorpromazine hydrochloride (CPZ-HCl were formulated by emulsion solvent evaporation technique. The effect of various processing variables, including PLGA concentration, theoretical drug loading, poly(vinyl alcohol (PVA concentration and the power of sonication were assessed systematically to obtain higher encapsulation efficiency and to minimize the nanoparticles size. By the optimization formulation process, the nanoparticles were obtained in submicron size from 325.5 ± 32.4 to 374.3 ± 10.1 nm for nanoparticles loaded with PPH and CPZ-HCl, respectively. Nanoparticles observed by scanning electron microscopy (SEM presented smooth surface and spherical shape. The encapsulation efficiency of nanoparticles loaded with PPH and CPZ-HCl were 83.9% and 71.0%, respectively. The drug loading were 51.1% and 39.4% for PPH and CPZ-HCl, respectively. Lyophilized nanoparticles with different PLGA concentration 0.8%, 1.3% and 1.6% (w/v in formulation process were evaluated for in vitro release in phosphate buffered saline (pH = 7.4 by using dialysis bags. The release profile for both drugs have shown that the rate of PPH and CPZ-HCl release were dependent on a size and amount of drugs in the nanoparticles.

  17. Chlorpromazine transformation by exposure to ultraviolet laser beams in droplet and bulk.

    Science.gov (United States)

    Andrei, Ionut Relu; Tozar, Tatiana; Dinache, Andra; Boni, Mihai; Nastasa, Viorel; Pascu, Mihail Lucian

    2016-01-01

    Multiple drug resistance requires a flexible approach to find medicines able to overcome it. One method could be the exposure of existing medicines to ultraviolet laser beams to generate photoproducts that are efficient against bacteria and/or malignant tumors. This can be done in droplets or bulk volumes. In the present work are reported results about the interaction of 266nm and 355nm pulsed laser radiation with microdroplets and bulk containing solutions of 10mg/ml Chlorpromazine Hydrochloride (CPZ) in ultrapure water. The irradiation effects on CPZ solution at larger time intervals (more than 30min) are similar in terms of generated photoproducts if the two ultraviolet wavelengths are utilized. The understanding of the CPZ parent compound transformation may be better evidenced, as shown in this paper, if studies at shorter than 30minute exposure times are made coupled with properly chosen volumes to irradiate. We show that at exposure to a 355nm laser beam faster molecular modifications of CPZ in ultrapure water solution are produced than at irradiation with 266nm, for both microdroplet and bulk volume samples. These effects are evidenced by thin layer chromatography technique and laser induced fluorescence measurements.

  18. The Effects of Chlorpromazine on Reproductive System and Function in Female Rats

    Directory of Open Access Journals (Sweden)

    Zahra Zamani

    2015-07-01

    Full Text Available Background: Chlorpromazine (CPZ, an antipsychotic drug, is associated with increased risk of sexual dysfunction through increasing prolactin levels. The current study evaluates the effect of CPZ-induced hyperprolactinemia on ovarian follicular growth, gonadotropins, and alteration of ovarian source hormones. Materials and Methods: In this experimental study, animals were divided into four groups, control and CPZ (n=8 per group. In the treated groups, CPZ was administered by gavage at doses of 3, 10 and 30 mg/kg per day for 28 days. On day 29 the animals were killed after which histopathological and histomorphometric analyses of the ovaries were performed. We evaluated the levels of prolactin serum, luteinizing hormone (LH, follicle-stimulating hormone (FSH, estradiol (E2 and progesterone. Results: The ovaries of the test groups showed numerous atretic follicles of various sizes. CPZ caused a significant difference between the test groups and the control group (P<0.05 on the amount of atresia and the size of the normal corpora lutea (CL. The increased dysfunction of the ovaries from the different groups depended on the amount of CPZ administered. The serum concentrations of prolactin and progesterone significantly increased (P<0.05, while the serum concentrations of estradiol, LH and FSH notably decreased (P<0.05, depending on the CPZ dose. CPZ-induced animals had unsuccessful mating and decreased pregnancy rate. Conclusion: The present findings suggest that CPZ-induced disturbances not only depend on prolactin level but the increased prolactin level is largely dose-dependent.

  19. Changes in Tissue Metals After Cadmium Intoxication and Intervention With Chlorpromazine in Male Rats 

    Institute of Scientific and Technical Information of China (English)

    YANGXIAO-FANG; WANGSHU-YI; 等

    2000-01-01

    Cadmium(Cd),one of the most dangerous heavy metals,has a very similar ionic radius to calcium(Ca),The interference of cadmium in calcium homeostasis may play an important role in cadmium toxicity.Recent reports indicate that calmodulin(CaM) inhibitors such as trifluoperazine and chlorpromazine(CPZ) could protect rodents against cadmium toxicity,It was also reported that pretreatment of mice with zine(Zn)could reduce the adverse effects induced by cadmium.The aim of this study is to determine whether Cd changes the balance of other essential metals such as Zn and copper(Cu) in rat tissues,and whether CPZ can reverse these changes which are induced by cadmium intoxication.Adult male Sprague-Dawley(SD) rats were injected intraperitoneally(ip) with cadmium chloride(CdCl2)(0.2,0.4,0.8mg Cd/kg body wight) alone and 0.4mg Cd/kg in association with CPZ(5mg/kg) daily for a week.The control animals were injected with normal saline only.The results showed that the cadmium content in the liver,kidney,and testis increased significantly with a dose-response relationship.Cadmium treatment markedly increased the Zn and Ca content in some of the tissues,Hepatic and renal metallothionein(MT) increased significantly after cadmium intoxication,CPZ treatment,howerver,reduced cadmium content in liver,but not blood and kidney.CPZ seemed to decrease the content of MT in liver and significantly increase the amounts of MT in kidney.These data suggest that the intervention of cadmium with tissue essential metals may play a role in cadium toxicity in rats,and calmodulin inhibitors to some extent can reduce the adverse effect of cadmium by decreasing the cadmium load in tissues and reversing the unbalance of essetial metals.

  20. Quenching of the intrinsic fluorescence of bovine serum albumin by chlorpromazine and hemin

    Directory of Open Access Journals (Sweden)

    Silva D.

    2004-01-01

    Full Text Available The binding of chlorpromazine (CPZ and hemin to bovine serum albumin was studied by the fluorescence quenching technique. CPZ is a widely used anti-psychotic drug that interacts with blood components, influences bioavailability, and affects function of several biomolecules. Hemin is an important ferric residue of hemoglobin that binds within the hydrophobic region of albumin with high specificity. Quenching of the intrinsic fluorescence of bovine serum albumin (BSA was observed by selectively exciting tryptophan residues at 290 nm. Emission spectra were recorded in the range from 300 to 450 nm for each quencher addition. Stern-Volmer graphs were plotted, and the quenching constant estimated for BSA solution titrated with hemin at 25ºC was 1.44 (± 0.05 x 10(5 M-1. Results showed that bovine albumin tryptophans are not equally accessible to CPZ, in agreement with the idea that polar or charged quenchers have more affinity for amino acid residues on the outer wall of the protein. Hemin added to albumin solution at a molar ratio of 1:1 quenched about 25% of their fluorescence. The quenching effect of CPZ on albumin-hemin solution was stronger than on pure BSA. This increase can be the result of combined conformational changes in the structure of albumin caused firstly by hemin and then by CPZ. Our results suggest that the primary binding site for hemin on bovine albumin may be located asymmetrically between the two tryptophans along the sequence formed by subdomains IB and IIA, closer to tryptophan residue 212.

  1. Bilateral skin conductance and the pupillary light-dark reflex: manipulation by chlorpromazine, haloperidol, scopolamine, and placebo.

    Science.gov (United States)

    Patterson, T; Venables, P H

    1981-01-01

    Cholinergic blocking with scopolamine produces skin conductance orientating response (SCOR) nonresponding in normal subjects. This may be one of a number of causes for nonresponding in schizophrenic subjects. Blockade of dopamine with haloperidol produces an increase in amplitude and shortening of recovery time in the SCOR of normal subjects. This result closely resembles that of Nielsen and Petersen (1976) who found a similar pattern of responding in normal subjects who scored high on a scale of schizophrenism. These results, along with those for chlorpromazine and the pupillographic effects of the three drugs are discussed in terms of biochemical working hypotheses of schizophrenic subclassification.

  2. Stability Indicating HPLC Method for Simultaneous Quantification of Trihexyphenidyl Hydrochloride, Trifluoperazine Hydrochloride and Chlorpromazine Hydrochloride from Tablet Formulation

    Directory of Open Access Journals (Sweden)

    P. Shetti

    2010-01-01

    Full Text Available A new, simple, precise, rapid, selective and stability indicating reversed-phase high performance liquid chromatographic (HPLC method has been developed and validated for simultaneous quantification of trihexyphenidyl hydrochloride, trifluoperazine hydrochloride and chlorpromazine hydrochloride from combined tablet formulation. The method is based on reverse-phase using C-18 (250×4.6 mm, 5 μm particle size column. The separation is achieved using isocratic elution by methanol and ammonium acetate buffer (1% w/v, pH 6.5 in the ratio of 85:15 v/v, pumped at flow rate 1.0 mL/min and UV detection at 215 nm. The column is maintained at 30 °C through out the analysis. This method gives baseline resolution. The total run time is 15 min. Stability indicating capability is established buy forced degradation experiment. The method is validated for specificity, accuracy, precision and linearity as per International conference of harmonisation (ICH. The method is accurate and linear for quantification of trihexyphenidyl hydrochloride, trifluoperazine hydrochloride and Chlorpromazine hydrochloride between 5 - 15 μg/mL, 12.5- 37.5 μg/mL and 62.5 - 187.5 μg/mL respectively.

  3. A Novel Melt-Dispersion Technique for Simplistic Preparation of Chlorpromazine-Loaded Polycaprolactone Nanocapsules

    Directory of Open Access Journals (Sweden)

    Thiresen Govender

    2015-06-01

    Full Text Available The aim of this study was to design, synthesize and optimize chlorpromazine hydrochloride (CPZ-loaded, poly-ε-caprolactone (PCL based nanocapsules, intended for site specific delivery to the frontal lobe, using a novel melt-dispersion technique that is non-arduous, inexpensive and devoid of any hazardous organic solvents. Experimental trials using a central composite design were performed on 13 statistically derived formulations of various combinations of PCL (1000–3000 mg and Polysorbate 80 (2%–5% v/v on the physicochemical and physicomechanical properties and interactive effects on PCL nanocapsule formulation. Differential scanning calorimetry (DSC, Temperature modulated differential scanning calorimetry (TMDSC and Fourier transform infrared spectroscopy (FTIR revealed that there was no thermodegardation of the constituents utilized in the melt dispersion technique. Nanocapsule yields achieved were very high however entrapment of CPZ proved to be relatively low due to the highly hydrophilic nature of CPZ and the processing of the nanocapsules post synthesis. Nanocapsule sizes were in the nanotherapeutic range and varied from 132.7 ± 6.8 nm to 566.6 ± 5.5 nm. Zeta potential ranged from 15.1 ± 0.65 mV to 28.8 ± 0.84 mV revealing capsules that were of incipient to moderate stability. Transmission electron microscopy revealed nanocapsules that were spherical shape, well individualized with a moderate degree of flocculation. In vitro CPZ release was biphasic for all formulations with an initial burst release followed by pseudo-steady controlled release over 30 days. The cytotoxicity of the optimized nanocapsule system on a PC12 neuronal cell line proved to be minimal. Following incorporation of the optimized nanocapsules within a polymeric membrane, in vivo implantation of the device in a New Zealand Albino rabbit model proved the efficacy of the system in achieving prolonged more targeted CPZ levels to the brain. Extensive in vitro

  4. Changes of the rats’ heart rate variability caused by chlorpromazine modulation of central noradrenergic neurotransmission during prolonged stress

    Directory of Open Access Journals (Sweden)

    O. Z. Мelnikova

    2012-03-01

    Full Text Available It’s established that under the prolonged stress there were changes of geometric and spectral indices of the rats’ heart rate variability (HRV, manifestations of which depended on duration of stressful factors acting and represented the stress reaction development from the stage of anxiety to the exhaustion phase. Application of chlorpromazine at the beginning and against the background of stress blocked the central alpha adrenoceptors and contributed to renewal of the most HRV indices into the limits of control values at the end of experiment. The results of research show that the modulation of functional state of central noradrenergic system plays a great role in the changes of HRV during prolonged stress.

  5. Voltammetric Determination of Homocysteine Using Multiwall Carbon Nanotube Paste Electrode in the Presence of Chlorpromazine as a Mediator

    Directory of Open Access Journals (Sweden)

    Fathali Gholami-Orimi

    2012-01-01

    Full Text Available We propose chlorpromazine (CHP as a new mediator for the rapid, sensitive, and highly selective voltammetric determination of homocysteine (Hcy using multiwall carbon nanotube paste electrode (MWCNTPE. The experimental results showed that the carbon nanotube paste electrode has a highly electrocatalytic activity for the oxidation of Hcy in the presence of CHP as a mediator. Cyclic voltammetry, double potential step chronoamperometry, and square wave voltammetry (SWV are used to investigate the suitability of CHP at the surface of MWCNTPE as a mediator for the electrocatalytic oxidation of Hcy in aqueous solutions. The kinetic parameters of the system, including electron transfer coefficient, and catalytic rate constant were also determined using the electrochemical approaches. In addition, SWV was used for quantitative analysis. SWV showed wide linear dynamic range (0.1–210.0 μM Hcy with a detection limit of 0.08 μM Hcy. Finally, this method was also examined as a selective, simple, and precise electrochemical sensor for the determination of Hcy in real samples.

  6. Effects of vitamin E supplementation on plasma membrane permeabilization and fluidization induced by chlorpromazine in the rat brain.

    Science.gov (United States)

    Maruoka, Nobuyuki; Murata, Tetsuhito; Omata, Naoto; Takashima, Yasuhiro; Fujibayashi, Yasuhisa; Wada, Yuji

    2008-03-01

    Neurotransmitter receptors play a key role in most research on antipsychotic drugs, but little is known about the effects of these drugs on the plasma membrane in the central nervous system. Therefore, we investigated whether chlorpromazine (CPZ), a typical phenothiazine antipsychotic drug, affects the plasma membrane integrity in the rat brain, and if so, whether these membrane alterations can be prevented by dietary supplementation with vitamin E, which has been shown to be an antioxidant and also a membrane-stabilizer. Leakage of [(18)F]2-fluoro-2-deoxy-D-glucose ([(18)F]FDG)-6-phosphate from rat striatal slices and decrease in 1,6-diphenyl-1,3,5-hexatriene fluorescence anisotropy were used as indexes for plasma membrane permeabilization and fluidization, respectively. CPZ induced leakage of [(18)F]FDG-6-phosphate from striatal slices, and the leakage was delayed in the vitamin E-supplemented group compared to that in the normal diet group. The decrease in plasma membrane anisotropy induced by CPZ was significantly attenuated by vitamin E supplementation. Chronic treatment with alpha-phenyl-N-tert-butyl nitrone, a free radical scavenger, had no effect on CPZ-induced plasma membrane permeabilization, and the treatment with CPZ did not induce lipid peroxidation. CPZ can reduce plasma membrane integrity in the brain, and this reduction can be prevented by vitamin E via its membrane-stabilizing properties, not via its antioxidant activity.

  7. CLINICAL RESEARCH ON LARGE DOSE OF CHLORPROMAZINE IN THE TREATMENT OF STATUS EPILEPTICUS%大剂量氯丙嗪治疗癫痫持续状态的临床研究

    Institute of Scientific and Technical Information of China (English)

    卢桂兰; 蔡毅; 曾志文

    2011-01-01

    [目的]探讨大剂量氯丙嗪治疗癫痫持续状态的疗效.[方法]予氯丙嗪25~50 mg加入生理盐水l00ml中静滴,0.83 mg/min.[结果]经大剂量氯丙嗪治疗后,患者于30~60 min内癫痫持续状态控制.[结论]大剂量氯丙嗪可治疗癫痫持续状态.%[Objective] To explore the effectiveness of high-dose chlorpromazine in the treatment of status epilepticus. [Methods] Mixed 25-50mg chlorpromazine with 100 ml normal saline solution and injected intravenously, 0.83mg per minute. [Results] With large doses of chlorpromazine treatment, status epilepticus would be under control within the 30-60 minutes. [Conclusion] Large dose of chlorpromazine can be used to treat status epilepticus.

  8. High resolution scanning electron microscopy of rabbit corneal endothelium to show effects of UV-visible irradiation in the presence of chlorpromazine

    Energy Technology Data Exchange (ETDEWEB)

    Lea, P.J.; Hollenberg, M.J.; Menon, I.A.; Temkin, R.J.; Persad, S.D.; Basu, P.K. (Univ. of Toronto, Ontario (Canada))

    1989-01-01

    The ultrastructure of rabbit cornea endothelial cells was examined by scanning electron microscopy (SEM) in freeze-cleaved corneas using a Hitachi S-570 scanning electron microscope in the high resolution mode (HRSEM). In order to study phototoxic effects in vitro, rabbit corneas (experimental) were cultured as organ culture in the presence of 5 micrograms/ml chlorpromazine (CPZ) and irradiated. For comparison, control 1 corneas were not irradiated but incubated in the dark without CPZ in the medium; control 2 corneas were also kept in the dark but in the presence of CPZ; control 3 corneas were irradiated with no CPZ in the medium. Cellular damage was not seen in the three types of control corneas, but in the experimental corneas the endothelial cells showed extensive disruption of the cell membrane and some deterioration of the intracellular components. Our study confirmed that HRSEM is a satisfactory new technique for visualizing damage of the intracellular organelles of corneal endothelium.

  9. Flow-injection spectrophotometric determination of bromate in bottled drinking water samples using chlorpromazine reagent and a liquid waveguide capillary cell.

    Science.gov (United States)

    Tóth, Ildikó V; Santos, Inês C; Azevedo, Cláudia F M; Fernandes, Jorge F S; Páscoa, Ricardo N M J; Mesquita, Raquel B R; Rangel, António O S S

    2013-01-01

    In this work, aiming to develop a simple, inexpensive method for the determination of low bromate levels in water samples, a liquid waveguide capillary cell (LWCC) was coupled to a FIA system. The long optical path (100 cm) of the LWCC was used to improve the sensitivity and the limit of detection without resorting to any off-line or in-line preconcentration processes. The spectrophotometric determination was based on the oxidation of chlorpromazine by bromate in an acidic medium, resulting in the formation of a colored radical product. Sulfamic acid was added to the reagent for minimizing the interference of nitrite, and a chelating ion exchange resin was used to remove major cationic interferences. The developed system allowed the determination of bromate within the range between 1 - 20 μg L(-1) with a detection limit of 0.2 μg L(-1).

  10. Analysis of Photo-Patch Testing of Chlorpromazine and Sulfanilamide%氯丙嗪和磺胺光斑贴试验分析

    Institute of Scientific and Technical Information of China (English)

    高露娟; 胡跃; 倪春雅; 徐昱; 马莉; 严淑贤; 窦侠

    2015-01-01

    目的:通过光斑贴试验分析氯丙嗪和磺胺引起光变应性接触性皮炎(photo‐allergic contact dermatitis ,PACD )的情况。方法:选择2006年1月—2012年12月在复旦大学附属华山医院接受光斑贴试验的光皮肤病患者。根据国际接触性皮炎研究组(ICDRG )的标准判读光斑贴试验结果。比较两种变应原PACD阳性率及每种变应原的PACD阳性率在不同性别、不同年龄段光皮肤病患者中的差异。结果:共4836例入组,其中接受氯丙嗪光斑贴试验者3993例,PACD阳性率44.3%;接受磺胺光斑贴试验者4836例,PACD阳性率6.9%;两种变应差异( P<0.0001)。接受氯丙嗪光斑贴试验的3993例中,男性PACD阳性率43.6%,女性阳性率44.7%,差异无统计学意义( P=0.51);接受磺胺光斑贴试验的4836例中,男性 PACD阳性率9.3%,女性阳性率5.4%,差异有统计学意义( P<0.0001)。氯丙嗪PACD阳性率随年龄增加而升高,不同年龄段间差异有统计学意义(P<0.0001);磺胺PACD阳性率在不同年龄段间差异无统计学意义(P=0.37)。结论:氯丙嗪 PACD阳性率明显高于磺胺。氯丙嗪PACD多见于中老年人。男性光皮肤病患者中磺胺PACD阳性率高于女性。%Objective:To investigate the incidence of photo‐allergic contact dermatitis (PACD)induced by chlorpromazine and sulfanilamide with photo‐patch testing (PPT ) .Methods :Patients who underwent PPT for suspected photo dermatoses in Huashan Hospital ,Fudan University from January 2006 to December 2012 were selected .PPT results were evaluated with the criteria of International Contact Dermatitis Research Group (ICDRG) .Photoallergic positive rate was compared between two allergen groups .And the photoallergic positive rate of each allergen was compared among different genders and ages .Results:A total of 4836 patients were enrolled .PACD positive rate was

  11. Effect of chlorpromazine combined with Platycodon grandiflorum on change of dopamine in rat striatum by microdialysis%桔梗与氯丙嗪伍用对大鼠脑纹状体多巴胺的影响

    Institute of Scientific and Technical Information of China (English)

    何新荣; 宦定才; 曹征; 刘萍

    2009-01-01

    目的:研究桔梗与氯丙嗪联合应用对大鼠脑纹状体单胺类神经递质多巴胺的影响,探讨中西药配伍应用后可能发生的药物相互作用与机制.方法:大鼠随机分成4组:生理盐水组、桔梗(生药15.2 g·kg~(-1)·d~(-1))单独给药组、氯丙嗪(20mg·kg~(-1)·d~(-1))单独给药组、氯丙嗪与桔梗(20 mg·kg~(-1)·d~(-1)+15.2 g·kg~(-1)·d~(-1))合并给药组,每组6只,给药10 d后,利用微透析法在大鼠脑纹状体取样,HPLC检测透析液中多巴胺水平.结果:药后140 min(取样点80 min)时,氯丙嗪+桔梗组中多巴胺水平(1.52±0.34)μg-L~(-1)显著高于氯丙嗪组(1.25±0.22)μg·L~(-1)(P<0.05)和生理盐水组(1.06±0.24)μg·L~(-1)(P<0.01).结论:桔梗与氯丙嗪合用后大鼠脑内多巴胺水平升高,治疗时同时给予桔梗,可以减少氯丙嗪的用量,达到保持疗效,降低其不良反应的目的.%Objective:To study the effects of chlorpromazine combined with Platycodon grandiflorum on the striatal extracellular dopamine Ievel in rats and to research the interaction and the mechanism of action after combining traditional Chinese medicine with western medicine.Method:Twenty four rats were randomly assigned into four groups:the control group,Platycodon group,chlorpromazine group and chlorpromazined combined with P. grandiflorum group.The level of dopamine in CSF microdialysis samples Was detected with high performance liquid chromatography with electrochemical detector after administration for 10 days.Result:The CSF level of DA(1.52±0.34)μg·L~(-1)was significantly higher(P<0.01)in chlorpromazine combined with P. grandiflorum group than that in the chlorpromazine group(1.25±0.22)μg·L~(-1)(P<0.05)and that in the normal control(1.06±0.24)μg·L~(-1)(P<0.01).Conclusion:The combining utilization of P. grandiflorum and chlorpromazine may increase the DA concentration of monoamine neurotransmitters,which results in under the therapeutic effect is maintained,the dosage of

  12. Follow-up study on influence of metabolism by risperidone and chlorpromazine%利培酮与氯丙嗪对代谢影响随访研究

    Institute of Scientific and Technical Information of China (English)

    王强; 瞿正万

    2011-01-01

    Objective:To explore the impact of chlorpromazine ,risperidone treatment on the blood glucose and fat level and body weigh in schizophrenia patients. Method: 198 schizophrenia patients were enrolled in the study. They were randomly admitted to risperidone therapy group and chlorpromazine therapy group. They are followed up one year. Data of the blood glucose and blood fat and body weight were collected at different point in the one year course of the study. Results: Both cholorpromazine group and risperidone group increased significantly in the index of total cholesterol ( TC ), triglyceride ( TG), fasting blood glucose ( FPG),glycated hemoglobin ( HbAlc), body weight and body mass index ( B MI ) while chlorpromazine group was significantly higher in these indexes. Conclusion:While chlorpromazine and risperidone can attect the blood glucose,blood fat and body weight in different ways, but they can both elevated the blood glucose, blood fat level and body weight.%目的:研究氯丙嗪与利培酮对精神分裂症患者血糖、血脂和体质量的影响.方法:198例精神分裂症患者随机分为氯丙嗪组与利培酮组,随访1年,采集患者空腹血糖、总胆固醇、和体质量的数据.结果:氯丙嗪组和利培酮组总胆固醇、三酞甘油、空腹血糖、糖化血红蛋白、体质量、体质量指数在治疗后均显著升高;以氯丙嗪组更显著为高.结论:氯丙嗪与利培酮对血糖、血脂和体质量的影响不同,但都可使之升高.

  13. Effect of chlorpromazine on lipid metabolism in aortas from cholesterol-fed rabbits and normal rats, in vitro: inhibition of sterol esterification and modification of phospholipid synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Bell, F.P.

    1983-06-01

    Chlorpromazine (CPZ), a major tranquilizer, was found to be a potent inhibitor of acylCoA:cholesterol acyltransferase (ACAT, EC 2.3.1.26) in isolated arterial microsomes and in intact arterial tissue from the rat and cholesterol-fed rabbit in vitro. In isolated rabbit arterial microsomes, CPZ resulted in a concentration-dependent inhibition of ACAT with 50% inhibition of (1-14C)oleoylCoA incorporation into (14C)cholesteryl esters occurring at 0.1 mM CPZ. CPZ also effectively inhibited the incorporation of (14C)oleate into triglycerides without affecting incorporation into diglycerides. Additionally, CPZ altered the pattern of arterial phospholipids synthesized from (1-14C)oleate. Incorporation into phosphatidylcholine was depressed while incorporation into phosphatidylinositol was increased. Since diglyceride synthesis appeared to be unaffected by CPZ, a redirection of phosphatidic acid into the CDP-diglyceride pathway of glycerolipid synthesis does not adequately account for the effect of CPZ on arterial phospholipid and triglyceride synthesis in these experiments.

  14. A Facile Electrochemical Preparation of Reduced Graphene Oxide@Polydopamine Composite: A Novel Electrochemical Sensing Platform for Amperometric Detection of Chlorpromazine

    Science.gov (United States)

    Palanisamy, Selvakumar; Thirumalraj, Balamurugan; Chen, Shen-Ming; Wang, Yi-Ting; Velusamy, Vijayalakshmi; Ramaraj, Sayee Kannan

    2016-01-01

    We report a novel and sensitive amperometric sensor for chlorpromazine (CPZ) based on reduced graphene oxide (RGO) and polydopamine (PDA) composite modified glassy carbon electrode. The RGO@PDA composite was prepared by electrochemical reduction of graphene oxide (GO) with PDA. The RGO@PDA composite modified electrode shows an excellent electro-oxidation behavior to CPZ when compared with other modified electrodes such as GO, RGO and GO@PDA. Amperometric i-t method was used for the determination of CPZ. Amperometry result shows that the RGO@PDA composite detects CPZ in a linear range from 0.03 to 967.6 μM. The sensor exhibits a low detection limit of 0.0018 μM with the analytical sensitivity of 3.63 ± 0.3 μAμM–1 cm–2. The RGO@PDA composite shows its high selectivity towards CPZ in the presence of potentially interfering drugs such as metronidazole, phenobarbital, chlorpheniramine maleate, pyridoxine and riboflavin. In addition, the fabricated RGO@PDA modified electrode showed an appropriate recovery towards CPZ in the pharmaceutical tablets. PMID:27650697

  15. UP LC-MS/MS法测定3种兽药制剂中违禁药物氯丙嗪%Determination of Chlorpromazine Illegally Added in 3 Kinds of Veterinary Preparations by UPLC-MS/MS

    Institute of Scientific and Technical Information of China (English)

    李波平; 花锦; 李涵; 陈谷峰; 刘能盛; 肖前; 李丹; 赵泉; 单利君

    2015-01-01

    建立了3种兽药制剂中违禁药物氯丙嗪的超高效液相色谱-串联质谱( UP LC-MS/MS )检测方法。用无水乙醇超声提取试样中违禁药物氯丙嗪,采用Waters ACQUITY UPLC BEH C18柱(50 mm×2.1 mm,1.7μm),乙腈和10 mmol/L乙酸铵+0.1%甲酸溶液流动相,梯度洗脱,电离喷雾电离方式(ESI+),多反应监测(MRM)定量。该方法线性关系良好,相关系数r2达到0.9956,回收率在88.3%~96.7%之间,相对标准偏差( RSD)介于3.7%~8.1%。方法的检出限为0.003 mg/kg。本方法适用于兽药制剂中氯丙嗪违法添加的定性、定量分析。%A method of determination of chlorpromazine illegally added in 3 kinds of veterinary preparations by ultra-performance liquid chromatography -tandem mass spectrometry ( UPLC -MS/MS ) was developed. Chlorpromazine was extracted with ethanol by ultrasonic wave and separated on the Waters ACQUITY UPLC BEH C18 column (50 mm×2.1 mm, 1.7μm) using the mobile phase of acetonitrile/mixture of 10 mmol/L ammonium acetate and 0.1%formic acid with gradient elution. Chlorpromazine was detected in electrospray ionization ( ESI+) mode using multiple reaction monitoring ( MRM ) . There was a good linear relationship with the correlation rate more than 0. 9956. The average recoveries ranged from 88. 3% to 96. 7%. The standard deviation was between 3.7% and 8.1%. The limit of detection was 0.003 mg/kg. The method was rapid, simple, sensitive and accurate. It was suitable for qualitative and quantitative analysis of the illicit drug chlorpromazine in veterinary preparations.

  16. The disability in patients with schizophrenia treated with chlorpromazine and risperidone%氯丙嗪与利培酮片对精神分裂症患者致残影响的对比研究

    Institute of Scientific and Technical Information of China (English)

    李和军; 杨杰

    2012-01-01

    目的 探讨氯丙嗪与利培酮片对精神分裂症患者致残的影响.方法 200例门诊或住院的精神分裂症患者完全随机分为对照组与研究组,各100例,采用残疾水平评定量表( WHODASⅡ)、社会功能缺陷筛选量表(SDSS)、生活质量评定量表(WHOQOL)分别于0.5、1、2年时对患者的残疾程度进行多维度评定并进行对比.结果 究组治疗后0.5、1、2年WHOQOL-BREF评分优于对照组,WHODAS评分[分别为(27±15)分比(38±13)分、(28±13)分比(39±15)分、(26±14)分比(36±18)分]、SDSS评分[分别为(11±2)分比(18±6)分、(8±2)分比(12±3)分、(8±2)分比(11±4)分]均优于对照组,差异均有统计学意义(均P<0.01).结论 利培酮片对改善精神分裂症患者社会功能,减轻残疾程度,降低致残率方面明显 优于氯丙嗪.%Objective To explore the disability in patients treated with schizophrenia with using respectively chlorpromazine and risperidone.Methods Two hundred outpatients or hospitalization patients with schizophrenia were randomly divided into chlorpromazine group( 100 cases) and risperidone group( 100 cases) ; the degree of disability by WHO disability assessment scale Ⅱ (WHO-DAS Ⅱ ),social disability screening schedule(SDSS),WHO quality of life(WHOQOL) at the time of half a year,one year and two years were ananlyzed.Results The scores of risperidone group in all scales were significantly higher in chlorpromazine group in each period ( P < 0.05 or P <0.001 ).The validity of consistency and correlation was high in all scales.Conclusion Risperidone is significantly better than chlorpromazine in terms of reducing the rate of disability,improving the social function and reducing the degree of disability.

  17. Effect of chlorpromazine on the steroidogenesis of rat ovarian grandlose cells in vitro%氯丙嗪对大鼠卵巢颗粒细胞分泌功能的影响

    Institute of Scientific and Technical Information of China (English)

    邬静; 袁慧; 彭双清

    2011-01-01

    为研究大鼠卵巢颗粒细胞(GC)的分泌功能,用氯丙嗪染毒体外培养的大鼠GC,采用MTT法检测细胞相对活力,ELISA法检测收集培养液中孕酮(P)和雌二醇(E2)的含量,半定量RT-PCR检测激素分泌相关调控基因FSHR、StAR、P450scc和P450arom mRNA的表达,免疫细胞化学染色法检测细胞中特异卵泡刺激素受体的表达.结果表明:经0.1、1.0和10.0 μmol/L氯丙嗪染毒24 h后,与对照组相比,细胞相对活力分别为87.95%、83.96%和74.48%,E2的分泌量和StAR mRNA相对表达水平分别从对照组的6.16 pg/μtg、2.014显著下降到3.70 pg/μg、0.311,呈现明显的剂量-效应关系,表明转运蛋白StAR可能是氯丙嗪影响颗粒细胞激素分泌的关键位点之一.%To study the toxic effects and explore the possible mechanism of chlorpromazine exposure to rat ovarian granulosa cell steroidogenesis in vitro, immature ovarian granulosa cells of wistar rat was primary cultured. After exposure to chlorpromazine for 24 h, cell viability was detected by MTT assay, content of progesterone (P) and estradiol (E2) collected from medium were detected by EL1SA assay; FSHR, StAR, P450scc and P450arom mRNA expression were detected by semi-quantitative RT-PCR, and expression of follicle stimulating hormone receptor-specific receptor(FSHR) in granulosa cells was detected by immunocytochemical staining assay. The results showed that chlorpromazine could significantly decrease the viability of rat ovarian granulosa cells, thus affect steroidogenesis and StAR maybe one of the key factors to affect the steroidogenesis of granulosa cells.

  18. 苯二氮卓类药物与氯氮平或氯丙嗪治疗失眠的对照研究%Treatment of insomnia with benzodiazepines and clozapine or chlorpromazine:a comparative study

    Institute of Scientific and Technical Information of China (English)

    杨如良

    2014-01-01

    目的:了解氯氮平和氯丙嗪治疗失眠的疗效。方法将52例精神疾病伴失眠的患者随机分氯氮平和氯丙嗪组(观察组)26例,苯二氮艹卓类组(对照组)26例,依据匹兹堡睡眠质量表(PSQI)对失眠程度进行评估。结果氯氮平和氯丙嗪组有效率88.46%,苯二氮艹卓组有效率96.15%,2组疗效无统计学差异(P>0.05)。结论苯二氮艹卓类药物与氯丙嗪和氯氮平治疗精神疾病失眠疗效相当,为了防止苯二氮艹卓类药物滥用,选用替代药物也是一种很好的选择。%Objective To understand the curative effect of clozapine and chlorpromazine in the treatment of insomnia . Methods 52 patients with mental illness associated with insomnia were randomly divided into a clozapine /chlorpromazine group and a benzodiazepines group ,each with 26 cases.The degree of insomnia was evaluated according to the Pittsburgh sleep quality index (PSQI).Results The effective rate of Clozapine/chlorpromazine group was 88.46% and that of benzodiaz-epines group was 96.15%.The curative effect of the two groups was almost the same .There was no statistical differences ( P>0.05).Conclusion The effectiveness of the two groups of drugs in the treatment of mental illness insomnia is basically e -qual.In order to prevent drug abuse of benzodiazepines , it is also a good choice to choose alternative medicines .

  19. Effectiveness of clozapine, haloperidol and chlorpromazine in schizophrenia during a five-year period Eficácia da clozapina, haloperidol e clorpromazina na esquizofrenia em um período de cinco anos

    Directory of Open Access Journals (Sweden)

    Dragan B. Ravanic

    2009-06-01

    Full Text Available OBJECTIVE: The aim of our study was to evaluate the effects of low doses of clozapine in flexible regime in comparison with haloperidol and chlorpromazine in long term. METHOD: The naturalistic study was prospective, active-controlled with 325 adult outpatients of both genders (140 females, with mean year age of 34.8 (range 21-57, suffering from chronic schizophrenia. The first onset of illness was at the mean of 27.9 years (range 17-38, and subjects had the mean year age of 4.1±0.5 previous relapses. The patients were allocated to receive haloperidol (105 subjects, dose range 2-15 mg, chlorpromazine (n=105, 100-400 mg or clozapine (n=115, 75-600 mg. The scores of psychometric instruments (GWB, PANSS, CGI were regularly assessed during 5 year period. RESULTS: The sixty-six responders were included in per-protocol analysis: 12, 10 and 16 with positive and 7, 6 and 15 with negative schizophrenic syndrome in haloperidol, chlorpromazine and clozapine group, respectively. The statistically significant differences in all psychometric scores was found, for both schizophrenic syndromes, favoring clozapine. The distribution of eighteen different types of adverse events, which we noted, were significantly different among treatment groups ( χ2=315.7, df=34, pOBJETIVO: O propósito deste estudo foi avaliar os efeitos de baixas doses de clozapina em regime flexível comparando com o uso de haloperidol e clorpromazina por período de 5 anos. MÉTODO: Um estudo prospectivo naturalístico, ativo-controlado foi realizado com 325 pacientes com idade média de 34,8 (variância 21-57. Todos com diagnóstico de esquizofrenia. No primeiro surto da doença os pacientes apresentavam idade média de 27,9 anos (variância 17-38 e os surtos subsequentes apareceram em média 4,1±0,5 anos após. Os pacientes foram orientados a receberem haloperidol (105 pacientes com dose entre 2 e 15 mg, clorpromazina (105 pacientes com dose entre 100 e 400 mg e clozapina (115 pacientes

  20. 酵母细胞壁的盐酸氯丙嗪微囊的制备和稳定性考察%Preparation of chlorpromazine hydrochloride microcapsules with yeast cell wall and evaluation on their stability

    Institute of Scientific and Technical Information of China (English)

    江涛; 李伟; 谭力清; 邓春兰; 李明; 于明安

    2012-01-01

    目的 以酵母细胞壁为囊材,制备盐酸氯丙嗪微囊,并观察其稳定性.方法 以载药量为评价指标,采用正交试验设计确定制备盐酸氯丙嗪微囊最佳处方和工艺,并对微囊含量的检测方法进行精密度、稳定性及准确性验证.光学显微镜观察微囊形态,考察其体外释放、高湿度和强光照射的稳定性.结果 在40℃,盐酸氯丙嗪与酵母细胞壁质量比为1∶3,时间为6h,微囊的平均载药量可达41.76%.改进的含量检测方法精密度、稳定性、准确性良好.光学显微镜下可见微囊囊壁完整,呈球形或椭球形,形态均一.盐酸氯丙嗪微囊500 min体外累积释放为94.89%.盐酸氯丙嗪微囊对湿度和光度稳定性显著增加.结论 酵母细胞壁可作为囊材用于制备微囊,且能增加药物的稳定性.%Objective To prepare chlorpromazine hydrochloride microcapsules by using yeast cell wall and observe their sta-bility. Methods The formula and procedure were optimized by orthogonal design, serving drug-loading rate as an index for evalua-tion. The method for determination of drug-loading was verified for precision and stability. The microcapsules were observed for mor-phology by optical microscopy, and evaluated for drug release in vitro as well as the drug stabilities to high humidity and highlight exposure. Results The optimal temperature, ratio of chlorpromazine hydrochloride to yeast cell wall and time for preparation of micro-capsules were 40℃, 1:3 and 6 h respectively. The drug-loading rate of microcapsules prepared under the optimal condition was 41. 76%. The modified method for determination of drug-load showed high precision, stability and accuracy. Optical microscopy showed that the microcapsules were in even sphere or oval shape, with intact walls. A portion of 94. 89% of total drug in the micro-capsules were released in vitro within 500 min. The drug stability in microcapsules to humidity and light increased. Conclusion

  1. Comparison of the anti-prion mechanism of four different anti-prion compounds, anti-PrP monoclonal antibody 44B1, pentosan polysulfate, chlorpromazine, and U18666A, in prion-infected mouse neuroblastoma cells.

    Directory of Open Access Journals (Sweden)

    Takeshi Yamasaki

    Full Text Available Molecules that inhibit the formation of an abnormal isoform of prion protein (PrP(Sc in prion-infected cells are candidate therapeutic agents for prion diseases. Understanding how these molecules inhibit PrP(Sc formation provides logical basis for proper evaluation of their therapeutic potential. In this study, we extensively analyzed the effects of the anti-PrP monoclonal antibody (mAb 44B1, pentosan polysulfate (PPS, chlorpromazine (CPZ and U18666A on the intracellular dynamics of a cellular isoform of prion protein (PrP(C and PrP(Sc in prion-infected mouse neuroblastoma cells to re-evaluate the effects of those agents. MAb 44B1 and PPS rapidly reduced PrP(Sc levels without altering intracellular distribution of PrP(Sc. PPS did not change the distribution and levels of PrP(C, whereas mAb 44B1 appeared to inhibit the trafficking of cell surface PrP(C to organelles in the endocytic-recycling pathway that are thought to be one of the sites for PrP(Sc formation. In contrast, CPZ and U18666A initiated the redistribution of PrP(Sc from organelles in the endocytic-recycling pathway to late endosomes/lysosomes without apparent changes in the distribution of PrP(C. The inhibition of lysosomal function by monensin or bafilomycin A1 after the occurrence of PrP(Sc redistribution by CPZ or U18666A partly antagonized PrP(Sc degradation, suggesting that the transfer of PrP(Sc to late endosomes/lysosomes, possibly via alteration of the membrane trafficking machinery of cells, leads to PrP(Sc degradation. This study revealed that precise analysis of the intracellular dynamics of PrP(C and PrP(Sc provides important information for understanding the mechanism of anti-prion agents.

  2. Comparison of the anti-prion mechanism of four different anti-prion compounds, anti-PrP monoclonal antibody 44B1, pentosan polysulfate, chlorpromazine, and U18666A, in prion-infected mouse neuroblastoma cells.

    Science.gov (United States)

    Yamasaki, Takeshi; Suzuki, Akio; Hasebe, Rie; Horiuchi, Motohiro

    2014-01-01

    Molecules that inhibit the formation of an abnormal isoform of prion protein (PrP(Sc)) in prion-infected cells are candidate therapeutic agents for prion diseases. Understanding how these molecules inhibit PrP(Sc) formation provides logical basis for proper evaluation of their therapeutic potential. In this study, we extensively analyzed the effects of the anti-PrP monoclonal antibody (mAb) 44B1, pentosan polysulfate (PPS), chlorpromazine (CPZ) and U18666A on the intracellular dynamics of a cellular isoform of prion protein (PrP(C)) and PrP(Sc) in prion-infected mouse neuroblastoma cells to re-evaluate the effects of those agents. MAb 44B1 and PPS rapidly reduced PrP(Sc) levels without altering intracellular distribution of PrP(Sc). PPS did not change the distribution and levels of PrP(C), whereas mAb 44B1 appeared to inhibit the trafficking of cell surface PrP(C) to organelles in the endocytic-recycling pathway that are thought to be one of the sites for PrP(Sc) formation. In contrast, CPZ and U18666A initiated the redistribution of PrP(Sc) from organelles in the endocytic-recycling pathway to late endosomes/lysosomes without apparent changes in the distribution of PrP(C). The inhibition of lysosomal function by monensin or bafilomycin A1 after the occurrence of PrP(Sc) redistribution by CPZ or U18666A partly antagonized PrP(Sc) degradation, suggesting that the transfer of PrP(Sc) to late endosomes/lysosomes, possibly via alteration of the membrane trafficking machinery of cells, leads to PrP(Sc) degradation. This study revealed that precise analysis of the intracellular dynamics of PrP(C) and PrP(Sc) provides important information for understanding the mechanism of anti-prion agents.

  3. Comparative study among acepromazine, chlorpromazine and methotrimeprazine in different doses, through bispectral index, term and pressure algimetry, in dogs / Estudo comparativo entre a acepromazina, clorpromazina e levomepromazina em diferentes doses, através do exame bispectral, termo e pressoalgimetria, em cães

    Directory of Open Access Journals (Sweden)

    Lidia Mitsuko Matsubara

    2009-12-01

    Full Text Available The study’s objective was to realize comparisons among different acepromazine, chlorpromazine and methotrimeprazine doses, evaluate parametric changes, test analgesia using press and term algimetry, and evaluate bispectral condition. 90 mongrel dogs were used, male and female, adult, weighting 10 to 15 Kg as a rule, distributed in 9 groups with 10 animals each. At first, second and third groups acepromazine was used at 0,1; 0,05 e 0,025 mg/Kg, respectively. At forth, fifth and sixth groups, chlorpromazine was used at 1,0; 0,5 and 0,25 mg/Kg, respectively. At seventh, eighth and ninth groups, methotrimeprazine at 1,0; 0,5 and 0,25 mg/Kg was used, respectively. All drugs were administered intravenously. Objects of study: heart rate (HR, non invasive blood pressure (SAP, MAP, DAP, respiratory rate (f, capnography (ETCO2, pulse oxymetry (SatO2, mouth and rectal temperature, bispectral index (BIS, electromyography (EMG%, press and term algimetry. Somatic analgesia was evaluated by animal’s response to nociceptives stimulus. We concluded that chlorpromazine had more hypotension. Dogs showed higher hypnosis level at chlorpromazine group, with evident myorelaxation. All groups showed analgesia to thermic and mechanic stimulus. Acepromazine group showed high duration to both pain stimuli. Bispectral index was shorten at chlorpromazine group at 1,0 mg/kg doses, showing higher hypnosis index, and acepromazine was the less depressing considering the bispectral index.Objetivou-se comparar, em diferentes doses, a acepromazina, a clorpromazina e a levomepromazina com relação às alterações paramétricas, à analgesia avaliada através da presso e termoalgimetria e a condição bispectral em 90 cães sem raça definida alocados em nove grupos. No primeiro, segundo e terceiro grupo foi empregada a acepromazina nas doses de 0,1; 0,05 e 0,025 mg/kg, respectivamente. No quarto, quinto e sexto grupo foi empregada a clorpromazina nas doses de 1,0; 0,5 e 0

  4. 氯丙嗪、奥氮平、齐拉西酮对慢性精神分裂症患者认知功能的影响比较%Comparison of the effects of chlorpromazine, olanzapine and ziprasidone on cognitive function of patients with chronic schizophrenia

    Institute of Scientific and Technical Information of China (English)

    金国林; 汤庆平; 徐松泉

    2013-01-01

    Objective To compare the effects of chlorpromazine,olanzapine and ziprasidone on cognitive function of patients with chronic schizophrenia.Methods A total of 120 patients with chronic schizophrenia were randomly divided into chlorpromazine group(n =38),olanzapine group(n =41) and ziprasidone group(n =41).The patients were subjected to the Brief Psychiatric Rating Scale(BPRS),Wisconsin Card Sorting Test(WCST),Personal and Social Function of Scale (PSP) and Wechsler Adult Intelligence Scale-Revised (WAIS-RC) assessment respectively,before and after treatment for 12 weeks.Results After treatment for 12 weeks,the score of BPRS significantly decreased in three groups compared with that before treatment [F (5,41) =6.49,P < 0.05].After treatment for 12 weeks,the results of WCST [F (5,47) =18.30,P < 0.05],PSP [F (5,47) =10.02,P < 0.05] and WAIS-RC [F(5,47) =6.74,P < 0.05] test in ziprasidone and olanzapine group were better than that of chlorpromazine group.Conclusion Chlorpromazine,olanzapine and ziprasidone could improve the cognitive function and mental syndrome of patients with chronic schizophrenia.In addition,the effect of ziprasidone and olanzapine was better than chlorpromazine.%目的 比较氯丙嗪、奥氮平和齐拉西酮对慢性精神分裂症患者认知功能的影响.方法 将120例慢性精神分裂症患者按数字表法随机分为三组,分别为氯丙嗪组(38例)、奥氮平组(41例)和齐拉西酮组(41例),于入组前、治疗后第12周时采用简明精神病量表(BPRS)、个人和社会功能量表(PSP)、威斯康星卡片分类测验(WCST)、修订韦氏成人智力量表(WAIS-RC)进行随访评定.结果 经12周治疗,三组治疗前后BPRS测试结果差异均有统计学意义[F(5,41) =6.49,P<0.05],而三组之间差异无统计学意义;第12周末,齐拉西酮组和奥氮平组WCST[F(5,47)=18.30,P<0.05]、PSP[F(5,47)=10.02,P<0.05]和WAIS-RC[F(5,47) =6.74,P <0.05]评分显著优于氯丙嗪组.结论 氯丙嗪、

  5. Acontrolled study of Amisulpride and chlorpromazin inrefractory schizophrenia%氨磺必利与氯丙嗪治疗难治性精神分裂症对照研究

    Institute of Scientific and Technical Information of China (English)

    杨敏; 申琪; 姜德圆; 张兰桂; 汪敏

    2014-01-01

    目的:探讨氨磺必利治疗难治性精神分裂症的疗效和安全性。方法:将43例难治性精神分裂症患者随机分为氨磺必利治疗组和氯丙嗪治疗组,于治疗前和治疗第1、2、4、8、12w末采用阳性与阴性症状量表评定临床疗效,副反应量表评定不良反应,并进行对比分析。结果:治疗前两组阳性与阴性症状量表各项得分无显著差异;治疗后两组总有效率无显著性差异;认知因子和阴性症状减分率,两组间有显著差异性;氨磺必利的不良反应较氯丙嗪轻。结论:氨磺必利对难治性精神分裂症疗效肯定,不良反应较轻,特别是在改善认知功能和阴性症状方面有较好的效果。%Objective:To explore the curative effect and safety of Amisulpride in refractory schizophrenia.Methods:43 patients with refractory schizophreni-a were randomly divide dintore search group and controlledgroup.Effectiveness and safe tywereassessed by the PANSS and Treatment Emergent Symptoms Scale before treatment and attheend sofweek1,2,4,8and12,respectively.Results:There were no significant difference sinscores of the Positive and Negative S-ymp-toms Scalbe foretreatment and in total effective rates aftertreatment between two groups;there were significant difference sincognitive factor and score reducing rate sofnegative symptoms.The side effects of Amisulpride were milder than that of chlorpromazin.Conclusion:Amisulpride is effective and has milder side effects in the treatment of refractory schizophrenia,especia-lly in improvingcognitive function and negative symptoms.

  6. 氯氮平与氯丙嗪对精神分裂症患者听觉感觉门控的比较:前瞻性病例对照研究%Comparison of the effects of clozapine and chlorpromazine on auditory sensory gating in patients with schizophrenia:a prospective case-control study

    Institute of Scientific and Technical Information of China (English)

    苏亮; 施慎逊; 王继军; 李惠; 王立伟; 张明园

    2011-01-01

    精神分裂症患者听觉感觉门控(以下简称感觉门控)P50受损,各种抗精神病药物对该P50的作用仍有争议.假设第二代抗精神病药物氯氮平治疗的精神分裂症患者比氯丙嗪治疗患者的感觉门控P50的改善明显.方法 前瞻性对照研究纳入刚住院的精神分裂症患者,由治疗医师决定氯氮平治疗者26例(研究组),氯丙嗪治疗者30例(对照组).氯氮平组有23例完成8周研究纳入分析,氯丙嗪组为20例.检测P50的方法为双短声刺激[听觉条件(S1)-测试刺激(S2)范式],检测时点为基线、治疗第4周和第8周.临床症状用阳性与阴性综合征量表(Positive and Negative Syndrome Scale,PANSS)评定.结果 两组年龄、性别、教育程度、病程和基线PANSS总分差异均无统计学意义.氯丙嗪组平均(标准差)治疗剂量为389(96)mg/d,氯氮平组为345(117)mg/d.重复测量的方差分析显示,氯氮平组颅顶中央脑区(central zone,Cz)P50比值(S2/S1)的下降比氯丙嗪组明显[基线为108%比106%,第4周94%比102%,第8周84%比95%,F=4.91,P=0.029],而S1和S2波幅差异无统计学意义.两组间S1和S2的波幅无明显差异.氯氮平组治疗后P50比值较治疗前下降(F=4.39,P=0.014),氯丙嗪组治疗前后P50比值没有明显变化.结论氯氮平治疗可以减轻精神分裂症患者感觉门控的受损程度;与氯丙嗪治疗相比,氯氮平治疗者的改善程度较明显.%Background: Patients with schizophrenia have deficits in their P5O auditory sensory gating but the effect of different antipsychotic medications on patients' P50 sensory gating remains controversial.Hypothesis: The improvement in P50 auditory sensory gating of patients with schizophrenia is greater when they are treated with the second generation antipsychotic clozapine than when treated with the first generation antipsychotic chlorpromazine.Methods: This prospective case-control study of inpatients with schizophrenia enrolled at the time of

  7. Study of effects of Risperidone and Chlorpromazine on cognitive function in patients with chronic schizophrenia%利培酮和氯丙嗪对慢性精神分裂症患者认知功能影响的对照研究

    Institute of Scientific and Technical Information of China (English)

    马文华; 王兆琴; 喻慧; 石莎莎; 林丽群

    2015-01-01

    目的::探讨利培酮对慢性精神分裂症患者认知功能的影响。方法:将符合入组标准的精神分裂症60例患者随机分为利培酮组和氯丙嗪组,每组30例。两组患者分别进行12周系统治疗,用阳性与阴性症状量表(PANSS)、修订韦氏记忆量表(WMS-RC)、中国成人智力量表( CISA)进行检查与评估,比较两组患者疗效和对认知功能的影响。结果:利培酮组患者的PANSS总分、阴性症状和一般病理性症状因子分均显著低于氯丙嗪组,两组患者之间差异有显著性(P<0.05),利培酮组患者的认知功能(包括认知总分、心智、再认、背数、图形识别)优于氯丙嗪组,两组患者存在显著差异(P<0.05)。结论:利培酮对慢性精神分裂症患者认知功能和阴性症状的疗效优于氯丙嗪疗效。%Objective:To study effects of Risperidone on cognitive function in patients with chronic schizophrenia. Methods:60 patients with schizophrenia were randomly divided into Risperidone group ( n=30 ) and Chlorpromazine group ( n=30 ) , and were treated for 12 weeks. The therapeutic response and cognitive function of the two groups were assessed by positive and negative symptom scale ( PANSS) , Wechsler adult memory scale ( WMS-RC) , and Chinese adult intelligence scale ( CISA) and compared. Results:The total score of PANSS, and the factor scores of negative symptoms and general pathological symptoms of Risperidone group were sig-nificantly lower than those of Chlorpromazine group, and the differences between the two groups were significant (P<0. 05). The scores of WMS-RC and CISA ( including total score of cognitive function, intelligence, recognition, digit remembering, pattern recog-nition) of Risperidone group were higher than those of Chlorpromazine group, and the differences between the two groups were signifi-cant (P<0. 05). Conclusions: The effects of Risperidone on cognitive function and negative symptoms in the patients

  8. 利培酮对首发精神分裂症患者血清α-肿瘤坏死因子的影响%Effect of risperidone and chlorpromazine on plasma level of TNF-α in patients with first-episode schizophrenia.

    Institute of Scientific and Technical Information of China (English)

    田博; 陆晓姿

    2011-01-01

    目的 探讨抗精神病药物对首发精神分裂症患者血清α-肿瘤坏死因子(TNF -α)的影响,并探讨TNF -α与精神病理之间的关系.方法 90例首发精神分裂症患者随机分为利培酮组(45例)和氯丙嗪组(45例),进行8周治疗,采用酶联免疫吸附法对治疗前后α-肿瘤坏死因子(TNF-α)进行检测,以40例健康志愿者为对照.同时采用阳性和阴性症状量表(PANSS)评估患者精神症状及其变化.结果 精神分裂症患者治疗前TNF -α水平显著高于对照组(t=3.08,P<0.01),治疗后4周末及8周末与对照组比较均无显著性差异(t=0.11,0.52,P>0.05),均较治疗前显著降低(P <0.05,P<0.01).治疗前及治疗后4周末血清TNF -α水平与对应PANSS总分及各因子分无显著相关(P>0.05),治疗后8周末TNF -α与阳性症状分及总分呈正相关.利培酮组患者TNF -α水平治疗后4周末无显著变化,治疗后8周末显著低于治疗前(P<0.05);氯丙嗪组患者治疗后4周末及8周末均显著低于治疗前(P<0.01).治疗后4周末血清TNF -a变化率与氯丙嗪日剂量呈显著正相关(P<0.05),利培酮日剂量与TNF -α变化率无相关,8周末两药日剂量与TNF - α变化率均无相关.结论 抗精神病药物对首发精神分裂症患者血TNF -α有抑制作用,血清TNF -α水平与精神病理之间有着一定关系.%Objective To explore the effect of antipsychotic drugs on plasma level of tumor necrosis factor-α (TNF-α ) in patients with first - episode schizophrenia, and to explore the relationship between TNF-a and the psychopathology of schizophrenia. Methods 90 patients with first - episode schizophrenia were randomized into risperidone group (45 cases) and chlorpromazine group (45 cases) treated with risperidone or chlorpromazine respectively for 8 weeks. Plasma level of TNF-a of patients was measured with ELISA at baseline and endpoint of the treatment, then was compared with that of 40 healthy volunteers

  9. Neuroleptic malignant syndrome associated with concomitant use of levodopa and benserazide hydrochloride, olanzapine, and chlorpromazine%多巴丝肼与奥氮平及氯丙嗪合用致抗精神病药恶性综合征

    Institute of Scientific and Technical Information of China (English)

    王海飞

    2015-01-01

    1例71岁男性帕金森病患者应用多巴丝肼(0.25 g,2次/d口服)治疗2年,因出现脑器质性精神障碍加用奥氮平2.5 mg,2次/d口服.第3天因患者出现兴奋躁动,肌内注射氯丙嗪50 mg.第5天患者出现发热(38.8℃)、肌酸激酶升高(424 U/L)、四肢肌强直.第11天患者体温39.2℃,出现木僵状态,尿液呈酱油样.实验室检查:外周血白细胞计数9.5×109/L,中性粒细胞0.9,肌酸激酶939 U/L.诊断为抗精神病药恶性综合征.停用奥氮平和多巴丝肼,给予纳洛酮、中/长链脂肪乳、复方氨基酸、肠内营养混悬液及地塞米松对症支持治疗.第13天,患者体温恢复正常.第15天,患者肌酸激酶降至109 U/L.第17天恢复多巴丝肼治疗.%A 71-year-old man with Parkinson' s disease received levodopa and benserazide hydrochloride 0.25 g twice daily for two years.Olanzapine 2.5 mg twice daily was added to his regimen for brain organic mental disorders.On day 3,the patient developed agitation and received an intramuscular injection of chlorpromazine 50 mg.On day 5,he developed temperature of 38.8 ℃,elevated serum creatine kinase (424 U/L),and muscle rigidity.On day 11,he presented with temperature of 39.2 ℃,stupor,and soy-colored urine.Laboratory tests showed the following findings:white blood cell count 9.5 × 109/L,neutrophile granulocyte 0.9,and creatine kinase 939 U/L.Neuroleptic malignant syndrome was diagnosed.Olanzapine and levodopa and benserazide hydrochloride were withdrawn.Meanwhile symptomatic and supportive treatments such as naloxone,medium and long chain fat emulsion,compound amino acid,enteral nutritional suspension,and dexamethasone were given.On day 13,his body temperature returned to within normal range.On day 15,the creatine kinase level decreased to 109 U/L.On day 17,levodopa and benserazide hydrochloride was resumed.

  10. Sulfato de atropina nos parâmetros hemodinâmicos e hemogasométricos de cães anestesiados com clorpromazina, dexmedetomidina e isoflurano Hemodynamic and hemogasometric in the atropine administration in dogs anesthetized with chlorpromazine and dexmedetomidine and isoflurane

    Directory of Open Access Journals (Sweden)

    Fabíola Niederauer Flôres

    2008-08-01

    , at least 7 days apart, in randomized blinded manner. Anesthesia was induced and maintained with isoflurane in mechanical ventilation. After instrumentation, the end-tidal isoflurane was maintained at 1,3%V throughout the study. After a 30 minutes stabilization period (M -15, baseline hemodynamic parameters and arterial blood gases were recorded and atropine (atropine group or 0.9% NaCl (saline group were administered. Fifteen minutes later, data were recorded again (M0 and a chlorpromazine- dexmedetomidine (Chlor-Dex combination was administered. Variables were measured for an additional 65 minutes after Chlor-Dex. A one-way ANOVA-Student-Newman-Keuls was used for comparisons within groups, while a paired t test was used for comparisons between groups (P£0,05. Heart rate was higher in atropine group after Chlor-Dex administration. Cardiac index (CI was reduced from baseline after Chlor-Dex in both treatments. Although mean CI values tended to be higher in atropine group, CI did not differ between groups. Chlor-Dex administration caused increased arterial blood pressure in dogs treated with atropine. Mean arterial pressure (MAP was significantly higher in the atropine group from 5 to 65 min after Chlor-Dex. The systemic vascular resistance index (SVRI increased from baseline in both groups after Chlor-Dex administration. No significant differences were observed for arterial blood gases. Atropine administration prior to Chlor-Dex resulted in increased arterial blood pressure. Bradycardia induced by the administration of these drugs was prevented by the anticholinergic given, however decrease in cardiac output was not prevented.

  11. Pharm GKB: gefitinib [PharmGKB

    Lifescience Database Archive (English)

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  12. Biokinetics and repeated exposure in in vitro assays : A detailed study into the behaviour of chlorpromazine and diazepam in different cell systems

    NARCIS (Netherlands)

    Broeders, J.J.W.

    2013-01-01

    The potential risk of compounds is commonly assessed with animal experimentation and extrapolation of these data to assess human health effects. The use of Integrated Testing o Strategies combines different methods, including in vitro tests and in silico methods, to perform risk assessment with less

  13. Biokinetics and repeated exposure in in vitro assays : A detailed study into the behaviour of chlorpromazine and diazepam in different cell systems

    OpenAIRE

    Broeders, J.J.W.

    2013-01-01

    The potential risk of compounds is commonly assessed with animal experimentation and extrapolation of these data to assess human health effects. The use of Integrated Testing o Strategies combines different methods, including in vitro tests and in silico methods, to perform risk assessment with less costs and less animal experiments. Although alternatives to animal tests have been developed and validated, research into alternatives for certain toxicological endpoints is yet limited. One of th...

  14. 氯丙嗪与舒必利对心电图影响的对比观察%A comparative investigation of chlorpromazine and sulpiride on ECG

    Institute of Scientific and Technical Information of China (English)

    李金亮; 黄前堂; 张晓霞; 王小强; 谢磊

    2001-01-01

    目的:探讨氯丙嗪、舒必利抗精神病药物对心电图的影响.方法:将同期单用氯丙嗪、舒必利治疗精神病分裂症患者心电图改变进行对比分析.结果:发现其心电图改变率,窦性心动过速,T波改变,束支传导阻滞等有显著差异,且氯丙嗪出现心电图异常的时间较舒必利短,心电图改变后恢复正常的时间较舒必利长.结论:氯丙嗪对心脏的毒性作用相对比舒必利更重一些.

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    Lifescience Database Archive (English)

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  17. Pharm GKB: imipramine [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available ine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxep...clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine fluvoxamine gefiti...l chlorpheniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan...opram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine...orpheniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan

  18. Effect of chlorpromazine hydrochloride acupoint-injection versus methylphenidate muscular injection for patients with intractable hiccup%氯丙嗪与利他林治疗顽固性呃逆疗效对比及护理

    Institute of Scientific and Technical Information of China (English)

    李玮; 张承菊; 陈龙梅; 潘发明

    2007-01-01

    目的 探讨盐酸氯丙嗪双侧足三里穴位注射与利他林肌肉注射治疗顽固性呃逆的临床效果比较.方法 将34例原发性肝癌合并顽固性呃逆的患者随机分为观察组和对照组,观察组20例,采用盐酸氯丙嗪双侧足三里穴位注射,对照组14例,采用利他林肌肉注射,并进行效果观察.结果 盐酸氯丙嗪双侧足三里穴位治疗效果明显优于利他林肌肉注射治疗.结论 顽固性呃逆应用盐酸氯丙嗪双侧足三里穴位治疗效果好,值得推广应用.

  19. HPLC法检测血清氯氮平、奋乃静、氯丙嗪及舒必利药物浓度%DETERMINATION OF CLOZAPINE, PERPHENAZINE, CHLORPROMAZINE AND SULPIRIDE IN SERUM BY HPLC

    Institute of Scientific and Technical Information of China (English)

    樊宁; 宋路生

    2005-01-01

    氯氮平、氯丙嗪、奋乃静及舒必利属于临床上常用的抗精神病药物,临床应用广泛,且疗效显著。但由于其可引起药源性锥体外系反应(EPS),如:巴金森氏症、静坐不能、急性肌张力障碍等等。特别是服用氯氮平可引起致命性副反应:粒细胞缺乏症,从而使其在临床上的应用受到限制。通过密切监测血药浓度和血象,可以预测其疗效和预防不良反应的发生,使其再次被广泛应用于临床。关于氯氮平、氯丙嗪、奋乃静和舒必利的药代动力学、血药浓度测定,血药浓度与临床疗效、不良反应的关系等,国内外已有不少文献报道。

  20. Pharm GKB: citalopram [PharmGKB

    Lifescience Database Archive (English)

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  1. Pharm GKB: tamoxifen [PharmGKB

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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  4. Pharm GKB: mianserin [PharmGKB

    Lifescience Database Archive (English)

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  5. Pharm GKB: clomipramine [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available codeine debrisoquine desipramine dextromethorphan doxepin duloxetine escitalopram flecainide fluoxetine flu...mipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine fluvoxam...e chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan...xetine carvedilol chlorpheniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan...zine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan

  6. Pharm GKB: paroxetine [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available e citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan...pram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan dox...rvedilol chlorpheniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan...e chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin...e citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide flu

  7. Pharm GKB: propafenone [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available e debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine fluvoxa...xetine carvedilol chlorpheniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan...zine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide ...omipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine fluvoxa...xetine carvedilol chlorpheniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan

  8. Pharm GKB: maprotiline [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available iramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan d...lomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin f...ine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine fluvoxamine gefitinib ha...lol chlorpheniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan... citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan

  9. Pharm GKB: codeine [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available pramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin fleca...lol chlorpheniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan...alopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxeti...e chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin...ne clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide

  10. Pharm GKB: thioridazine [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available dilol chlorpheniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan...ram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine f...lozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine fluvoxamine gefitin...dilol chlorpheniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan...ram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxe

  11. Pharm GKB: carvedilol [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available arvedilol chlorpheniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan...ne citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fl...lomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine fluvox...ine carvedilol chlorpheniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan...romazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecain

  12. Pharm GKB: haloperidol [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan...ne codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine fluvoxamine gefitinib hal...heniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan...amine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan dox...ne citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fl

  13. Evaluation of proximal therapeutic effect and distal social function restoration of olanzapine on schizophrenia patients%奥氮平对精神分裂症患者近期疗效及远期社会功能恢复效果评价

    Institute of Scientific and Technical Information of China (English)

    王长虹; 赵峥; 李晏; 潘苗; 刘旭

    2002-01-01

    Objective To evaluate the efficacy and prognosis of olanzapine in treatment of the schizophrenia. Methods A randomized controlled clinical study was performed to compare the efficacy and prognosis of olanzapine to that of chlorpromazine. 60 patients with schizophrenia were divided two groups. 32cases were treated with olanzapine. 28 cases were treated with chlorpromazine .Results The significant effect rate and effective rate on olanzapine group were 63% and 82% respectively ; which in chlorpromazine group were 32% and 50% .There were less side effects, and less recurrent rate in olanzapine. Conclusion Olanzapine is one of the safe and effective atypical antipsychotic for schizophrenia with significantly fewer side effects.

  14. Drug interference in the Bradford and 2,2'-bicinchoninic acid protein assays.

    Science.gov (United States)

    Marshall, T; Williams, K M

    1991-11-01

    The interference of a range of drugs and related substances has been investigated in the Bradford Coomassie brilliant blue (CBB) protein dye-binding assay and the 2,2'-bicinchoninic acid (BCA) protein assays. Chlorpromazine was the only substance to interfere in the CBB assay but the interference was slight. In contrast, the BCA reagent interacted strongly with chlorpromazine, the penicillins, vitamin C, and paracetamol and the mode of interference varied with the test substance. The chlorpromazine produced turbidity and an atypical color. The penicillins show a slow but normal color response while vitamin C and paracetamol gave an immediate and intense response.

  15. Clinical analysis of treatingneuroleptic malignant syndrome induced by depression byusing fluoxetine combined with chlorpromazine%氟西汀联合氯丙嗪治疗抑郁症发生恶性综合征5例临床分析

    Institute of Scientific and Technical Information of China (English)

    陈世文; 刘中霖

    2015-01-01

    Objective To describe the clinical features of 5 depressionpatients who complicated with neuroleptic malignant syndrome ( NMS), in order to learn more about this disease. Methods Five depression patients complicated with NMS were included. Clinical features, laboratory data ( routine analysis of blood, serum myocardial enzymes, thyroid function ) and treatment were retrospectively studied and related literatures were reviewed.Results All of the five cases presented as muscular rigidity, fever, autonomic instability and an altered level of consciousness, andthe levels of white cells and serum myocardial enzymeselevated. Two cases had Low T3 syndrome.All patients were rescued by drug discontinuance and supportive treatment. Conclusions Treating depressionwith fluoxetine combined with chlorpromazineseemed easy to complicate NMS, especially the patients with low T3 syndrome.Thyroid dysfunction should be excluded in all depression patients ,oncethyroid dysfunction or including low T3 syndrome was approved, the using of antipsychotics should be. Appropriate care for these patients may include an increased awareness of possible cautious.%目的:探讨5例抑郁症患者并发恶性综合征的临床资料,以提高对该病的认识和诊治水平。方法分析5例抑郁症患者并发恶性综合征的临床表现、辅助检查(血常规、肌酶、甲状腺功能)及治疗。结果5例患者均出现明显的强直、高热、自主神经功能紊乱和意识障碍等症状。5例患者均出现白细胞及肌酶升高。2例患者存在低 T3综合征。5例患者均给予停药、对症支持治疗,均恢复良好。结论氟西汀联合氯丙嗪治疗抑郁症容易并发恶性综合征,尤其是伴有低T3综合征的患者。对抑郁症患者应该常规检查甲状腺功能,一旦发现有甲状腺功能低下或低T3综合征时,应谨慎联合使用抗精神病药以防止出现恶性综合征。

  16. 氯氮平片和氯丙嗪片对慢性精神分裂症患者体质量和糖脂代谢的影响%Influence of clozapine tablet and chlorpromazine tablet on body weight and metabolism of glucose and lipid in the treatment of chronic schizophrenia patients

    Institute of Scientific and Technical Information of China (English)

    林建荣; 何凤贞; 赵德信; 温预关; 侯静; 陈国中

    2007-01-01

    目的 研究氯氮平片和氯丙嗪片(均为抗精神分裂症药)对分裂症患者糖脂代谢和体质量的影响.方法 于治疗前后对89例服氯氮平和83例服氯丙嗪患者做血糖、胰岛素、血脂和体质量测定及相关因素分析.结果 用药90,180天,氯氮平组糖尿病发生率为7.9%及23.6%;而氯丙嗪组为1.1%及3.6%.2组90天时空腹和餐后2 h血糖均升高,而180天时,继续升高(P<0.01).用药90天时,2组体质量较基线分别增高5.5%,4.8%;而180天分别增高9.1%,7.4%.2组胰岛素180天较基线明显增加有显著性差异(P<0.01),组间无差别(P>0.05).2组胆固醇和甘油三脂均较基线明显增高(P<0.01).氯氮平组的血糖、胰岛素、血脂与体质量变化和血药浓度均有一定相关性(γ=0.21~0.99).结论 2种药对糖脂代谢和体质量均有作用,治疗期间要进行检测.

  17. 奎硫平与氯丙嗪治疗精神分裂症的多中心随机双盲对照试验%A Comparison Study on Efficacy and Safety of Quetiapine and Chlorpromazine in The Treatment of Schizophrenia

    Institute of Scientific and Technical Information of China (English)

    张鸿燕; 王希林; 刘粹; 舒良; 李华芳; 顾牛范; 李婷; 马崔; 陈远光; 李静; 黄明生

    2003-01-01

    目的:评价富马酸奎硫平治疗精神分裂症的疗效和安全性,并与经典抗精神病药氯丙嗪对照.方法:本研究采用多中心、随机平行、双盲双模拟对照试验方法.共入组符合研究方案的病例237例,奎硫平组119例,氯丙嗪组118例.两组药物剂量均为每天300~750 mg.结果:两组的主要疗效指标阳性和阴性症状量表(PANSS)、简明精神病量表(BPRS)评分在治疗结束时与基线比较均有显著下降(P<0.01);根据PANSS减分率评定临床总有效率,奎硫平组的有效率为61.61%,氯丙嗪组的有效率为64.81%,两组之间无显著性差异;奎硫平组的药物不良反应发生率为44.54%,氯丙嗪组的发生率是76.27%.其中以震颤、肌紧张和静坐不能等明显少于对照组;实验室检查两组均无严重异常.结论:富马酸奎硫平是一种新的安全有效的抗精神病药物.

  18. Drug: D02615 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available PTICS N05C HYPNOTICS AND SEDATIVES N05CB Barbiturates, combinations N05CB02 Barbiturates in combination with other drugs D02615 Chlorpromazine - promethazine mixt PubChem: 17396785 ...

  19. Membrane specific drugs as radiosensitizers

    Energy Technology Data Exchange (ETDEWEB)

    George, K.C.; Mishra, K.P.; Shenoy, M.A.; Singh, B.B.; Srinivasan, V.T.; Verma, N.C.

    1981-01-01

    Procaine, paracetamol, and chlorpromazine showed inhibition of post irradiation repair. The chlorpromazie effect could be further augmented by treatment of cells with procaine. Chlorpromazine was also found to be preferentially toxic to hypoxid bacterial cells, and the survivors showed extreme radiosensitivity to gamma rays. Chlorpromazine was found to inhibit tumour growth in swiss mice when given intraperitoneally as well as when injected directly into the tumour. When combined with single x-ray doses, significant radiosensitization was observed in two in vivo tumours sarcoma 180A and fibrosarcoma. These results indicated that chlorpromazine may prove a good drug for combined chemo-radiotherapy of solid tumours. Investigations continued studying various aspects such as effectiveness in other tumour lines, distribution in healthy and tumour bearing animals, hyperthermia and drug combination effects, and encapsulation of the drug in artificial liposomes and blood cells. (ERB)

  20. Effect of autonomic blocking agents and structurally related substances on the “salt arousal of drinking”

    NARCIS (Netherlands)

    Wied, D. de

    1966-01-01

    The effect of autonomic blocking agents and structurally related substances was studied in rats in which thirst was produced by the administration of a hypertonic sodium chloride solution. Scopolamine, methamphetamine, amphetamine, chlorpromazine, atropine, mecamylamine, hexamethonium, nethalide, in

  1. Pharm GKB: sparteine [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available *21, CYP2D6 *44, CYP2D6 *5 and debrisoquine, dextromethorphan, sparteine Level of Evidence Level 4 Type Othe...lozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine fluvoxamine gefitin... carvedilol chlorpheniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan...heniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan...omipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine fluvoxa

  2. Effect of therapeutic chemical agents in vitro and on experimental meningoencephalitis due to Naegleria fowleri.

    Science.gov (United States)

    Kim, Jong-Hyun; Jung, Suk-Yul; Lee, Yang-Jin; Song, Kyoung-Ju; Kwon, Daeho; Kim, Kyongmin; Park, Sun; Im, Kyung-Il; Shin, Ho-Joon

    2008-11-01

    Naegleria fowleri is a ubiquitous, pathogenic free-living amoeba; it is the most virulent Naegleria species and causes primary amoebic meningoencephalitis (PAME) in laboratory animals and humans. Although amphotericin B is currently the only agent available for the treatment of PAME, it is a very toxic antibiotic and may cause many adverse effects on other organs. In order to find other potentially therapeutic agents for N. fowleri infection, the present study was undertaken to evaluate the in vitro and in vivo efficacies of miltefosine and chlorpromazine against pathogenic N. fowleri. The result showed that the growth of the amoeba was effectively inhibited by treatment with amphotericin B, miltefosine, and chlorpromazine. When N. fowleri trophozoites were treated with amphotericin B, miltefosine, and chlorpromazine, the MICs of the drug were 0.78, 25, and 12.5 microg/ml, respectively, on day 2. In experimental meningoencephalitis of mice that is caused by N. fowleri, the survival rates of mice treated with amphotericin B, miltefosine, and chlorpromazine were 40, 55, and 75%, respectively, during 1 month. The average mean time to death for the amphotericin B, miltefosine, and chlorpromazine treatments was 17.9 days. In this study, the effect of drugs was found to be optimal when 20 mg/kg was administered three times on days 3, 7, and 11. Finally, chlorpromazine had the best therapeutic activity against N. fowleri in vitro and in vivo. Therefore, it may be a more useful therapeutic agent for the treatment of PAME than amphotericin B.

  3. Effect of tricyclic drugs on mitochondrial membrane.

    Directory of Open Access Journals (Sweden)

    Eto,Kohei

    1985-08-01

    Full Text Available The effects of tricyclic drugs (clomipramine, imipramine, chlorpromazine and promethazine on isolated liver mitochondria of rats were examined. All the drugs tested accelerated state 4 respiration. Their stimulative potency at concentrations below 100 microM was in the order of chlorpromazine greater than clomipramine greater than imipramine, promethazine. On state 3 respiration, the chlorine containing drugs had an inhibitive effect at high concentrations, while the other drugs seemed to have a slightly stimulative effect. These drugs stimulated latent ATPase activity of mitochondria. Clomipramine and chlorpromazine inhibited 2, 4-dinitrophenol-stimulated ATPase activity in a dose-dependent fashion. Imipramine also inhibited 2, 4-dinitrophenol-stimulated ATPase activity at high concentrations. Promethazine, however, had almost no effect. All the drugs induced potassium release from mitochondrial vesicles, and their potency was in the order of clomipramine greater than chlorpromazine greater than imipramine greater than promethazine. These results suggest that clomipramine, imipramine, chlorpromazine and promethazine cause impediments in both mitochondrial respiration and ion compartmentation, and that the chlorine containing drugs are more toxic than others on the functions of the mitochondrial membrane.

  4. Comparative Cytochrome P450 In Vitro Inhibition by Atypical Antipsychotic Drugs

    OpenAIRE

    Guillermo Gervasini; Caballero, Maria J.; Carrillo, Juan A.; Julio Benitez

    2013-01-01

    The goal of this study was to assess in human liver microsomes the inhibitory capacity of commonly used antipsychotics on the most prominent CYP450 drug metabolizing enzymes (CYP1A2, CYP2C9, CYP2D6, and CYP3A). Chlorpromazine was the only antipsychotic that inhibited CYP1A2 activity (IC50 = 9.5  μ M), whilst levomepromazine, chlorpromazine, and thioridazine significantly decreased CYP2D6-mediated formation of 1′-hydroxybufuralol (IC50 range, 3.5–25.5  μ M). Olanzapine inhibited CYP3A-catalyze...

  5. The effects of centrally acting muscle relaxants on the intrathecal noradrenaline-induced facilitation of the flexor reflex mediated by group II afferent fibers in rats.

    Science.gov (United States)

    Sakitama, K

    1993-11-01

    The effects of centrally acting muscle relaxants on the flexor reflex mediated by group II afferent fibers (group II flexor reflex) in anesthetized intact rats and on the intrathecal noradrenaline-HCl-induced facilitation of the group II flexor reflex in anesthetized spinal rats were investigated. In anesthetized intact rats, mephenesin, tolperisone-HCl, chlorpromazine-HCl and baclofen inhibited the group II flexor reflex dose-dependently, whereas the inhibitory effect of tizanidine-HCl was bell-shaped. The effect of diazepam tended to be saturated. In anesthetized spinal rats, mephenesin, tolperisone-HCl, chlorpromazine-HCl, diazepam and baclofen also depressed the group II flexor reflex, but tizanidine-HCl slightly increased it. The intrathecal noradrenaline-HCl-induced facilitation of the group II flexor reflex was not affected by mephenesin or diazepam, but was inhibited by tizanidine-HCl, tolperisone-HCl, chlorpromazine-HCl and baclofen. These results suggest that compounds with centrally acting muscle relaxant activity depress the group II flexor reflex in different manners, and the inhibition of descending noradrenergic tonic facilitation within the spinal cord participates in the depressant action of the group II flexor reflex produced by tolperisone-HCl, tizanidine-HCl, chlorpromazine-HCl and baclofen.

  6. Clinical Investigation Program, Fiscal Year 1991

    Science.gov (United States)

    1992-02-03

    106 Jesse , Steven W.: 88/65 (0) Pediatric Intubation Training Utilizing the Feline Model ................................... 108 Jesse, Steven W...90/44 (0) Comparison of Intramuscular Meperidine and Promethazine, with and without Chlorpromazine for Pediatric Sedation ...Pediatrics KEY WORDS: Echocardiography , Puberty StudyQObjtiv: To establish echocardiographic standard for healthy adolescents based on Tanner staging

  7. Galactorrhea and hyperprolactinemia associated with chest wall injury.

    Science.gov (United States)

    Morley, J E; Dawson, M; Hodgkinson, H; Kalk, W J

    1977-11-01

    A 48 year old premenopausal woman presented with galactorrhea and amenorrhea associated with chest wall burns. Basal serum prolactin levels were raised, and were further elevated by the administration of L-dopa, chlorpromazine and TRH. Intercostal nerve block and bromocryptine treatment reduced prolactin levels to normal, but did not noticably reduce milk secretion.

  8. The Effects of Nicotine on MK-801-induced Attentional Deficits: An Animal Model of Schizophrenia

    Science.gov (United States)

    2002-01-01

    antipsychotic effects when used in schizophrenic patients. Chlorpromazine (Thorazine) is a “conventional antipsychotic ,” or a neuroleptic - a class of...drugs that also includes Haloperidol (Haldol) (Dixon, Lehman, & Levine, 1995; Love, 1996; Stahl, 2000). Conventional antipsychotics are rarely...prescribed now because of their negative side effects including: cognitive and neurologic deficits (such as sedation, confusion, and tardive dyskinesia

  9. Pharm GKB: perphenazine [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available hlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin fl...lopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetin...hlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin fl...lopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetin...chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan

  10. Pharm GKB: desipramine [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available omazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecaini...debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine fluvoxamine gefitinib haloperidol im...pheniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan...promazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecai...apine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxe

  11. Pharm GKB: risperidone [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available pram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine ...lorpheniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan...m clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine flu...ne clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine fluvoxamine gef...ine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine fluvoxamine ge

  12. Pharm GKB: nortriptyline [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available uch individuals are referred to as poor metabolizers of drugs such as debrisoquin, dextromethorphan and the ...eniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan...lozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine fluvoxamine gefitin...eine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine fluvoxamine gefitinib haloperid...pramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine fluvoxamin

  13. Pharm GKB: chlorpheniramine [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available hlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin fl...lopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetin...hlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan...lopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetin... chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan

  14. Pharm GKB: doxepin [PharmGKB

    Lifescience Database Archive (English)

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  18. Pharm GKB: mexiletine [PharmGKB

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    Full Text Available lorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan...opram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine...lorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan...opram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine...arvedilol chlorpheniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan

  19. Pharm GKB: timolol [PharmGKB

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    Full Text Available amine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine fluvoxamine ...deine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine fluvoxamine gefitinib haloperi... chlorpheniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan...pram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan dox...orpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flec

  20. Pharm GKB: morphine [PharmGKB

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  1. Pharm GKB: tramadol [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available d activity of the CYP2D6 isoenzyme of cytochrome P450. These individuals are poor metabolizers of debrisoquine, dextromethorphan...lomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine fluvox...lomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin f...chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin f...clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fl

  2. Combinatorial Strategies and High Throughput Screening in Drug Discovery Targeted to the Channel of Botulinum Neurotoxin

    Science.gov (United States)

    2006-09-01

    M2 protein2 and its derivative, memantine, which blocks the NMDA receptor channel3, and is approved by the FDA for the treatment of dementia ...The antipsychotic chlorpromazine4, an open channel blocker of the nicotinic acetylcholine receptor (nAChR) channel5, and numerous local

  3. Effects of tricyclic compounds and other drugs having a membrane stabilizing action on analgesia, tolerance to and dependence on morphine.

    Science.gov (United States)

    Contreras, E; Tamayo, L; Quijada, L

    1977-08-01

    Several drugs affecting nerve cell excitability, by opposing ion movements in membranes, were tested in mice rendered tolerant to or dependent on morphine. The purpose of the study was to investigate whether these drugs share the ability to attenuate morphine tolerance and dependence exhibited by tricyclic antidepressants. Tolerance to morphine was decreased by the administration of imipramine, doxepin, promethazine, propranolol, lidocaine and quinidine. Chlorpromazine and carbamazepine were ineffective. The intensity of the abstinence syndrome provoked by naloxone was decreased by chlorpromazine, imipramine, doxepin, lidocaine, quinidine and propranolol. Diphenyl. hydantion and carbamazepine had no effect. The results are discussed in relation with the blockade of ion conductance and their interference with the release of neurotransmitters produced by the drugs assayed.

  4. Use of psychotropics in the world.

    Science.gov (United States)

    Itil, T M; Reisberg, B; Simeon, S

    1978-01-01

    A questionnaire regarding medication preferences for major categories of psychiatric disorders was sent to 1,059 psychiatric drug investigators in 53 countries. 264 questionnaires were returned, of which 165 were appropriate for this survey. A total of 87 different psychotropic drugs were selected. Chlorpromazine was the medication most frequently cited in the treatment of schizophrenia. Amitriptyline and imipramine together accounted for the vast majority of medication chosen for all varieties of depression. In the treatment of mania, chlorpromazine was chosen by almost one-third of our sample, lithium by only one-fifth. Chlordiazepoxide and diazepam were equally preferred in the treatment of alcoholism. Most psychiatrists preferred not to use any psychotropic medications consistently in treating patients with organic brain syndromes. The implications of this study are discussed and compared uith similar studies in more limited geographical regions and in children.

  5. Pediatric psychopharmacology outside the U.S.A.

    Science.gov (United States)

    Simeon, J; Utech, C; Simeon, S; Itil, T M

    1974-07-01

    To obtain information on the use of psychotropic drugs children outside the U.S.A., 251 questionnaires were mailed to institutions in 53 countries. Seventy-three responses from 34 countries were analyzed. The percentage of patients receiving drugs under the care of these respondents ranged from 0 to 100% (mean 39%). A total of 56 different drugs were selected for eleven psychiatric disorders. No regional differences were apparent, except for infrequently used drugs. Respondents differed widely in the number of drugs selected and maximum dosages. The most popular drugs used in most disorders were diazepam, thioridazine, chlorpromazine, chlordiazepoxide, imipramine, amitriptyline, haloperidol and methylphenidate. Highest agreements among respondents were for imipramine in enuresis, diazepam in anxiety, chlorpromazine in psychosis and thioridazine in hyperkinesis. The results of this survey illustrate important problems in interpreting cross-cultural data in pediatric psychopharmacology, and recommendations for future research are made.

  6. Peptide-induced emesis in dogs: possible relevance to radiation-induced emesis. Final report Oct 80-Sep 81

    Energy Technology Data Exchange (ETDEWEB)

    Carpenter, D.O.

    1982-09-01

    Results of earlier investigators indicate that radioemesis is mediated by some humoral agent(s). Peptides are likely candiates since they exert a number of biological effects and are released from storage sites by various stimuli, including radiation. Peptides at various concentrations were injected singly intravenously into conscious dogs, and the dog's emetic response was observed. Of the peptides tested, neurotensin, angiotensin II, vasopressin, oxytocin, and TRH produced consistent emetic responses. Inhibition of drug-induced emesis was studied both centrally (chlorpromazine) and peripherally (domperidone) acting dopamine antagonists. Results indicate inhibition by chlorpromazine, which crosses the blood brain barrier, but only partial blockade by domperidone, which does not cross the blood brain barrier. Preliminary studies were conducted attempting to characterize types of receptors on area postrema neurons. Single-cell recordings from these neurons, challenged by iontophoretic administration of various neurotransmitters, show stimulation by glutamic acid and serotonin and inhibiiton by norepinephrine.

  7. Are there schizophrenics for whom drugs may be unnecessary or contraindicated?

    Science.gov (United States)

    Rappaport, M; Hopkins, H K; Hall, K; Belleza, T; Silverman, J

    1978-01-01

    This study reports that there are schizophrenics who do relatively well long term without the routine or continuous use of antipsychotic medication. Specially selected young males undergoing an acute schizophrenic episode were followed, after hospitalization, for up to three years. While hospitalized they were assigned randomly to either placebo or chlorpromazine treatment. Many unmedicated-while-in-hospital patients showed greater long-term improvement, less pathology at follow-up, fewer rehospitalizations and better overall function in the community than patients who were given chlorpromazine while in the hospital. Factors related to post-hospital outcome were good premorbid history and short-lived paranoid characteristics. Considerations which may have an effect on the successful management of acute schizophrenic patients not on medication are mentioned. The findings underline the need for further study of how to utilize antipsychotic medication more selectively in the treatment of schizophrenia.

  8. In vitro interaction between psychotropic drugs and alcohol dehydrogenase activity.

    Science.gov (United States)

    Roig, M G; Bello, F; Burguillo, F J; Cachaza, J M; Kennedy, J F

    1991-03-01

    A series of CNS-stimulating and -depressant drugs have been studied for their in vitro interaction with horse liver alcohol dehydrogenase (ADH) activity. The depressant drugs studied included barbital, phenobarbital, thiopental, nitrazepam, chlorpromazine, sulpiride, clomethiazole, Li2CO3, diazepam, phenytoin, ethosuximide, morphine, and codeine. The stimulant drugs were theophylline, caffeine, amphetamine, imipramine, chlorimipramine, amitriptyline, and tranylcypromine. The results were as follows. First, ADH activity was inhibited by the action of chlorpromazine, tranylcypromine, imipramine, chlorimipramine, amitriptyline, sulpiride, amphetamine, codeine, ethosuximide, morphine, clomethiazole, nitrazepam, Li2CO3, theophylline, and phenobarbital, in descending order of inhibitory effect. Second, inhibition followed by activation of ADH activity was observed for imipramine and chlorimipramine. Third, activation of ADH activity was observed for phenytoin. Finally, the following drugs were not seen to exert any effect on ADH activity: barbital, thiopental, diazepam, and caffeine.

  9. Behavior analysis and the growth of behavioral pharmacology

    OpenAIRE

    Laties, Victor G.

    2003-01-01

    Psychologists, particularly those influenced by the work of B. F. Skinner, played a major part in the development of behavioral pharmacology in the 1950s and 1960s. Revolutionary changes in pharmacology and psychiatry, including the discovery of powerful therapeutic agents such as chlorpromazine and reserpine, had produced a surge of interest in drug research. Pharmaceutical companies began hiring psychologists with operant conditioning backgrounds so as to compete successfully in the search ...

  10. Inhibitory effects of psychotropic drugs on the acetylcholine receptor-operated potassium current (IK.ACh) in guinea-pig atrial myocytes.

    Science.gov (United States)

    Okada, Muneyoshi; Watanabe, Shinya; Matada, Takashi; Asao, Yoko; Hamatani, Ramu; Yamawaki, Hideyuki; Hara, Yukio

    2013-01-01

    Influences of psychotropic drugs, six antipsychotics and three antidepressants, on acetylcholine receptor-operated potassium current (IK.ACh) were examined by a whole-cell patch clamp method in freshly isolated guinea-pig atrial myocyte. IK.ACh was induced by a superfusion of carbachol (CCh) or by an intracellular application of guanosine 5'-[thio] triphosphate (GTPγS). To elucidate mechanism for anticholinergic action, IC50 ratio, the ratio of IC50 for GTPγS-activated IK.ACh to CCh-induced IK.ACh, was calculated. Antipsychotics and antidepressants inhibited CCh-induced IK.ACh in a concentration-dependent manner. The IC50 values were as follows; chlorpromazine 0.53 μM, clozapine 0.06 μM, fluphenazine 2.69 μM, haloperidol 2.66 μM, sulpiride 42.3 μM, thioridazine 0.07 μM, amitriptyline 0.03 μM, imipramine 0.22 μM and maprotiline 1.81 μM. The drugs, except for sulpiride, inhibited GTPγS-activated IK.ACh with following IC50 values; chlorpromazine 1.71 μM, clozapine 14.9 μM, fluphenazine 3.55 μM, haloperidol 2.73 μM, thioridazine 1.90 μM, amitriptyline 7.55 μM, imipramine 7.09 μM and maprotiline 5.93 μM. The IC50 ratio for fluphenazine and haloperidol was close to unity. The IC50 ratio for chlorpromazine, clozapine, thioridazine, amitriptyline, imipramine and maprotiline was much higher than unity. The present findings suggest that the psychotropics studied suppress IK.ACh. Chlorpromazine, clozapine, thioridazine, amitriptyline, imipramine, maprotiline and sulpiride are preferentially acting on muscarinic receptor. Fluphenazine and haloperidol may act on G protein and/or potassium channel.

  11. Neurobehavioral and Immunological Toxicity of Pyridostigmine, Permethrin and DEET in Males and Females

    Science.gov (United States)

    2000-05-01

    diazepam : Effects on performance in dostigmine bromide, DEET, and permethrin. J. Toxicol. Environ. the running rat. Life Sci. 42:1925-1931; 1988. Health 48...exposed to one of eight different ported that chlorpromazine and chlordiazepoxide impaired experimental conditions. The delay of reinforcement was ei...389-394, 1999. 19 31. van Haaren, F.; Katon, E.; Anderson, K. G. The effects of chlordiazepoxide on low-rate behavior are gender-dependent. Pharmacol

  12. Ultrasonic Vocalizations by Adult Rats (Rattus norvegicus)

    Science.gov (United States)

    1991-12-01

    begun. Diazepam , chlordiazepoxide , morphine, or naloxone was administered I.P. prior to placing the rat in the tailshock apparatus. Four different...by chlordiazepoxide and diazepam . Drug Dev. Res., 5, 185-193 (1985). Gardner, C.R., and Budhram, P. Effects of agents which interact with central... diazepam , and chlorpromazine, attenuate these vocalizations. Recent work by Kaltwasser (1990) examined the occurrence of vocalizations in response to

  13. Liquid-liquid Extraction System Based on Non-ionic Surfactant-salt-H2O and Mechanism of Drug Extraction

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Extraction behavior of chlorpromazine hydrochloride (CPZ) and procaine hydro- chloride (PCN) in the system described in the title was studied.Research shows that the extraction efficiency of CPZ can amount to 96% by twice extraction,while that of PCN is 77%.This system produces the distribution coefficients (KD) of 12.3 and 2.6 respectively for CPZ and PCN.Extraction mechanism is deduced according to ultraviolet and molecular fluorescence spectra variation of the drugs in the system studied.

  14. Mesolimbic and Nigrostriatal Dopaminergic Systems: Behavioral Neuropharmacology.

    Science.gov (United States)

    1985-08-01

    dopamine agonists could result from sustained dopamine synthesis inhibition or depletion of dopamine stores (Tarsy and Baldessarini 1974) and by chronic...enzyme in catecholamine synthesis , are decreased in the brains of Parkinsonian patients, both in the substantia nigra and in the ventral tegmental area... methadone or chlorpromazine in the guinea-pig. Psychopharmacology 48:132-146 Elkhawad AO, Woodruff GN (1975) Studies on the behavioural pharmacology of a

  15. Robustness testing in the determination of seven drugs in animal muscle by liquid chromatography–tandem mass spectrometry

    OpenAIRE

    Oca Casado, Mª Leticia; Rubio Martínez, Laura; Ortiz Fernández, Mª Cruz; Sarabia Peinador, Luis Antonio; García, I.

    2016-01-01

    In this work, the robustness of the sample preparation procedure for the determination of six tranquilizers (xylazine, azaperone, propionylpromazine, chlorpromazine, haloperidol, and azaperol) and a beta-blocker (carazolol) in animal muscle by LC/MS–MS was assessed through the experimental design methodology. A 2III7 − 4 fractional factorial design was performed to evaluate the influence of seven variables on the final concentration of the seven drugs in the samples, in accordance with what i...

  16. Effects of antipsychotics on bone mineral density and prolactin levels \\ud in patients with schizophrenia: a 12-month prospective study

    OpenAIRE

    2014-01-01

    Objective: Effects of conventional and atypical antipsychotics on bone mineral density (BMD) and serum prolactin levels (PRL) were examined in patients with schizophrenia.\\ud \\ud Methods: One hundred and sixty-three first-episode inpatients with schizophrenia were recruited, to whom one of three conventional antipsychotics (perphenazine, sulpiride, and chlorpromazine) or one of three atypical antipsychotics (clozapine, quetiapine, and aripiprazole)\\ud was prescribed for 12 months as appropria...

  17. Phenothiazines solution complexity - Determination of pKa and solubility-pH profiles exhibiting sub-micellar aggregation at 25 and 37°C.

    Science.gov (United States)

    Pobudkowska, Aneta; Ràfols, Clara; Subirats, Xavier; Bosch, Elisabeth; Avdeef, Alex

    2016-10-10

    The ionization constants (pKa) and the pH-dependent solubility (log S-pH) of six phenothiazine derivatives (promazine hydrochloride, chlorpromazine hydrochloride, triflupromazine hydrochloride, fluphenazine dihydrochloride, perphenazine free base, and trifluoperazine dihydrochloride) were determined at 25 and 37°C. The pKa values of these low-soluble surface active molecules were determined by the cosolvent method (n-propanol/water at 37°C and methanol/water at 25°C). The log S-pH profiles were measured at 24h incubation time in 0.15M phosphate buffers. The log S-pH "shape-template" method, which critically depends on accurate pKa values (determined independently of solubility data), was used to propose speciation models, which were subsequently refined by rigorous mass-action weighted regression procedure described recently. Differential scanning calorimetry (DSC), UV-visible spectrophotometry, potentiometric, and high performance liquid chromatography (HPLC) measurements were used to characterize the compounds. The intrinsic solubility (S0) values of the three least-soluble drugs (chlorpromazine·HCl, triflupromazine·HCl, and trifluoperazine·2HCl) at 25°C were 0.5, 1.1, and 2.7μg/mL (resp.). These values increased to 5.5, 9.2, and 8.7μg/mL (resp.) at the physiological temperature. The enthalpies of solution for the latter compounds were exceptionally high positive (endothermic) values (99-152kJ·mol(-1)). Cationic sub-micellar aggregates were evident (from the distortions in the log S-pH profiles) for chlorpromazine, fluphenazine, perphenazine, and trifluoperazine at 25°C. The effects persisted at 37°C for chlorpromazine and trifluoperazine. The solids in suspension were apparently amorphous in cases where the drugs were introduced as the chloride salts.

  18. Synthesis of amino derivatives of 10-(diphenylmethylene)-4-azatricyclo[5.2.1.0(2,6)]dec-8-ene-3,5-dione as potential psychotropic and/or anti HIV agents.

    Science.gov (United States)

    Kossakowski, Jerzy; Wojciechowska, Anna; Kozioł, Anna E

    2006-01-01

    A series of amino derivatives of 10-(diphenylmethylene)-4-azatricyclo[5.2.1.0(2.6)]dec-8-ene-3,5-dione, analogues of chlorpromazine and aminoperazine have been prepared. These compounds are expected to have antipsychotic and/or anti HIV activity. Molecular structure of III was confirmed by an X-ray structure analysis. The cytotoxicity and anti HIV activity of derivatives I-IV were determined.

  19. CNS Depressant and Antiepileptic Activities of the Methanol Extract of the Leaves of Ipomoea Aquatica Forsk

    OpenAIRE

    Dhanasekaran Sivaraman; Palayan Muralidaran

    2010-01-01

    The central nervous system (CNS) depressant and antiepileptic activities of the methanol extract of the leaves of Ipomoea aquatica Forsk (IAF) were investigated on various animal models including pentobarbitone sleeping time and hole-board exploratory behavior for sedation tests and strychnine, picrotoxin and pentylenetetrazole-induced convulsions in mice. IAF (200 and 400 mg/kg, p.o.), like chlorpromazine HCl (1 mg/kg, i.m.), produced a dose-dependent prolongation of pentobarbitone sleeping ...

  20. Termite usage associated with antibiotic therapy: enhancement of aminoglycoside antibiotic activity by natural products of Nasutitermes corniger (Motschulsky 1855)

    OpenAIRE

    2009-01-01

    Abstract Background Several species from Insecta are used as remedies. Among these species, the termite Nasutitermes corniger is commonly used in traditional medicine in Northeast Brazil. The present work tests the modifying antibiotic activity of Nasutitermes corniger, a termite used in folk medicine in Northeastern region of Brazil. Methods Chlorpromazine and decocts of N. corniger were collected from two different plant species used in the traditional medicine were tested for their antimic...

  1. Interactions between six psychotherapeutic drugs and plastic containers. Influence of plastic material and infusion solutions.

    Science.gov (United States)

    Airaudo, C B; Gayte-Sorbier, A; Bianchi, C; Verdier, M

    1993-06-01

    The interactions of chlorpromazine, clomipramine, maprotiline and viloxazine hydrochlorides, and of clorazepate dipotassium salt and diazepam with polyvinyl chloride (PVC) and Stedim 6 infusion bags were studied. Stedim 6, is anew multilayer film whose inner layer is made of polyethylene. The drugs were in 5% dextrose and 0.9% sodium chloride isotonic solutions and the influence of these was also considered. The remaining concentrations of each drug were determined at regular time intervals in a 24-h period, by a spectrofluorometric method for chlorpromazine hydrochloride and by ultraviolet spectrophotometric methods for the other drugs. No binding was observed for viloxazine and maprotiline hydrochlorides whatever the infusion solution and the plastic container. A slight retention in PVC bags, but not in Stedim 6 ones, was noted for clomipramine hydrochloride and clorazepate dipotassium salt. This was more marked in the sodium chloride solution than in the dextrose one. Diazepam and chlorpromazine hydrochloride were bound both in PVC and Stedim 6 bags, but more in the former and more again in the sodium chloride solution than in the dextrose one. The results were explained in terms of the degree of crystallinity of the plastic material and the degree of lipophilicity of the drugs. Practical consequences are discussed.

  2. Further studies on the neuroleptic profile of manassantin A.

    Science.gov (United States)

    Rao, K V; Puri, V N; el-Sawaf, H A

    1990-04-25

    In an earlier preliminary study, manassantin A, a neolignoid from Saururus cernuus was found to show neuroleptic type activity in mice when given by the i.p. route. It blocked the stereotypy and hyperactivity caused by amphetamine at doses comparable to those of haloperidol, but unlike the latter, did not show catalepsy or ptosis at atoxic doses. In the present study, a more detailed comparison of manassantin A with haloperidol and in some cases with chlorpromazine and reserpine using a variety of neuroleptic parameters and by various routes of administration is described. Results of the present study clearly show that the drug is readily absorbed from various routes of administration and shows many of the patterns of neuroleptic activity. Manassantin A was comparable to haloperidol in many of the tests but unlike the latter, did not produce antiadrenergic or anticholinergic effects. Manassantin A was found to bind weakly to calf caudate membranes (IC50 3500 nM) while haloperidol (IC50 5 nM) and chlorpromazine (IC50 50 nM) inhibited [3H]haloperidol binding. Manassantin A also did not affect the dopamine-induced adenylate cyclase activity in rat caudate nuclei (IC50 greater than 10,000 nM) while haloperidol (IC50 700 nM) and chlorpromazine (IC50 350 nM) inhibited the enzyme synthesis. These biochemical and behavioral tests suggest that manassantin A exhibits a selective neuroleptic profile and may be considered to behave as an atypical agent.

  3. The effects by neuroleptics, antimycotics and antibiotics on disulfide reducing enzymes from the human pathogens Acanthamoeba polyphaga and Naegleria fowleri.

    Science.gov (United States)

    Ondarza, Raúl N; Iturbe, Angélica; Hernández, Eva

    2007-01-01

    This paper discusses the effects of two neuroleptic agents, chlorpromazine and trifluoperazine; three antimycotics, amphotericin B, ketoconazole and miconazole and four antibiotics, pentamidine, rifampicin, mepacrine and metronidazole on the NADPH-dependent disulfide reducing enzymes cystine reductase (CysR), glutathione reductase (GR) trypanothione reductase (TR) and a putative disulfide reductase for compound X in Acanthamoeba polyphaga from the human pathogens A. polyphaga and Naegleria fowleri. Against A. polyphaga, all nine drugs studied had the capacity to inhibit the putative disulfide reductase from the trophozoites at a concentration of 32microg/ml during a 24h incubation and they were: the neuroleptics trifluoperazine (100%) and chlorpromazine (96%), the antimycotics miconazole (89%) ketoconazole (81%) and amphotericin B, (53%) and the antibiotics pentamidine (89%), rifampicin (64%), mepacrine (57%) and metronidazole (14%). Only six of the nine drugs simultaneously inhibited CysR, GR and the putative disulfide reductase. In N. fowleri, the most potent inhibitors of trypanothione reductase were amphotericin B and miconazole which inhibited 100% at a concentration of 32microg/ml during the 24h incubation followed by the neuroleptics trifluoperazine (92%) and chlorpromazine (80%) and the antibiotic mepacrine (70%). All these also inhibited CysR and GR from the trophozoites other than mepacrine which inhibited only CysR and TR. Ketoconazole, rifampicin (which did not affect CysR), pentamidine and metronidazole had opposite effects since they did not inhibit but increased the amount of the three thiols.

  4. Evaluation of Factors Affecting Continuous Performance Test Identical Pairs Version Score of Schizophrenic Patients in a Japanese Clinical Sample

    Directory of Open Access Journals (Sweden)

    Takayoshi Koide

    2012-01-01

    Full Text Available Aim. Cognitive impairment in schizophrenia strongly relates to social outcome and is a good candidate for endophenotypes. When we accurately measure drug efficacy or effects of genes or variants relevant to schizophrenia on cognitive impairment, clinical factors that can affect scores on cognitive tests, such as age and severity of symptoms, should be considered. To elucidate the effect of clinical factors, we conducted multiple regression analysis using scores of the Continuous Performance Test Identical Pairs Version (CPT-IP, which is often used to measure attention/vigilance in schizophrenia. Methods. We conducted the CPT-IP (4-4 digit and examined clinical information (sex, age, education years, onset age, duration of illness, chlorpromazine-equivalent dose, and Positive and Negative Symptom Scale (PANSS scores in 126 schizophrenia patients in Japanese population. Multiple regression analysis was used to evaluate the effect of clinical factors. Results. Age, chlorpromazine-equivalent dose, and PANSS-negative symptom score were associated with mean d′ score in patients. These three clinical factors explained about 28% of the variance in mean d′ score. Conclusions. As conclusion, CPT-IP score in schizophrenia patients is influenced by age, chlorpromazine-equivalent dose and PANSS negative symptom score.

  5. Evaluation of factors affecting continuous performance test identical pairs version score of schizophrenic patients in a Japanese clinical sample.

    Science.gov (United States)

    Koide, Takayoshi; Aleksic, Branko; Kikuchi, Tsutomu; Banno, Masahiro; Kohmura, Kunihiro; Adachi, Yasunori; Kawano, Naoko; Iidaka, Tetsuya; Ozaki, Norio

    2012-01-01

    Aim. Cognitive impairment in schizophrenia strongly relates to social outcome and is a good candidate for endophenotypes. When we accurately measure drug efficacy or effects of genes or variants relevant to schizophrenia on cognitive impairment, clinical factors that can affect scores on cognitive tests, such as age and severity of symptoms, should be considered. To elucidate the effect of clinical factors, we conducted multiple regression analysis using scores of the Continuous Performance Test Identical Pairs Version (CPT-IP), which is often used to measure attention/vigilance in schizophrenia. Methods. We conducted the CPT-IP (4-4 digit) and examined clinical information (sex, age, education years, onset age, duration of illness, chlorpromazine-equivalent dose, and Positive and Negative Symptom Scale (PANSS) scores) in 126 schizophrenia patients in Japanese population. Multiple regression analysis was used to evaluate the effect of clinical factors. Results. Age, chlorpromazine-equivalent dose, and PANSS-negative symptom score were associated with mean d' score in patients. These three clinical factors explained about 28% of the variance in mean d' score. Conclusions. As conclusion, CPT-IP score in schizophrenia patients is influenced by age, chlorpromazine-equivalent dose and PANSS negative symptom score.

  6. Simultaneous determination of three banned psychiatric drugs in pig feed and tissue using solid-phase reactor on-line oxidizing and HPLC-fluorescence detection.

    Science.gov (United States)

    Qi, Liang; Duan, Li-Min; Sun, Xiao-Huan; Zhang, Jing; Zhang, Zhi-Qi

    2015-10-01

    The banned addition of psychiatric drugs such as phenothiazines to animal feed and foodstuffs increases the risk of human organ lesion. Phenothiazines usually exhibit weak native fluorescence and can be oxidized to strongly fluorescent compounds. In this study, a novel, sensitive and convenient method of HPLC-fluorescence detection based on post-column on-line oxidizing with lead dioxide solid-phase reactor has been developed for simultaneous determination of three banned psychotropic drugs, promethazine, chlorpromazine and thioridazine. Three compounds were successfully separated on an Agilent TC-C18 column with mobile phase of acetonitrile (A) and water (B), both containing 0.5% (v/v) formic acid. A gradient elution was programmed and fluorimetric detection was performed at λex /λem of 332/373 nm for promethazine, 340/380 nm for chlorpromazine and 352/432 nm for thioridazine. The calibration graphs gave good linearity over the concentration ranges of 30.0-4976.4 µg/L for promethazine, 2.0-2153.2 µg/L for chlorpromazine, and 15.0-3088.0 µg/L for thioridazine, and correlation coefficients (r) were ≥0.995. The method was applied to the determination of phenothiazines in pig feed and pig tissue, and the average spiked recoveries were in the range 69.1-115.4%.

  7. The effects of typical and atypical antipsychotics on the electrical activity of the brain in a rat model

    Directory of Open Access Journals (Sweden)

    Oytun Erbaş

    2013-09-01

    Full Text Available Objective: Antipsychotic drugs are known to have strongeffect on the bioelectric activity in the brain. However,some studies addressing the changes on electroencephalography(EEG caused by typical and atypical antipsychoticdrugs are conflicting. We aimed to compare the effectsof typical and atypical antipsychotics on the electricalactivity in the brain via EEG recordings in a rat model.Methods: Thirty-two Sprague Dawley adult male ratswere used in the study. The rats were divided into fivegroups, randomly (n=7, for each group. The first groupwas used as control group and administered 1 ml/kg salineintraperitoneally (IP. Haloperidol (1 mg/kg (group 2,chlorpromazine (5 mg/kg (group 3, olanzapine (1 mg/kg(group 4, ziprasidone (1 mg/ kg (group 5 were injectedIP for five consecutive days. Then, EEG recordings ofeach group were taken for 30 minutes.Results: The percentages of delta and theta waves inhaloperidol, chlorpromazine, olanzapine and ziprasidonegroups were found to have a highly significant differencecompared with the saline administration group (p<0.001.The theta waves in the olanzapine and ziprasidonegroups were increased compared with haloperidol andchlorpromazine groups (p<0.05.Conclusion: The typical and atypical antipsychotic drugsmay be risk factor for EEG abnormalities. This studyshows that antipsychotic drugs should be used with caution.J Clin Exp Invest 2013; 4 (3: 279-284Key words: Haloperidol, chlorpromazine, olanzapine,ziprasidone, EEG, rat

  8. Termite usage associated with antibiotic therapy: enhancement of aminoglycoside antibiotic activity by natural products of Nasutitermes corniger (Motschulsky 1855

    Directory of Open Access Journals (Sweden)

    Almeida-Filho Geraldo G

    2009-09-01

    Full Text Available Abstract Background Several species from Insecta are used as remedies. Among these species, the termite Nasutitermes corniger is commonly used in traditional medicine in Northeast Brazil. The present work tests the modifying antibiotic activity of Nasutitermes corniger, a termite used in folk medicine in Northeastern region of Brazil. Methods Chlorpromazine and decocts of N. corniger were collected from two different plant species used in the traditional medicine were tested for their antimicrobial activity against strains of Escherichia coli resistant to aminoglycosides. The growth of two bacterial strains of E. coli was tested using decocts and chlorpromazine alone or associeted with aminogycosides. Results The MIC and MBC values were ≥1024 μg/ml for both strains of E. coli assayed. A significant synergism was observed between both decocts and chlorpromazine when assyed with neomycin. This synergism with neomycin indicates the involvement of an efflux system in the resistance to this aminoglycoside. Conclusion Therefore it is suggested that natural products from N. corniger could be used as a source of zoo-derived natural products with modifying antibiotic activity to aminoglycosides, being a new weapon against the bacterial resistance to antibiotics.

  9. 抗精神疾病药物对首发分裂症患者泌乳素及性功能影响的对照研究%Prolactin-control study on prolactin and sexual function change with antipsychotic drugs in ifrst-episode schizophrenics

    Institute of Scientific and Technical Information of China (English)

    孙霞

    2014-01-01

    目的:探讨抗精神疾病药物对首发分裂症患者泌乳素及性功能影响的对照研究。方法:对72例患者随机分为三组,使用不同药物首发精神疾病患者的泌乳素以及性功能影响进行分析。结果:①氯丙嗪以及利培酮这两组药物对于精神分裂患者泌乳素的波动有显著影响,治疗前后,相关系数有显著差异。②氯丙嗪组以及利培酮组性功能明显下降,达到60%~70%。结论:氯丙嗪及利培酮泌乳素升高明显,性功能下降明显,奎硫平表现良好。%Objective Prolactin and sexual function change with antipsychotic drugs in first-episode schizophrenics were investigated in this study.Methods 72 patients were randomly divided into three groups,and Prolactin and sexual function change with antipsychotic drugs in first episode schizophrenia were analyzed.Results①Chlorpromazine and risperidone have a significant impact in prolactin change,and the correlation coefficient was significantly different before and after treatment.②Sexual function in chlorpromazine and risperidone group was decreased to 60%~70%.Conclusion Prolactin change in chlorpromazine and risperidone increased significantly,and sexual function was significantly decreased as well.Quetiapine have good performance.

  10. Creutzfeldt-Jakob disease, Heidenhain variant: case report with MRI (DWI) findings; Doenca de Creutzfeldt-Jakob forma Heidenhain: relato de caso com achados de ressonancia magnetica e DWI

    Energy Technology Data Exchange (ETDEWEB)

    Arruda, Walter Oleschko; Bordignon, Kelly C.; Milano, Jeronimo B.; Ramina, Ricardo [Instituto de Neurologia de Curitiba, PR (Brazil)]. E-mail: warruda@speednet.com.br

    2004-06-01

    Creutzfeldt-Jakob disease (CJD) is a pre senile dementia characterized by rapidly progressive mental deterioration, myoclonic jerking, and other less common neurological signs. Few accentuates cases have been described in Brazil. A 54-year-old white woman, was admitted in our service with a month history of progressive, bilateral cortical blindness. After admission, she developed right partial motor seizures (right facial, upper and lower limbs), she became progressively aphasic (mixed aphasia). Seizures were controlled with phenytoine, but she developed choreoathetotic movements on her right dimidium, with partial control after introduction of chlorpromazine 25 mg q/d. She could no longer stand up or walk due to severe ataxia. The first EEG (October, 2001) showed left hemisphere severe seizure activity (status epilepticus partial is). She was delivered home with enteral nutrition, phenytoine, chlorpromazine and mepacrine 100 mg q d. The following laboratory tests were negative or normal: blood series, platelets, ESR, kidney and liver function, copper, ceruloplasmin, Vedril, HIV, HTLV-1, lactate, and cerebral Dsa (performed in other service). A spinal tap with normal opening pressure was perform and CSFR examination was normal. CSFR 14-3-3 protein was positive, CSF specific neuronal enolase 7.5 ng/ml(normal). Genetic study of PRNP gene did not disclosed any known mutation. A MRI (October, 2001) showed areas of hyperintense signal (T 2 and FLAIR) without Gd-enhancement on T1, in the left temporal lobe and in both occipital lobes; basal ganglia have a normal appearance. DWI imaging showed bright areas at the same sites. An EEG (March, 2002) disclosed a periodical sharp triphasic waves pattern, suggestive of CJD. A second MRI (April, 2002) showed mild generalized atrophy, no ventricular dilatation, and the hyperintense sites disappeared. She remained clinically stable and under use of chlorpromazine and mepacrine until she died due to pulmonary complications on April

  11. Development and application of resistive pulse spectroscopy: studies on the size, form and deformability of red blood cells

    Energy Technology Data Exchange (ETDEWEB)

    Yee, J.P.

    1979-01-01

    The following studies were conducted using the resistive pulse spectroscopy (RPS) technique: cumulative spectra and individual pulse forms for rigid latex polymer spheres; acquisition and analysis of RPS spectral data by means of special computer program; interaction of red blood cells with glutaraldehyde; membrane properties of erythrocytes undergoing abrupt osmotic hemolysis; reversible effects of the binding of chlorpromazine HCl at the red cell membrane surface; effects of high cholesterol diet on erythrocytes of guinea pigs; and multi-population analysis for a mixture of fetal and maternal red cells. (HLW)

  12. A comparative study of the plasma membrane permeabilization and fluidization induced by antipsychotic drugs in the rat brain

    OpenAIRE

    Murata, Tetsuhito; Maruoka, Nobuyuki; Omata, Naoto; Takashima, Yasuhiro; Fujibayashi, Yasuhisa; Yonekura, Yoshiharu; Wada, Yuji

    2007-01-01

    We compared the potency of the interaction of three antipsychotic drugs, i.e., chlorpromazine (CPZ), haloperidol (HAL) and sulpiride (SUL), with the plasma membrane in the rat brain. CPZ loading ( 100 M) dose-dependently increased both membrane permeability (assessed as [18F]2-fluoro-2-deoxy-D-glucose-6-phosphate release from brain slices) and membrane fluidity (assessed as the reduction in the plasma membrane anisotropy of 1,6-diphenyl-1,3,5-hexatriene). On the other hand, a higher concent...

  13. Pharmacological response of systemically derived focal epileptic lesions

    Energy Technology Data Exchange (ETDEWEB)

    Remler, M.P.; Sigvardt, K.; Marcussen, W.H.

    1986-11-01

    Focal epileptic lesions were made in rats by systemic focal epileptogenesis. In this method, a focal lesion of the blood-brain barrier (BBB) is produced by focal alpha irradiation followed by repeated systemic injection of a convulsant drug that cannot cross the normal BBB, resulting in a chronic epileptic focus. Changes in the spike frequency of these foci in response to various drugs was recorded. The controls, saline and chlorpromazine, produced no change. Phenytoin, phenobarbital, chlordiazepoxide, and valproic acid produced the expected decrease in spike frequency. Pentobarbital and diazepam produced a paradoxical increase in spike frequency.

  14. Prescribing pattern of antipsychotic medications in patients with schizophrenia in a tertiary care hospital

    Directory of Open Access Journals (Sweden)

    H. K. Sushma

    2015-02-01

    Conclusions: Schizophrenia is mostly seen in males, middle age group and unemployed people. The present study showed that combination therapy is preferred for the treatment of Schizophrenia. Despite several side-effects, typical antipsychotics, especially trifluoperazine was the most commonly used drug, followed by chlorpromazine either alone or in combination. Among atypical antipsychotics, risperidone was commonly used followed by quetiapine and asenapine. Most of the patients received trihexyphenidyl, an anticholinergic drug along with antipsychotics to reduce extra pyramidal side-effects. [Int J Basic Clin Pharmacol 2015; 4(1.000: 134-138

  15. Effects of drugs on schedule-controlled running of mice in a circular runway.

    Science.gov (United States)

    Lehr, E; Morse, W H; Dews, P B

    1985-01-01

    Partially food deprived mice ran in a 1-m circular runway. Every 30 circuits, diluted evaporated milk was delivered. Under control conditions mice averaged 0.18 circuits/s for 1 h. The rate was reduced to 0.11 circuits/s 1 h after gavage of Tylose (cellulose derivative) vehicle. Amphetamine, chlordiazepoxide and pentobarbital increased the rate of responding over some dose range, but chlorpromazine, clozapine, imipramine and morphine caused only decreases in responding at effective dose levels. The results are generally similar to reports of effects of the drugs on responses of much briefer duration occurring at similar rates.

  16. Rapid determination of some psychotropic drugs in complex matrices by tandem dispersive liquid-liquid microextraction followed by high performance liquid chromatography.

    Science.gov (United States)

    Asghari, Alireza; Fahimi, Ebrahim; Bazregar, Mohammad; Rajabi, Maryam; Boutorabi, Leila

    2017-03-15

    Simple and rapid determinations of some psychotropic drugs in some pharmaceutical wastewater and human plasma samples were successfully accomplished via the tandem dispersive liquid-liquid microextraction combined with high performance liquid chromatography-ultraviolet detection (TDLLME-HPLC-UV). TDLLME of the three psychotropic drugs clozapine, chlorpromazine, and thioridazine was easily performed through two consecutive dispersive liquid-liquid microextractions. By performing this convenient method, proper sample preconcentrations and clean-ups were achieved in just about 7min. In order to achieve the best extraction efficiency, the effective parameters involved were optimized. The optimal experimental conditions consisted of 100μL of CCl4 (as the extraction organic solvent), and the pH values of 13 and 2 for the donor and acceptor phases, respectively. Under these optimum experimental conditions, the proposed TDLLME-HPLC-UV technique provided a good linearity in the range of 5-3000ngmL(-1) for the three psychotropic drugs with the correlation of determinations (R(2)s) higher than 0.996. The limits of quantification (LOQs) and limits of detection (LODs) obtained were 5.0ngmL(-1) and 1.0-1.5ngmL(-1), respectively. Also the proper enrichment factors (EFs) of 96, 99, and 88 for clozapine, chlorpromazine, and thioridazine, respectively, and good extraction repeatabilities (relative standard deviations below 9.3%, n=5) were obtained.

  17. [Serotonin syndrome. Which treatment and when?].

    Science.gov (United States)

    Jaunay, E; Gaillac, V; Guelfi, J D

    2001-11-17

    A TOXIC REACTION: Prevalence of the serotonin syndrome is increasing and can be fatal. The physiopathological hypothesis is principally supported by excess stimulation of the central (5HT1a) serotonin receptors. There are various serotonin drugs and associations implied. Monoamine oxidase inhibitors appear to be the major culprits. RECENTLY REVISED CLINICAL DIAGNOSIS FACTORS: The classical triad of neuropsychiatric, neuromuscular and neurovegetative symptoms, described in 1991 by Sternbach, has recently been modified. The syndrome is however protein-like and differential diagnosis remains the neuroleptic malignant syndrome. FIRST-LINE THERAPEUTIC MEASURES: Prevention of the syndrome and its early discovery are essential. Withdrawal of the imputable drugs often resolves the symptoms within 24 hours. Symptomatic and supportive care remains the pillar to treatment. ORIENTATION TOWARDS SPECIFIC TREATMENTS: Several non-selective anti-serotonin treatments have been tested without much success. In the absence of prospective studies, current therapeutic strategies rely on case reports demonstrating the relative efficacy of cyproheptadine and chlorpromazine. The proposed treatment, as soon as severe or persisting symptoms are observed, is administration of 8 to 30 mg cyproheptadine per os, and in the case of failure or contraindication, followed by 50 to 100 mg of intramuscular chlorpromazine, renewed when necessary.

  18. Interaction of mescaline with phenothiazines: effect on behavior, body temperature, and tissue levels of hallucinogen in mice.

    Science.gov (United States)

    Shah, N S; Jacobs, J R; Jones, J T; Hedden, M P

    1975-10-01

    Mescaline (25 mg/kg; 66 muc/kg) was injected (ip) in mice 45 min before chlorpromazine (CPZ, 2.5, 5, 15 mg/kg), thioridazine (10, 30, 45 mg/kg), or chlorpromazine-sulfoxide (CPZ-SO, 15 mg/kg). Excitement, agitation, slight increase in ventilation and occasional head-shaking were seen 30 min after mescaline and continued for 30-45 min thereafter; locomotor activity and the number of scratching events were significantly increased during this period. CPZ (2.5, 5, 15 mg/kg) and thioridazine (10, 30, 45 mg/kg) partially or completely blocked mescaline-induced gross behavior; CPZ-SO (15 mg/kg) was not effective. Increased scratching responses and locomotor activity induced by mescaline were antagonized by all doses of CPZ and thioridazine; at higher doses, both CPZ (7.5, 15 mg/kg) and thioridazine (45 mg/kg) induced cataleptic-like condition and marked hypothermia. Tissue levels of mescaline, examined 3 hr after its administration, were increased by all doses of CPZ and a higher dose of thioridazine (45 mg/kg); CPZ-SO and lower doses of thioridazine had no effect.

  19. Uptake of phenothiazines by the harvested chylomicrons ex vivo model: influence of self-nanoemulsifying formulation design.

    Science.gov (United States)

    Shahnaz, Gul; Hartl, Markus; Barthelmes, Jan; Leithner, Katharina; Sarti, Federica; Hintzen, Fabian; Rahmat, Deni; Salvenmoser, Willi; Bernkop-Schnürch, Andreas

    2011-09-01

    The aim of this study was to examine the potential of self-nanoemulsifying drug delivery systems (SNEDDS) on the uptake of the lipophilic and poorly water soluble phenothiazines thioridazine and chlorpromazine with the isolated plasma derived chylomicron (CM) ex vivo model. The multi-component delivery systems were optimized by evaluating their ability to self-emulsify when introduced to an aqueous medium under gentle agitation. The uptake of phenothiazines by isolated plasma derived chylomicrons was investigated with short chain triglyceride (SCT) SNEDDS, medium chain triglyceride (MCT) SNEDDS, and long chain triglyceride (LCT) SNEDDS. SNEDDS were also evaluated for their stabilities, dispersibilities, percentage transmittances and by particle size analyses. For thioridazine a 5.6-fold and for chlorpromazine a 3.7-fold higher CM uptake could be observed using a LCT-SNEDDS formulation compared to the drugs without formulation. In contrast, ex vivo uptake by isolated CM was not significantly increased by SNEDDS formulations based on MCT and SCT. Compared with isolated CM, the CM sizes were increased 2.5-fold in LCT-SNEDDS, whereas in MCT-SNEDDS or SCT-SNEDDS only a small, non-significant (P<0.05) increase in CM size was observed. These results show that distinct SNEDDS formulations containing phenothiazines are efficiently uptaken by plasma derived chylomicrons ex vivo.

  20. Herbal therapy associated with antibiotic therapy: potentiation of the antibiotic activity against methicillin – resistant Staphylococcus aureus by Turnera ulmifolia L

    Directory of Open Access Journals (Sweden)

    Lima Edeltrudes O

    2009-05-01

    Full Text Available Abstract Background Staphylococcus genus is widely spread in nature being part of the indigenous microbiota of skin and mucosa of animal and birds. Some Staphylococcus species are frequently recognized as etiological agents of many animal and human opportunistic infections This is the first report testing the antibiotic resistance-modifying activity of Turnera ulmifolia against methicillin-resistant Staphylococcus aureus – MRSA strain. Methods In this study an ethanol extract of Turnera ulmifolia L. and chlorpromazine were tested for their antimicrobial activity alone or in combination with aminoglycosides against an MRSA strain. Results The synergism of the ethanol extract and aminoglycosides were verified using microdillution method. A synergistic effect of this extract on gentamicin and kanamycin was demonstrated. Similarly, a potentiating effect of chlorpromazine on kanamycin, gentamicin and neomycin, indicating the involvement of an efflux system in the resistance to these aminoglycosides. Conclusion It is therefore suggested that extracts from Turnera ulmifolia could be used as a source of plant-derived natural products with resistance-modifying activity, constituting a new weapon against the problem of bacterial resistance to antibiotics demonstrated in MRSA strains.

  1. Psychotropic drug profiles: comparisons by topographic maps of absolute power.

    Science.gov (United States)

    Coppola, R; Herrmann, W M

    1987-01-01

    In a double-blind fourfold crossover design, 11 subjects were randomly assigned to placebo, 10 mg diazepam, 75 mg amitriptyline, and 75 mg chlorpromazine. During a simple vigilance task, 12 midline and left hemisphere leads were recorded before and 3 h after drug administration. The EEG was quantified by spectrum analysis, the topographic structure displayed by brain mapping techniques, and the results compared with earlier studies which used the same design and drugs. Diazepam showed the expected increase in beta; however, fast beta was increased as much as slow beta. Amitriptyline showed an increase of slow wave power and a reduction of alpha. In contrast to earlier studies, a decrease of fast beta was found. In addition, the spatial pattern of alpha changed from an occipital to a parietal maximum. Chlorpromazine showed an increase in the theta band. In occipital regions, there was a small decrease of fast beta; however, centrally there was an increase of both slow and fast beta. These results were confirmed by a multivariate analysis of variance.

  2. The effect of antipsychotics on sexual function in male patients with schizophrenia, a correlation analysis%抗精神病药对男性精神分裂症患者性功能影响的相关性分析

    Institute of Scientific and Technical Information of China (English)

    占归来; 沈文龙; 饶顺曾; 李晨虎; 张红

    2011-01-01

    目的 探讨抗精神病药喹硫平、利培酮、氯丙嗪及氯氮平对男性精神分裂症患者性功能影响的差异及相关因素分析.方法 将门诊就诊的男性精神分裂症患者120例,随机分为喹硫平组38例、利培酮组41例、氯丙嗪39例、氯氮平组42例.应用酶联免疫吸附法检测血清泌乳素、放射免疫法检测睾酮水平,检测各组患者治疗前及治疗第12周末的血清泌乳素(PRL)和睾酮水平.分别于基线及治疗第12周末使用简明男性性功能量表、阳性与阴性症状量表(PANSS)评估性功能及精神症状,于治疗第12周末用副反应量表(TESS)评估药物治疗的不良反应.结果 治疗第12周末,利培酮组、氯丙嗪组、氯氮平组的性功能量表总分较治疗前降低(P<0.05).利培酮组和氯丙嗪组治疗第12周末的血清泌乳素水平高于基线水平[利培酮组:(12±5)ng/ml,(22±6)ng/ml,t=13.92,P<0.01;氯丙嗪组:(13±6)ng/ml,(19±5)ng/ml,t=8.27,P<0.01],喹硫平组和氯氮平组无明显变化.利培酮组和氯丙嗪组治疗第12周末的血睾酮水平低于基线水平:利培酮组:(0.77±0.21)ng/ml,(0.27±0.11)ng/ml,t=13.22,P<0.01;氯丙嗪组:(0.90±0.11)ng/ml,(0.32±0.14)ng/ml,t=11.27,P<0.01;喹硫平组和氯氮平组无明显变化.影响男性精神分裂症患者性功能的因素有泌乳素、睾酮、年龄及TESS分.结论 抗精神病药物中,利培酮和氯丙嗪易引起血清泌乳素升高和血清睾酮降低,氯氮平具有较多药物不良反应,这些可能造成男性精神分裂症患者的性功能减退.%Objective To investigate the differential effect of antipsychotics,quetiapine,risperi-done ,chlorpromazine ,and clozapine ,on male sexual function in schizophrenia patients,and explore their related factors.Methods 120 male outpatients with schizophrenia were randomly divided into quetiapine (n=38) ,risperidone(n=41) ,chlorpromazine(n= 39) and clozapine group (n = 42).Enzyme linked im

  3. Acute antipsychotic treatments induce distinct c-Fos expression patterns in appetite-related neuronal structures of the rat brain.

    Science.gov (United States)

    Rajkumar, Ramamoorthy; See, Lionel Kee Yon; Dawe, Gavin Stewart

    2013-05-01

    A number of atypical antipsychotic drugs are known to perturb appetite regulation causing greater hyperphagia in humans and rodents than earlier generation typical agents. However, the neuronal structures that underlie hyperphagic effects are poorly understood. Arcuate nucleus (ArcN), paraventricular hypothalamic nucleus (PVN), paraventricular thalamic nucleus (PVA) and nucleus incertus (NI) have been implicated in appetite regulation. The NI is the principal source of the relaxin-3 (RLN3) peptide, which is reported to have orexigenic effects. Moreover, ArcN, PVN, and PVA receive RLN3 immunoreactive fibers from the NI and express relaxin family peptide type 3 (RXFP3) receptor. The present study was designed to evaluate the acute effects of clozapine (atypical), chlorpromazine (typical) and fluphenazine (typical) on c-Fos expression (a marker of neuronal response) in these appetite-related centers of the rat brain. The numbers of c-Fos expressing neurons in these structures were counted in immunofluorescence stained brain sections. Acute treatment with clozapine, chlorpromazine and fluphenazine differentially influenced c-Fos expression in these brain structures. This study is also the first demonstration that antipsychotics influence the NI. The patterns of the effects of these antipsychotics are related to their reported hyperphagic properties.

  4. Forensic toxicological analyses of drugs in tissues in formalin solutions and in fixatives.

    Science.gov (United States)

    Uekusa, Kyoko; Hayashida, Makiko; Ohno, Youkichi

    2015-04-01

    Forensic toxicological drug analyses of human specimens are usually performed immediately after autopsy or on frozen preserved tissues. Occasionally, cases require analysis of drugs from tissues fixed in formalin solution. To improve the estimation of the level of drug in tissues following formalin fixation, we studied drug concentrations in human tissues, liver and kidney, that were collected from a drug-positive autopsy case. Parts of tissues were preserved in formalin solution for 1, 3, 6 and 13 months. Tissues obtained before and after preservation, along with tissue-exposed fixatives, were assayed using gas chromatography-mass spectrometry; all of the samples were assayed for the presence of drugs and changes in the drug concentrations both before and after preservation in formalin. Concentrations of assayed drugs decreased upon fixation in formalin; levels of these drugs did not necessarily show further decreases during subsequent storage in fixative, up to 13 months. Distinct trends in drug levels were found in liver and kidney. In liver, the levels of chlorpromazine, levomepromazine, and promethazine decreased to 23-39% at 1 month after preservation; all 3 of these drugs were detected at all tested time points of preservation. Bromazepam was not detected at 13 months after preservation. Milnacipran was the most unstable after preservation in formalin solution among all of the assayed drugs. In kidney, all assayed drugs exhibited reduced stability during preservation compared to levels in liver. Methamphetamine and methylenedioxymethamphetamine were not detected in any time points of tissues. The proportions of the drugs that remained within the tissues differed between liver and kidney. Also, S-oxide compounds of chlorpromazine and levomepromazine, which were not observed before preservation, were detected in fixed liver tissues and their fixatives at 3, 6 and 13 months of preservation. These results suggest that analyses in formalin-fixed tissues need to

  5. Effects of calmodulin antagonists on radiation-induced lipid peroxidation in microsomes

    Energy Technology Data Exchange (ETDEWEB)

    Varshney, R.; Kale, R.K. (Jawaharlal Nehru Univ., New Delhi (India). School of Life Sciences)

    1990-11-01

    Rat liver microsomes were irradiated with {gamma}-rays at a dose of 1.31 Gy s{sup -1}. The extent of lipid peroxidation, measured in terms of malondialdehyde (MDA) formed, increased with radiation dose. The presence of calmodulin antagonists during irradiation decreased lipid peroxidation. The order of their protective efficiency was: chlorpromazine (CPZ)>promethazine (PMZ)>trimeprazine (TMZ). Their protective effect was diminished in the presence of ferrous (Fe{sup 2+}) ions and was restored on addition of EDTA. However, calmodulin antagonists considerably inhibited radiation-induced lipid peroxidation in the presence of ferric (Fe{sup 3+}) ions. Calmodulin antagonists also decreased the cytochrome P-450 content of microsomes. These results are discussed with respect to their applicability to radiotherapy. A possible mechanism for the inhibition of radiation-induced lipid peroxidation is suggested. (author).

  6. [Serotonin syndrome].

    Science.gov (United States)

    Lheureux, P; Penaloza, A; De Cottenier, V; Ullmann, U; Gris, M

    2002-10-01

    The serotonin syndrome is a hyperserotoninergic state resulting from an excess of intrasynaptic 5-hydroxytryptamine, induced by multiple psychotropic agents, but also non psychiatric drugs. It is a potentially dangerous and sometimes lethal condition. The clinical manifestations usually include cognitive, neuromuscular and autonomic features and are mediated by the action of serotonin on various subtypes of receptors. The main differential diagnosis is the neuroleptic malignant syndrome. Treatment is mainly supportive. No pharmacological agent has been definitely demonstrated really effective. However, reports of cases treated with the 5-HT2 blockers, including cyproheptadine or chlorpromazine have suggested that these agents could have some efficacy. Serotonin syndrome is a toxic condition which requires heightened clinical awareness among physicians in order to prevent, recognize, and treat the condition promptly.

  7. Ceramide formation is involved in Lactobacillus acidophilus-induced IFN-beta response in dendritic cells

    DEFF Research Database (Denmark)

    Fuglsang, Eva; Henningsen, Louise; Frøkiær, Hanne

    of sphingomyelin to ceramide by acid sphingomyelinase (ASMase) at the outer leaflet of the PM is a key event in endocytosis of gram-positive Lactobacillus acidophilus (L. acidophilus) and the subsequent induction of IFN-beta in DCs and, as the gram-negative Escherichia coli (E. coli) does not induce appreciable...... amounts of IFN-beta, the ASMase activity would affect endocytosis and the ensuing cytokine response of L. acidophilus and E. coli differently. SMase or an inhibitor of ASMase and acid ceramidase, chlorpromazine (CPZ), was added to DCs prior to stimulation with either of the bacteria. Endocytosis...... of fluorescent bacteria +/- FITC-dextran was measured by flow cytometry and gene expression and cytokine response of IFN-beta and IL-12 was measured by qPCR and ELISA, respectively. Addition of SMase increased the uptake of L. acidophilus and L. acidophilus-induced IL-12/IFN-beta but showed no effect...

  8. Behavior analysis and the growth of behavioral pharmacology.

    Science.gov (United States)

    Laties, Victor G

    2003-01-01

    Psychologists, particularly those influenced by the work of B. F. Skinner, played a major part in the development of behavioral pharmacology in the 1950s and 1960s. Revolutionary changes in pharmacology and psychiatry, including the discovery of powerful therapeutic agents such as chlorpromazine and reserpine, had produced a surge of interest in drug research. Pharmaceutical companies began hiring psychologists with operant conditioning backgrounds so as to compete successfully in the search for new drugs. Psychologists, most of whom were skilled in the behavior-analytic approach, started to assume prominent positions as authors and editors for the Journal of Pharmacology and Experimental Therapeutics as its emphasis on behavior increased. This also proved true with the other publications founded to deal with the popularity of behavioral pharmacology. Especially important were contributions by B. F. Skinner, Peter B. Dews, and Joseph V. Brady.

  9. Cultural psychiatry in the French-speaking world.

    Science.gov (United States)

    Westermeyer, Joseph

    2013-01-01

    For the last five centuries, France's international influence has been constant. This has been particularly evident in the areas of general culture, history and science. In psychiatry, the role of Pinel during the French Revolution, and the discovery of the first psychotropic agent, chlorpromazine, by Delay and Deniker are two outstanding historical facts. This chapter examines the contributions of French social scientists in the understanding of the sequelae of colonial exploitation, racism and political oppression. The establishment of a multi-ethnic society in France and Francophile regions of the world has led to the gradual creation of a cultural psychiatry rich in terminological influences, clinical understanding, training programs and research. Closer connections between French psychiatric thought and Anglophile psychiatry is likely to produce beneficial effects.

  10. Dosage of conventional neuroleptic medication and subjective cognitive functioning in schizophrenia.

    Science.gov (United States)

    Krausz, M; Moritz, S; Lambert, M; Naber, D

    2000-03-01

    Subjective cognitive and perceptual disturbances as assessed with the Frankfurt Complaint Questionnaire (FCQ) were correlated with chlorpromazine equivalents in 40 schizophrenic inpatients, who were treated with conventional neuroleptics. In line with previous research using 'objective' neuropsychological tests, both correlations and partial correlations (controlling for the effects of psychopathology, extrapyramidal symptoms and length of illness) confirmed that higher neuroleptic doses significantly worsen several cognitive and perceptual domains (r = 0.44 -0.54; P < or = 0.005 -0.05) with the possible exception of mnestic functions (r = 0.21 -0.24, n.s.) and language (r = 0.37 -0.38, P < 0.1). The clinical importance of self-report scales for evaluating both the risks and benefits of neuroleptic treatment is discussed.

  11. A comparative study of the effects of sparteine, lupanine and lupin extract on the central nervous system of the mouse.

    Science.gov (United States)

    Pothier, J; Cheav, S L; Galand, N; Dormeau, C; Viel, C

    1998-08-01

    Lupin is toxic because of its alkaloid content, sparteine and lupanine in particular. Although the pharmacological properties of sparteine are well known those of lupanine have not been much studied. This paper reports procedures for extraction, purification and crystallization of lupanine, and methods for the preparation of an extract for injection of Lupinus mutabilis Sweet, and for the determination of the acute toxicity and maximum non-lethal dose (DL0) of lupanine, sparteine and lupin extract in the mouse. The three substances were tested on the central nervous system (CNS) for locomotor activity, for interaction with specific drugs used for treatment of the CNS (the stimulant drugs amphetamine and pentetrazol and the depressant drugs pentobarbital and chlorpromazine) and for analgesic activity. The results indicate that lupanine and lupin extract are less toxic than sparteine and that at the doses studied the three products have a weak sedative effect on the CNS.

  12. Studies on accumulation of (14C)-mescaline in brain homogenates: effects of psychotropic and other agents.

    Science.gov (United States)

    Shah, N S; Gulati, O D

    1975-01-01

    Incubation of rat brain homogenates or 14,500 g pellet isolated from the homogenate with (14C)-mescaline was associated with accumulation of (14C)-mescaline in the pellet. 1.33 mumol/ml of chlorpromazine, trifluoperazine, fluphenazine, imipramine, desmethylimipramine, nortriptyline and amitriptyline inhibited the accumulation of mescaline. Lower concentrations (0.133-0.44 mumol/ml) of the psychotropic drugs were less effective. The tricyclic antidepressants were less potent than the tranquilizers. Although the trimethoxyphenylacetic acid (TMPA) levels of the pellet were also reduced by the psychotropic drugs, the TMPA:mescaline ratios were unchanged indicating that the drugs had no effect on the metabolism of mescaline. The inhibition of accumulation of mescaline by the high concentrations of tranquilizers may divert more of the hallucinogen to the receptor site. Thus, an explanation for the reported worsening of clinical syndrome of hallucinogenic poisoning by tranquilizers is provided.

  13. Stedim 6 and Clearflex, two new multilayer materials for infusion containers. Comparative study of their compatibility with five drugs versus glass flasks and polyvinyl chloride bags.

    Science.gov (United States)

    Tchiakpé, L; Airaudo, C B; Abdelmalik, O M; Gayte-Sorbier, A; Verdier, M; Guerri, J

    1995-01-01

    Stedim 6 and Clearflex, two new polyethylene-lined materials for infusion bags, were studied for their compatibility with disodium clodronate, chlorpromazine and maprotiline hydrochlorides, diazepam, and clorazepate dipotassium salt, comparatively with borosilicate glass flasks and polyvinyl chloride bags. Diazepam, the only drug to exhibit a marked sorption in PVC bags (the loss reached 25% of the initial concentration after a contact duration of 72 h), showed lower sorption in Stedim 6 bags (loss about 11% under the same conditions) and none in Clearflex bags. No significant difference was observed between the infusion solutions used as vehicles of the drugs (5% dextrose and 0.9% sodium chloride isotonic solutions). The results are discussed in terms of lipophilicity of the drugs and crystallinity of the polymers.

  14. Avaliação do efeito da clorpromazina sobre a função renal de cães submetidos à isquemia e reperfusão

    Directory of Open Access Journals (Sweden)

    Liliana B. de Menezes

    2010-02-01

    Full Text Available A isquemia renal está presente em diferentes situações como em cirurgias renais, vasculares e no transplante renal. O objetivo deste trabalho foi avaliar a integridade e a função renal de cães submetidos à isquemia e reperfusão com ou sem aplicação de clorpromazina. Para tanto foram utilizados 12 cães distribuídos aleatoriamente em dois grupos de seis indivíduos: grupo A com isquemia e reperfusão sem tratamento por clorpromazina e o grupo B com isquemia e reperfusão tratados previamente com clorpromazina. De cada cão foi coletado sangue e urina antes da isquemia, no inicio da reperfusão, após 120 minutos de reperfusão e semanalmente até 28º dia pós-cirúrgico para verificar possíveis efeitos tardios da isquemia/reperfusão. Avaliações da integridade e função renal foram feitas por exame físico, concentração sérica de ureia e creatinina e determinação da GGT urinária. A avaliação da relação proteína urinária/creatinina urinária (PU/CU e atividade da GGT urinária são exames mais sensíveis para detectar lesão tubular aguda que o exame de urina de rotina, uma vez que estas variáveis apresentaram alteração mais precocemente. Não houve ação protetora da clorpromazina conforme constatado por meio da urinálise, dosagens séricas de ureia e creatinina, excreção urinária de GGT e PU/CU.Renal ischemia may occur in different situations such as vascular or renal surgery and also in renal transplantation. This study evaluates renal function in dogs submitted to ischemia and reperfusion after chlorpromazine application. Twelve adult mongrel dogs were distributed into two groups with six animals each. Group A was composed of dogs submitted to renal ischemia and reperfusion without previous administration of chlorpromazine. Group B was composed of dogs with renal ischemia and reperfusion previously treated with chlorpromazine. In order to evaluate the possible ischemia/reperfusion late effects, blood and

  15. Membrane fusion inducers, chloroquine and spermidine increase lipoplex-mediated gene transfection

    Energy Technology Data Exchange (ETDEWEB)

    Wong-Baeza, Carlos; Bustos, Israel; Serna, Manuel; Tescucano, Alonso; Alcantara-Farfan, Veronica; Ibanez, Miguel [Biochemistry Department, National Polytechnic Institute (IPN), Mexico City 11340 (Mexico); Montanez, Cecilia [Department of Genetics and Molecular Biology, Centre for Research and Advanced Studies (CINVESTAV), IPN, Mexico City 07360 (Mexico); Wong, Carlos [Biochemistry Department, National Polytechnic Institute (IPN), Mexico City 11340 (Mexico); Baeza, Isabel, E-mail: ibaeza@encb.ipn.mx [Biochemistry Department, National Polytechnic Institute (IPN), Mexico City 11340 (Mexico)

    2010-05-28

    Gene transfection into mammalian cells can be achieved with viral and non-viral vectors. Non-viral vectors, such as cationic lipids that form lipoplexes with DNA, are safer and more stable than viral vectors, but their transfection efficiencies are lower. Here we describe that the simultaneous treatment with a membrane fusion inducer (chlorpromazine or procainamide) plus the lysosomotropic agent chloroquine increases lipoplex-mediated gene transfection in human (HEK293 and C-33 A) and rat (PC12) cell lines (up to 9.2-fold), as well as in situ in BALB/c mice spleens and livers (up to 6-fold); and that the polyamine spermidine increases lipoplex-mediated gene transfection and expression in cell cultures. The use of these four drugs provides a novel, safe and relatively inexpensive way to considerably increase lipoplex-mediated gene transfection efficiency.

  16. Hypothalamic pituitary disorders expressed by galactorrhea. A dynamic evaluation.

    Science.gov (United States)

    Perez-Lopez, F R

    1975-11-01

    Physiologic and pathologic production of milk involves complex relations between the mammary glands, hormones, and the central nervous system. In all the galactorrhea syndromes there is a functional or mechanical problem at the pituitary level, with abnormal secretion or reserve of prolactin secretion. Stimulatory agents of prolactin, like thyrotropin releasing hormone (TRH), chlorpromazine, amnio acids, and insulin, can be helpful in the study of the hypothalamic pituitary functional reserve, while the osmotic tests seem to provide a clear distinction between functional and tumoral causes. The inhibitory agents of prolactin secretion, L-dopa and CB 154, permit the study of the negative control of the hormone. In addition, CB 154 appears to be an effective treatment for functional galactorrhea. Hyperprolactinemia appears to exert an inhibitory influence on gonadotropins. Clomiphene, acting on the hypothalamus, and LHRH, acting on the gonadotropes, permit the assessment of the gonadotropic hypothalamic-hypophyseal axis.

  17. Effects of ganglion blocking agents on nicotine extensor convulsions and lethality in mice

    Science.gov (United States)

    Aceto, M. D.; Bentley, H. C.; Dembinski, J. R.

    1969-01-01

    1. The ganglion blocking agents, chlorisondamine, pentamethonium, mecamylamine, decamethonium and hexamethonium all block nicotine extensor convulsions when administered intraventricularly in mice. Tetraethylammonium was inactive. 2. For the intraventricular route, there is a relationship between ganglionic blocking potency and blocking of nicotine extensor convulsions. Indirect evidence suggests that the site(s) of action of nicotine extensor convulsions and lethality is central in origin and associated with brain areas near the ventricles. 3. When ganglion blocking agents are given orally, subcutaneously or intravenously varying degrees of protection can be observed probably depending on factors such as whether or not the drugs cross the blood-brain barrier, absorption, etc., and the effectiveness in protecting mice from nicotine is not related to ganglionic blocking potency. 4. Atropine and morphine given intraventricularly or subcutaneously did not protect mice from the LD95 of nicotine. Chlorpromazine gave very erratic results and phenobarbitone was effective subcutaneously and to a lesser extent intraventricularly. PMID:4390479

  18. Therapeutical management of tetanus in Kundhi buffalo calf at Hyderabad, Sindh.

    Directory of Open Access Journals (Sweden)

    Yousaf A

    2016-08-01

    Full Text Available The study was going to evaluate the therapeutic management of kundhi buffalo calf suffering from tetanus in Sindh (Pakistan. It was caused by a specific neurotoxin produced by Clostridium tetani in necrotic tissue. Tetanus was diagnosed in Kundhi buffalo calf on the basis of their clinical signs, high temperature, contracting of whole body muscles and arduousness of hind legs that is developed into the whole body of an animal. Positive rods shaped Clostridium tetani were present in the blood of the diseased animal. Treatment was recommended with anti-tetanus serum, Penicillin G Procaine, Meloxicam, Chlorpromazine, Dexamethasone and Dextrose 5%. Feeding to the calf through the stomach tube and the urinary catheter was administered to ease out the problem of urine retention. After treatment for 10 days animal complete recover to the healthy condition.

  19. Antipsychotic treatment and the Rorschach Perceptual Thinking Index (PTI) in psychotic disorder patients: Effects of treatment.

    Science.gov (United States)

    Biagiarelli, Mario; Curto, Martina; Di Pomponio, Ileana; Comparelli, Anna; Baldessarini, Ross J; Ferracuti, Stefano

    2017-02-16

    The Rorschach-based Perceptual Thinking Index (PTI) is used to identify and rate features of psychotic disorders, but effects of antipsychotic treatment on such ratings is not clear. Accordingly, we examined potential effects of antipsychotic drugs on PTI measures in 114 patients with a psychotic or bipolar-I disorder. Use and doses of antipsychotic drugs (as chlorpromazine-equivalent [CPZ-eq] mg/day) were unrelated to PTI total or subscale scores in any diagnostic group. PTI scores were independently and significantly associated with psychotic symptomatic severity (PANSS score) and less with female sex. These findings support the validity and value of the PTI in identifying features of psychosis even in the presence of antipsychotic treatment.

  20. Galactogogues: medications that induce lactation.

    Science.gov (United States)

    Gabay, Michael P

    2002-08-01

    Galactogogues are medications that aid in initiating and maintaining adequate milk production. Most exert their pharmacologic effects through interactions with dopamine receptors, resulting in increased prolactin levels and thereby augmenting milk supply. Metoclopramide remains the galactogogue of choice due to its documented record of efficacy and safety in women and infants. Domperidone crosses the blood brain barrier and into the breast milk to a lesser extent than metoclopramide, decreasing the risk of toxicity to both mother and infant possibly making it an attractive alternative. Traditional antipsychotics, sulpiride and chlorpromazine, have been evaluated, but adverse events limit their use. Human growth hormone, thyrotrophin-releasing hormone, and oxytocin have also been studied. Finally, a natural product, fenugreek, has been purported to be effective in anecdotal reports. Use of this agent may be warranted after considering risks versus benefits.

  1. Risk of extrapyramidal syndrome in schizophrenic patients treated with antipsychotics: a population-based study.

    Science.gov (United States)

    Yang, S-Y; Kao Yang, Y-H; Chong, M-Y; Yang, Y-H; Chang, W-H; Lai, C-S

    2007-04-01

    To compare the prevalence of extrapyramidal syndrome (EPS) between the first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs), the co-prescribing rate of anti-Parkinson drugs (APDs) of each antipsychotic drug was analyzed using population database. Fourteen antipsychotics had been prescribed during the 5-year study period. Among the SGAs, quetiapine had the lowest crude co-prescribing rate of APDs (27.09%), whereas risperidone had the highest rate (66.50%). Among the FGAs, thioridazine and loxapine had the lowest (60.99%) and highest rates (96.35%), respectively. The rankings of the co-prescribing rate of APDs among antipsychotics, in increasing order, were quetiapine, clozapine, olanzapine, thioridazine, zotepine, chlorpromazine, risperidone, sulpiride, clotiapine, flupentixol, haloperidol, zuclopentixol, trifluoperazine, and loxapine. The results indicate that the risk of EPS appears to be lower in SGAs than in FGAs; however, the considerably high rate of EPS in some of the newer generation of antipsychotics warrants clinical attention.

  2. Pathogenesis of drug induced acneform eruptions

    Directory of Open Access Journals (Sweden)

    Lobo Audrey

    1992-01-01

    Full Text Available To determine the pathogenesis of drug induced acneform eruption (DAE, 44 patients were evaluated clinically and representative samples histologically. INAH and corticosteroids were the main offenders in 38.6 percent and 36.4 percent patients respectively. Chloroquin precipitated lesions in 9.1 percent of the patients. There were significant differences in the duration of drug-intake before onset, morphology and severity of lesions. Histological differences with different drugs were also noted. Based on clinical and histological findings, pathogenesis of lesions caused by different drugs could be suggested. Keratinization of follicular epithelium was the main effect with corticosteroids and INAH. Suppuration of follicular epithelium was an additional early event with corticosteroids. Type III allergic reaction was responsible for iodine lesions and delayed hypersensitivity for chlorpromazine and chloroquine induced lesions.

  3. Inhibition of Bacterial RNase P RNA by Phenothiazine Derivatives

    Directory of Open Access Journals (Sweden)

    Shiying Wu

    2016-09-01

    Full Text Available There is a need to identify novel scaffolds and targets to develop new antibiotics. Methylene blue is a phenothiazine derivative, and it has been shown to possess anti-malarial and anti-trypanosomal activities. Here, we show that different phenothiazine derivatives and pyronine G inhibited the activities of three structurally different bacterial RNase P RNAs (RPRs, including that from Mycobacterium tuberculosis, with Ki values in the lower μM range. Interestingly, three antipsychotic phenothiazines (chlorpromazine, thioridazine, and trifluoperazine, which are known to have antibacterial activities, also inhibited the activity of bacterial RPRs, albeit with higher Ki values than methylene blue. Phenothiazines also affected lead(II-induced cleavage of bacterial RPR and inhibited yeast tRNAPhe, indicating binding of these drugs to functionally important regions. Collectively, our findings provide the first experimental data showing that long, noncoding RNAs could be targeted by different phenothiazine derivatives.

  4. Cyanide - Mechanism of Prophylaxis and Effect on Cytochrome Oxidase.

    Science.gov (United States)

    1981-08-15

    152:1074-1077, 1958. Cooperstein, S. J. and Lazaro , A.: A microspectrophotometric method for the determination of cytochrome oxidase. J. biol. Chem...5 mg/kg); A--A CPZ + NaNO (100 mg/kg) + KCN (10 mg/kg); 0 -- 0 CPZ + Na2S203 (1 gm/kg) + KCN (15 mg/kg); A---A CPZ + NaNO2 (100 mg/)Cg) + Na2S203...chlorpromazine (10 mg/kg), NaqO 2 (100 w.g/kg) and A Na S 03 (1gm/kg). G - C Saline control; A - A KCN; S - CPZ + Na 2S 20 3+ KCN; 0 - 0 CPZ + NaNO 2 + KCN

  5. Diagnosis and implications in the therapeutic management of patient with afebrile neurolepctic malignant syndrome

    Science.gov (United States)

    Gomes, Rafael Quintes Ducasble; dos Santos-Júnior, Amilton; Dias, Gabriel Augusto de Araujo Silva; Cais, Carlos Filinto da Silva

    2016-01-01

    This report aims at raising clinical awareness for the diagnosis of atypical presentations of neuroleptic malignant syndrome (NMS). We describe the case of a female patient with NMS symptoms, except fever, after starting the use of chlorpromazine. The afebrile condition delayed the consideration of NMS by the emergency clinicians who provided her initial assessment. Before this consideration, an anticholinergic agent, not recommended at this condition, was inadvertently prescribed. This might have contributed to the worsening of symptoms. NMS is a life-threatening idiosyncratic reaction most often seen as complication of antipsychotic treatment. Its clinical spectrum is broad and its diagnosis should be considered even if the patients do not fulfill all the possible described symptoms. PMID:27606070

  6. Neuroleptic Malignant Syndrome in a Patient with Tongue Cancer: A Report of a Rare Case

    Directory of Open Access Journals (Sweden)

    Osamu Baba

    2013-01-01

    Full Text Available Background. Neuroleptic malignant syndrome (NMS is a rare but life-threatening complication of neuroleptic drugs, which are used widely in head and neck cancer (HANC patients who develop delirium. Methods and Results. Postoperative delirium in a 39-year-old man with tongue cancer was treated with haloperidol and chlorpromazine. Three days after the first administration of antipsychotics, the patient exhibited elevated body temperature, autonomic and extrapyramidal symptoms, and impaired consciousness. A definitive diagnosis was made using the research diagnostic criteria for NMS in the DSM-IV, and the antipsychotics were immediately discontinued. The patient was given dantrolene and bromocriptine to treat the NMS. The patient’s hyperthermia, elevated creatinin kinase (CK, and muscle rigidity improved gradually, with all symptoms of NMS resolving completely by 13 days after the diagnosis. Conclusions. HANC surgeons must be alert for early signs of NMS and use antipsychotics conservatively to avoid NMS and its potentially fatal outcome.

  7. White spot syndrome virus enters crayfish hematopoietic tissue cells via clathrin-mediated endocytosis.

    Science.gov (United States)

    Huang, Jiajun; Li, Fang; Wu, Junjun; Yang, Feng

    2015-12-01

    White spot syndrome virus (WSSV) is a major pathogen of aquacultured shrimp. However, the mechanism of its entry remains poorly understood. In this study, by analyzing the internalization of WSSV using crayfish hematopoietic tissue (HPT) cells, we showed that WSSV virions were engulfed by cell membrane invaginations sharing the features of clathrin-coated pits and then internalized into coated cytoplasmic vesicles. Further investigation indicated that WSSV internalization was significantly inhibited by chlorpromazine (CPZ) but not genistein. The internalized virions were colocalized with endogenous clathrin as well as transferrin which undergoes clathrin-dependent uptake. Preventing endosome acidification by ammonium chloride (NH4Cl) or chloroquine (CQ) dramatically reduced WSSV entry as well. Moreover, disturbance of dynamin activity or depletion of membrane cholesterol also blocked WSSV uptake. These data indicate that WSSV enters crayfish HPT cells via clathrin-mediated endocytosis in a pH-dependent manner, and membrane cholesterol as well as dynamin is critical for efficient viral entry.

  8. Issues in the management of acute agitation: how much current guidelines consider safety?

    Directory of Open Access Journals (Sweden)

    Bruno ePacciardi

    2013-05-01

    Full Text Available Agitated behavior constitutes up to 10% of emergency psychiatric interventions. Pharmacological tranquilization is often used as a valid treatment for agitation but a strong evidence base does not underpin it. Available literature shows different recommendations, supported by research data, theoretical considerations or clinical experience. Rapid tranquilization is mainly based on parenteral drug treatment and the few existing guidelines on this topic, when suggesting the use of first generation antipsychotics and benzodiazepines, include drugs with questionable tolerability profile such as chlorpromazine, haloperidol, midazolam and lorazepam. In order to systematically evaluate safety concerns related to the adoption of such guidelines, we reviewed them independently from principal diagnosis while examining tolerability data for suggested treatments. There is a growing evidence about safety profile of second generation antipsychotics for rapid tranquilization but further controlled studies providing definitive data in this area are urgently needed.

  9. Antipsychotic Medications and Risk of Acute Coronary Syndrome in Schizophrenia: A Nested Case-Control Study

    Science.gov (United States)

    Liu, Hsing-Cheng; Yang, Shu-Yu; Liao, Ya-Tang; Chen, Chiao-Chicy; Kuo, Chian-Jue

    2016-01-01

    Background This study assessed the risk of developing acute coronary syndrome requiring hospitalization in association with the use of certain antipsychotic medications in schizophrenia patients. Methods A nationwide cohort of 31,177 inpatients with schizophrenia between the ages of 18 and 65 years whose records were enrolled in the National Health Insurance Research Database in Taiwan from 2000 to 2008 and were studied after encrypting the identifications. Cases (n = 147) were patients with subsequent acute coronary syndrome requiring hospitalization after their first psychiatric admission. Based on a nested case-control design, each case was matched with 20 controls for age, sex and the year of first psychiatric admission using risk-set sampling. The effects of antipsychotic agents on the development of acute coronary syndrome were assessed using multiple conditional logistic regression and sensitivity analyses to confirm any association. Results We found that current use of aripiprazole (adjusted risk ratio [RR] = 3.68, 95% CI: 1.27–10.64, p<0.05) and chlorpromazine (adjusted RR = 2.96, 95% CI: 1.40–6.24, p<0.001) were associated with a dose-dependent increase in the risk of developing acute coronary syndrome. Although haloperidol was associated with an increased risk (adjusted RR = 2.03, 95% CI: 1.20–3.44, p<0.01), there was no clear dose-dependent relationship. These three antipsychotic agents were also associated with an increased risk in the first 30 days of use, and the risk decreased as the duration of therapy increased. Sensitivity analyses using propensity score-adjusted modeling showed that the results were similar to those of multiple regression analysis. Conclusions Patients with schizophrenia who received aripiprazole, chlorpromazine, or haloperidol could have a potentially elevated risk of developing acute coronary syndrome, particularly at the start of therapy. PMID:27657540

  10. Eficácia de três drogas sobre a aura migranosa: um estudo randomizado placebo controlado Efficacy of three drugs in the treatment of migrainous aura: a randomized, placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Marcelo E. Bigal

    2002-06-01

    Full Text Available A despeito da enorme quantidade de pesquisas referentes à classificação, epidemiologia, diagnóstico, fisiopatologia e tratamento da migrânea, a aura migranosa permanece bem menos estudada. O objetivo do presente estudo é, portanto, verificar a evolução da aura em pacientes submetidos a placebo e a três diferentes drogas disponíveis em unidades públicas de saúde brasileiras. Foram estudados 86 pacientes em vigência de crise de migrânea com aura, apresentando aura no momento da randomização. Após a randomização os pacientes recebiam uma das seguintes substâncias, por via endovenosa: placebo, dipirona, clorpromazina, sulfato de magnésio. O sulfato de magnésio foi superior ao placebo (p In spite of the enormous amount of research regarding classification, epidemiology, diagnosis, pathophisiology and treatment of migraines, aura, one of its hallmarks, stays much less studied. The objective of this study is, therefore, to evaluate the evolution of aura in patients submitted to placebo and three different drugs available in Brazilian public health units. We studied 86 patients during an acute migrainous attack, with aura at the moment of the evaluation. Patients were randomized to receive one of the following substances, in a parenteral route: placebo, dipyrone, chlorpromazine and magnesium sulphate. Magnesium sulphate was superior to placebo (p <0,05 30 and 60 minutes after its administration. Dipyrone and chlorpromazine reduced the duration of the aura, when compared to placebo, 60 minutes following their administration. Our findings make possible some speculations about the pathophisiology of migraine, as well as about the therapeutic approach of patients presenting migrainous aura.

  11. A STUDY OF THE NUCLEOSIDE TRI- AND DIPHOSPHATE ACTIVITIES OF RAT LIVER MICROSOMES

    Science.gov (United States)

    Ernster, Lars; Jones, Lois C.

    1962-01-01

    Rat liver microsomes catalyze the hydrolysis of the triphosphates of adenosine, guanosine, uridine, cytidine, and inosine into the corresponding diphosphates and inorganic orthophosphate. The activities are stimulated by Na2S2O4, and inhibited by atebrin, chlorpromazine, sodium azide, and deaminothyroxine. Sodium deoxycholate inhibits the ATPase activity in a progressive manner; the release of orthophosphate from GTP and UTP is stimulated by low, and inhibited by high, concentrations of deoxycholate, and that from CTP and ITP is unaffected by low, and inhibited by high, concentrations of deoxycholate. Subfractionation of microsomes with deoxycholate into ribosomal, membrane, and soluble fractions reveals a concentration of the triphosphatase activity in the membrane fraction. Rat liver microsomes also catalyze the hydrolysis of the diphosphates of the above nucleosides into the corresponding monophosphates and inorganic orthophosphate. Deoxycholate strongly enhances the GDPase, UDPase, and IDPase activities while causing no activation or even inhibition of the ADPase and CDPase activities. The diphosphatase is unaffected by Na2S2O4 and is inhibited by azide and deaminothyroxine but not by atebrin or chlorpromazine. Upon fractionation of the microsomes with deoxycholate, a large part of the GDPase, UDPase, and IDPase activities is recovered in the soluble fraction. Mechanical disruption of the microsomes with an Ultra Turrax Blender both activates and releases the GDPase, UDPase, and IDPase activities, and the former effect occurs more readily than the latter. The GDPase, UDPase, and IDPase activities of the rat liver cell reside almost exclusively in the microsomal fraction, as revealed by comparative assays of the mitochondrial, microsomal, and final supernatant fractions of the homogenate. The microsomes exhibit relatively low nucleoside monophosphatase and inorganic pyrophosphatase activities, and these are unaffected by deoxycholate or mechanical treatment

  12. Effects of transport inhibitors on the cellular uptake of carboxylated polystyrene nanoparticles in different cell lines.

    Directory of Open Access Journals (Sweden)

    Tiago dos Santos

    Full Text Available Nanotechnology is expected to play a vital role in the rapidly developing field of nanomedicine, creating innovative solutions and therapies for currently untreatable diseases, and providing new tools for various biomedical applications, such as drug delivery and gene therapy. In order to optimize the efficacy of nanoparticle (NP delivery to cells, it is necessary to understand the mechanisms by which NPs are internalized by cells, as this will likely determine their ultimate sub-cellular fate and localisation. Here we have used pharmacological inhibitors of some of the major endocytic pathways to investigate nanoparticle uptake mechanisms in a range of representative human cell lines, including HeLa (cervical cancer, A549 (lung carcinoma and 1321N1 (brain astrocytoma. Chlorpromazine and genistein were used to inhibit clathrin and caveolin mediated endocytosis, respectively. Cytochalasin A and nocodazole were used to inhibit, respectively, the polymerisation of actin and microtubule cytoskeleton. Uptake experiments were performed systematically across the different cell lines, using carboxylated polystyrene NPs of 40 nm and 200 nm diameters, as model NPs of sizes comparable to typical endocytic cargoes. The results clearly indicated that, in all cases and cell types, NPs entered cells via active energy dependent processes. NP uptake in HeLa and 1321N1 cells was strongly affected by actin depolymerisation, while A549 cells showed a stronger inhibition of NP uptake (in comparison to the other cell types after microtubule disruption and treatment with genistein. A strong reduction of NP uptake was observed after chlorpromazine treatment only in the case of 1321N1 cells. These outcomes suggested that the same NP might exploit different uptake mechanisms to enter different cell types.

  13. Drug-induced activation of SREBP-controlled lipogenic gene expression in CNS-related cell lines: Marked differences between various antipsychotic drugs

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    Vik-Mo Audun O

    2006-10-01

    Full Text Available Abstract Background The etiology of schizophrenia is unknown, but neurodevelopmental disturbances, myelin- and oligodendrocyte abnormalities and synaptic dysfunction have been suggested as pathophysiological factors in this severe psychiatric disorder. Cholesterol is an essential component of myelin and has proved important for synapse formation. Recently, we demonstrated that the antipsychotic drugs clozapine and haloperidol stimulate lipogenic gene expression in cultured glioma cells through activation of the sterol regulatory element-binding protein (SREBP transcription factors. We here compare the action of chlorpromazine, haloperidol, clozapine, olanzapine, risperidone and ziprasidone on SREBP activation and SREBP-controlled gene expression (ACAT2, HMGCR, HMGCS1, FDPS, SC5DL, DHCR7, LDLR, FASN and SCD1 in four CNS-relevant human cell lines. Results There were marked differences in the ability of the antipsychotic drugs to activate the expression of SREBP target genes, with clozapine and chlorpromazine as the most potent stimulators in a context of therapeutically relevant concentrations. Glial-like cells (GaMg glioma and CCF-STTG1 astrocytoma cell lines displayed more pronounced drug-induced SREBP activation compared to the response in HCN2 human cortical neurons and SH-SY5Y neuroblastoma cells, indicating that antipsychotic-induced activation of lipogenesis is most prominent in glial cells. Conclusion Our present data show a marked variation in the ability of different antipsychotics to induce SREBP-controlled transcriptional activation of lipogenesis in cultured human CNS-relevant cells. We propose that this effect could be relevant for the therapeutic efficacy of some antipsychotic drugs.

  14. Estudo do mecanismo da hiperglicemia e da hipertensão arterial, produzidas pelo veneno de escorpião, no cão

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    Lineu Freire-Maia

    1961-04-01

    Full Text Available In the present paper we studied the mechanism of the hyperglycemia and hypertension evoked by the intravenous injection of scorpion venom (Tityus bahiensis in the dog. We used 34 dogs, of both sex, weighing between 4.3 to 22 kg. These animals were divided in 3 groups and the following experiments were performed: in the first group (8 dogs the animals were adrenalectomized after the intravenous injection of chlorpromazine; in the second group (16 dogs the animals were injected with ganglionic blocking drugs (9.295 Ciba and hexamethonium; in the third group (10 dogs the naimals were injected with dibenamine, and in 3 of them the adrenal glands were removed. The dogs of each group were injected intravenously with aqueous extract of 2 telsons of scorpion/kg; the average weight of each telson was 6,5 mg. The following results were obtained: 1 The hyperglycemia evoked by scorpion venom, in adrenalectomized dogs, was inhibited by chlorpromazine; 2 Ganglionic blocking drugs (9.295 Ciba and hexamthonium were inefective as far as the hyperglycemic and pressor effects of venom are concerned; 3 In the animals treated with dibenamine, the venom produced a fall in blood pressure, both in the controle and in the adrenalectomized. The present experiments suggest that the scorpion venom has, besides the central action already described by other investigators, an adrenergic action, very similar to the adrenaline. On basis of our experiments we think that the adrenergic action is responsible, in part, by the productrion of hyperglycemia and hypertension.

  15. In Vitro Interaction of 5-Hydroxytrptamine with Cytosolic Molybdenum Hydroxylases as a Potential Inhibitor for Initial Rates Activities

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    Abdullah M. Al-Mohizea

    2010-01-01

    Full Text Available Problem statement: The role of 5-HT has been investigated in many behavioral activities. Thus, studies using raphe lesion showed that 5-HT is involved in sleep, general activity levels, habituation, aggression, pain sensitivity and morphine analgesia, avoidance behavior, self-stimulation and water consumption. Approach: The metabolic interaction between serotonin (5- hydroxytrptamine and indole-3-aldehyde and xanthine via aldehyde oxidase (EC 1.2.3.1 and xanthine oxidase (EC 1.1.3.22, respectively, were studied in liver tissue homogenate of Dunkin-Hartley guinea pigs by following the decrease in substrate concentration using spectrophotometer. Homogenates of liver were incubated with indole-3-aldehyde in the presence and absence of serotonin or (chlorpromazine and allopurinol a potent and selective inhibitors for aldehyde oxidase and xanthine oxidase, respectively. Oxidation of indole-3-aldehyde to indole-3-acetic acid was reduced up to 63.2% in the presence of serotonin (100 µM, while oxidation of xanthine to uric acid was reduced up to 51.6% under the same conditions. Results: In comparison, incubation of the substrates with their specific inhibitors (100 µM of chlorpromazine and 100 µM allopurinol give almost complete inhibition. These results demonstrate that in the guinea pig liver a metabolic interaction between serotonin and indole-3-aldehyde or xanthine via molybdenum hydroxylases system may take place in liver, which is the main tissue for xenobiotics detoxification. Conclusion: The overall conclusion from this research is that serotonin could be a protector for neurons and other tissue from the insult of oxidation of aldehydes and xanthines by molybdenum hydroxylases.

  16. FhCaBP2: a Fasciola hepatica calcium-binding protein with EF-hand and dynein light chain domains.

    Science.gov (United States)

    Thomas, Charlotte M; Timson, David J

    2015-09-01

    FhCaBP2 is a Fasciola hepatica protein which belongs to a family of helminth calcium-binding proteins which combine an N-terminal domain containing two EF-hand motifs and a C-terminal dynein light chain-like (DLC-like) domain. Its predicted structure showed two globular domains joined by a flexible linker. Recombinant FhCaBP2 interacted reversibly with calcium and manganese ions, but not with magnesium, barium, strontium, copper (II), colbalt (II), iron (II), nickel, lead or potassium ions. Cadmium (II) ions appeared to bind non-site-specifically and destabilize the protein. Interaction with either calcium or magnesium ions results in a conformational change in which the protein's surface becomes more hydrophobic. The EF-hand domain alone was able to interact with calcium and manganese ions; the DLC-like domain was not. Alteration of a residue (Asp-58 to Ala) in the second EF-hand motif in this domain abolished ion-binding activity. This suggests that the second EF-hand is the one responsible for ion-binding. FhCaBP2 homodimerizes and the extent of dimerization was not affected by calcium ions or by the aspartate to alanine substitution in the second EF-hand. The isolated EF-hand and DLC-like domains are both capable of homodimerization. FhCaBP2 interacted with the calmodulin antagonists trifluoperazine, chlorpromazine, thiamylal and W7. Interestingly, while chlorpromazine and thiamylal interacted with the EF-hand domain (as expected), trifluoperazine and W7 bound to the DLC-like domain. Overall, FhCaBP2 has distinct biochemical properties compared with other members of this protein family from Fasciola hepatica, a fact which supports the hypothesis that these proteins have different physiological roles.

  17. Effect of Infusions of Non-Antibiotic Antibacterials Alone and in Combination with Cephradine on Milk Yield of Buffaloes Affected with Clinical Mastitis

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    M. Yousaf*, G. Muhammad1, M. Z. Khan2 and S. U. Rahman3

    2010-01-01

    Full Text Available The objective of the present study was to evaluate the effect of four non-antibiotic antibacterials alone or in combination with cephradine in buffaloes on milk yield of mastitis affected quarters. For this purpose, 270 clinically mastitic quarters were grouped in randomized pattern. Non-antibiotic antibacterials viz., 2.5% chlorpromazine (2 ml, 4% lidocaine (10 ml, 10% povidone-iodine (10 ml and 99.5% dimethylsulphoxide (20 ml alone and in combination with first generation cephalosporin (cephradine 500 mg were instilled into clinically mastitic quarters daily for five days. The group administered cephradine alone served as control. Mean milk yield (L/quarter per day was recorded before administration of treatment and over a period of 4 weeks post initiation of treatment. Among the 4 non-antibiotic antibacterials tested alone, chlorpromazine (CPZ showed significantly higher (P<0.05 recuperative effect on the milk yield of clinically mastitic quarters of dairy buffaloes. However, dimethylsulphoxide (DMSO when infused alone, further aggravated (P<0.05 the milk yield loss, indicating negative effect on milk yield improvement. Adjuncting cephradine with each of the non-antibiotic antibacterials, the lidocaine-cephradine group showed the highest effect (p<0.05 on net recovery of milk yield on day 28 post initiation of treatment. It was concluded that that CPZ can be used in clinical mastitis in buffaloes as a low cost alternative to expensive branded antibiotics. Further, the use of lidocaine with cepheradnie was superior to all other combination regimens in milk yield recovery.

  18. Solubility and pKa determination of six structurally related phenothiazines.

    Science.gov (United States)

    Domańska, Urszula; Pelczarska, Aleksandra; Pobudkowska, Aneta

    2011-12-12

    Solubilities of six structurally related phenothiazines, namely chlorpromazine hydrochloride, fluphenazine dihydrochloride, promazine hydrochloride, thioridazine hydrochloride, trifluoperazine dihydrochloride, and triflupromazine hydrochloride at constant pH were measured in the temperature range from 290 K to 350 K in three important drugs solvents: water, ethanol and 1-octanol using the dynamic method and UV-vis method. Dissociation constants and corresponding pK(a) values of drugs were obtained with Bates-Schwarzenbach method at temperature 298.15K in the buffer solutions. Our experimental pK(a) values for chlorpromazine hydrochloride, fluphenazine dihydrochloride, promazine hydrochloride, thioridazine hydrochloride, trifluoperazine dihydrochloride, and triflupromazine hydrochloride are 9.15, 10.01, 9.37, 8.89, 8.97, and 9.03, respectively. The basic thermal properties of pure drugs i.e. melting and solid-solid phase transition as well as glass-transition temperatures, the enthalpy of melting and phase transitions and the molar heat capacity at glass transition (at constant pressure) were measured with differential scanning microcalorimetry (DSC) technique. Molar volumes were calculated with Barton group contribution method. The experimental solubility data were correlated by means of three commonly known G(E) equations: the Wilson, NRTL and UNIQUAC with the assumption that the systems studied here have revealed simple eutectic mixtures. The root-mean-square deviations of temperature were used for the precision of the correlation. The activity coefficients of drugs at saturated solutions in each correlated binary mixture were calculated from the experimental data. These new data will help in all prediction-methods and their precision.

  19. Inhibitory and lytic effects of phenothiazine derivatives and related tricyclic neuroleptic compounds, on Entamoeba histolytica HK9 and HM1 trophozoites.

    Science.gov (United States)

    Ondarza, R N; Hernández, E; Iturbe, A; Hurtado, G

    2000-08-01

    It has been shown previously that tricyclic neuroleptics like clomipramine and chlorpromazine have lethal effects on Leishmania donovani and L. major, and other studies indicate that the phenothiazine inhibitors of trypanothione reductase are potential anti-trypanosomal and anti-leishmanial drugs. With this in mind and our original observation on the presence of trypanothione in Entamoeba histolytica HK9, we examined the possible inhibitory effects of various phenothiazine and tricyclic derivatives on this human parasite. We found that drugs like clomipramine (KD002), the most potent in vitro inhibitor of trypanothione reductase among 30 tricyclic compounds tested, at 25 microM after 24 h of culture under aerobic conditions, caused a substantial decrease in the number of E. histolytica HK9 trophozoites, from approx. 15 x 10(6) to 5.37 x 10(6) cells, and at 100 microM to 0.8 x 10(6) cells. A substantial inhibitory effect on cell proliferation could also be demonstrated with metronidazol (used clinically against amoebiasis). Under similar experimental conditions other tricyclic and phenothiazine derivatives (OFKs), designed originally to inhibit the trypanothione reductase of trypanosomatides, had an inhibitory effect of 16 to 95%. For comparison, similar results were obtained using clomipramine and a phenothiazine derivative (OFK006) with Trypanosoma cruzi and Crithidia luciliae, except that with the latter the inhibitory effect of clomipramine was less dramatic. Experiments comparing two E. histolytica strains showed that normal cell proliferation under anaerobiosis was higher in strain HK9 than in HM1, which is highly virulent, but that metronidazol and clomipramine were less effective against HM1. Two other drugs tested, diphenydramine (KD005) and a phenothiazine derivative (OFK008), also had significant but lower inhibitory effects on both strains. The inhibitory activity on cell proliferation and the lytic effects on this human parasite by the tricyclic

  20. 上海地区560例光斑贴试验结果分析%Analysis of Photopatch Testing Results of 560 Cases in Shanghai District

    Institute of Scientific and Technical Information of China (English)

    胡跃; 唐慧; 王朵勤; 盛友渔; 杨勤萍

    2015-01-01

    Objective:To explore the roles of contact allergens and photoallergens in the treatment of several inflammatory skin diseases by retrospectively analyzing the photopatch testing results of 560 patients from the Dermatology Department during January 2014 and December 2014 .Methods:A total of 560 patients undergoting photopatch testing were collected .The positive rates of photoallergic contact dermatitis(PACD) ,as well as those of allergic contact dermatitis(ACD) among the 20 types of allergens were compared by evaluating the photopatch testing results based on criteria from the International Contact Dermatitis Research Group (ICDRG) .Results:Among the 560 patients ,there were 378 cases (65 .17% ) with PACD positive , 342 cases (58 .97% ) with ACD positive ,and 62 cases (10 .69% ) with both PACD‐ and ACD‐positive .The most common allergens among PACD‐positive patients were chlorpromazine (56 .81% ) ,thiomersal (12 .19% ) ,and formaldehyde (7 .89% ) , whereas the most common allergens among ACD‐positive patients were formaldehyde (22 .04% ) , potassium dichromate (21 .14% ) , and chlorpromazine (14 .70% ) . Furthermore , the most common allergens among PACD‐ and ACD‐ positive patients were chlorpromazine (6 .27% ) ,thiomersal (2 .33% ) ,and nickel sulfate (1 .61% ) .Conclusions:Photoallergens and contact allergens may be related to the pathogenesis of inflammatory skin diseases such as chronic actinic dermatitis ,facial dermatitis ,and eczema .%目的:回顾分析2014年1月—12月皮肤科门诊进行的560例皮肤炎性疾病患者光斑贴试验结果,探讨接触性变应原和光接触性变应原在一些皮肤炎性疾病中的作用。方法:收集接受光斑贴试验检测的皮肤炎性疾病患者患者560例,根据国际接触性皮炎研究组(International Contact Dermatitis Research Group ,ICDRG)的标准判读光斑贴试验结果,比较20种变应原的光接触性皮炎(photoallergic contact dermatitis

  1. The 2-year follow-up of schizophrenic patients treated with different antipsychotic drugs maintenance therapy%不同抗精神病药维持治疗的精神分裂症患者2年复发的随访

    Institute of Scientific and Technical Information of China (English)

    兰胜作; 陈明; 江昆伙; 黄声江; 王文华; 黄腊根; 武剑锋

    2013-01-01

    目的:探讨不同抗精神病药维持治疗的精神分裂症患者的复发率是否存在差异. 方法:对首次发病住院的425例精神分裂症患者出院时分别采用氯丙嗪(n=38),奋乃静(n=41),舒必利(n=52),氯氮平(n=81),利培酮(n=63),奥氮平(n=58),奎硫平(n=44),阿立哌唑(n=48)等8种抗精神病药维持治疗,以自制调查表及阳性和阴性症状量表(PANSS)观察其2年内复发率及服药依从性.结果:425例患者2年内总复发率为64.06%.复发率从高到低依次为氯丙嗪、奋乃静、舒必利、阿立哌唑、奎硫平、利培酮、氯氮平、奥氮平.奥氮平组的复发率显著低于氯丙嗪、奋乃静及舒必利组(x2=5.01,4.63,4.35;P均<0.05);氯氮平组的复发率显著低于氯丙嗪组、奋乃静组(x2=4.06,4.05,P均<0.05),其余各组间复发率比较均无统计学意义(P>0.05).8种药物的服药依从性差异无统计学意义(P>0.05).结论:精神分裂症首次发病患者出院后不同种类抗精神病药维持治疗2年的复发率存在差异.%Objective:Explore the relapse rate of schizophrenia with the use of different antipsychotic drugs maintenance and whether there are significant differences.Method:The first onset of schizophrenia hospitalized patients discharged chlorprumazine(n =38),perphenazine (n =41),sulpiride (n =52),clozapine (n =81),risperidone (n =63),olanzapine (n =58),quetiapine (n =44),aripiprazole (n =48) and eight antipsychotics drugs maintenance treatment,the self-made questionnaire and the positive and negative symptoms scale (PANSS) were used to observe their relapse rate and drug compliance within 2 years.Results:The total relapse rate of 425 patients was 64.06% within 2 years; the relapse rate from high to low in turn is chlorpromazine,perphenazine,sulpiride,aripiprazole,quetiapine,risperidone,clozapine,olanzapine.Olanzapine group relapse rate significantly lower than chlorpromazine,perphenazine and sulpiride group (x2 =5

  2. Tegumental Ca-stimulated adenosine triphosphatase activity in adult Schistosoma mansoni worms Atividade da adenosina trifosfatase estimulada pelo Ca no tegumento de vermes adultos de Schistosoma mansoni

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    Italo M. Cesari

    1989-09-01

    Full Text Available A Ca-stimulated ATPase activity (pH 9.5 associated with the tegumental membrane enriched (TME fraction of Schistosoma mansoni adults was partially inhibited by NAP-taurine or by increasing concentrations of chlorpromazine; endogenous calmodulin was found associated with the TME fraction. A similar activity (pH 8.6 was histochemically visualized whithin the tegument of fixed worms on the cytoplasmic leaflet of both the doubel surface membrane and the basement membrane; this reaction was inhibited by 1 µM chloropromazine and it was also observed on the inner side of double membrane vesicles present in the TME fraction. No ATPase activity could be seen at alkaline pH with added Mg or Na/K ions. Without ATP, the addition of external Ca to the fixed worms induced the appearance of lead precipitates on the tegumental discoid bodies; this reaction was inhibited by molybdate and not by chlorpromazine. The intrategumentary regulation of calcium by the systems described and the possible use of phenothiazines against schistosimes are discussed.A atividade ATPse (pH 9.5 estimulada por ions de Ca associados a uma fração enriquecida de membranas do tegumento (fração EMT de vermes adultos de Schistosoma mansoni, foi inibida pro NAP-taurina ou por concentrações crescentes de clorpromacina. Foi encontrada calmodulina enfogena associada principlamente a esta fração. Em vermes adultos fixados com glutaraldeido se detectou histoquimicamente uma atividade ATPase similar (pH 8.6 na face citoplasmática da dupla membrana de superfície e da membrana por 1 µM de clorpromacina e foi também observada na face interna de vesículas de dupla membrana presentes na fração EMT. Não se pôde detectar atividade ATpase em pH alcalino na presença de ions de Mg ou Na/K. A adição externa de Ca, sem ATP, aos vermes fixados induz ao aparecimento de precipitados nos corpos discóides do tegumento; esta reação foi inibida. Os resultados são discutidos em relação a

  3. The Impact of Cannabis Use on the Dosage of Antipsychotic Drugs in Patients Admitted on the Psychiatric Ward at the University Hospital of the West Indies

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    P Thomas

    2015-03-01

    Full Text Available Objective: To assess the impact of cannabis use on the efficacy of antipsychotic drugs in male subjects presenting to the University Hospital of the West Indies (UHWI with psychotic episodes. Methods: Male subjects, 18–40 years old, admitted to the psychiatric ward of the UHWI between February 2013 and May 2013, diagnosed with schizophrenia, schizophreniform disorder and who tested positive for ∆9-tetrahydrocannabinol were recruited for the study. On day one, consenting subjects were assessed using the Brief Psychiatric Rating Scale (BPRS. Patients were prescribed seven days of an oral antipsychotic medication (haloperidol, chlorpromazine, risperidone, quetiapine, olanzapine. Medicated subjects were then reassessed using the BPRS on days three and seven. Statistical analysis involved the use of Student’s t-test and repeated measure analysis of variance. Results: In total, 20 subjects were recruited (mean age = 26.00 ± 5.96 years. Subjects were grouped based on the daily chlorpromazine equivalent (CPZE dose given on day one into CPZE1 (CPZE dose of 100–300mg; n = 8 and CPZE2 (CPZE dose of 400–1250 mg; n = 12. There was no significant difference in the total BPRS score between the groups on day one (CPZE1 = 41.38 ± 16.47 versus CPZE2 = 49.42 ± 25.58; p = 0.44; similar findings were obtained for the positive (26.75 ± 9.27 versus 31.83 ± 17.30; p = 0.46 and negative (14.63 ± 7.73 versus 17.58 ± 9.74; p = 0.48 symptom component on the BPRS. For subjects in CPZE1, there was no significant decrease in total BPRS score [F(2,21 = 0.07, p = 0.93] over the study period. For CPZE2, significant reduction in total BPRS scores was achieved [F(2,33 =7.12, p = 0.01], contributed by significant decrease in the positive [F(2,33 = 5.64, p = 0.02 and negative [F(2,33 = 7.53, p = 0.01 symptom components of the BPRS. Conclusion: The findings of this study purport that male cannabis users presenting with psychotic disorders may not achieve optimal

  4. Hyperglycemia and antipsychotic medications.

    Science.gov (United States)

    Haupt, D W; Newcomer, J W

    2001-01-01

    Type 2 diabetes mellitus and impaired glucose tolerance are associated with antipsychotic treatment. Risk factors for type 2 diabetes and impaired glucose tolerance include abdominal adiposity, age, ethnic status, and certain neuropsychiatric conditions. While impaired glucose metabolism was first described in psychotic patients prior to the introduction of antipsychotic medications, treatment with antipsychotic medications is associated with impaired glucose metabolism, exacerbation of existing type 1 and 2 diabetes, new-onset type 2 diabetes mellitus, and diabetic ketoacidosis, a severe and potentially fatal metabolic complication. The strength of the association between antipsychotics and diabetes varies across individual medications, with the largest number of reports for chlorpromazine, clozapine, and olanzapine. Recent controlled studies suggest that antipsychotics can impair glucose regulation by decreasing insulin action, although effects on insulin secretion are not ruled out. Antipsychotic medications induce weight gain, and the potential for weight gain varies across individual agents with larger effects observed again for agents like chlorpromazine, clozapine, and olanzapine. Increased abdominal adiposity may explain some treatment-related changes in glucose metabolism. However, case reports and recent controlled studies suggest that clozapine and olanzapine treatment may also be associated with adverse effects on glucose metabolism independent of adiposity. Dyslipidemia is a feature of type 2 diabetes, and antipsychotics such as clozapine and olanzapine have also been associated with hypertriglyceridemia, with agents such as haloperidol, risperidone, and ziprasidone associated with reductions in plasma triglycerides. Diabetes mellitus is associated with increased morbidity and mortality due to both acute (e.g., diabetic ketoacidosis) and long-term (e.g., cardiovascular disease) complications. A progressive relationship between plasma glucose levels and

  5. Drugs affecting the eye.

    Science.gov (United States)

    Taylor, F

    1985-08-01

    This discussion reviews drugs that affect the eye, including antihyperglycemic agents; corticosteroids; antirheumatic drugs (quinolines, indomethacin, and allopurinol); psychiatric drugs (phenothiazine, thioridazine, and chlorpromazine); drugs used in cardiology (practolol, amiodarone, and digitalis gylcosides); drugs implicated in optic neuritis and atrophy, drugs with an anticholinergic action; oral contraceptives (OCs); and topical drugs and systemic effects. Refractive changes, either myopic or hypermetropic, can occur as a result of hyperglycemia, and variation in vision is sometimes a presenting symptom in diabetes mellitus. If it causes a change in the refraction, treatment of hyperglycemia almost always produces a temporary hypermetropia. A return to the original refractive state often takes weeks, sometimes months. There is some evidence that patients adequately treated with insulin improve more rapidly than those taking oral medication. Such patients always should be referred for opthalmological evaluation as other factors might be responsible, but it might not be possible to order the appropriate spectacle correction for some time. The most important ocular side effect of the systemic adiministration of corticosteroids is the formation of a posterior subcapsular cataract. Glaucoma also can result from corticosteroids, most often when they are applied topically. Corticosteroids have been implicated in the production of benign intracranial hypertension, which is paradoxical because they also are used in its treatment. The most important side effect of drugs such as chloroquine and hydroxychloroquine is an almost always irreversible maculopathy with resultant loss of central vision. Corneal and retinal changes similar to those caused by the quinolines have been reported with indomethacin, but there is some question about a cause and effect relationship. The National Registry of Drug Induced Ocular Side Effects in the US published 30 case histories of

  6. Successful five-day perfusion preservation of the canine kidney.

    Science.gov (United States)

    McAnulty, J F; Ploeg, R J; Southard, J H; Belzer, F O

    1989-01-01

    Over 20 years ago, successful 3-day-perfusion preservation of canine kidneys was obtained. Since then, consistent 5-day preservation has not been reported. In this study, we investigated how the perfusate calcium concentration affected both mitochondrial function and posttransplant viability in dog kidneys preserved for 5 days. Dog kidneys were preserved by machine perfusion (5 degrees C) using a hydroxyethyl starch-gluconate solution that contained either 0.0, 0.5, 1.5, or 5.0 mM calcium. Mitochondria isolated from preserved kidneys has a loss of respiratory control when either 0.0, 1.5, or 5.0 mM calcium were present. However, the use of a perfusate with 0.5 mM calcium preserved the mitochondrial function at levels equivalent to controls for 5 days. Transplantation of kidneys preserved for 5 days with 0.0 or 1.5 mM calcium yielded poor survival (0% and 17%, respectively). The use of a 0.5-mM calcium perfusate increased posttransplant survival to 63% (5 of 8 transplanted). Donor pretreatment of kidneys with chlorpromazine (2.5 mg/kg i.v.) did not improve the function of mitochondria isolated from preserved kidneys but did increase survival in the 1.5-mM calcium group to 67% (4 of 6 transplanted) and in the 0.5 mM calcium group to 100% (7 of 7 transplanted). This is the first report to document consistently successful 5-day preservation of canine kidneys and clearly shows the importance of the perfusate calcium concentration in long-term kidney preservation. The specific mechanism by which calcium or chlorpromazine exert their effect is not known, but it is apparent that excessively high or low concentrations of calcium are damaging to the preserved organ, and an optimal calcium concentration combined with metabolic inhibition of calcium-dependent pathways can significantly improve the function of organs preserved for extended time periods.

  7. Receptor mapping in psychiatric patients with SPECT; Rezeptor-SPECT-Untersuchungen bei psychiatrischen Patienten

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    Schlegel, S. [Mainz Univ. (Germany). Psychiatrische Klinik

    1997-06-01

    This paper summarizes some data of our studies with the single-photon-emission-computerized tomography (SPECT), focussing on the dopamine-D2- and the benzodiazepine receptor mapping. Benzodiazepine receptors: Central benzodiazepine receptors (BZr) can be visualized with iomazenil which is an analogue of the benzodiazepine antagonist flumazenil, labeled with 123-iodine. Since the involvement of the BZr system is discussed in the pathogenesis of anxiety and depression, patients with these disorders were investigated. A third study investigated the BZr-occupancy during benzodiazepine treatment (lorazepam). Results: (a) Patients with panic disorders had lower iomazenil uptake values compared to epileptic patients. (b) Depressed patients showed a positive correlation between severity of illness and frontal uptake. (c) BZr occupancy during lorazepam treatment was measurable, but not associated with lorazepam plasma levels. Dopamine-D2-receptors: With 123-I-iodobenzamide (IBZM), and iodine-labeled dopamine receptor ligand, the D2 receptor density can be measured by a semiquantitative approach (striatum/frontal cortex=ST/FC). Therefore, we investigated the D2-receptor occupancy during treatment with typical and atypical neuroleptics in relationship to dosages (normalized with different formulas of chlorpromazine equivalents), side effects, and prolactin plasma levels. Results: Dependent on the selected formula for chlorpromazine equivalents, the ST/FC ratio was correlated with dosages. Side effects and prolactin plasma levels showed a negative association with lower ST/FC ratios. (orig.) [Deutsch] Der Beitrag soll einen Ueberblick ueber verschiedene eigene Studien geben, die die Darstellung von Dopamin-D2- und Benzodiazepinrezeptoren mit der Single-Photon-Emissions-Computertomographie (SPECT) untersuchten. Benzodiazepinrezeptoren: Jomazenil, der mit 123-Jod markierte Benzodiazepinantagonist Flumazenil, ermoeglicht die Darstellung der zentralen Benzodiazepinrezeptoren (BZr

  8. Translocation of PEGylated quantum dots across rat alveolar epithelial cell monolayers

    Directory of Open Access Journals (Sweden)

    Fazlollahi F

    2011-11-01

    Full Text Available Farnoosh Fazlollahi1,8, Arnold Sipos1,2, Yong Ho Kim1,2, Sarah F Hamm-Alvarez6, Zea Borok1–3, Kwang-Jin Kim1,2,5–7, Edward D Crandall1,2,4,8 1Will Rogers Institute Pulmonary Research Center, 2Department of Medicine, 3Department of Biochemistry and Molecular Biology, 4Department of Pathology, 5Department of Physiology and Biophysics, 6Department of Pharmacology and Pharmaceutical Sciences, 7Department of Biomedical Engineering, 8Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA, USA Background: In this study, primary rat alveolar epithelial cell monolayers (RAECM were used to investigate transalveolar epithelial quantum dot trafficking rates and underlying transport mechanisms. Methods: Trafficking rates of quantum dots (PEGylated CdSe/ZnS, core size 5.3 nm, hydrodynamic size 25 nm in the apical-to-basolateral direction across RAECM were determined. Changes in bioelectric properties (ie, transmonolayer resistance and equivalent active ion transport rate of RAECM in the presence or absence of quantum dots were measured. Involvement of endocytic pathways in quantum dot trafficking across RAECM was assessed using specific inhibitors (eg, methyl-ß-cyclodextrin, chlorpromazine, and dynasore for caveolin-, clathrin-, and dynamin-mediated endocytosis, respectively. The effects of lowering tight junctional resistance on quantum dot trafficking were determined by depleting Ca2+ in apical and basolateral bathing fluids of RAECM using 2 mM EGTA. Effects of temperature on quantum dot trafficking were studied by lowering temperature from 37°C to 4°C. Results: Apical exposure of RAECM to quantum dots did not elicit changes in transmonolayer resistance or ion transport rate for up to 24 hours; quantum dot trafficking rates were not surface charge-dependent; methyl-ß-cyclodextrin, chlorpromazine, and dynasore did not decrease quantum dot trafficking rates; lowering of temperature

  9. Reasonable selection of neovascular glaucoma therapy%新生血管性青光眼治疗方案合理性选择

    Institute of Scientific and Technical Information of China (English)

    宋哲; 赛自金

    2013-01-01

    新生血管性青光眼(neovascular glaucoma,NVG)在临床中随着基础病如:糖尿病、高血压等的增多而越来越多.虽然其诊断简单,但是治疗却比较复杂,在晚期,由于患者疼痛,解除患者痛苦采用多种方法如睫状体冷冻、光凝术、球后酒精注射、氯丙嗪术、甚至眼球摘除术.摘除眼球给患者带来诸多不便,面对错综复杂的治疗方案,那么如何选择比较科学合理方法对患者尤为重要,目前尽可能避免眼球摘除术;慎用酒精或者氯丙嗪球后注射术.应结合眼科新进展采用多种方法控制眼压,减轻患者痛苦,制订科学而合理的个体化治疗是治疗NVG必然趋势.%Neovascular glaucoma (NVG)is increasing in clinical with the increase of basic diseases such as diabetes mellitus, hypertension. It is easy to diagnose, but the treatment is more complex. In the late, because the pain of patients, a variety of methods such as the ciliary body cryotherapy, photocoagulation, retrobulbar alcohol injection, chlorpromazine, even enucleation of eyeball were used to relieve pain of patients. Enucleation of eyeball brings inconvenience to the patients. Then how to choose the reasonable method is particularly important for patients, in the face of complicated treatments, as far as possible to avoid enucleation. Alcohol or retrobulbar injection of chlorpromazine should be careful used and should be combined with the new progress in the Department of Ophthalmology. Using a variety of methods to control intraocular pressure, alleviate the suffering of patients, to formulate a scientific and reasonable individualized treatment is the treatment of NVG trend.

  10. The uptake of soluble and particulate antigens by epithelial cells in the mouse small intestine.

    Science.gov (United States)

    Howe, Savannah E; Lickteig, Duane J; Plunkett, Kyle N; Ryerse, Jan S; Konjufca, Vjollca

    2014-01-01

    Intestinal epithelial cells (IECs) overlying the villi play a prominent role in absorption of digested nutrients and establish a barrier that separates the internal milieu from potentially harmful microbial antigens. Several mechanisms by which antigens of dietary and microbial origin enter the body have been identified; however whether IECs play a role in antigen uptake is not known. Using in vivo imaging of the mouse small intestine, we investigated whether epithelial cells (enterocytes) play an active role in the uptake (sampling) of lumen antigens. We found that small molecular weight antigens such as chicken ovalbumin, dextran, and bacterial LPS enter the lamina propria, the loose connective tissue which lies beneath the epithelium via goblet cell associated passageways. However, epithelial cells overlying the villi can internalize particulate antigens such as bacterial cell debris and inert nanoparticles (NPs), which are then found co-localizing with the CD11c+ dendritic cells in the lamina propria. The extent of NP uptake by IECs depends on their size: 20-40 nm NPs are taken up readily, while NPs larger than 100 nm are taken up mainly by the epithelial cells overlying Peyer's patches. Blocking NPs with small proteins or conjugating them with ovalbumin does not inhibit their uptake. However, the uptake of 40 nm NPs can be inhibited when they are administered with an endocytosis inhibitor (chlorpromazine). Delineating the mechanisms of antigen uptake in the gut is essential for understanding how tolerance and immunity to lumen antigens are generated, and for the development of mucosal vaccines and therapies.

  11. Inhibition of RNA recruitment and replication of an RNA virus by acridine derivatives with known anti-prion activities.

    Directory of Open Access Journals (Sweden)

    Zsuzsanna Sasvari

    Full Text Available BACKGROUND: Small molecule inhibitors of RNA virus replication are potent antiviral drugs and useful to dissect selected steps in the replication process. To identify antiviral compounds against Tomato bushy stunt virus (TBSV, a model positive stranded RNA virus, we tested acridine derivatives, such as chlorpromazine (CPZ and quinacrine (QC, which are active against prion-based diseases. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that CPZ and QC compounds inhibited TBSV RNA accumulation in plants and in protoplasts. In vitro assays revealed that the inhibitory effects of these compounds were manifested at different steps of TBSV replication. QC was shown to have an effect on multiple steps, including: (i inhibition of the selective binding of the p33 replication protein to the viral RNA template, which is required for recruitment of viral RNA for replication; (ii reduction of minus-strand synthesis by the tombusvirus replicase; and (iii inhibition of translation of the uncapped TBSV genomic RNA. In contrast, CPZ was shown to inhibit the in vitro assembly of the TBSV replicase, likely due to binding of CPZ to intracellular membranes, which are important for RNA virus replication. CONCLUSION/SIGNIFICANCE: Since we found that CPZ was also an effective inhibitor of other plant viruses, including Tobacco mosaic virus and Turnip crinkle virus, it seems likely that CPZ has a broad range of antiviral activity. Thus, these inhibitors constitute effective tools to study similarities in replication strategies of various RNA viruses.

  12. Study on cellular internalization of poly(vinyldiaminotriazine)-based hydrosen bonding type non-viral trans-gene vector

    Institute of Scientific and Technical Information of China (English)

    YE GuiXiang; CAO ZhiQiang; LIN Lin; CHEN DaYong; LIU WenGuang

    2008-01-01

    Previously we successfully prepared poly(vinyldiaminotriazine)(PVDT)-based non-viral vectors which complexed plasmid DNA via hydrogen bonding with adenine-thymine base pairs. In this report, surface charges and complex sizes of this system were further examined. The results showed that PVDT-based polymer could cover surface charges of DNA resulting in slightly negative or neutral complexes. It was also found that the complex sizes were governed by two events: the aggregation induced by the instability of neutral particles, and more compact complexes produced by PVDT-based polymers. In the study of cellular uptake, chlorpromazine and filipin III were used to inhibit clathrin- and caveolae-mediated endocytosis, respectively. We found that PVDT-based systems were transported into cells via a non-clathrin, non-caveolae mediated endocytosis. This special process was studied by temperature inhibition and kinetics assays. It was revealed that such a pathway was characterized by (i) a more energy dependent process and (ii) a much slow transfection-effective internalization.

  13. The presence of serum alters the properties of iron oxide nanoparticles and lowers their accumulation by cultured brain astrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Geppert, Mark; Petters, Charlotte [University of Bremen, Centre for Biomolecular Interactions Bremen (Germany); Thiel, Karsten [Fraunhofer Institute for Manufacturing Technology and Advanced Materials (Germany); Dringen, Ralf, E-mail: ralf.dringen@uni-bremen.de [University of Bremen, Centre for Biomolecular Interactions Bremen (Germany)

    2013-01-15

    Iron oxide nanoparticles (IONPs) are considered for various diagnostic and therapeutic applications. Such particles are able to cross the blood-brain barrier and are taken up into brain cells. To test whether serum components affect the properties of IONPs and/or their uptake into brain cells, we have incubated dimercaptosuccinate-coated magnetic IONPs without and with fetal calf serum (FCS) and have exposed cultured brain astrocytes with IONPs in the absence or presence of FCS. Incubation with FCS caused a concentration-dependent increase in the average hydrodynamic diameter of the particles and of their zeta-potential. In the presence of 10 % FCS, the diameter of the IONPs increased from 57 {+-} 2 to 107 {+-} 6 nm and the zeta-potential of the particles from -22 {+-} 5 to -9 {+-} 1 mV. FCS affected also strongly the uptake of IONPs by cultured astrocytes. The efficient time- and temperature-dependent cellular accumulation of IONPs was lowered with increasing concentration of FCS by up to 90 %. In addition, in the absence of serum, endocytosis inhibitors did not alter the IONP accumulation by astrocytes, while chlorpromazine or wortmannin lowered significantly the accumulation of IONPs in the presence of FCS, suggesting that clathrin-mediated endocytosis and macropinocytosis are involved in astrocytic IONP uptake from serum-containing medium. These data demonstrate that the presence of FCS strongly affects the properties of IONPs as well as their accumulation by cultured brain cells.

  14. Clathrin-mediated endocytosis of gold nanoparticles in vitro.

    Science.gov (United States)

    Ng, Cheng Teng; Tang, Florence Mei Ai; Li, Jasmine Jia'en; Ong, Cynthia; Yung, Lanry Lin Yue; Bay, Boon Huat

    2015-02-01

    Gold nanoparticles (AuNPs) have potential biomedical and scientific applications. In this study, we evaluated the uptake and internalization of FBS-coated 20 nm AuNPs into lung fibroblasts and liver cells by different microscopy techniques. AuNP aggregates were observed inside MRC5 lung fibroblasts and Chang liver cells under light microscopy, especially after enhancement with automegallography. Clusters of AuNPs were observed to be adsorbed on the cell surface by scanning electron microscopy. Ultrathin sections showed that AuNPs were mainly enclosed within cytoplasmic vesicles when viewed under transmission electron microscopy. We also investigated the mechanism of uptake for AuNPs, using endocytosis inhibitors and quantification of Au with inductively coupled plasma mass spectrometry. Cells treated with concanavalin A and chlorpromazine showed significant decrease of Au uptake in MRC5 lung fibroblasts and Chang liver cells, respectively, implying that the uptake of AuNPs was facilitated by clathrin-mediated endocytosis. It would therefore appear that uptake of 20 nm AuNPs in both cell types with different tissues of origin, was dependent upon clathrin-mediated endocytosis.

  15. Early postnatal exposure to lithium in vitro induces changes in AMPAR mEPSCs and vesicular recycling at hippocampal glutamatergic synapses

    Indian Academy of Sciences (India)

    Shreya M Ankolekar; Sujit K Sikdar

    2015-06-01

    Lithium is an effective mood stabilizer but its use is associated with many side effects. Electrophysiological recordings of miniature excitatory postsynaptic currents (mEPSCs) mediated by glutamate receptor AMPA-subtype (AMPARs) in hippocampal pyramidal neurons revealed that CLi (therapeutic concentration of 1 mM lithium, from days in vitro 4–10) decreased the mean amplitude and mean rectification index (RI) of AMPAR mEPSCs. Lowered mean RI indicate that contribution of Ca2+-permeable AMPARs in synaptic events is higher in CLi neurons (supported by experiments sensitive to Ca2+-permeable AMPAR modulation). Co-inhibiting PKA, GSK-3 and glutamate reuptake was necessary to bring about changes in AMPAR mEPSCs similar to that seen in CLi neurons. FM1-43 experiments revealed that recycling pool size was affected in CLi cultures. Results from minimum loading, chlorpromazine treatment and hyperosmotic treatment experiments indicate that endocytosis in CLi is affected while not much difference is seen in modes of exocytosis. CLi cultures did not show the high KCl associated presynaptic potentiation observed in control cultures. This study, by calling attention to long-term lithium-exposure-induced synaptic changes, might have implications in understanding the side effects such as CNS complications occurring in perinatally exposed babies and cognitive dulling seen in patients on lithium treatment.

  16. Ionic liquid-impregnated agarose film two-phase micro-electrodriven membrane extraction (IL-AF-μ-EME) for the analysis of antidepressants in water samples.

    Science.gov (United States)

    Mohamad Hanapi, Nor Suhaila; Sanagi, Mohd Marsin; Ismail, Abd Khamim; Wan Ibrahim, Wan Aini; Saim, Nor'ashikin; Wan Ibrahim, Wan Nazihah

    2017-03-01

    The aim of this study was to investigate and apply supported ionic liquid membrane (SILM) in two-phase micro-electrodriven membrane extraction combined with high performance liquid chromatography-ultraviolet detection (HPLC-UV) for pre-concentration and determination of three selected antidepressant drugs in water samples. A thin agarose film impregnated with 1-hexyl-3-methylimidazolium hexafluorophosphate, [C6MIM] [PF6], was prepared and used as supported ionic liquid membrane between aqueous sample solution and acceptor phase for extraction of imipramine, amitriptyline and chlorpromazine. Under the optimized extraction conditions, the method provided good linearity in the range of 1.0-1000μgL(-1), good coefficients of determination (r(2)=0.9974-0.9992) and low limits of detection (0.1-0.4μgL(-1)). The method showed high enrichment factors in the range of 110-150 and high relative recoveries in the range of 88.2-111.4% and 90.9-107.0%, for river water and tap water samples, respectively with RSDs of ≤7.6 (n=3). This method was successfully applied to the determination of the drugs in river and tap water samples. It is envisaged that the SILM improved the perm-selectivity by providing a pathway for targeted analytes which resulted in rapid extraction with high degree of selectivity and high enrichment factor.

  17. Arylperoxyl radicals. Formation, absorption spectra, and reactivity in aqueous alcohol solutions

    Energy Technology Data Exchange (ETDEWEB)

    Alfassi, Z.B.; Khaikin, G.I.; Neta, P. (National Inst. of Standards and Technology, Gaithersburg, MD (United States))

    1995-01-05

    Aryl radicals (phenyl, 4-biphenylyl, 2-naphthyl, 1-naphthyl, and 9-phenanthryl) were produced by the reaction of the corresponding aryl bromide with solvated electrons and reacted rapidly with oxygen to produce the arylperoxyl radicals. These radicals exhibit optical absorptions in the visible range, with [lambda][sub max] at 470, 550, 575, 650, and 700 nm, respectively. Arylperoxyl radicals react with 2,2[prime]-azinobis(3-ethylbenzothiazoiine-6-sulfonate ion) (ABTS), chlorpromazine, and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox C) by one-electron oxidation. The rate constants k for these reactions, determined from the rate of formation of the one-electron oxidation products as a function of substrate concentration, vary between 4 [times] 10[sup 6] and 2 [times] 10[sup 9] L mol[sup [minus]1] s[sup [minus]1] and increase in the order phenyl-, 4-biphenyl-, 2-naphthyl-, 1-naphthyl-, and 9-phenanthrylperoxyl, the same order as the absorption peaks of these radicals. Good correlation was found between log k and the energy of the absorption peak. 16 refs., 2 figs., 2 tabs.

  18. Neural Inhibition of Dopaminergic Signaling Enhances Immunity in a Cell-Non-autonomous Manner.

    Science.gov (United States)

    Cao, Xiou; Aballay, Alejandro

    2016-09-12

    The innate immune system is the front line of host defense against microbial infections, but its rapid and uncontrolled activation elicits microbicidal mechanisms that have deleterious effects [1, 2]. Increasing evidence indicates that the metazoan nervous system, which responds to stimuli originating from both the internal and the external environment, functions as a modulatory apparatus that controls not only microbial killing pathways but also cellular homeostatic mechanisms [3-5]. Here we report that dopamine signaling controls innate immune responses through a D1-like dopamine receptor, DOP-4, in Caenorhabditis elegans. Chlorpromazine inhibition of DOP-4 in the nervous system activates a microbicidal PMK-1/p38 mitogen-activated protein kinase signaling pathway that enhances host resistance against bacterial infections. The immune inhibitory function of dopamine originates in CEP neurons and requires active DOP-4 in downstream ASG neurons. Our findings indicate that dopamine signaling from the nervous system controls immunity in a cell-non-autonomous manner and identifies the dopaminergic system as a potential therapeutic target for not only infectious diseases but also a range of conditions that arise as a consequence of malfunctioning immune responses.

  19. Common symptoms in advanced cancer.

    Science.gov (United States)

    Lagman, Ruth L; Davis, Mellar P; LeGrand, Susan B; Walsh, Declan

    2005-04-01

    The key points of this article are anorexia and cachexia are: A major cause of cancer deaths. Several drugs are available to treat anorexia and cachexia. Dyspnea in cancer usually is caused by several factors. Treatment consists of reversing underlying causes, empiric bronchodilators, cortico-steroids--and in the terminally ill patients-opioids, benzodiazepines,and chlorpromazine. Delirium is associated with advanced cancer. Empiric treatment with neuroleptics while evaluating for reversible causes is a reasonable approach to management. Nausea and vomiting are caused by extra-abdominal factors (drugs,electrolyte abnormalities, central nervous system metastases) or intra-abdominal factors (gastroparesis, ileus, gastric outlet obstruction, bowel obstruction). The pattern of nausea and vomiting differs depending upon whether the cause is extra- or intra-abdominal. Reversible causes should be sought and empiric metoclopramide or haloperidol should be initiated. Fatigue may be caused by anemia, depression, endocrine abnormalities,or electrolyte disturbances that should be treated before using empiric methylphenidate. Constipation should be treated with laxatives and stool softeners. Both should start with the first opioid dose.

  20. 无抽搐电痉挛治疗恶性综合征1例%Modified electroconvulsive therapy in the treatment of neuroleptic malignant syndrome

    Institute of Scientific and Technical Information of China (English)

    杨勇; 何永光; 王飚

    2011-01-01

    @@ 随着新型抗精神病药物的广泛应用,药物所致恶性综合征发生率似已降低,但仍难以完全避免.电痉挛治疗作为恶性综合征的一种特殊治疗手段,国外文献报道较多,而国内报道极少.本文报道1例应用无抽搐电痉挛治疗恶性综合征的经验,并结合文献进行讨论.%Neuroleptic malignant syndrome (NMS) has become less prevalent with the widespread use of second-generation antipsychotics but it remains a serious problem. The use of modified electroconvulsive therapy (MECT) in the treatment of NMS is reported widely in the West but there are few such reports from China. We review the literature and report on one case of a 38-year-old male patient with schizophrenia regularly treated with chlorpromazine and clozapine who developed NMS soon after conversion to treatment with risperidone. The patient received 14 treatments with MECT over a 45-day period and the biochemical and clinical markers of NMS gradually returned to normal.

  1. Roles of octopaminergic and dopaminergic neurons in mediating reward and punishment signals in insect visual learning.

    Science.gov (United States)

    Unoki, Sae; Matsumoto, Yukihisa; Mizunami, Makoto

    2006-10-01

    Insects, like vertebrates, have considerable ability to associate visual, olfactory or other sensory signals with reward or punishment. Previous studies in crickets, honey bees and fruit-flies have suggested that octopamine (OA, invertebrate counterpart of noradrenaline) and dopamine (DA) mediate various kinds of reward and punishment signals in olfactory learning. However, whether the roles of OA and DA in mediating positive and negative reinforcing signals can be generalized to learning of sensory signals other than odors remained unknown. Here we first established a visual learning paradigm in which to associate a visual pattern with water reward or saline punishment for crickets and found that memory after aversive conditioning decayed much faster than that after appetitive conditioning. Then, we pharmacologically studied the roles of OA and DA in appetitive and aversive forms of visual learning. Crickets injected with epinastine or mianserin, OA receptor antagonists, into the hemolymph exhibited a complete impairment of appetitive learning to associate a visual pattern with water reward, but aversive learning with saline punishment was unaffected. By contrast, fluphenazine, chlorpromazine or spiperone, DA receptor antagonists, completely impaired aversive learning without affecting appetitive learning. The results demonstrate that OA and DA participate in reward and punishment conditioning in visual learning. This finding, together with results of previous studies on the roles of OA and DA in olfactory learning, suggests ubiquitous roles of the octopaminergic reward system and dopaminergic punishment system in insect learning.

  2. The impact of neuroleptic dosage and extrapyramidal side effects on schizophrenic basic symptoms.

    Science.gov (United States)

    Moritz, S; Krausz, M; Gottwalz, E; Andresen, B

    2000-01-01

    The impact of neuroleptic medication and extrapyramidal symptoms on abnormal subjective experiences in schizophrenia, also termed basic symptoms, as assessed with the Frankfurt Complaint Questionnaire (FCQ) was investigated in 40 schizophrenic patients medicated with conventional neuroleptics. Basic symptoms are thought to reflect the subjective side of schizophrenic vulnerability and to underlie schizophrenic symptomatology. It was expected that basic symptoms would inversely correlate with chlorpromazine equivalents, since neuroleptics not only improve acute schizophrenic symptoms but also have prophylactic properties. However, a significant positive correlation with neuroleptic dosage and extrapyramidal symptoms emerged, suggesting that basic symptoms as operationalized in the FCQ partly reflect neuroleptic-induced deficits. The results remained unchanged when global psychopathology was controlled for. In line with previous research, basic symptoms correlated with thought disorder but not with positive symptoms. However, when the effects of neuroleptic-induced disturbances were controlled for, thought disorder also insignificantly correlated with basic symptoms. Our findings confirm previous results that question the construct validity of the FCQ. Moreover, the need to control for confounding variables (such as medication) is emphasized by comparing different psychiatric groups.

  3. The action of psychotropic drugs on DOPA induced behavioural responses in mice.

    Science.gov (United States)

    Berendsen, H; Leonard, B E; Rigter, H

    1976-01-01

    The "DOPA potentiation" test in mice was investigated for its usefulness in the detection of compounds with antidepressant properties. It was found that the anti-depressant drugs imipramine, amitriptyline, 5-methylamino-acetyl-6-methyl-5,6-dihydro-phenanthridine-HCl (Org OI77) and 1,2,3,4,10,14b-hexahydro-2-methyl-dibenzo[c,f]pyrazino[1,2-a]azepine-HCl (mianserin, Org GB 94) potentiated the behavioural effect of DOPA in groups of mice which had been treated 17 h previously with the monoamine oxidase inhibitor (MAOI) iproniazid. However, the DOPA response was also potentiated by a variety of centrally acting drugs which do not have antidepressant properties (atropine, methysergide, chlordiazepoxide, apomorphine). The peptide hormones ACTH4-10 and desglycinamide lysine vasopressin had equivocal effects while melanocyte stimulating hormone release-inhibiting factor (MIF) had no effect on the DOPA response. The DOPA response was inhibited by the neuroleptics chlorpromazine and haloperidol. There appeared to be no correlation between the effects of the drugs on the behavioural responses elicited by DOPA and the changes found in the brain concentration of noradrenaline, dopamine, serotonin, gamma-aminobutyric acid, tryptophan and tyrosine. It is concluded that the "DOPA potentiation" test cannot be considered as a reliable test in the detection of anti-depressant compounds.

  4. Sequential cloud-point extraction for toxicological screening analysis of medicaments in human plasma by high pressure liquid chromatography with diode array detector.

    Science.gov (United States)

    Madej, Katarzyna; Persona, Karolina; Wandas, Monika; Gomółka, Ewa

    2013-10-18

    A complex extraction system with the use of cloud-point extraction technique (CPE) was developed for sequential isolation of basic and acidic/neutral medicaments from human plasma/serum, screened by HPLC/DAD method. Eight model drugs (paracetamol, promazine, chlorpromazine, amitriptyline, salicyclic acid, opipramol, alprazolam and carbamazepine) were chosen for the study of optimal CPE conditions. The CPE technique consists in partition of an aqueous sample with addition of a surfactant into two phases: micelle-rich phase with the isolated compounds and water phase containing a surfactant below the critical micellar concentration, mainly under influence of temperature change. The proposed extraction system consists of two chief steps: isolation of basic compounds (from pH 12) and then isolation of acidic/neutral compounds (from pH 6) using surfactant Triton X-114 as the extraction medium. Extraction recovery varied from 25.2 to 107.9% with intra-day and inter-day precision (RSD %) ranged 0.88-1087 and 5.32-17.96, respectively. The limits of detection for the studied medicaments at λ 254nm corresponded to therapeutic or low toxic plasma concentration levels. Usefulness of the proposed CPE-HPLC/DAD method for toxicological drug screening was tested via its application to analysis of two serum samples taken from patients suspected of drug overdosing.

  5. Potential anti-cancer drugs commonly used for other indications.

    Science.gov (United States)

    Hanusova, Veronika; Skalova, Lenka; Kralova, Vera; Matouskova, Petra

    2015-01-01

    An increasing resistance of mammalian tumor cells to chemotherapy along with the severe side effects of commonly used cytostatics has raised the urgency in the search for new anti-cancer agents. Several drugs originally approved for indications other than cancer treatment have recently been found to have a cytostatic effect on cancer cells. These drugs could be expediently repurposed as anti-cancer agents, since they have already been tested for toxicity in humans and animals. The groups of newly recognized potential cytostatics discussed in this review include benzimidazole anthelmintics (albendazole, mebendazole, flubendazole), anti-hypertensive drugs (doxazosin, propranolol), psychopharmaceuticals (chlorpromazine, clomipramine) and antidiabetic drugs (metformin, pioglitazone). All these drugs have a definite potential to be used especially in combinations with other cytostatics; the chemotherapy targeting of multiple sites now represents a promising approach in cancer treatment. The present review summarizes recent information about the anti-cancer effects of selected drugs commonly used for other medical indications. Our aim is not to collect all the reported results, but to present an overview of various possibilities. Advantages, disadvantages and further perspectives regarding individual drugs are discussed and evaluated.

  6. Modulation of Visceral Nociception, Inflammation and Gastric Mucosal Injury by Cinnarizine

    Directory of Open Access Journals (Sweden)

    Omar M.E. Abdel-Salam

    2007-01-01

    Full Text Available The effect of cinnarizine, a drug used for the treatment of vertigo was assessed in animal models of visceral nociception, inflammation and gastric mucosal injury. Cinnarizine (1.25–20 mg/kg, s.c. caused dose-dependent inhibition of the abdominal constrictions evoked by i.p. injection of acetic acid by 38.7–99.4%. This effect of cinnarizine (2.5 mg/kg was unaffected by co-administration of the centrally acting dopamine D2 receptor antagonists, sulpiride, haloperidol or metoclopramide, the peripherally acting D2 receptor antagonist domperidone, but increased by the D2 receptor agonist bromocryptine and by the non-selective dopamine receptor antagonist chlorpromazine. The antinociception caused by cinnarizine was naloxone insenstive, but enhanced by propranolol, atropine and by yohimbine. The antinociceptive effect of cinnarizine was prevented by co-treatment with the adenosine receptor blocker theophylline or by the ATP-sensitive potassium channel (KATP blocker glibenclamide. Cinnarizine at 2.5 mg/kg reversed the baclofen-induced antinociception. Cinnarizine at 2.5 mg/kg reduced immobility time in the Porsolt’s forced-swimming test by 24%. Cinnarizine inhibited the paw oedema response to carrageenan and reduced gastric mucosal lesions caused by indomethacin in rats. It is suggested that cinnarizine exerts anti-infl ammatory, antinociceptive and gastric protective properties. The mechanism by which cinnarizine modulates pain transmission is likely to involve adenosine receptors and KATP channels.

  7. [Madness is Conforming to One's Own Norms, and No Others: Psychiatry in Post-war Quebec].

    Science.gov (United States)

    Perreault, Isabelle

    2015-01-01

    In the early 1950s, both the publication of the first Diagnostic and Statistical Manual (DSM-I) and the advent of psychopharmacology - particularly the development of chlorpromazine (Thorazine - RP4650) - set the stage for models of psychiatric thought, research and practice that remain dominant today. It was during this pivotal period, in 1955, that the Département de psychiatrie de l'Université de Montréal was founded by a cohort of young researchers newly arrived from well-known universities in France and the northeastern United States. This influential group quickly became staunch critics of the province's religion-based asylum system and lobbied for a government review that culminated into the 1962 Commission d'étude des hôpitaux psychiatriques (popularly known as the Bédard Report). What followed in Quebec between 1965 and 1975 was the secularization of psychiatric institutions and widespread deinstitutionalization. This paper illuminates cultural changes and intellectual shifts that have been overlooked in historical studies of post-war psychiatry by exploring the expansion of such "anti-psychiatry" schools of thought in Quebec in this period.

  8. The common marmoset (Callithrix jacchus) as a model for neuroleptic-induced acute dystonia.

    Science.gov (United States)

    Fukuoka, T; Nakano, M; Kohda, A; Okuno, Y; Matsuo, M

    1997-12-01

    To examine whether acute dystonia is induced by neuroleptic treatment, common marmosets were treated with haloperidol orally twice a week over 25 weeks until dystonic behavior was elicited. Movement disorders such as acute dystonia were observed 6 weeks after the initial treatment, and had appeared in all treated animals by 25 weeks. Once these movement disorders were induced, they consistently reappeared after further treatment with haloperidol, and once haloperidol dosing was discontinued, the episodes vanished. Then, various neuroleptic drugs (bromperidol, chlorpromazine, risperidone thioridazine, sulpiride, tiapride, and clozapine) or a nonneuroleptic drug (diazepam) were administered orally instead of haloperidol in the above animals. All the neuroleptic drugs except for clozapine elicited similar abnormal behavior, while diazepam failed to induce any dystonia. An anticholinergic drug, trihexyphenidyl, which is known to reduce acute dystonia in patients, was also given orally to the above haloperidol-sensitized animals, followed by further treatment with haloperidol 30 min later. This clearly suppressed the induction of dystonia by haloperidol. The similarity between these findings for haloperidol-pretreated common marmosets and clinical findings suggests that the present model is useful for predicting the potential of antipsychotics to induce acute dystonia in humans.

  9. Patch photopatch test at Manipal

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    Panja Arindrajit

    1994-01-01

    Full Text Available Patch and photopatch testing was performed on 55 patients with history of photosensitivity using Scandanavian photo patch test antigens obtained from Chemotechnique Diagnostics AB Sweden. The commonest reactions were seen to perfume mix 4 (21.0%, PABA 3 (15.78%, promethazine hydrochloride 3 (15.78%, chlorpromazine hydrochloride 3 (15.78%, balsam of peru 2 (10.52%, usnic acid, hexachlorophane, musk ambrette and 6 methyl coumarin showed 1 positive reaction each (5.26% suggesting either phototoxicity or photo sensitization. Patch and photo patch test positive reaction suggesting allergic sensitisation was seen to balsam of peru 3 (23.0% perfume mix 3 (23.0% promethazine hydrochloride 2 (15.3% and PABA, 6 methyl coumarin, tribromosalicylanilide, atranorin and wood mix showed positive reaction in one case each (7.69%. We conclude that photoxic or photo allergic reaction is a problem in India and patch photo patch test should be performed in all cases of idiopathic light eruptions to rule out photo sensitisation and in cases where photo sensitivity of exogenous origin is suspected.

  10. Deep venous thrombosis and pulmonary embolism in psychiatric settings

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    Els G. Van Neste

    2009-03-01

    Full Text Available Background and objectives: Deep venous thrombosis and pulmonary embolism are serious, possibly life-threatening events which are often ignored in psychiatric settings. This article investigates which psychiatric patients are at increased risk of developing a venous thromboembolism. To our knowledge we are the first to perform a literature review of clinical studies relating venous thrombosis and pulmonary embolism to psychotropic drugs and mental disorders. Methods: A Medline search for English studies using the appropriate search terms was performed. In addition, cross references of the relevant articles` literature references were considered. We withheld 12 observational studies, 29 case-reports and one review-article. Results: We found evidence that low potency antipsychotic drugs like chlorpromazine and thioridazine, and clozapine for treatment of resistant schizophrenia have an increased risk of venous thromboembolism. There is no evidence that antidepressants, benzodiazepines or mood stabilizers have a similar effect. Also psychiatric conditions like physical restraint, catatonia and neuroleptic malignant syndrome are related to a higher incidence of deep venous thrombosis. Conclusions: Limitations of the studies and hypotheses about underlying biological mechanisms are reviewed. The rationale for prophylactic measures is discussed and recommendations to prevent deep venous thrombosis and pulmonary embolism are given.

  11. Regulatory volume decrease in Leishmania mexicana: effect of anti-microtubule drugs

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    Francehuli Dagger

    2013-02-01

    Full Text Available The trypanosomatid cytoskeleton is responsible for the parasite's shape and it is modulated throughout the different stages of the parasite's life cycle. When parasites are exposed to media with reduced osmolarity, they initially swell, but subsequently undergo compensatory shrinking referred to as regulatory volume decrease (RVD. We studied the effects of anti-microtubule (Mt drugs on the proliferation of Leishmania mexicana promastigotes and their capacity to undergo RVD. All of the drugs tested exerted antiproliferative effects of varying magnitudes [ansamitocin P3 (AP3> trifluoperazine > taxol > rhizoxin > chlorpromazine]. No direct relationship was found between antiproliferative drug treatment and RVD. Similarly, Mt stability was not affected by drug treatment. Ansamitocin P3, which is effective at nanomolar concentrations, blocked amastigote-promastigote differentiation and was the only drug that impeded RVD, as measured by light dispersion. AP3 induced 2 kinetoplasts (Kt 1 nucleus cells that had numerous flagella-associated Kts throughout the cell. These results suggest that the dramatic morphological changes induced by AP3 alter the spatial organisation and directionality of the Mts that are necessary for the parasite's hypotonic stress-induced shape change, as well as its recovery.

  12. Mass spectrometric detection of short-lived drug metabolites generated in an electrochemical microfluidic chip.

    Science.gov (United States)

    van den Brink, Floris T G; Büter, Lars; Odijk, Mathieu; Olthuis, Wouter; Karst, Uwe; van den Berg, Albert

    2015-02-03

    The costs of drug development have been rising exponentially over the last six decades, making it essential to select drug candidates in the early drug discovery phases before proceeding to expensive clinical trials. Here, we present novel screening methods using an electrochemical chip coupled online to mass spectrometry (MS) or liquid chromatography (LC) and MS, to generate phase I and phase II drug metabolites and to demonstrate protein modification by reactive metabolites. The short transit time (∼4.5 s) between electrochemical oxidation and mass spectrometric detection, enabled by an integrated electrospray emitter, allows us to detect a short-lived radical metabolite of chlorpromazine which is too unstable to be detected using established test routines. In addition, a fast way to screen candidate drugs is established by recording real-time mass voltammograms, which allows one to identify the drug metabolites that are expected to be formed upon oxidation by applying a linear potential sweep and simultaneously detect oxidation products. Furthermore, detoxification of electrochemically generated reactive metabolites of paracetamol was mimicked by their adduct formation with the antioxidant glutathione. Finally, the potential toxicity of reactive metabolites can be investigated by the modification of proteins, which was demonstrated by modification of carbonic anhydrase I with electrochemically generated reactive metabolites of paracetamol. With this series of experiments, we demonstrate the potential of this electrochemical chip as a complementary tool for a variety of drug metabolism studies in the early stages of drug discovery.

  13. Approaches to the Development of Human Health Toxicity Values for Active Pharmaceutical Ingredients in the Environment.

    Science.gov (United States)

    Sorell, Tamara L

    2016-01-01

    Management of active pharmaceutical ingredients (API) in the environment is challenging because these substances represent a large and diverse group of compounds. Advanced wastewater treatment technologies that can remove API tend to be costly. Because of the potential resources required to address API in the environment, there is a need to establish environmental benchmarks that can serve as targets for treatment and release. To date, there are several different approaches that have been taken to derive human health toxicity values for API. These methods include traditional risk assessment approaches that calculate "safe" doses using experimental data and uncertainty (safety) factors; point of departure (POD), which starts from a therapeutic human dose and applies uncertainty factors; and threshold of toxicological concern (TTC), a generic approach that establishes threshold values across broad classes of chemicals based on chemical structure. To evaluate the use of these approaches, each of these methods was applied to three API commonly encountered in the environment: acetaminophen, caffeine, and chlorpromazine. The results indicate that the various methods of estimating toxicity values produce highly varying doses. Associated doses are well below typical intakes, or toxicity thresholds cannot be derived due to a lack of information. No uniform approach can be applied to establishing thresholds for multiple substances. Rather, an individualized approach will need to be applied to each target API.

  14. Development of a Medication Monitoring System for an Integrated Multidisciplinary Program of Assertive Community Treatment (IMPACT Team

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    Nicole B. Washington, DO, Assistant Professor

    2012-01-01

    Full Text Available Purpose: The primary goal was to improve medication management oversight for a severely mentally ill (SMI community-based population by developing a medication monitoring system based on current guidelines to optimize pharmacotherapy and minimize potential medication-related adverse effects. The secondary goal was improvement in coordination of care between healthcare providers. Methods: Guidelines for medication used for psychiatric indications were reviewed. A database of medication for psychiatric indications with monitoring recommendation was developed. Results: Medication regimens for 68 members of the Integrated Multidisciplinary Program of Assertive Community Treatment (IMPACT program qualified for review. Fourteen medications, carbamazepine, chlorpromazine, clozapine, fluphenazine and fluphenazine long-acting injections (LAI, haloperidol and haloperidol LAI, lithium, lurasidone, olanzapine, paliperidone and paliperidone LAI, perphenazine, quetiapine, risperidone and risperidone LAI, valproic acid/divalproex, and ziprasidone, were identified. In total, 111 medications are used on a monthly basis. Each member receives more than one medication qualifying for review. Additional monitoring parameters that were evaluated included changes in laboratory orders for members with insulin-dependent diabetes. Annual lipid panels were changed to every 6 months, if applicable. Conclusions and Future Directions: This medication monitoring program was developed to help ensure IMPACT members receive the most effective care and minimize potential medication-related adverse effects. The secondary goal was to improve coordination of care. Medication monitoring will be added as a continuous quality assurance measure. Lab results will be reviewed at least monthly. The medication monitoring program will be evaluated annually.

  15. Study on PEG-(NH4)2SO4 Aqueous Two-Phase System and Distribution Behavior of Drugs

    Institute of Scientific and Technical Information of China (English)

    LI, Lei(李蕾); HE, Chi-Yang(何池洋); LI, She-Hong(李社红); LIU, Feng(刘锋); SU, Shun(苏顺); KONG, Xiang-Xu(孔祥旭); LI, Na(李娜); LI, Ke-An(李克安)

    2004-01-01

    The distribution behavior of chlorpromazine hydrochloride (CPZ), procaine hydrochloride (PCN) and procaine amide hydrochloride (PCNA) in polyethylene glycol (PEG800 or PEG1500)-(NH4)2SO4 aqueous two-phase systems has been investigated. The result shows that the PEG-(NH4)2SO4 aqueous two-phase system has potential extraction capability in small molecular drug separation. In PEG800-(NH4)2SO4 system, the extraction efficiencies (E)of CPZ, PCN and PCNA amount to 92.8%, 74.5% and 74.4%, respectively, with the distribution coefficients (KD)being 25.7, 5.9 and 5.8, correspondingly. In PEG1500-(NH4)2SO4 system, the extraction efficiencies (E) of CPZ,PCN and PCNA are 93.7%, 71.3% and 63.2%, respectively, with distribution coefficients (KD) of 39.6, 6.6 and 5.0,correspondingly. Based on the study on ultraviolet and fluorescence spectra and also distribution behavior of the drugs in PEG-(NH4)2SO4 aqueous two-phase system, extraction mechanism was further proposed that both hydrogen bond and hydrophobic interaction are involved in extraction.

  16. Phytochemical Prospection and Modulation of Antibiotic Activity In Vitro by Lippia origanoides H.B.K. in Methicillin Resistant Staphylococcus aureus

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    Humberto Medeiros Barreto

    2014-01-01

    Full Text Available The Lippia origanoides H.B.K. ethanol extract (LOEE and hexane (LOHEX, dichloromethane (LODCM, and ethyl acetate (LOEA fractions were tested for their antimicrobial activity alone or in combination with antibiotics against a methicillin resistant Staphylococcus aureus (MRSA strain. The natural products did not show antimicrobial activity against multidrug resistant strain at the clinically significant concentrations tested. However, a modulatory effect in the antibacterial activity of the neomycin and amikacin was verified when LOEE, LOHEX and LODCM were added to the growth medium at subinhibitory concentrations. A similar modulation was found when the natural products were changed for chlorpromazine, an inhibitor of bacterial efflux pumps, suggesting the involvement of resistance mediated by efflux system in the MRSA tested. The fractions LOHEX and LODCM showed a modulatory activity bigger than their majority compounds (carvacrol, thymol, and naringenin, indicating that this activity is not due to their majority compounds only, but it is probably due to a synergism between their chemical components. These results indicate that L. origanoides H.B.K. can be a source of phytochemicals able to modify the phenotype of resistance to aminoglycosides in MRSA.

  17. Fungicide efflux and the MgMFS1 transporter contribute to the multidrug resistance phenotype in Zymoseptoria tritici field isolates.

    Science.gov (United States)

    Omrane, Selim; Sghyer, Hind; Audéon, Colette; Lanen, Catherine; Duplaix, Clémentine; Walker, Anne-Sophie; Fillinger, Sabine

    2015-08-01

    Septoria leaf blotch is mainly controlled by fungicides. Zymoseptoria tritici, which is responsible for this disease, displays strong adaptive capacity to fungicide challenge. It developed resistance to most fungicides due to target site modifications. Recently, isolated strains showed cross-resistance to fungicides with unrelated modes of action, suggesting a resistance mechanism known as multidrug resistance (MDR). We show enhanced prochloraz efflux, sensitive to the modulators amitryptiline and chlorpromazine, for two Z. tritici strains, displaying an MDR phenotype in addition to the genotypes CYP51(I381V Y461H) or CYP51(I381V ΔY459/) (G460) , respectively, hereafter named MDR6 and MDR7. Efflux was also inhibited by verapamil in the MDR7 strain. RNA sequencing lead to the identification of several transporter genes overexpressed in both MDR strains. The expression of the MgMFS1 gene was the strongest and constitutively high in MDR field strains. Its inactivation in the MDR6 strain abolished resistance to fungicides with different modes of action supporting its involvement in MDR in Z. tritici. A 519 bp insert in the MgMFS1 promoter was detected in half of the tested MDR field strains, but absent from sensitive field strains, suggesting that the insert is correlated with the observed MDR phenotype. Besides MgMfs1, other transporters and mutations may be involved in MDR in Z. tritici.

  18. Flow Injection Analysis with Chemiluminescence detection for Determination of Two Phenothiazines

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    Hijran S. Jabbar

    2015-03-01

    Full Text Available A new flow injection analysis-chemiluminescence (FIA-CL method for determination of two phenothiazine derivatives "chlorpromazine hydrochloride (CPZ and promethazine hydrochloride (PTZ" described. The redox reaction between Fe(III and phenothiazines was taken as a base of this new method. A well-defined volume of CPZ or PTZ and luminol solution is injected simultaneously by means of two injection valves in accordance with the merging zone principle. Calibration graphs were constructed in the range of (0.05 – 1.4μg/ml for CPZ with correlation coefficient of (0.9972 and in the range of (0.5 – 40μg/ml for PTZ with correlation coefficient of (0.9978. The precision and accuracy of the method were checked by calculation of relative standard deviation (RSD and relative error percentage (%E for two different levels of concentrations. The method was relatively free from common excipients and it is applied successfully for the determination of CPZ and PTZ in pharmaceutical formulations. The results obtained were in good agreement with those obtained by a reference method in British Pharmacopoeia.

  19. Regional cerebral blood flow in schizophrenics

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    Uchino, J.; Ohta, Y.; Nakane, Y.; Mori, H.; Hirota, N.; Yonekura, M.

    1987-01-01

    The present study on schizophrenics dealt with the relationship of regional cerebral blood flow (rCBF) to age, disease duration, and treatment length with chlorpromazine hydrochloride (CPZ). Regional cerebral blood flow in 28 cerebral regions of interest was measured by iv injection of /sup 133/X in 54 schizophrenic patients and 39 healthy volunteers. Neither age nor dosage of CPZ significantly influenced rCBF. All patients, including 11 treated for a short period of time (6 months or less), were characterized by having a decreased rCBF over the whole cerebrum. Thirty-four patients treated for a long period of time (2 years or more) had a varied rCBF distribution in the left hemisphere, with the most predominant feature being the decrease in rCBF in the frontal lobe (i.e., hypofrontality); however, there was no linear correlation between rCBF and disease duration. A decreased rCBE in the right occipital region was seen in patients with paranoid schizophrenia, suggesting that manifestations of symptoms may depend on disturbed regions. These results suggest that cerebral dysfunction in schizophrenic patients may not be restricted to the frontal lobe, but cover the whole cerebrum, and that nonuniform dysfunction in various regions of the cerebrum, including the frontal lobe, may be involved in manifestations of symptoms.

  20. CNS Depressant and Antiepileptic Activities of the Methanol Extract of the Leaves of Ipomoea Aquatica Forsk

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    Dhanasekaran Sivaraman

    2010-01-01

    Full Text Available The central nervous system (CNS depressant and antiepileptic activities of the methanol extract of the leaves of Ipomoea aquatica Forsk (IAF were investigated on various animal models including pentobarbitone sleeping time and hole-board exploratory behavior for sedation tests and strychnine, picrotoxin and pentylenetetrazole-induced convulsions in mice. IAF (200 and 400 mg/kg, p.o., like chlorpromazine HCl (1 mg/kg, i.m., produced a dose-dependent prolongation of pentobarbitone sleeping time and suppression of exploratory behavior. IAF (200 and 400 mg/kg produced dose-dependent and significant increases in onset to clonic and tonic convulsions and at 400 mg/kg, showed complete protection against seizures induced by strychnine and picrotoxin but not with pentylenetetrazole. Acute oral toxicity test, up to 14 days, did not produce any visible signs of toxicity. These results suggest that potentially antiepileptic compounds are present in leaf extract of IAF that deserve the study of their identity and mechanism of action.

  1. Adenylate cyclase toxin promotes internalisation of integrins and raft components and decreases macrophage adhesion capacity.

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    César Martín

    Full Text Available Bordetella pertussis, the bacterium that causes whooping cough, secretes an adenylate cyclase toxin (ACT that must be post-translationally palmitoylated in the bacterium cytosol to be active. The toxin targets phagocytes expressing the CD11b/CD18 integrin receptor. It delivers a catalytic adenylate cyclase domain into the target cell cytosol producing a rapid increase of intracellular cAMP concentration that suppresses bactericidal functions of the phagocyte. ACT also induces calcium fluxes into target cells. Biochemical, biophysical and cell biology approaches have been applied here to show evidence that ACT and integrin molecules, along with other raft components, are rapidly internalized by the macrophages in a toxin-induced calcium rise-dependent process. The toxin-triggered internalisation events occur through two different routes of entry, chlorpromazine-sensitive receptor-mediated endocytosis and clathrin-independent internalisation, maybe acting in parallel. ACT locates into raft-like domains, and is internalised, also in cells devoid of receptor. Altogether our results suggest that adenylate cyclase toxin, and maybe other homologous pathogenic toxins from the RTX (Repeats in Toxin family to which ACT belongs, may be endowed with an intrinsic capacity to, directly and efficiently, insert into raft-like domains, promoting there its multiple activities. One direct consequence of the integrin removal from the cell surface of the macrophages is the hampering of their adhesion ability, a fundamental property in the immune response of the leukocytes that could be instrumental in the pathogenesis of Bordetella pertussis.

  2. Role of Phenothiazines and Structurally Similar Compounds of Plant Origin in the Fight against Infections by Drug Resistant Bacteria

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    Leonard Amaral

    2013-02-01

    Full Text Available Phenothiazines have their primary effects on the plasma membranes of prokaryotes and eukaryotes. Among the components of the prokaryotic plasma membrane affected are efflux pumps, their energy sources and energy providing enzymes, such as ATPase, and genes that regulate and code for the permeability aspect of a bacterium. The response of multidrug and extensively drug resistant tuberculosis to phenothiazines shows an alternative therapy for the treatment of these dreaded diseases, which are claiming more and more lives every year throughout the world. Many phenothiazines have shown synergistic activity with several antibiotics thereby lowering the doses of antibiotics administered to patients suffering from specific bacterial infections. Trimeprazine is synergistic with trimethoprim. Flupenthixol (Fp has been found to be synergistic with penicillin and chlorpromazine (CPZ; in addition, some antibiotics are also synergistic. Along with the antibacterial action described in this review, many phenothiazines possess plasmid curing activities, which render the bacterial carrier of the plasmid sensitive to antibiotics. Thus, simultaneous applications of a phenothiazine like TZ would not only act as an additional antibacterial agent but also would help to eliminate drug resistant plasmid from the infectious bacterial cells.

  3. Prototypical antipsychotic drugs protect hippocampal neuronal cultures against cell death induced by growth medium deprivation

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    Williams Sylvain

    2006-03-01

    Full Text Available Abstract Background Several clinical studies suggested that antipsychotic-based medications could ameliorate cognitive functions impaired in certain schizophrenic patients. Accordingly, we investigated the effects of various dopaminergic receptor antagonists – including atypical antipsychotics that are prescribed for the treatment of schizophrenia – in a model of toxicity using cultured hippocampal neurons, the hippocampus being a region of particular relevance to cognition. Results Hippocampal cell death induced by deprivation of growth medium constituents was strongly blocked by drugs including antipsychotics (10-10-10-6 M that display nM affinities for D2 and/or D4 receptors (clozapine, haloperidol, (±-sulpiride, domperidone, clozapine, risperidone, chlorpromazine, (+-butaclamol and L-741,742. These effects were shared by some caspases inhibitors and were not accompanied by inhibition of reactive oxygen species. In contrast, (--raclopride and remoxipride, two drugs that preferentially bind D2 over D4 receptors were ineffective, as well as the selective D3 receptor antagonist U 99194. Interestingly, (--raclopride (10-6 M was able to block the neuroprotective effect of the atypical antipsychotic clozapine (10-6 M. Conclusion Taken together, these data suggest that D2-like receptors, particularly the D4 subtype, mediate the neuroprotective effects of antipsychotic drugs possibly through a ROS-independent, caspase-dependent mechanism.

  4. Levodopa-induced dyskinesias in Parkinson's disease: clinical and pharmacological classification.

    Science.gov (United States)

    Luquin, M R; Scipioni, O; Vaamonde, J; Gershanik, O; Obeso, J A

    1992-01-01

    Levodopa-induced dyskinesias (LID) in Parkinson's disease (PD) may be classified into three main categories: "On" dyskinesias, diphasic dyskinesias (DD), and "off" periods. The study of 168 parkinsonian patients showed that about half (n = 84) showed one pattern of LID only. A combination of two was present in 68, and 16 had the three presentation patterns. A fairly good correlation between type of dyskinesia and presentation pattern was established. Chorea, myoclonus, and dystonic movements occurred during the "on" period. Dystonic postures, particularly affecting the feet, were mainly present in the "off" period, but a few patients had a diphasic presentation. Repetitive stereotyped movements of the lower limbs always corresponded to DD. Acute pharmacological tests using dopamine agonists (subcutaneous apomorphine 3-8 mg; intravenous lisuride 0.1-0.15 mg) and dopamine antagonists (intravenous sulpiride 200-400 mg and intravenous chlorpromazine 25 mg) were performed in 40 patients. Dopamine agonists enhanced "on" dyskinesias and markedly reduced or abolished "off" period dystonia and DD. Dopamine antagonists reduced all types of LID but usually aggravated parkinsonism. These clinical and pharmacological results indicate that LID in PD are a heterogeneous phenomenon difficult to explain on the basis of a single pathophysiological mechanism.

  5. Clinical Practice Associated with a Switch from and to Ziprasidone during Routine Inpatient Treatment of Patients with Schizophrenia

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    Matthias J. Müller

    2011-01-01

    Full Text Available Ziprasidone (ZIP shows a low propensity for metabolic side effects but can prolong QTc time. It is unclear how these features translate into clinical reality. Charts of inpatients with schizophrenia and switched from (ZIP−,n=27 or to ZIP (ZIP+,n=24 were reviewed. Clinical data including documented switch reasons were anonymously analyzed. Comorbidity, body mass index (BMI at admission, illness severity, side effects, illness duration, and length of stay were comparable in both groups. About 2/3 of ZIP+ were women (1/3 of ZIP−,P=0.035; ZIP+ patients were younger (P=0.017, had higher BMI values (P=0.042, and received higher chlorpromazine equivalents before switch (P=0.004 whereas ZIP doses were comparable (136 versus 141 mg/d. More patients in ZIP− versus ZIP+ were switched because of previous weight gain (P=0.006 and depression (P=0.085 whereas single reasons for ZIP− versus ZIP+ were mainly persisting positive symptoms (P=0.089 and patients' choice (P=0.10. The results of the naturalistic study corroborate controlled trials.

  6. Decrease in temporal gyrus gray matter volume in first-episode, early onset schizophrenia: an MRI study.

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    Jinsong Tang

    Full Text Available BACKGROUND: Loss of gray matter has been previously found in early-onset schizophrenic patients. However, there are no consistent findings between studies due to different methods used to measure grey matter volume/density and influences of confounding factors. METHODS: The volume of gray matter (GM was measured in 29 first episode early-onset schizophrenia (EOS and 34 well-matched healthy controls by using voxel-based morphometry (VBM. Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS. The correlations between the GM volume and PANSS scores, age of psychosis onset, duration of psychosis, and chlorpromazine (CPZ equivalent value were investigated. RESULTS: Relative to healthy subjects, the patients with first episode EOS showed significantly lower GM volume in the left middle and superior temporal gyrus. The loss of GM volume negatively correlated with PANSS-positive symptoms (p = 0.002, but not with PANSS-negative symptoms, PANSS-general psychopathology, and PANSS-total score. No significant correlation was found between GM volume and age of psychosis onset, duration of psychosis, and CPZ equivalent value. CONCLUSION: Patients with first episode EOS have evidence of reduced GM in the left middle and superior temporal gyrus. Structural abnormalities in the left middle and superior temporal gyrus may contribute to the pathophysiology of schizophrenia.

  7. New approaches to the management of schizophrenia: focus on aberrant hippocampal drive of dopamine pathways

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    Perez SM

    2014-07-01

    Full Text Available Stephanie M Perez, Daniel J LodgeDepartment of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center, San Antonio, TX, USAAbstract: Schizophrenia is a disease affecting up to 1% of the population. Current therapies are based on the efficacy of chlorpromazine, discovered over 50 years ago. These drugs block dopamine D2-like receptors and are effective at primarily treating positive symptoms in a subset of patients. Unfortunately, current therapies are far from adequate, and novel treatments require a better understanding of disease pathophysiology. Here we review the dopamine, gamma-aminobutyric acid (GABA, and glutamate hypotheses of schizophrenia and describe a pathway whereby a loss of inhibitory signaling in ventral regions of the hippocampus actually drives a dopamine hyperfunction. Moreover, we discuss novel therapeutic approaches aimed at attenuating ventral hippocampal activity in a preclinical model of schizophrenia, namely the MAM GD17 rat. Specifically, pharmacological (allosteric modulators of the α5 GABAA receptor, neurosurgical (deep brain stimulation, and cell-based (GABAergic precursor transplants therapies are discussed. By better understanding the underlying circuit level dysfunctions in schizophrenia, novel treatments can be advanced that may provide better efficacy and a superior side effect profile to conventional antipsychotic medications.Keywords: dopamine, GABA, glutamate, schizophrenia, hippocampus, MAM rat

  8. [New findings on the diagnosis and therapy of prion diseases].

    Science.gov (United States)

    Begić, Lejla; Mulaomerović, Adaleta; Berbić, Selma; Zigić, Zlata

    2002-01-01

    Spongiform encephalopathies are the fatal diseases, that affect the brain tissue of mammals. They are caused by a conformational changed prion protein. There is no adequate diagnostic test for in vivo identification of prion protein. Disease can be diagnosed only by clinical sings and EEG in new variant of Creutzfeldt-Jakob disease. Post mortem, histopathological examination of brain tissue reveals spongiform changes and immunohistochemistry detects disease-related prion protein. Appropriate diagnostic in vivo tests are not developed yet; therefore extensive researches are ongoing aimed to introduce such methods. This review describes a few promising experimental methods, which may develop into diagnostic tests in the future: detection of prions in urine samples, PMCA (protein misfolding cyclic amplification), DATAS (differential analysis of transcripts with alternative splicing), SELEX (in vitro selection), detection of prions in tonsils and detection of copper and manganese dysbalance in tissues. Current therapy strategy is based on testing of some known drugs (quinacrine, chlorpromazine), and antioxidant and antibody treatments. The detection of NSE (neuron-specific enolase) and cholesterol in meat products reveals the presence of brain and spinal cord tissue. The spreading of spongiform encephalopathies can be diminished by utilising the adequate in vivo diagnostic tests, effective therapy strategy and preventive steps.

  9. On the role of calcium in indole-3-acetic acid movement and graviresponse in etiolated pea epicotyls

    Science.gov (United States)

    Migliaccio, F.; Galston, A. W.

    1989-01-01

    To determine whether Ca2+ plays a special role in the early graviresponse of shoots, as has been reported for roots, we treated etiolated pea epicotyls with substances known to antagonize Ca2+ (La3+), to remove Ca2+ from the wall (spermidine, EGTA), to inhibit calmodulin mediated reactions (chlorpromazine), or to inhibit IAA transport (TIBA). We studied the effect of these substances on IAA and Ca2+ uptake into 7 mm long subapical 3rd internode etiolated pea epicotyl sections and pea leaf protoplasts, on pea epicotyl growth, and graviresponse and on lateral IAA redistribution during gravistimulation. Our results support the view that adequate Ca2+ in the apoplast is required for normal IAA uptake, transport and graviresponse. Experiments with protoplasts indicate that Ca2+ may be controlling a labile membrane porter, possibly located on the external surface of cell membrane, while inhibitor experiments suggest that calmodulin is also implicated in both the movement of IAA and graviresponse. Since a major transfer of Ca2+ through free space during graviresponse has not yet been demonstrated, and since inhibition of calcium channels does not affect IAA redistribution (Migliaccio and Galston, 1987, Plant Physiology 85:542), we conclude that no clear evidence links prior Ca2+ movement with IAA redistribution during graviresponse in stems.

  10. Partial purification and characterization of a Ca(2+)-dependent protein kinase from pea nuclei

    Science.gov (United States)

    Li, H.; Dauwalder, M.; Roux, S. J.

    1991-01-01

    Almost all the Ca(2+)-dependent protein kinase activity in nuclei purified from etiolated pea (Pisum sativum, L.) plumules is present in a single enzyme that can be extracted from chromatin by 0.3 molar NaCl. This protein kinase can be further purified 80,000-fold by salt fractionation and high performance liquid chromatography, after which it has a high specific activity of about 100 picomoles per minute per microgram in the presence of Ca2+ and reaches half-maximal activation at about 3 x 10(-7) molar free Ca2+, without calmodulin. It is a monomer with a molecular weight near 90,000. It can efficiently use histone III-S, ribosomal S6 protein, and casein as artificial substrates, but it phosphorylates phosvitin only weakly. Its Ca(2+)-dependent kinase activity is half-maximally inhibited by 0.1 millimolar chlorpromazine, by 35 nanomolar K-252a and by 7 nanomolar staurosporine. It is insensitive to sphingosine, an inhibitor of protein kinase C, and to basic polypeptides that block other Ca(2+)-dependent protein kinases. It is not stimulated by exogenous phospholipids or fatty acids. In intact isolated pea nuclei it preferentially phosphorylates several chromatin-associated proteins, with the most phosphorylated protein band being near the same molecular weight (43,000) as a nuclear protein substrate whose phosphorylation has been reported to be stimulated by phytochrome in a calcium-dependent fashion.

  11. The 5-HT hypothesis of schizophrenia.

    Science.gov (United States)

    Akhondzadeh, S

    2001-03-01

    Schizophrenia is a serious psychiatric illness that is responsible for a substantial proportion of mental illness worldwide. Symptoms include hallucination, delusions, thought disorder and negative symptoms, including poverty of thought and emotion, and social withdrawal. Early theories of schizophrenia implicated disturbed serotonin (5-HT) neurotransmission, but these were largely overshadowed by the dopamine theory of schizophrenia, which became established after the introduction of chlorpromazine. However, the importance of 5-HT in CNS function is once again being recognized. The ability of antipsychotic drugs to diminish positive symptoms has been correlated with their ability to block dopamine D(2) receptors, although negative symptoms are not as effectively treated by typical neuroleptics. There is increasing interest in the correlation between negative symptoms of schizophrenia and 5-HT(2) receptors. The rationale for these studies is the hypothesis that abnormal neurotransmission at 5-HT(2) receptors may be involved in the pathophysiology of schizophrenia. This review highlights recent pharmacological and clinical advances in the understanding of the potential use of serotonin 5-HT(2) receptor antagonists in the treatment of schizophrenia.

  12. [Antipsychotic medication change and reduction of rehospitalization in clients of ACT-J].

    Science.gov (United States)

    Satake, Naoko

    2011-01-01

    Polypharmacy and high-dose treatment of antipsychotics have been major problems in Japanese mental health. Although importance of simplifying prescription has been recognized, polypharmacy and high-dose medication especially for Schizophrenia remains prevalent. It's considered that psycho-social approach; for example, improvement of coping skills and social support such as care management can make reform of treatment efficiently and also improve patient's QOL. In ACT service, Medication, rehabilitation and social support work closely together and it could make prescription change even for SMI patients. Low-dose medication leads improvement of cognitive function and furthermore social activity. Considering the higher dose of antipsychotics prescribed concurrency in Japan, it's important to evaluate the change in medication for patients of ACT in Japan. We did one year follow up study about prescription change for 52 patients who have used ACT program at ACT-J team for more than one year at the end of December 2009. It was found that the dosage antipsychotics significantly decreased from 1131.3 mg converted to the relative potency equivalent of 100 mg of Chlorpromazine (CPZ eq), to 731.3 mg (CPZ eq) over the course of the 12 months. But there was no significant change about polyphamacy. Also it could be possible to reduce rehospitalization under the ACT program. Because recovery model could make improve not only drop out from psychiatric service, but user's dependency for hospitalization.

  13. Editor's choice

    Directory of Open Access Journals (Sweden)

    Pinder RM

    2012-07-01

    Full Text Available Roger M PinderEditor-In-Chief, Neuropsychiatric Disease and TreatmentSchizophrenia remains one of the most debilitating and intractable illnesses in psychiatry. Despite the availability of effective drug treatment since the beginning of the psychopharmacological era in the early 1960s with the introduction of the first antipsychotic chlorpromazine, the subsequent development of second generation or atypical antipsychotics, and the effectiveness of certain types of psychotherapy, many patients are unresponsive and remain unwell for several years or relapse after apparent response. Only clozapine has proven efficacy in treatment-resistant schizophrenia, but many patients still do not respond. Polypharmacy is common, with many physicians choosing to augment rather than switch medications. Schizophrenia may be in part a neurodevelopmental disorder and involve changes in brain structure, and credence has been given to the idea that the prodromal phase, before overt symptoms have appeared, should already have been addressed with aggressive treatment. Various aspects of schizophrenia and its treatment, as well as the associated use of antipsychotic drugs in the treatment of the manic phase of bipolar disorder and Tourette syndrome, have been covered in the pages of Neuropsychiatric Disease and Treatment during the first half of 2012.

  14. The effects of interleukin-10 on mouse photoallergic contact dermatitis%白介素-10对小鼠光变态反应性接触性皮炎的影响

    Institute of Scientific and Technical Information of China (English)

    刘藕根; 何黎

    2003-01-01

    目的:探讨白介素(IL)-10在光变态反应性接触性皮炎(photoallergic contact dermatitis,PACD)发病中的作用.方法:选用BALB/C纯系雌性小鼠建立氯丙嗪(chlorpromazine,CPZ)所致的PACD模型,采用腹腔或皮内注射重组小鼠IL-10的方法,于激发48 h后检测小鼠耳肿度,局部皮损活检行苏木精-伊红染色,计数单一核细胞浸润数.结果:小鼠皮内和腹腔注射重组小鼠IL-10后,耳肿度值、单一核细胞浸润数均较阳性对照组(单纯的PACD模型)低.结论:小鼠体内IL-10对CPZ诱导的PACD的光诱导和光激发阶段均起抑制作用.

  15. Evaluation of a liver micronucleus assay in young rats (III): a study using nine hepatotoxicants by the Collaborative Study Group for the Micronucleus Test (CSGMT)/Japanese Environmental Mutagen Society (JEMS)-Mammalian Mutagenicity Study Group (MMS).

    Science.gov (United States)

    Takasawa, Hironao; Suzuki, Hiroshi; Ogawa, Izumi; Shimada, Yasushi; Kobayashi, Kazuo; Terashima, Yukari; Matsumoto, Hirotaka; Aruga, Chinami; Oshida, Keiyu; Ohta, Ryo; Imamura, Tadashi; Miyazaki, Atsushi; Kawabata, Masayoshi; Minowa, Shigenori; Hayashi, Makoto

    2010-04-30

    We have been investigating a liver micronucleus assay to detect genotoxic chemicals using young rats for several years, and had established its advantages with respect to using autonomous proliferation of young rat hepatocytes. Nine chemicals known to induce hepatotoxic effects such as necrosis (2,6-dinitrotolune, bromobenzene, isoniazid, phenacetin, allyl alcohol and thioacetamide), cholestasis (chlorpromazine hydrochloride and alpha-naphthyl isothiocyanate) and oxidative stress (clofibrate) were selected for this study. A liver micronucleus assay was conducted in 4-week-old male F344 rats using two or three dose levels of test chemicals given orally by gavage to evaluate the compound's ability to induce micronucleated hepatocytes. Several of these test chemicals were additionally examined in a peripheral blood micronucleus assay conducted concurrently and in the same animals. The genotoxic rodent hepatocarcinogen, 2,6-dinitrotoluene showed a positive result in the liver micronucleus assay, but the nongenotoxic hepatocarcinogens, clofibrate and thioacetamide gave negative responses. Bromobenzene, known to produce DNA adducts but is noncarcinogenic in rodent liver, was judged equivocal in this assay. alpha-Naphthyl isothiocyanate is noncarcinogenic and showed negative response in the liver. The other four chemicals, known to be either noncarcinogenic or carcinogenic in other non-liver target organs, showed negative results in the liver micronucleus assay. Based on the results in the present study and previous report described above, it was concluded that this technique is able to effectively predict genotoxic rodent hepatocarcinogenicity, and does not give false positives due to hepatotoxicity.

  16. NOVEL ATYPICAL ANTIPSYCHOTIC AGENTS

    Directory of Open Access Journals (Sweden)

    Vijay Vinay

    2011-05-01

    Full Text Available Antipsychotics are a group of drugs commonly but not exclusively used to treat psychosis. Antipsychotic agents are grouped in two categories: Typical and Atypical antipsychotics. The first antipsychotic was chlorpromazine, which was developed as a surgical anesthetic. The first atypical anti-psychotic medication, clozapine, was discovered in the 1950s, and introduced in clinical practice in the 1970s. Both typical and atypical antipsychotics are effective in reducing positive and negative symptoms of schizophrenia. Blockade of D2 receptor in mesolimbic pathway is responsible for antipsychotic action. Typical antipsychotics are not particularly selective and also block Dopamine receptors in the mesocortical pathway, tuberoinfundibular pathway, and the nigrostriatal pathway. Blocking D2 receptors in these other pathways is thought to produce some of the unwanted side effects. Atypical antipsychotics differ from typical psychotics in their "limbic-specific" dopamine type 2 (D2-receptor binding and high ratio of serotonin type 2 (5-HT2-receptor binding to D2. Atypical antipsychotics are associated with a decreased capacity to cause EPSs, TD, narcoleptic malignant syndrome, and hyperprolactinemia. Atypical antipsychotic agents were developed in response to problems with typical agents, including lack of efficacy in some patients, lack of improvement in negative symptoms, and troublesome adverse effects, especially extrapyramidal symptoms (EPSs and tardive dyskinesia (TD.

  17. Psychotropic drug effects on gene transcriptomics relevant to Alzheimer disease.

    Science.gov (United States)

    Lauterbach, Edward C

    2012-01-01

    Psychotropics are widely prescribed in Alzheimer disease (AD) without regard to their pathobiological effects. Results summarize a comprehensive survey of psychotropic effects on messenger ribonucleic acid (mRNA) expression for 52 genes linked to AD. Pending future investigations, current data indicate that atypical antipsychotics, lithium, and fluoxetine reduce AD risk, whereas other drug classes promote risk. Risk may be attenuated by antipsychotics and lithium (down-regulate TNF), atypical antipsychotics (down-regulate TF), risperidone (down-regulates IL1B), olanzapine (up-regulates TFAM, down-regulates PRNP), fluoxetine (up-regulates CLU, SORCS1, NEDD9, GRN, and ECE1), and lithium coadministered with antipsychotics (down-regulates IL1B). Risk may be enhanced by neuroleptics (up-regulate TF), haloperidol (up-regulates IL1B and PION), olanzapine (down-regulates THRA and PRNP, up-regulates IL1A), and chlorpromazine, imipramine, maprotiline, fluvoxamine, and diazepam (up-regulate IL1B). There were no results for dextromethorphan-plus-quinidine. Fluoxetine effects on CLU, NEDD9, and GRN were statistically robust. Drug effects on specific variants, polymorphisms, genotypes, and other genes (CCR2, TF, and PRNP) are detailed. Translational AD risk applications and their limitations related to specific genes, mutations, variants, polymorphisms, genotypes, brain site, sex, clinical population, AD stage, and other factors are discussed. This report provides an initial summary and framework to understand the potential impact of psychotropic drugs on AD-relevant genes.

  18. Ca2+-Calmodulin is Involved in Betacyanin Accumulation Induced by Dark in C3 Halophyte Suaeda salsa

    Institute of Scientific and Technical Information of China (English)

    Chang-Quan Wang; Bao-Shan Wang

    2007-01-01

    The C3 halophyte Suaeda salsa was used to investigate the roles of Ca2+, Ca2+ channels, and calmodulin (CaM) in betacyanin metabolism. Seeds of S. salsa were cultured in both the dark and light for 3 days. The fresh weight and betacyanin content were much higher in S. salsa seedlings formed in the dark than in seedlings formed in the light. The addition of Ca2+ to the half-strength MS nutrient solution promoted betacyanin accumulation in the dark, whereas Ca2+ depletion by EGTA suppressed the dark-induced betacyanin accumulation in shoots of S. salsa. The Ca2+ channel blocker LaCl3 also inhibited dark-induced betacyanin accumulation. The highest activity of CaM and the maximum betacyanin content decreased by 51% and 45%, respectively, in shoots of S. salsa seedlings treated with the potent CaM antagonist chlorpromazine in the dark. Furthermore, the other CaM antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) also inhibited the activity of CaM and dark-dependent betacyanin accumulation, whereas its less active structural analog N-(6-aminohexyl)-1-naphthalenesulfonamide (W-5) had little effect on the responses to dark of S. salsa seedlings. These results suggest that Ca2+, Ca2+-regulated ion channels, and CaM play an important role in dark-induced betacyanin accumulation in the shoots of the C3 halophyte S. salsa.

  19. Interaction of solutions containing phenothiazines exposed to laser radiation with materials surfaces, in view of biomedical applications.

    Science.gov (United States)

    Simon, Agota; Alexandru, Tatiana; Boni, Mihai; Damian, Victor; Stoicu, Alexandru; Dutschk, Victoria; Pascu, Mihail Lucian

    2014-11-20

    Phenothiazine drugs - chlorpromazine (CPZ), promazine (PZ) and promethazine (PMZ) - were exposed to 266 nm (fourth harmonic of the Nd:YAG pulsed laser radiation) in order to be modified at molecular level and to produce an enhancement of their antibacterial activity. The irradiated samples were analysed by several methods: pH and surface tension measurements, UV-vis-NIR absorption spectroscopy, laser induced fluorescence and thin layer chromatography. The purpose of these investigations was to study and describe the modified properties of the medicines to further investigate their specific interactions with materials such as cotton, polyester and Parafilm M as a model smooth surface. The textile materials may be impregnated with phenothiazines drug solutions exposed to laser radiation in order to be used in treatments applied on the surface of the organism. Some of the phenothiazines solutions exposed prolonged time intervals to laser radiation have much better activity against several bacteria. Therefore, in the paper, it is reported the wetting behaviour of CPZ, PZ and PMZ solutions, irradiated for time intervals between 1 and 240 min, on the surfaces of the three textures in order to draw a conclusion about their wettability as a function of time.

  20. Serendipity and psychopharmacology.

    Science.gov (United States)

    Howland, Robert H

    2010-10-01

    This article describes several examples where the development of drugs and devices for use in psychiatry followed from initial serendipitous observations. The potential psychotropic properties of chlorpromazine (Thorazine(®)) were first noted in surgical patients when the drug was being investigated as a potentiator of anesthesia. Similar findings were noted with iproniazid (Marsilid(®)), developed for the treatment of tuberculosis, and the drug was later released for clinical use as an antidepressant agent. The development of meprobamate (Miltown(®)), an approved treatment for anxiety, evolved from initial efforts to find a chemical that would inhibit the enzymatic destruction of the antibiotic drug penicillin. The psychiatric uses of lamotrigine (Lamictal(®)) and vagus nerve stimulation were prompted by initial observations that epilepsy patients receiving these treatments had positive mood effects. Nurses should be familiar with the concept of serendipity, as they often are in the best position to observe, record, and report on unexpected clinical effects in patients taking any kind of prescription or nonprescription medication.

  1. The role of serendipity in the discovery of the clinical effects of psychotropic drugs: beyond of the myth.

    Science.gov (United States)

    López-Muñoz, Francisco; Baumeister, Alan A; Hawkins, Mike F; Alamo, Cecilio

    2012-01-01

    The serendipity is the faculty for making a discovery through a combination of accident and sagacity. In psychopharmacology, the serendipity played a key role in the discovery of many psychotropic drugs, although there are marked disputes in this regard, possibly due to semantic differences in relation to the meaning of this term. We have implemented an operational definition of serendipity based on the discovery of something unexpected or not sought intentionally, irrespective of the systematic process leading to the accidental observation. The present paper analyses some representative examples of discoveries in the field of psychopharmacology according to different serendipitous intervention patterns. Following this approach there would be four different imputability patterns: pure serendipitous discoveries (valproic acid/valproate); serendipitous observation leading to a non-serendipitous discoveries (imipramine); non-serendipitous discoveries secondarily associated with serendipitous observation (barbiturates); non-serendipitous discoveries (haloperidol). We can conclude that pure serendipitous discoveries in this field are not very frequent, most common being a mixed pattern; an initial serendipitous observation which leads to a non-serendipitous discovery of clinical utility. This is the case of imipramine, lithium salts, chlorpromazine or meprobamate.

  2. Decrease in olfactory and taste receptor expression in the dorsolateral prefrontal cortex in chronic schizophrenia.

    Science.gov (United States)

    Ansoleaga, Belén; Garcia-Esparcia, Paula; Pinacho, Raquel; Haro, Josep Maria; Ramos, Belén; Ferrer, Isidre

    2015-01-01

    We have recently identified up- or down-regulation of the olfactory (OR) and taste (TASR) chemoreceptors in the human cortex in several neurodegenerative diseases, raising the possibility of a general deregulation of these genes in neuropsychiatric disorders. In this study, we explore the possible deregulation of OR and TASR gene expression in the dorsolateral prefrontal cortex in schizophrenia. We used quantitative polymerase chain reaction on extracts from postmortem dorsolateral prefrontal cortex of subjects with chronic schizophrenia (n = 15) compared to control individuals (n = 14). Negative symptoms were evaluated premortem by the Positive and Negative Syndrome and the Clinical Global Impression Schizophrenia Scales. We report that ORs and TASRs are deregulated in the dorsolateral prefrontal cortex in schizophrenia. Seven out of eleven ORs and four out of six TASRs were down-regulated in schizophrenia, the most prominent changes of which were found in genes from the 11p15.4 locus. The expression did not associate with negative symptom clinical scores or the duration of the illness. However, most ORs and all TASRs inversely associated with the daily chlorpromazine dose. This study identifies for the first time a decrease in brain ORs and TASRs in schizophrenia, a neuropsychiatric disease not linked to abnormal protein aggregates, suggesting that the deregulation of these receptors is associated with altered cognition of these disorders. In addition, the influence of antipsychotics on the expression of ORs and TASRs in schizophrenia suggests that these receptors could be involved in the mechanism of action or side effects of antipsychotics.

  3. Cognitive effects of antipsychotic dosage and polypharmacy: a study with the BACS in patients with schizophrenia and schizoaffective disorder.

    Science.gov (United States)

    Elie, D; Poirier, M; Chianetta, Jm; Durand, M; Grégoire, Ca; Grignon, S

    2010-07-01

    Antipsychotic polypharmacy and high doses have been associated with poorer outcome, longer hospital stays, and increased side effects. The present naturalistic study assessed the cognitive effects of antipsychotics in 56 patients with a diagnosis of schizophrenia or schizoaffective disorder, using the Brief Assessment of Cognition in Schizophrenia (BACS). Antipsychotic daily dose (ADD) was expressed as mg risperidone equivalents/day (RIS eq), using a model based on drug doses from the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) study for second generation antipsychotics (SGA) and chlorpromazine equivalents for first generation antipsychotics (FGA), with a 1/1 equivalence between haloperidol and risperidone. Increasing age was associated with polypharmacy, FGA prescription and decreasing BACS score. FGA prescription, in turn, predicted a poorer cognitive functioning, independently of age, PANSS subscores and ADD. ADD was associated with decreasing cognitive scores, an effect that remained significant after controlling for age, PANSS or polypharmacy. The detrimental cognitive effects of polypharmacy, in turn, appeared to be mediated by ADD. Different methods of data fitting suggested that ADD above 5-6 mg RIS eq/day were associated with lower BACS scores. Overall, these results show that increasing antipsychotic daily dose is associated with poorer cognitive functioning at doses lower than previously thought, independently of the number of antipsychotic drugs.

  4. In Vitro Cytotoxicity and Phototoxicity Assessment of Acylglutamate Surfactants Using a Human Keratinocyte Cell Line

    Directory of Open Access Journals (Sweden)

    Abhay Kyadarkunte

    2014-07-01

    Full Text Available In the current study, human keratinocyte cell line was used as in vitro cell culture model to elucidate the effects of the fatty acid chain length of acylglutamate (amino acid-based surfactant namely, sodium cocoyl glutamate, sodium lauroyl glutamate, and sodium myristoyl glutamate on their cytotoxicity and the ultraviolet B induced phototoxicity. The endpoint used to assess toxicity was a tetrazolium-based assay whereas, the phototoxic potential of acylglutamate surfactants was predicted using two models namely, the Photo-Irritation Factor and Mean Photo Effect. The results of this study showed that the fatty acid chain length of acylglutamate greatly influences toxic effects on human keratinocyte cells. In addition, all the acylglutamate surfactants tested on human keratinocyte cells demonstrated significantly less cytotoxicity (when irradiated and non-irradiated with ultraviolet B light; p < 0.05 and no phototoxic potential was observed in any of the acylglutamate surfactants, when compared with the positive control chlorpromazine. In conclusion, the in vitro studies confirm the suitability of sodium lauroyl glutamate destined for the synthesis and stabilization of lipid nanoparticles.

  5. Mephedrone (4-methylmethcathinone)-related deaths.

    Science.gov (United States)

    Maskell, Peter D; De Paoli, Giorgia; Seneviratne, Collin; Pounder, Derrick J

    2011-04-01

    Four deaths related to the drug 4-methylmethcathinone (mephedrone) are reported. Qualitative and quantitative analysis of mephedrone was performed by high-performance liquid chromatography-diode-array detection. Of the four deaths, one was attributed to the adverse effects of mephedrone, with cardiac fibrosis and atherosclerotic coronary artery disease as a contributing factor. A 49-year-old female insufflated mephedrone; analysis disclosed mephedrone in femoral venous blood (0.98 mg/L). The second death was attributed solely to mephedrone. A 19-year-old male took mephedrone as well as alcohol and "ecstasy"; analysis disclosed mephedrone (2.24 mg/L femoral venous blood) and 3-trifluoromethylphenylpiperazine (3-TFMPP). In the third fatality, a 55-year-old female was found dead in bed; the death was attributed to the combined effects of mephedrone and methadone. Analysis of femoral venous blood revealed the prescribed drugs diazepam, nordiazepam, olazepine, and chlorpromazine metabolites together with methadone (0.3 mg/L) and mephedrone (0.13 mg/L). In the fourth case, a 17-year-old male car driver was involved in a vehicular collision and died of multiple blunt force injuries. Analysis revealed mephedrone in femoral venous blood (0.24 mg/L).

  6. Intracellular trafficking pathways in silver nanoparticle uptake and toxicity in Caenorhabditis elegans.

    Science.gov (United States)

    Maurer, Laura L; Yang, Xinyu; Schindler, Adam J; Taggart, Ross K; Jiang, Chuanjia; Hsu-Kim, Heileen; Sherwood, David R; Meyer, Joel N

    2016-09-01

    We used the nematode Caenorhabditis elegans to study the roles of endocytosis and lysosomal function in uptake and subsequent toxicity of silver nanoparticles (AgNP) in vivo. To focus on AgNP uptake and effects rather than silver ion (AgNO3) effects, we used a minimally dissolvable AgNP, citrate-coated AgNPs (CIT-AgNPs). We found that the clathrin-mediated endocytosis inhibitor chlorpromazine reduced the toxicity of CIT-AgNPs but not AgNO3. We also tested the sensitivity of three endocytosis-deficient mutants (rme-1, rme-6 and rme-8) and two lysosomal function deficient mutants (cup-5 and glo-1) as compared to wild-type (N2 strain). One of the endocytosis-deficient mutants (rme-6) took up less silver and was resistant to the acute toxicity of CIT-AgNPs compared to N2s. None of those mutants showed altered sensitivity to AgNO3. Lysosome and lysosome-related organelle mutants were more sensitive to the growth-inhibiting effects of both CIT-AgNPs and AgNO3. Our study provides mechanistic evidence suggesting that early endosome formation is necessary for AgNP-induced toxicity in vivo, as rme-6 mutants were less sensitive to the toxic effects of AgNPs than C. elegans with mutations involved in later steps in the endocytic process.

  7. Hydrogen sulfide donor sodium hydrosulfide-induced heat tolerance in tobacco (Nicotiana tabacum L) suspension cultured cells and involvement of Ca(2+) and calmodulin.

    Science.gov (United States)

    Li, Zhong-Guang; Gong, Ming; Xie, Hong; Yang, Lan; Li, Jing

    2012-04-01

    Hydrogen sulfide (H(2)S) is considered as a new emerging cell signal in higher plants. Hydrogen sulfide donor, sodium hydrosulfide, pretreatment significantly increased survival percentage of tobacco suspension cultured cells under heat stress and regrowth ability after heat stress, and alleviated decrease in vitality of cells, increase in electrolyte leakage and accumulation of malondialdehyde (MDA). In addition, sodium hydrosulfide-induced heat tolerance was markedly strengthened by application of exogenous Ca(2+) and its ionophore A23187, respectively, while this heat tolerance was weakened by addition of Ca(2+) chelator ethylene glycol-bis(b-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA), plasma membrane channel blocker La(3+), as well as calmodulin (CaM) antagonists chlorpromazine (CPZ) and trifluoperazine (TFP), respectively, but intracellular channel blocker ruthenium red (RR) did not. These results suggested that sodium hydrosulfide pretreatment could improve heat tolerance in tobacco suspension cultured cells and the acquisition of this heat tolerance requires the entry of extracellular Ca(2+) into cells across the plasma membrane and the mediation of intracellular CaM.

  8. A comparative study of the plasma membrane permeabilization and fluidization induced by antipsychotic drugs in the rat brain.

    Science.gov (United States)

    Murata, Tetsuhito; Maruoka, Nobuyuki; Omata, Naoto; Takashima, Yasuhiro; Fujibayashi, Yasuhisa; Yonekura, Yoshiharu; Wada, Yuji

    2007-10-01

    We compared the potency of the interaction of three antipsychotic drugs, i.e. chlorpromazine (CPZ), haloperidol (Hal) and sulpiride (Sul), with the plasma membrane in the rat brain. CPZ loading (> or = 100 microM) dose-dependently increased both membrane permeability (assessed as [18F]2-fluoro-2-deoxy-D-glucose-6-phosphate release from brain slices) and membrane fluidity (assessed as the reduction in the plasma membrane anisotropy of 1,6-diphenyl-1,3,5-hexatriene). On the other hand, a higher concentration of Hal (1 mM) was required to observe these effects. However, Sul failed to change membrane permeability and fluidity even at a high concentration (1 mM). These results indicated the following ranking of the potency to interact with the membrane: CPZ>Hal>Sul. The difference among antipsychotic drugs in the potency to interact with the plasma membrane as revealed in the present study may be partly responsible for the difference among the drugs in the probability of inducing extrapyramidal side-effects such as parkinsonism and tardive dyskinesia.

  9. In vitro and in vivo protein phosphorylation in Avena sativa L. coleoptiles: effects of Ca2+, calmodulin antagonists, and auxin

    Science.gov (United States)

    Veluthambi, K.; Poovaiah, B. W.

    1986-01-01

    In vitro and in vivo protein phosphorylations in oat (Avena sativa L.) coleoptile segments were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and by two-dimensional gel electrophoresis. In vitro phosphorylation of several polypeptides was distinctly promoted at 1 to 15 micromolar free Ca2+ concentrations. Ca2(+)-stimulated phosphorylation was markedly reduced by trifluoperazine, chlorpromazine, and naphthalene sulfonamide (W7). Two polypeptides were phosphorylated both under in vitro and in vivo conditions, but the patterns of phosphorylation of several other polypeptides were different under the two conditions indicating that the in vivo phosphorylation pattern of proteins is not truly reflected by in vitro phosphorylation studies. Trifluoperazine, W7, or ethylene glycol-bis-(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA) + calcium ionophore A23187 treatments resulted in reduced levels of in vivo protein phosphorylation of both control and auxin-treated coleoptile segments. Analysis by two-dimensional electrophoresis following in vivo phosphorylation revealed auxin-dependent changes of certain polypeptides. A general inhibition of phosphorylation by calmodulin antagonists suggested that both control and auxin-treated coleoptiles exhibited Ca2+, and calmodulin-dependent protein phosphorylation in vivo.

  10. Spectrofluorimetric determination of certain biologically active phenothiazines in commercial dosage forms and human plasma.

    Science.gov (United States)

    Mohamed, Abdel-Maaboud I; Abdelmageed, Osama H; Salem, Hesham; Nagy, Dalia M; Omar, Mahmoud A

    2013-01-01

    A validated simple and sensitive spectrofluorimetric method was developed for the determination of chlorpromazine hydrochloride, promethazine hydrochloride, trifluperazine hydrochloride, thioridazine hydrochloride, perazine maleate and oxomemazine. The method was based on condensation of malonic acid/acetic anhydride (MAA) under the catalytic effect of the tertiary amine moiety of the studied phenothiazines to provide a deep yellow to brown colour with green fluorescence. Relative fluorescence intensity of the products was measured at λ exc 398 nm and λ em 432 nm. Different variables affecting the reaction were studied and optimized. The method was successfully applied for the determination of the studied drugs in commercial dosage forms. The lower detection limits allowed the application of this method for the determination of the compounds in plasma as an example of a biological fluid. In addition, the method was considered specific for the determination of tertiary amines in the presence of primary and secondary amines; as a result, it was deemed suitable for the determination of the cited drugs in the presence of their degradation products resulting from N-dealkylation or oxidation of the corresponding sulphoxides or sulphones.

  11. Prevention of cumene hydroperoxide induced oxidative stress in cultured neonatal rat myocytes by scavengers and enzyme inhibitors.

    Science.gov (United States)

    Persoon-Rothert, M; Egas-Kenniphaas, J M; van der Valk-Kokshoorn, E J; Mauve, I; van der Laarse, A

    1990-10-01

    Oxidative stress induced by cumene hydroperoxide was studied in cultured neonatal rat myocytes. A progressive increase of irreversible cell injury as determined by leakage of the cytoplastic enzyme alpha-hydroxybutyrate dehydrogenase (alpha-HBDH) from the cells was noted at concentrations ranging from 25-100 microM cumene hydroperoxide (incubation time 90 min). Cumene hydroperoxide-induced damage was reduced or prevented by several compounds: the application of Trolox C, a water-soluble vitamin E analogue, and of phospholipase A2 inhibitors chlorpromazine and (to a lesser extent) quinacrine prevented alpha-HBDH release. ICRF-159, a chelator of divalent cations, ascorbic acid, a potent antioxidant, and the cysteine protease inhibitor leupeptin did not reduce the cumene hydroperoxide-induced cytotoxicity. Detoxification of hydroperoxides by the glutathione peroxidase system results in an increased flux through the pentose phosphate shunt and loss of NADPH. Glucose inhibited the cumene hydroperoxide-induced alpha-HBDH release, probably by replenishing NADPH. These results indicate that cumene hydroperoxide, after exhaustion of the glutathione system, induces irreversible injury in cultured myocytes by a mechanism that depends to a large extent on deterioration of cellular membranes caused by lipid peroxidation and phospholipase activation.

  12. New approaches to the management of schizophrenia: focus on aberrant hippocampal drive of dopamine pathways.

    Science.gov (United States)

    Perez, Stephanie M; Lodge, Daniel J

    2014-01-01

    Schizophrenia is a disease affecting up to 1% of the population. Current therapies are based on the efficacy of chlorpromazine, discovered over 50 years ago. These drugs block dopamine D2-like receptors and are effective at primarily treating positive symptoms in a subset of patients. Unfortunately, current therapies are far from adequate, and novel treatments require a better understanding of disease pathophysiology. Here we review the dopamine, gamma-aminobutyric acid (GABA), and glutamate hypotheses of schizophrenia and describe a pathway whereby a loss of inhibitory signaling in ventral regions of the hippocampus actually drives a dopamine hyperfunction. Moreover, we discuss novel therapeutic approaches aimed at attenuating ventral hippocampal activity in a preclinical model of schizophrenia, namely the MAM GD17 rat. Specifically, pharmacological (allosteric modulators of the α5 GABAA receptor), neurosurgical (deep brain stimulation), and cell-based (GABAergic precursor transplants) therapies are discussed. By better understanding the underlying circuit level dysfunctions in schizophrenia, novel treatments can be advanced that may provide better efficacy and a superior side effect profile to conventional antipsychotic medications.

  13. Atypical properties of several classes of antipsychotic drugs on the basis of differential induction of Fos-like immunoreactivity in the rat brain.

    Science.gov (United States)

    Oka, Takuro; Hamamura, Takashi; Lee, Youmei; Miyata, Shinji; Habara, Toshiaki; Endo, Shiro; Taoka, Hideki; Kuroda, Shigetoshi

    2004-11-26

    Acute administration of typical and atypical antipsychotics has been reported to induce regionally distinct patterns of c-Fos expression in the rat forebrain. Furthermore, atypical index, the difference in the extent of increased Fos-like immunoreactivity (Fos-LI) in the nucleus accumbens (NAc) shell versus the dorsolateral striatum (DLSt), has been proposed to classify antipsychotics into typical or atypical antipsychotics. The present study was conducted to investigate the atypical properties of 24 antipsychotics that are used in Japan and blonanserin, a novel 5-HT2A and D2 receptor antagonist. We systematically examined the effects of the drugs on Fos-LI in the NAc and DLSt in the rat brain using immunohistochemistry and calculated the atypical index, comparing with those of haloperidol and clozapine. Floropipamide, oxypertine, nemonapride, pimozide and mosapramine, as well as clozapine, olanzapine, quetiapine and risperidone, showed high positive atypical index. Zotepine, perospirone, sulpiride, moperone, sultopride, thioridazine, carpipramine, clocapramine and blonanserin showed moderate ones. In contrast, fluphenazine, bromperidol, timiperone, spiperone, propericiazine, perphenazine, chlorpromazine and levomepromazine had negative atypical index like haloperidol. These results suggest that not only so-called atypical antipsychotics, but also several conventional drugs, possess atypical properties.

  14. [Hyperemesis gravidarum: a rare but potentially severe complication of the first trimester of pregnancy].

    Science.gov (United States)

    Macle, Lucie; Varlet, Marie-Noëlle; Cathébras, Pascal

    2010-06-20

    Although nausea and vomiting are common symptoms in early pregnancy, hyperemesis gravidarum (HG) is a rare complication of the first trimester of pregnancy. This condition is defined as intractable vomiting occurring before 20 weeks of gestation, with fluid and electrolyte disturbance, significant weight loss, and ketonuria, leading to hospitalization in the absence of other cause than pregnancy. Some biological disturbances found in HG, such as hyperthyroidism and hepatic cytolysis, which are correlated with the importance of vomiting, are without severe clinical consequences, but may represent diagnostic pitfalls. The aetiology is unknown, but human chorionic gonadotropin hormones likely play the first role. Psychological disturbance is currently seen as the result of the burden and stress of HG rather than a causal factor. Maternal outcome may be severe in the absence of treatment, but pregnancy outcome seems good, as far as the condition has been adequately controlled. The management of HG includes IV rehydration, thiamine supplementation, antiemetic drugs (doxylamine, metoclopramide and chlorpromazine being the first-line choices), and in severe cases, nasogastric or parenteral nutrition. A psychological support is often necessary.

  15. Small GTPase Rab14 down-regulates UT-A1 urea transport activity through enhanced clathrin-dependent endocytosis.

    Science.gov (United States)

    Su, Hua; Liu, Bingchen; Fröhlich, Otto; Ma, Heping; Sands, Jeff M; Chen, Guangping

    2013-10-01

    The UT-A1 urea transporter plays an important role in the urinary concentration mechanism. However, the molecular mechanisms regarding UT-A1 trafficking, endocytosis, and degradation are still unclear. In this study, we identified the small GTPase Rab14 as a binding partner to the C terminus of UT-A1 in a yeast 2-hybrid assay. Interestingly, UT-A1 binding is preferential for the GDP-bound inactive form of Rab14. Coinjection of Rab14 in Xenopus oocytes results in a decrease of UT-A1 urea transport activity, suggesting that Rab14 acts as a negative regulator of UT-A1. We subsequently found that Rab14 reduces the cell membrane expression of UT-A1, as evidenced by cell surface biotinylation. This effect is blocked by chlorpromazine, an inhibitor of the clathrin-mediated endocytic pathway, but not by filipin, an inhibitor of the caveolin-mediated endocytic pathway. In kidney, Rab14 is mainly expressed in IMCD epithelial cells with a pattern identical to UT-A1 expression. Consistent with its role in participating in clathrin-mediated endocytosis, Rab14 localizes in nonlipid raft microdomains and codistributes with Rab5, a marker of the clathrin-mediated endocytic pathway. Taken together, our study suggests that Rab14, as a novel UT-A1 partner, may have an important regulatory function for UT-A1 urea transport activity in the kidney inner medulla.

  16. Evaluation of drug-induced neurotoxicity based on metabolomics, proteomics and electrical activity measurements in complementary CNS in vitro models.

    Science.gov (United States)

    Schultz, Luise; Zurich, Marie-Gabrielle; Culot, Maxime; da Costa, Anaelle; Landry, Christophe; Bellwon, Patricia; Kristl, Theresa; Hörmann, Katrin; Ruzek, Silke; Aiche, Stephan; Reinert, Knut; Bielow, Chris; Gosselet, Fabien; Cecchelli, Romeo; Huber, Christian G; Schroeder, Olaf H-U; Gramowski-Voss, Alexandra; Weiss, Dieter G; Bal-Price, Anna

    2015-12-25

    The present study was performed in an attempt to develop an in vitro integrated testing strategy (ITS) to evaluate drug-induced neurotoxicity. A number of endpoints were analyzed using two complementary brain cell culture models and an in vitro blood-brain barrier (BBB) model after single and repeated exposure treatments with selected drugs that covered the major biological, pharmacological and neuro-toxicological responses. Furthermore, four drugs (diazepam, cyclosporine A, chlorpromazine and amiodarone) were tested more in depth as representatives of different classes of neurotoxicants, inducing toxicity through different pathways of toxicity. The developed in vitro BBB model allowed detection of toxic effects at the level of BBB and evaluation of drug transport through the barrier for predicting free brain concentrations of the studied drugs. The measurement of neuronal electrical activity was found to be a sensitive tool to predict the neuroactivity and neurotoxicity of drugs after acute exposure. The histotypic 3D re-aggregating brain cell cultures, containing all brain cell types, were found to be well suited for OMICs analyses after both acute and long term treatment. The obtained data suggest that an in vitro ITS based on the information obtained from BBB studies and combined with metabolomics, proteomics and neuronal electrical activity measurements performed in stable in vitro neuronal cell culture systems, has high potential to improve current in vitro drug-induced neurotoxicity evaluation.

  17. Simultaneous monitoring of photocatalysis of three pharmaceuticals by immobilized TiO2 nanoparticles: chemometric assessment, intermediates identification and ecotoxicological evaluation.

    Science.gov (United States)

    Khataee, A R; Fathinia, M; Joo, S W

    2013-08-01

    In this study, the photocatalytic degradation of a mixture of three pharmaceuticals, Metronidazole (MET), Atenolol (ATL) and Chlorpromazine (CPR), was quantified simultaneously during the UV/TiO2 process. The investigated TiO2 was Millennium PC-500 immobilized on ceramic plates by sol-gel based method. The partial least squares modeling was successfully applied for the multivariate calibration of the spectrophotometric data. The central composite design was applied to model and optimize the UV/TiO2 process. Predicted values of removal efficiency were found to be in good agreement with experimental values for MET, ATL and CPR (R(2)=0.947 and Adj-R(2)=0.906, R(2)=0.977 and Adj-R(2)=0.960 and R(2)=0.982 and Adj-R(2)=0.969, respectively). The optimum initial concentration of pharmaceuticals, reaction time and UV light intensity was found to be 10 mg L(-1), 150 min and 38.45 W m(-2), respectively. The main degradation intermediates of pharmaceuticals produced in this process were identified by GC-MS technique. The chronic ecotoxicity of pharmaceuticals was evaluated using aquatic species Spirodela polyrrhiza prior to and after photocatalysis. The TOC results (90% removal after 16 h) and ecotoxicological experiments revealed that the photocatalysis process could effectively mineralize and reduce the ecotoxicity of the pharmaceuticals from their aqueous solutions.

  18. Second derivative spectrophotometric determination of partition coefficients of phenothiazine derivatives between human erythrocyte ghost membranes and water.

    Science.gov (United States)

    Kitamura, K; Goto, T; Kitade, T

    1998-08-01

    The absorption spectra of six phenothiazine derivatives, chlorpromazine, triflupromazine, promazine, promethazine, trifluoperazine and prochlorperazine, measured in the solutions containing various amounts of human erythrocyte ghosts (HEG) showed bathocromic shifts according to the amount of HEG. Due to the strong background signals caused by HEG, the baseline compensation was incomplete, even though the sample and the reference solutions contained the same amount of HEG, hence further spectral information could not be obtained. The second derivative spectra of these absorption spectra clearly showed the derivative isosbestic points, indicating that the residual background signal effects were entirely eliminated. The derivative intensity differences of the phenothiazines (DeltaD values) before and after the addition of HEG were measured at a specific wavelength. Using the DeltaD values, the partition coefficients (K(p)) of these drugs were calculated and obtained with R.S.D. of below 10 %. The fractions of partitioned phenothiazines calculated from the K(p) values agreed well with the experimental values. The results indicate that the derivative method can be applicable to the determination of partition coefficients of drugs to HEG without any separation procedures.

  19. Drug-induced erythrocyte membrane internalization.

    Science.gov (United States)

    Ben-Bassat, I; Bensch, K G; Schrier, S L

    1972-07-01

    In vitro erythrocyte membrane internalization, resulting in the formation of membrane-lined vacuoles, can be quantified by a radioisotopic method. A complex of (37)Co-labeled vitamin B(12) and its plasma protein binders is first adsorbed to the cell surface, and after vacuoles are formed, the noninternalized label is removed by washing and trypsin treatment. The residual radioactivity represents trapped label and can be used to measure the extent of membrane internalization. Using this method, it was found that in addition to primaquine, a group of membrane-active drugs, specifically hydrocortisone, vinblastine, and chlorpromazine can induce membrane internalization in erythrocytes. This is a metabolic process dependent on drug concentration, temperature, and pH. Vacuole formation by all agents tested can be blocked by prior depletion of endogenous substrates or by poisoning the erythrocytes with sodium fluoride and sulfhydryl blocking agents. This phenomenon resembles in some respects the previously reported membrane internalization of energized erythrocyte ghosts. It is suggested that membrane internalization is dependent on an ATP-energized state and is influenced by the balance between the concentrations of magnesium and calcium in the membrane. This study provides a basis for proposing a unifying concept of the action of some membrane-active drugs, and for considering the role of erythrocyte membrane internalization in pathophysiologic events.

  20. Psychosocial interventions for premature ejaculation

    Directory of Open Access Journals (Sweden)

    Tamara Melnik

    .88, 95% CI 2.06 to 3.70; Men: MD 2.52, CI 1.65 to 3.39 and couples' sexual satisfaction (MD -25.10, 95% CI -47.95 to -2.25, versus waiting list. AUTHORS' CONCLUSIONS: Overall, there is weak and inconsistent evidence regarding the effectiveness of psychological interventions for the treatment of premature ejaculation. Three of the four included randomised controlled studies of psychotherapy for PE reported our primary outcome (Improvement in IELT, and the majority have a small sample size. The early success reports (97.8% of Masters and Johnson could not be replicated. One study found a significant improvement from baseline in the duration of intercourse, sexual satisfaction and sexual function with a new functional-sexological treatment and behavior therapy compared to waiting list. One study showed that the combination of chlorpromazine and BT was superior to chlorpromazine alone. Randomised trials with larger group samples are still needed to further confirm or deny the current available evidence for psychological interventions for treating PE.

  1. Abnormal glycosylated hemoglobin as a predictive factor for glucose metabolism disorders in antipsychotic treatment

    Institute of Scientific and Technical Information of China (English)

    XU Leping; JI Juying; DUAN Yiyang; SHI Hui; ZHANG Bin; SHAO Yaqin; SUN Jian

    2007-01-01

    The aim of this study was to observe the changes in glucose metabolism after antipsychotic(APS)therapy,to note the influencing factors,as well as to dicuss the relationship between the occurrence of glucose metabolism disorders of APS origin and abnormal glycosylated hemoglobin(HbA1c)levels.One hundred and fifty-two patients with schizophrenia,whose fasting plasma glucose(FPG)and 2-h plasma glucose (2hPG)in the oral glucose tolerance test(2HPG)were normal,were grouped according to the HbA1c levels,one normal and the other abnormal,and were randomly enrolled into risperidone,clozapine and chlorpromazine treatment for six weeks.The FPG and 2hPG were measured at the baseline and at the end of the study.In the group with abnormal HbA1c and clozapine therapy,2HPG was higher after the study[(9.5±1.8)mmol/L]than that before the study[(7.2±1.4)mmol/L]and the difierence was statistically significant(P<0.01).FPG had no statistically significant difference before and after the study in any group(P>0.05).HbA1c levels and drugs contributing to 2HPG at the end of study had statistical cross-action(P<0.01).In the abnormal HbA1c group,2HPG after the study was higher in the clozapine treatment group [(9.5±1.8)mmol/L]than in the risperidone treatment group [(7.4±1.7)mmol/L]and the chlorpromazine treatment group[(7.3±1.6)mmol/L].The differences were statistically significant(P<0.01).In the normal HbA1c group there was no statistically significant difierence before and after the study in any group(P>0.05).2HPG before[(7.1±1.6)mmol/L]and after the study[(8.1±1.9)mmol/L]was higher in the abnormal HbA1c group than in the normal HbA1c group[(6.2±1.4)mmol/L vs(6.5±1.4)mmol/L]with the difierence being statistically significant(P<0.01 vs P<0.001).As compared with normal HbA1c group,the relative risk (RR)of glucose metabolism disease occurrence was 4.7 in the abnormal HDA1C group wlth the difierence being statistically significant(P<0.001).Patients with abnormal HbA1c

  2. Bloqueio do nervo alveolar mandibular com ropivacaína a 0,5 % em gatos Bockage of the jaw’s alveolar nerve with 0.5% ropivacaine in cats

    Directory of Open Access Journals (Sweden)

    Vanessa Martins Fayad Milken

    2006-04-01

    Full Text Available Objetivou-se, com este experimento, avaliar a ação da ropivacaína a 0,5% no bloqueio do nervo alveolar mandibular de gatos. Vinte gatos adultos, sem raça definida, machos ou fêmeas, receberam clorpromazina (1,0mg kg-1, VO e propofol (3,0mg kg-1, IV. Ropivacaína a 0,5% foi administrada com uma agulha 13x3,8 em forma de "L", inserida no ângulo da mandíbula direita, aproximadamente 1,0cm rostral ao processo angular e 0,5cm dorsal à superfície medial do ramo da mandíbula, a fim de depositá-la próximo ao nervo alveolar mandibular, no forame mandibular. As freqüências cardíaca e respiratória foram mensuradas antes da administração da clorpromazina, 20 minutos após administração desta (T0, 20 minutos após o bloqueio do nervo alveolar mandibular com ropivacaína (T20 e, em intervalos de 20 minutos, até a volta da sensibilidade na região anestesiada. Observou-se o período de latência e a duração da anestesia por meio do pinçamento da pele e gengiva da região lateral direita da mandíbula. Encontrou-se início da anestesia após 22 minutos, com duração de 164,25 minutos. Os parâmetros de freqüência cardíaca e freqüência respiratória tiveram alterações, porém sem significado clínico para a espécie. A ropivacaína a 0,5% anestesia a região dos dentes pré-molares, molares, caninos, incisivos, pele e mucosa oral e lábio inferior, sem causar efeitos colaterais.This study intended to evaluate the 0.5% ropivacaine action on the alveolar mandibular nerve block in cats. Twenty adult cats, non-defined breed, male or female, received chlorpromazine (1.0 mg kg-1 VO and propofol (3,0 mg/kg IV. Ropivacaine at 0.5% was administrated with an "L" 13x3,8 needle, inserted in the angle of the right mandible, close to 1.0cm rostral to the angular process and 0.5cm dorsal to the medial surface of the mandible branch, intending to deposit close to the alveolar mandibular nerve, at the mandibular forame. The heart and respiratory

  3. Standard electrochemical behavior of high-quality, boron-doped polycrystalline diamond thin-film electrodes

    Science.gov (United States)

    Granger; Witek; Xu; Wang; Hupert; Hanks; Koppang; Butler; Lucazeau; Mermoux; Strojek; Swain

    2000-08-15

    Standard electrochemical data for high-quality, boron-doped diamond thin-film electrodes are presented. Films from two different sources were compared (NRL and USU) and both were highly conductive, hydrogen-terminated, and polycrystalline. The films are acid washed and hydrogen plasma treated prior to use to remove nondiamond carbon impurity phases and to hydrogen terminate the surface. The boron-doping level of the NRL film was estimated to be in the mid 1019 B/cm3 range, and the boron-doping level of the USU films was approximately 5 x 10(20) B/cm(-3) based on boron nuclear reaction analysis. The electrochemical response was evaluated using Fe-(CN)6(3-/4-), Ru(NH3)6(3+/2+), IrCl6(2-/3-), methyl viologen, dopamine, ascorbic acid, Fe(3+/2+), and chlorpromazine. Comparisons are made between the apparent heterogeneous electron-transfer rate constants, k0(app), observed at these high-quality diamond films and the rate constants reported in the literature for freshly activated glassy carbon. Ru(NH3)6(3+/2+), IrCl6(2-/3-), methyl viologen, and chlorpromazine all involve electron transfer that is insensitive to the diamond surface microstructure and chemistry with k0(app) in the 10(-2)-10(-1) cm/s range. The rate constants are mainly influenced by the electronic properites of the films. Fe(CN)6(3-/4-) undergoes electron transfer that is extremely sensitive to the surface chemistry with k0(app) in the range of 10(-2)-10(-1) cm/s at the hydrogen-terminated surface. An oxygen surface termination severely inhibits the rate of electron transfer. Fe(3+/2+) undergoes slow electron transfer at the hydrogen-terminated surface with k0(app) near 10(-5) cm/s. The rate of electron transfer at sp2 carbon electrodes is known to be mediated by surface carbonyl functionalities; however, this inner-sphere, catalytic pathway is absent on diamond due to the hydrogen termination. Dopamine, like other catechol and catecholamines, undergoes sluggish electron transfer with k0(app) between 10

  4. Survey Research on Medication Management Safety of Inpatients with Schizophrenia%住院精神分裂症患者用药管理安全性的调查研究

    Institute of Scientific and Technical Information of China (English)

    牟建明

    2016-01-01

    Objective To research the medication management safety of inpatients with schizophrenia. Methods The medi-cation and safety of inpatients with schizophrenia were analyzed and the notes of medication management in inpatients with schizophrenia were obtained. Results The medication methods of inpatients with schizophrenia included the single-drug treatment and combined medication, among them, the single-drug treatment included risperidone, aripiprazole, clozapine, paralest, sulpiride, quetiapine fumarate and chlorpromazine, the combined medication included two-drug medication and three-drug medication, the male patients mainly used the drugs with rapid curative effect such as clozapine, sulpiride, chlorpromazine and quetiapine fumarate, and the female patients mostly used the drugs with less effect on endocrine secre-tion such as risperidone for treatment. Conclusion Normally, we should try to adopt the single treatment method, only when the patient’s disease condition is serious and the single drug fails to obtain the treatment effect, can we consider the com-bined treatment, and we can’t stop drug administration suddenly in order to prevent the recurrence of disease condition af-ter the drug treatment achieves the effect.%目的:研究住院精神分裂症患者的用药管理安全性。方法分析住院精神分裂症患者的用药及安全性,得出住院精神分裂症患者用药管理的注意事项。结果住院精神分裂症患者的用药方法有单一药物治疗和联合用药两种。其中单一药物治疗包括利培酮、阿立哌唑、氯氮平、盐酸苯海索、舒必利、富马酸奎硫平、氯丙嗪。联合用药包括两联用药和三联用药。男性患者主要应用氯氮平、舒必利、氯丙嗪、富马酸奎硫平等疗效较为迅速的药物,女性患者多应用利培酮等对内分泌影响较小的药物进行治疗。结论正常情况下,应尽量采取单一治疗方法。只有当

  5. Alterative application of five anticonvulsants according to the half life for the treatment of status epilepticus in children with severe viral encephalitis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: Traditional subhibernation therapy may easily cause complications, such as respiratory depression and hyportension because of application of chlorpromazine hydrochloride and promethazine in a large dosage.OBJECTIVE: To observe therapeutic effect of modified subhibernation therapy (alterative application of five anticonvulsants according to the half life) on status epilepticus in children with severe viral encephalitis (VE).DESIGN: Contrast observation.SETTING: Department of Pediatrics, the First Hospital of Jilin University.PARTICIPANTS: The participants in present study were 96 patients withsevere viral encephalitis including 52 boys and 44 girls who received treatment in the Department of Pediatrics, the First Hospital of Jilin University from February 2000 to March 2006. All children met the diagnostic criteria of Zhufutong Practice Pediatrics (the seventh edition). Two weeks ago, they ever got upper respiratory infection or enteronitis and so on before the onset, spirit abnormal, behavior disorder, limbs act disorder, vomit, headache, convulsion,nervous system masculine signs such as limbs act disord, autonomic nerve damage manifestation, brain nerve palsy, dysreflexia, meningeal irritation sign, cerebrospinal fluid and electroencephalography (EEG)abnormity. All parents provided the confirmed consent. The patients were randomly divided into control group (n =40) and experimental group (n =56).METHODS: Patients in the control group received anticonvulsion, ice compress and routine treatment. The convulsion was treated with five drugs: 0.5 mg/kg wintermin and phenergan, respectively, 100 g/L chlorpromazine hydrochloride (0.5 mL/kg), 5 mg/kg luminal, 0.3 mg/kg ansiolin. When convulsion attacked,those five drugs were given alternatively; however, those were not given if the convulsion did not attack.Children in the experimental group were treated with improved subhibernation therapy based on routine treatment. The dosages of anticonvulsants were as the

  6. Interleukin-6: the missing element of the neurocognitive deterioration in schizophrenia? The focus on genetic underpinnings, cognitive impairment and clinical manifestation.

    Science.gov (United States)

    Frydecka, Dorota; Misiak, Błażej; Pawlak-Adamska, Edyta; Karabon, Lidia; Tomkiewicz, Anna; Sedlaczek, Paweł; Kiejna, Andrzej; Beszłej, Jan Aleksander

    2015-09-01

    The influence of the immune system deregulation on the risk of schizophrenia is increasingly recognized. The aim of this study was to assess the influence of serum interleukin-6 (IL-6) level together with the polymorphism in its gene (IL6 -174G/C) and high sensitivity C-reactive protein (hsCRP) levels on clinical manifestation and cognition in schizophrenia patients. We recruited 151 patients with schizophrenia and 194 healthy control subjects. Psychopathology was evaluated using Operational Criteria for Psychotic Illness checklist, Positive and Negative Syndrome Scale (PANSS) and Scales for Assessment of Positive and Negative Symptoms. Cognitive performance in schizophrenia patients was assessed using following tests: Rey Auditory Verbal Learning Test, Trail Making Test, Verbal Fluency Tests, Stroop and subscales from Wechsler Adults Intelligence Scale-R-Pl (Similarities, Digit Symbol Coding, Digit Span Forward and Backward). Serum IL-6 and hsCRP levels were significantly higher in schizophrenia patients in comparison with healthy controls. Both hsCRP and IL-6 levels were associated with insidious psychosis onset, duration of illness and chronic schizophrenia course with deterioration. After adjustment for age, education level, number of years of completed education, illness duration, total PANSS score, depression severity and chlorpromazine equivalent, there was still a positive association between IL-6 and hsCRP levels and worse cognitive performance. The IL6 -174G/C polymorphism did not influence IL-6 level, but it was associated with the severity of positive symptoms. Our results suggest that elevated IL-6 levels may play the role in cognitive impairment and serve as potential inflammatory biomarker of deterioration in schizophrenia.

  7. Cell uptake mechanisms of PAMAM G4-FITC dendrimer in human myometrial cells

    Science.gov (United States)

    Oddone, Natalia; Zambrana, Ana I.; Tassano, Marcos; Porcal, Williams; Cabral, Pablo; Benech, Juan C.

    2013-07-01

    The high incidence and severity of diseases which involve smooth muscle dysfunction dictates the need of continued search for novel therapeutic strategies to treat these conditions. Dendrimers are branched macromolecules with multiple end-groups that can be functionalized for applications which include drug delivery. There is no data regarding the cellular uptake mechanisms used by dendrimers in smooth muscle human myometrial cells (HMC). Polyamidoamine G4 dendrimers were conjugated with fluorescein isothiocyanate (FITC) and the resulting conjugate (G4-FITC) was characterized using high-performance liquid chromatography, nuclear magnetic resonance, and atomic force microscopy. G4-FITC showed to have no significant effect on the primary culture HMC viability up to 48 h. HMC incubated with G4-FITC were analyzed by laser confocal microscopy. Peri-nuclear fluorescence distribution was observed at 5 h of incubation or more (24, 36, and 48 h). At 24 h, G4-FITC partially co-localized with lysotracker. Uptake of G4-FITC by HMC was slightly inhibited by filipin (8.0 ± 3.9 %) and significantly inhibited by chlorpromazine (63.5 ± 3.7 %). In non-electroporated HMC, G4-FITC was never observed inside the cell nucleus. Interestingly, we detected G4-FITC inside the nuclear domain of some electroporated cells. Thus, electroporation changed intracellular G4-FITC localization. Isolated nuclei of HMC incubated with G4-FITC showed fluorescence signal inside the nuclear domain. The results suggest that in HMC, G4-FITC is taken up by clathrin-mediated endocytosis with endosomal and lysosomal localization at 24 h. The combination of electroporation and dendrimers could be an interesting technology to electrotransfer drugs into smooth muscle cells cytosol and nuclei.

  8. Olfactory Receptors in Non-Chemosensory Organs: The Nervous System in Health and Disease

    Science.gov (United States)

    Ferrer, Isidro; Garcia-Esparcia, Paula; Carmona, Margarita; Carro, Eva; Aronica, Eleonora; Kovacs, Gabor G.; Grison, Alice; Gustincich, Stefano

    2016-01-01

    Olfactory receptors (ORs) and down-stream functional signaling molecules adenylyl cyclase 3 (AC3), olfactory G protein α subunit (Gαolf), OR transporters receptor transporter proteins 1 and 2 (RTP1 and RTP2), receptor expression enhancing protein 1 (REEP1), and UDP-glucuronosyltransferases (UGTs) are expressed in neurons of the human and murine central nervous system (CNS). In vitro studies have shown that these receptors react to external stimuli and therefore are equipped to be functional. However, ORs are not directly related to the detection of odors. Several molecules delivered from the blood, cerebrospinal fluid, neighboring local neurons and glial cells, distant cells through the extracellular space, and the cells’ own self-regulating internal homeostasis can be postulated as possible ligands. Moreover, a single neuron outside the olfactory epithelium expresses more than one receptor, and the mechanism of transcriptional regulation may be different in olfactory epithelia and brain neurons. OR gene expression is altered in several neurodegenerative diseases including Parkinson’s disease (PD), Alzheimer’s disease (AD), progressive supranuclear palsy (PSP) and sporadic Creutzfeldt-Jakob disease (sCJD) subtypes MM1 and VV2 with disease-, region- and subtype-specific patterns. Altered gene expression is also observed in the prefrontal cortex in schizophrenia with a major but not total influence of chlorpromazine treatment. Preliminary parallel observations have also shown the presence of taste receptors (TASRs), mainly of the bitter taste family, in the mammalian brain, whose function is not related to taste. TASRs in brain are also abnormally regulated in neurodegenerative diseases. These seminal observations point to the need for further studies on ORs and TASRs chemoreceptors in the mammalian brain. PMID:27458372

  9. Recruitment of endocytosis in sonopermeabilization-mediated drug delivery: a real-time study

    Science.gov (United States)

    Derieppe, Marc; Rojek, Katarzyna; Escoffre, Jean-Michel; de Senneville, Baudouin Denis; Moonen, Chrit; Bos, Clemens

    2015-07-01

    Microbubbles (MBs) in combination with ultrasound (US) can enhance cell membrane permeability, and have the potential to facilitate the cellular uptake of hydrophilic molecules. However, the exact mechanism behind US- and MB-mediated intracellular delivery still remains to be fully understood. Among the proposed mechanisms are formation of transient pores and endocytosis stimulation. In our study, we investigated whether endocytosis is involved in US- and MB-mediated delivery of small molecules. Dynamic fluorescence microscopy was used to investigate the effects of endocytosis inhibitors on the pharmacokinetic parameters of US- and MB-mediated uptake of SYTOX Green, a 600 Da hydrophilic model drug. C6 rat glioma cells, together with SonoVue® MBs, were exposed to 1.4 MHz US waves at 0.2 MPa peak-negative pressure. Collection of the signal intensity in each individual nucleus was monitored during and after US exposure by a fibered confocal fluorescence microscope designed for real-time imaging. Exposed to US waves, C6 cells pretreated with chlorpromazine, an inhibitor of clathrin-mediated endocytosis, showed up to a 2.5-fold significant increase of the uptake time constant, and a 1.1-fold increase with genistein, an inhibitor of caveolae-mediated endocytosis. Both inhibitors slowed down the US-mediated uptake of SYTOX Green. With C6 cells and our experimental settings, these quantitative data indicate that endocytosis plays a role in sonopermeabilization-mediated delivery of small molecules with a more predominant contribution of clathrin-mediated endocytosis.

  10. Clathrin-dependent endocytosis plays a predominant role in cellular uptake of double-stranded RNA in the red flour beetle.

    Science.gov (United States)

    Xiao, Da; Gao, Xiwu; Xu, Jiaping; Liang, Xiao; Li, Qingqing; Yao, Jianxiu; Zhu, Kun Yan

    2015-05-01

    RNA interference (RNAi) is a highly conserved gene regulatory mechanism in eukaryotic organisms; however, an understanding of mechanisms of cellular uptake of double-stranded RNA (dsRNA) in different organisms remains elusive. By using pharmacological inhibitors of different endocytic pathways in conjunction with RNAi of a marker gene (lethal giant larvae, TcLgl) in the red flour beetle (Tribolium castaneum), we demonstrated that two inhibitors (chlorpromazine and bafilomycin-A1) of clathrin-dependent endocytosis can nearly abolish or significantly diminish RNAi of TcLgl, whereas methyl-β-cyclodextrin and cytochalasin-D, known to inhibit other endocytic pathways, showed no effect on RNAi of TcLgl. By using Cy3-labeled TcLgl dsRNA, we observed significantly reduced cellular uptake of TcLgl dsRNA in midgut cells after larvae were injected with each of the two clathrin-dependent endocytosis inhibitors. By using an "RNAi of RNAi" strategy, we further demonstrated that suppression of each transcript of the four key genes encoding clathrin heavy chain (TcChc), clathrin coat assembly protein AP50 (TcAP50), vacuolar (H(+))-ATPase subunit H (TcVhaSFD) and a ras-related protein (TcRab7) in clathrin-dependent endocytosis by RNAi can significantly impair RNAi of TcLgl. These results support our conclusion that clathrin-dependent endocytosis is a major mechanism in cellular uptake of dsRNA in T. castaneum. Our study also provides new insights into improving RNAi efficiency by enhancing dsRNA endosomal release.

  11. Nausea and vomiting in advanced cancer: the Cleveland Clinic protocol.

    Science.gov (United States)

    Gupta, Mona; Davis, Mellar; LeGrand, Susan; Walsh, Declan; Lagman, Ruth

    2013-03-01

    Nausea and vomiting are common and distressing symptoms in advanced cancer. Both are multifactorial and cause significant morbidity, nutritional failure, and reduced quality of life. Assessment includes a detailed history, physical examination and investigations for reversible causes. Assessment and management will be influenced by performance status, prognosis, and goals of care. Several drug classes are effective with some having the added benefit of multiple routes of administration. It is our institution's practice to recommend metoclopramide as the first drug with haloperidol as an alternative antiemetic. Dexamethasone should be used for patients with central nervous system metastases or bowel obstruction. If your patient is near death, empiric metoclopramide, haloperidol or chlorpromazine is used without further investigation. For patients with a better prognosis, we exclude reversible causes and use the same first-line antiemetics, metoclopramide and haloperidol. For those who do not respond to first-line single antiemetics, olanzapine is second line and ondansetron is third. Rarely do we use combination therapy or cannabinoids. Olanzapine as a single agent has a distinct advantage over antiemetic combinations. It improves compliance, reduces drug interactions and has several routes of administration. Antiemetics, anticholinergics, octreotide and dexamethasone are used in combination to treat bowel obstruction. In opiod-na'ive patients, we prefer haloperidol, glycopyrrolate and an opioid as the first-line treatment and add or substitute octreotide and dexamethasone in those who do not respond. Non-pharmacologic interventions (mechanical stents and percutaneous endoscopic gastrostomy tubes) are used when nausea is refractory to medical management or for home-going management to relieve symptoms, reduce drug costs and rehospitalization.

  12. Typical and Atypical Antipsychotic Drugs Increase Extracellular Histamine Levels in the Rat Medial Prefrontal Cortex: Contribution of Histamine H1 Receptor Blockade

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    Kjell A Svensson

    2012-05-01

    Full Text Available Atypical antipsychotics such as clozapine and olanzapine have been shown to enhance histamine turnover and this effect has been hypothesized to contribute to their improved therapeutic profile compared to typical antipsychotics. In the present study, we examined the effects of antipsychotic drugs on histamine (HA efflux in the mPFC of the rat by means of in vivo microdialysis and sought to differentiate the receptor mechanisms which underlie such effects. Olanzapine and clozapine increased mPFC HA efflux in a dose related manner. Increased HA efflux was also observed after quetiapine, chlorpromazine and perphenazine treatment. We found no effect of the selective 5-HT2A antagonist MDL100907, 5-HT2c antagonist SB242084 or the 5-HT6 antagonist Ro 04-6790 on mPFC HA efflux. HA efflux was increased following treatment with selective H1 receptor antagonists pyrilamine, diphenhydramine and triprolidine, the H3 receptor antagonist ciproxifan and the mixed 5HT2A/H1 receptor antagonist ketanserin. The potential novel antipsychotic drug FMPD, which has a lower affinity at H1 receptors than olanzapine, did not affect HA efflux. Similarly, other antipsychotics with lower H1 receptor affinity (risperidone, aripiprazole and haloperidol were also without effect on HA efflux. Perfusion of clozapine and pyrilamine into the TMN, but not the mPFC, increased local HA efflux. Finally, HA efflux after antipsychotic treatment was significantly correlated with affinity at H1 receptors whereas 9 other receptors, including 5-HT2A, were not. These results demonstrate that both typical and atypical antipsychotics increase mPFC histamine efflux and this effect may be mediated via antagonism of histamine H1 receptors.

  13. Different pH-sensitivity patterns of 30 sodium channel inhibitors suggest chemically different pools along the access pathway

    Science.gov (United States)

    Lazar, Alexandra; Lenkey, Nora; Pesti, Krisztina; Fodor, Laszlo; Mike, Arpad

    2015-01-01

    The major drug binding site of sodium channels is inaccessible from the extracellular side, drug molecules can only access it either from the membrane phase, or from the intracellular aqueous phase. For this reason, ligand-membrane interactions are as important determinants of inhibitor properties, as ligand-protein interactions. One-way to probe this is to modify the pH of the extracellular fluid, which alters the ratio of charged vs. uncharged forms of some compounds, thereby changing their interaction with the membrane. In this electrophysiology study we used three different pH values: 6.0, 7.3, and 8.6 to test the significance of the protonation-deprotonation equilibrium in drug access and affinity. We investigated drugs of several different indications: carbamazepine, lamotrigine, phenytoin, lidocaine, bupivacaine, mexiletine, flecainide, ranolazine, riluzole, memantine, ritanserin, tolperisone, silperisone, ambroxol, haloperidol, chlorpromazine, clozapine, fluoxetine, sertraline, paroxetine, amitriptyline, imipramine, desipramine, maprotiline, nisoxetine, mianserin, mirtazapine, venlafaxine, nefazodone, and trazodone. We recorded the pH-dependence of potency, reversibility, as well as onset/offset kinetics. As expected, we observed a strong correlation between the acidic dissociation constant (pKa) of drugs and the pH-dependence of their potency. Unexpectedly, however, the pH-dependence of reversibility or kinetics showed diverse patterns, not simple correlation. Our data are best explained by a model where drug molecules can be trapped in at least two chemically different environments: A hydrophilic trap (which may be the aqueous cavity within the inner vestibule), which favors polar and less lipophilic compounds, and a lipophilic trap (which may be the membrane phase itself, and/or lipophilic binding sites on the channel). Rescue from the hydrophilic and lipophilic traps can be promoted by alkalic and acidic extracellular pH, respectively. PMID:26441665

  14. Different pH-sensitivity patterns of 30 sodium channel inhibitors suggest chemically different pools along the access pathway.

    Directory of Open Access Journals (Sweden)

    Alexandra eLazar

    2015-09-01

    Full Text Available The major drug binding site of sodium channels is inaccessible from the extracellular side, drug molecules can only access it either from the membrane phase, or from the intracellular aqueous phase. For this reason, ligand-membrane interactions are as important determinants of inhibitor properties, as ligand-protein interactions. One way to probe this is to modify the pH of the extracellular fluid, which alters the ratio of charged vs. uncharged forms of some compounds, thereby changing their interaction with the membrane. In this electrophysiology study we used three different pH values: 6.0, 7.3 and 8.6 to test the significance of the protonation-deprotonation equilibrium in drug access and affinity. We investigated drugs of several different indications: carbamazepine, lamotrigine, phenytoin, lidocaine, bupivacaine, mexiletine, flecainide, ranolazine, riluzole, memantine, ritanserin, tolperisone, silperisone, ambroxol, haloperidol, chlorpromazine, clozapine, fluoxetine, sertraline, paroxetine, amitriptyline, imipramine, desipramine, maprotiline, nisoxetine, mianserin, mirtazapine, venlafaxine, nefazodone and trazodone. We recorded the pH-dependence of potency, reversibility, as well as onset/offset kinetics. As expected, we observed a strong correlation between the acidic dissociation constant (pKa of drugs and the pH-dependence of their potency. Unexpectedly, however, the pH-dependence of reversibility or kinetics showed diverse patterns, not simple correlation. Our data are best explained by a model where drug molecules can be trapped in at least two chemically different environments: A hydrophilic trap (which may be the aqueous cavity within the inner vestibule, which favors polar and less lipophilic compounds, and a lipophilic trap (which may be the membrane phase itself, and/or lipophilic binding sites on the channel. Rescue from the hydrophilic and lipophilic traps can be promoted by alkalic and acidic extracellular pH, respectively.

  15. Chapter 40: history of neurology in France.

    Science.gov (United States)

    Clarac, François; Boller, François

    2010-01-01

    The history of neurology in France is characterized by the very high degree of centralization in that country where "everything seems to happen in Paris," and yet the considerable degree of autonomous diversity in the evolution of some other medical schools such as Montpellier and Strasbourg. It could be argued that France saw the birth of clinical neurology as a separate discipline since Jean Martin Charcot at the Salpêtrière Hospital obtained a chair of diseases of the nervous system in 1892, a first in the history of the academic world. The chapter shows, however, that the work of Charcot was preceded by a long evolution in medical thinking, which culminated with the introduction of experimental medicine developed by Claude Bernard and François Magendie, and by the study of aphasia by Paul Broca and its localization of language in a specific area of the brain. Many of the great neurologists of France like Duchenne de Boulogne, Gilles de la Tourette, Joseph Babinski and Pierre Marie gravitated around Charcot while others like Charles-Edward Brown-Sequard and Jules Dejerine developed their talents independently. The history of Sainte-Anne Hospital further illustrates this independence. It also shows the relation between neurology and psychiatry with Henri Ey, Jean Delay and Pierre Deniker, who collaborated with Henri Laborit in the clinical development of chlorpromazine. Sainte Anne also saw the birth of modern neuropsychology with Henry Hécaen. Jean Talairach and his group developed human stereotaxic neurosurgery and a 3-dimensional brain atlas that is used around the world. The chapter also mentions institutions (the CNRS and INSERM) that have contributed to developments partially independently from medical schools. It concludes with a presentation of schools located outside of Paris that have played a significant role in the development of neurology. Six of the most important ones are described: Montpellier, Toulouse, Bordeaux, Strasbourg, Lyon, and

  16. Half a century of antipsychotics and still a central role for dopamine D2 receptors.

    Science.gov (United States)

    Kapur, Shitij; Mamo, David

    2003-10-01

    A review of the history of antipsychotics reveals that while the therapeutic effects of chlorpromazine and reserpine were discovered and actively researched almost concurrently, subsequent drug development has been restricted to drugs acting on postsynaptic receptors rather than modulation of dopamine release. The fundamental property of atypical antipsychotics is their ability to produce an antipsychotic effect in the absence of extrapyramidal side effects (EPS) or prolactin elevation. Modulation of the dopamine D2 receptor remains both necessary and sufficient for antipsychotic drug action, with affinity to the D2-receptor being the single most important discriminator between a typical and atypical drug profile. Most antipsychotics, including atypical antipsychotics, show a dose-dependent threshold of D2 receptor occupancy for their therapeutic effects, although the precise threshold is different for different drugs. Some atypical antipsychotics do not appear to reach the threshold for EPS and prolactin elevation, possibly accounting for their atypical nature. To link the biological theories of antipsychotics to their psychological effects, a hypothesis is proposed wherein psychosis is a state of aberrant salience of stimuli and ideas, and antipsychotics, via modulation of the mesolimbic dopamine system, dampen the salience of these symptoms. Thus, antipsychotics do not excise psychosis: they provide the neurochemical platform for the resolution of symptoms. Future generations of antipsychotics may need to move away from a "one-size-fits-all polypharmacy-in-a-pill" approach to treat all the different aspects of schizophrenia. At least in theory a preferred approach would be the development of specific treatments for the different dimensions of schizophrenia (e.g., positive, negative, cognitive, and affective) that can be flexibly used and titrated in the service of patients' presenting psychopathology.

  17. Inhibitors of alphavirus entry and replication identified with a stable Chikungunya replicon cell line and virus-based assays.

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    Leena Pohjala

    Full Text Available Chikungunya virus (CHIKV, an alphavirus, has recently caused epidemic outbreaks and is therefore considered a re-emerging pathogen for which no effective treatment is available. In this study, a CHIKV replicon containing the virus replicase proteins together with puromycin acetyltransferase, EGFP and Renilla luciferase marker genes was constructed. The replicon was transfected into BHK cells to yield a stable cell line. A non-cytopathic phenotype was achieved by a Pro718 to Gly substitution and a five amino acid insertion within non-structural protein 2 (nsP2, obtained through selection for stable growth. Characterization of the replicon cell line by Northern blotting analysis revealed reduced levels of viral RNA synthesis. The CHIKV replicon cell line was validated for antiviral screening in 96-well format and used for a focused screen of 356 compounds (natural compounds and clinically approved drugs. The 5,7-dihydroxyflavones apigenin, chrysin, naringenin and silybin were found to suppress activities of EGFP and Rluc marker genes expressed by the CHIKV replicon. In a concomitant screen against Semliki Forest virus (SFV, their anti-alphaviral activity was confirmed and several additional inhibitors of SFV with IC₅₀ values between 0.4 and 24 µM were identified. Chlorpromazine and five other compounds with a 10H-phenothiazinyl structure were shown to inhibit SFV entry using a novel entry assay based on a temperature-sensitive SFV mutant. These compounds also reduced SFV and Sindbis virus-induced cytopathic effect and inhibited SFV virion production in virus yield experiments. Finally, antiviral effects of selected compounds were confirmed using infectious CHIKV. In summary, the presented approach for discovering alphaviral inhibitors enabled us to identify potential lead structures for the development of alphavirus entry and replication phase inhibitors as well as demonstrated the usefulness of CHIKV replicon and SFV as biosafe surrogate

  18. Inhibitors of alphavirus entry and replication identified with a stable Chikungunya replicon cell line and virus-based assays.

    Science.gov (United States)

    Pohjala, Leena; Utt, Age; Varjak, Margus; Lulla, Aleksei; Merits, Andres; Ahola, Tero; Tammela, Päivi

    2011-01-01

    Chikungunya virus (CHIKV), an alphavirus, has recently caused epidemic outbreaks and is therefore considered a re-emerging pathogen for which no effective treatment is available. In this study, a CHIKV replicon containing the virus replicase proteins together with puromycin acetyltransferase, EGFP and Renilla luciferase marker genes was constructed. The replicon was transfected into BHK cells to yield a stable cell line. A non-cytopathic phenotype was achieved by a Pro718 to Gly substitution and a five amino acid insertion within non-structural protein 2 (nsP2), obtained through selection for stable growth. Characterization of the replicon cell line by Northern blotting analysis revealed reduced levels of viral RNA synthesis. The CHIKV replicon cell line was validated for antiviral screening in 96-well format and used for a focused screen of 356 compounds (natural compounds and clinically approved drugs). The 5,7-dihydroxyflavones apigenin, chrysin, naringenin and silybin were found to suppress activities of EGFP and Rluc marker genes expressed by the CHIKV replicon. In a concomitant screen against Semliki Forest virus (SFV), their anti-alphaviral activity was confirmed and several additional inhibitors of SFV with IC₅₀ values between 0.4 and 24 µM were identified. Chlorpromazine and five other compounds with a 10H-phenothiazinyl structure were shown to inhibit SFV entry using a novel entry assay based on a temperature-sensitive SFV mutant. These compounds also reduced SFV and Sindbis virus-induced cytopathic effect and inhibited SFV virion production in virus yield experiments. Finally, antiviral effects of selected compounds were confirmed using infectious CHIKV. In summary, the presented approach for discovering alphaviral inhibitors enabled us to identify potential lead structures for the development of alphavirus entry and replication phase inhibitors as well as demonstrated the usefulness of CHIKV replicon and SFV as biosafe surrogate models for anti

  19. Characterization of a β-Adrenergic-Like Octopamine Receptor in the Oriental Fruit Fly, Bactrocera dorsalis (Hendel

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    Hui-Min Li

    2016-09-01

    Full Text Available The biogenic amine octopamine plays a critical role in the regulation of many physiological processes in insects. Octopamine transmits its action through a set of specific G-protein coupled receptors (GPCRs, namely octopamine receptors. Here, we report on a β-adrenergic-like octopamine receptor gene (BdOctβR1 from the oriental fruit fly, Bactrocera dorsalis (Hendel, a destructive agricultural pest that occurs in North America and the Asia-Pacific region. As indicated by RT-qPCR, BdOctβR1 was highly expressed in the central nervous system (CNS and Malpighian tubules (MT in the adult flies, suggesting it may undertake important roles in neural signaling in the CNS as well as physiological functions in the MT of this fly. Furthermore, its ligand specificities were tested in a heterologous expression system where BdOctβR1 was expressed in HEK-293 cells. Based on cyclic AMP response assays, we found that BdOctβR1 could be activated by octopamine in a concentration-dependent manner, confirming that this receptor was functional, while tyramine and dopamine had much less potency than octopamine. Naphazoline possessed the highest agonistic activity among the tested agonists. In antagonistic assays, mianserin had the strongest activity and was followed by phentolamine and chlorpromazine. Furthermore, when the flies were kept under starvation, there was a corresponding increase in the transcript level of BdOctβR1, while high or low temperature stress could not induce significant expression changes. The above results suggest that BdOctβR1 may be involved in the regulation of feeding processes in Bactrocera dorsalis and may provide new potential insecticide leads targeting octopamine receptors.

  20. Characterization of a β-Adrenergic-Like Octopamine Receptor in the Oriental Fruit Fly, Bactrocera dorsalis (Hendel)

    Science.gov (United States)

    Li, Hui-Min; Jiang, Hong-Bo; Gui, Shun-Hua; Liu, Xiao-Qiang; Liu, Hong; Lu, Xue-Ping; Smagghe, Guy; Wang, Jin-Jun

    2016-01-01

    The biogenic amine octopamine plays a critical role in the regulation of many physiological processes in insects. Octopamine transmits its action through a set of specific G-protein coupled receptors (GPCRs), namely octopamine receptors. Here, we report on a β-adrenergic-like octopamine receptor gene (BdOctβR1) from the oriental fruit fly, Bactrocera dorsalis (Hendel), a destructive agricultural pest that occurs in North America and the Asia-Pacific region. As indicated by RT-qPCR, BdOctβR1 was highly expressed in the central nervous system (CNS) and Malpighian tubules (MT) in the adult flies, suggesting it may undertake important roles in neural signaling in the CNS as well as physiological functions in the MT of this fly. Furthermore, its ligand specificities were tested in a heterologous expression system where BdOctβR1 was expressed in HEK-293 cells. Based on cyclic AMP response assays, we found that BdOctβR1 could be activated by octopamine in a concentration-dependent manner, confirming that this receptor was functional, while tyramine and dopamine had much less potency than octopamine. Naphazoline possessed the highest agonistic activity among the tested agonists. In antagonistic assays, mianserin had the strongest activity and was followed by phentolamine and chlorpromazine. Furthermore, when the flies were kept under starvation, there was a corresponding increase in the transcript level of BdOctβR1, while high or low temperature stress could not induce significant expression changes. The above results suggest that BdOctβR1 may be involved in the regulation of feeding processes in Bactrocera dorsalis and may provide new potential insecticide leads targeting octopamine receptors. PMID:27669213

  1. Development and validation of a quantitative, high-throughput, fluorescent-based bioassay to detect schistosoma viability.

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    Emily Peak

    Full Text Available BACKGROUND: Schistosomiasis, caused by infection with the blood fluke Schistosoma, is responsible for greater than 200,000 human deaths per annum. Objective high-throughput screens for detecting novel anti-schistosomal targets will drive 'genome to drug' lead translational science at an unprecedented rate. Current methods for detecting schistosome viability rely on qualitative microscopic criteria, which require an understanding of parasite morphology, and most importantly, must be subjectively interpreted. These limitations, in the current state of the art, have significantly impeded progress into whole schistosome screening for next generation chemotherapies. METHODOLOGY/PRINCIPAL FINDINGS: We present here a microtiter plate-based method for reproducibly detecting schistosomula viability that takes advantage of the differential uptake of fluorophores (propidium iodide and fluorescein diacetate by living organisms. We validate this high-throughput system in detecting schistosomula viability using auranofin (a known inhibitor of thioredoxin glutathione reductase, praziquantel and a range of small compounds with previously-described (gambogic acid, sodium salinomycin, ethinyl estradiol, fluoxetidine hydrochloride, miconazole nitrate, chlorpromazine hydrochloride, amphotericin b, niclosamide or suggested (bepridil, ciclopirox, rescinnamine, flucytosine, vinblastine and carbidopa anti-schistosomal activities. This developed method is sensitive (200 schistosomula/well can be assayed, relevant to industrial (384-well microtiter plate compatibility and academic (96-well microtiter plate compatibility settings, translatable to functional genomics screens and drug assays, does not require a priori knowledge of schistosome biology and is quantitative. CONCLUSIONS/SIGNIFICANCE: The wide-scale application of this fluorescence-based bioassay will greatly accelerate the objective identification of novel therapeutic lead targets/compounds to combat

  2. Uso de olanzapina e eletroconvulsoterapia em um paciente com esquizofrenia catatônica refratária e antecedentes de síndrome neuroléptica maligna Olanzapina y ECT en un enfermo con esquizofrenia catatónica refractaria y alto riesgo de síndrome neuroléptico maligno Olanzapine and ECT combined therapy in a refractory catatonic subtype schizophrenia patient with previous neuroleptic malignant syndrome episodes

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    Pedro Gomes de Alvarenga

    2005-12-01

    Full Text Available Este artigo descreve a história clínica e o manejo de um paciente masculino adulto com esquizofrenia catatônica refratária a dois neurolépticos típicos (haloperidol e clorpromazina e a outro agente atípico (risperidona, e com antecedente de dois episódios de síndrome neuroléptica maligna em vigência de neurolépticos típicos. Os autores optaram pela associação de eletroconvulsoterapia (ECT e olanzapina (7,5 mg. Foram obtidos consideráveis benefícios para o paciente.Presentamos un relato clínico referente a la historia precedente y al desarrollo de un enfermo varón con esquizofrenia catatónica refractaria a los neurolépticos convencionales (clorpromazina y haloperidol y a otro agente de nueva generación (risperidona. El enfermo presentó, en dos ocasiones, síndrome neuroléptico maligno, provocado por el uso de los neurolépticos convencionales. Los autores emplearon ECT y olanzapina (7,5 mg obteniendo considerable éxito clínico.This article describes the clinical history and management of an adult male patient with refractory catatonic schizophrenia to two typically used neurolpetic medications (haloperidol and chlorpromazine and to another atypical agent (risperidone.The patient had also presented two neuroleptic malignant syndrome episodes due to typical neuroleptic agents. The authors combined ECT and olanzapine (7.5 mg as treatment, and a considerable clinical improvement was obtained.

  3. Association of typical versus atypical antipsychotics with symptoms and quality of life in schizophrenia.

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    Koichiro Fujimaki

    Full Text Available BACKGROUND: Several reports on patients with chronic schizophrenia suggest that atypical versus typical antipsychotics are expected to lead to better quality of life (QOL and cognitive function. Our aim was to examine the association of chronic treatment with typical or atypical antipsychotics with cognitive function, psychiatric symptoms, QOL, and drug-induced extrapyramidal symptoms in long-hospitalized patients with schizophrenia. METHODOLOGY AND PRINCIPAL FINDINGS: The Hasegawa Dementia Scale-Revised (HDS-R, Brief Psychiatric Rating Scale (BPRS, the Schizophrenia Quality of Life Scale, translated into Japanese (JSQLS, and the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS were used to evaluate cognitive function, psychiatric symptoms, QOL, and drug-induced extrapyramidal symptoms. We examined the correlation between the dose of antipsychotics and each measure derived from these psychometric tests. The student t-test was used to compare scores obtained from psychometric tests between patients receiving typical and atypical antipsychotics. Results showed significant correlations between chlorpromazine (CPZ-equivalent doses of typical antipsychotics and atypical antipsychotics, and the total BPRS score and BPRS subscale scores for positive symptoms. CPZ-equivalent doses of typical antipsychotics were correlated with the JSQLS subscale score for dysfunction of psycho-social activity and DIEPSS score. Furthermore, the total BPRS scores, BPRS subscale score for positive symptoms, the JSQLS subscale score for dysfunction of psycho-social activity, and the DIEPSS score were significantly higher in patients receiving typical antipsychotics than atypical antipsychotics. CONCLUSION AND SIGNIFICANCE: These findings suggest that long-term administration of typical antipsychotics has an unfavorable association with feelings of difficulties mixing in social situations in patients with chronic schizophrenia.

  4. The influence of surface charge on serum protein interaction and cellular uptake: studies with dendritic polyglycerols and dendritic polyglycerol-coated gold nanoparticles

    Science.gov (United States)

    Bewersdorff, Tony; Vonnemann, Jonathan; Kanik, Asiye; Haag, Rainer; Haase, Andrea

    2017-01-01

    Nanoparticles (NPs) have gained huge interest in the medical field, in particular for drug delivery purposes. However, binding of proteins often leads to fast NP uptake and rapid clearance, thereby hampering medical applications. Thus, it is essential to determine and control the bio–nano interface. This study investigated the serum protein interactions of dendritic polyglycerols (dPGs), which are promising drug delivery candidates by means of two dimensional gel electrophoresis (2DE) in combination with mass spectrometry. In order to investigate the influence of surface charge, sulfated (sulfated dendritic polyglycerol [dPGS]) and non-sulfated (dPGOH) surfaces were applied, which were synthesized on a gold core allowing for easier separation from unbound biomolecules through centrifugation. Furthermore, two different sizes for dPGS were included. Although size had only a minor influence, considerable differences were detected in protein affinity for dPGS versus dPGOH surfaces, with dPGOH binding much less proteins. Cellular uptake into human CD14+ monocytes was analyzed by flow cytometry, and dPGOH was taken up to a much lower extent compared to dPGS. By using a pull-down approach, possible cellular interaction partners of serum pre-incubated dPGS-Au20 NPs from the membrane fraction of THP-1 cells could be identified such as for instance the transferrin receptor or an integrin. Clathrin-mediated endocytosis was further investigated using chlorpromazine as an inhibitor, which resulted in a 50% decrease of the cellular uptake of dPGS. This study could confirm the influence of surface charge on protein interactions and cellular uptake of dPGS. Furthermore, the approach allowed for the identification of possible uptake receptors and insights into the uptake mechanism. PMID:28352171

  5. [Effect of plasma membrane ion permeability modulators on respiration and heat output of wheat roots].

    Science.gov (United States)

    Alekseeva, V A; Gordon, L Kh; Loseva, N L; Rakhimova, G G; Tsentsevitskiĭ, A N

    2006-01-01

    A study was made of changes in the rates of respiration, heat production, and membrane characteristics in cells of excised roots of wheat seedlings under the modulation of plasma membrane ion permeability by two membrane active compounds: valinomycin (20 microM (V50)) and chlorpromazine (50 microM (CP50) and 100 microM (CP100)). Both compounds increased the loss of potassium ions, which correlated with the lowering of membrane potential, rate of respiration, and heat production after a 2 h exposure. The differences in alteration of these parameters were due to specific action of either compound on the membrane and to the extent of ion homeostasis disturbance. V20 had a weak effect on the studied parameters. V50 caused an increase of the rate of respiration and heat production, which enhanced following a prolonged action (5 h) and were associated with ion homeostatis restoration. The extent of alteration of membrane characteristics (an increase of potassium loss by roots, and lowering of cell membrane potential) as well as energy expense under the action of CP50 during the first period were more pronounced than in the presence of V50. During a prolonged action of CP50, the increase of respiration intensity and heat production correlated with partial recovery of ion homeostatis in cells. Essential lowering of membrane potential and substantial loss of potassium by cells, starting from the early stages of their response reaction, were followed by inhibition of respiration rate and heat production. Alterations of the structure and functional characteristics of excised root cells indicate the intensification of the membrane-tropic effect of a prolonged action of CP100, and the lack of cell energy resources.

  6. Therapeutic MSC exosomes are derived from lipid raft microdomains in the plasma membrane

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    Soon Sim Tan

    2013-12-01

    Full Text Available Background: Mesenchymal stem cell (MSC was previously shown to secrete lipid vesicles that when purified by high performance liquid chromatography as a population of homogenously sized particles with a hydrodynamic radius of 55–65 nm reduce infarct size in a mouse model of myocardial ischemia/reperfusion injury. As these vesicles exhibit many biophysical and biochemical properties of exosomes, they were identified as exosomes. Here we investigated if these lipid vesicles were indeed exosomes that have an endosomal biogenesis. Method: In most cells, endocytosis is thought to occur at specialized microdomains known as lipid rafts. To demonstrate an endosomal origin for MSC exosomes, MSCs were pulsed with ligands e.g. transferrin (Tfs and Cholera Toxin B (CTB that bind receptors in lipid rafts. The endocytosed ligands were then chased to determine if they were incorporated into the exosomes. Results: A fraction of exogenous Tfs was found to recycle into MSC exosomes. When MSCs were pulsed with labelled Tfs in the presence of chlorpromazine, an inhibitor of clathrin-mediated endocytosis, Tf incorporation in CD81-immunoprecipitate was reduced during the chase. CTB which binds GM1 gangliosides that are enriched in lipid rafts extracted exosome-associated proteins, CD81, CD9, Alix and Tsg101 from MSC-conditioned medium. Exogenous CTBs were pulse-chased into secreted vesicles. Extraction of Tf- or CTB-binding vesicles in an exosome preparation mutually depleted each other. Inhibition of sphingomyelinases reduced CTB-binding vesicles. Conclusion: Together, our data demonstrated that MSC exosomes are derived from endocytosed lipid rafts and that their protein cargo includes exosome-associated proteins CD81, CD9, Alix and Tsg101.

  7. Anti-calmodulins and tricyclic adjuvants in pain therapy block the TRPV1 channel.

    Science.gov (United States)

    Oláh, Zoltán; Jósvay, Katalin; Pecze, László; Letoha, Tamás; Babai, Norbert; Budai, Dénes; Otvös, Ferenc; Szalma, Sándor; Vizler, Csaba

    2007-06-20

    Ca(2+)-loaded calmodulin normally inhibits multiple Ca(2+)-channels upon dangerous elevation of intracellular Ca(2+) and protects cells from Ca(2+)-cytotoxicity, so blocking of calmodulin should theoretically lead to uncontrolled elevation of intracellular Ca(2+). Paradoxically, classical anti-psychotic, anti-calmodulin drugs were noted here to inhibit Ca(2+)-uptake via the vanilloid inducible Ca(2+)-channel/inflamatory pain receptor 1 (TRPV1), which suggests that calmodulin inhibitors may block pore formation and Ca(2+) entry. Functional assays on TRPV1 expressing cells support direct, dose-dependent inhibition of vanilloid-induced (45)Ca(2+)-uptake at microM concentrations: calmidazolium (broad range) > or = trifluoperazine (narrow range) chlorpromazine/amitriptyline>fluphenazine>W-7 and W-13 (only partially). Most likely a short acidic domain at the pore loop of the channel orifice functions as binding site either for Ca(2+) or anti-calmodulin drugs. Camstatin, a selective peptide blocker of calmodulin, inhibits vanilloid-induced Ca(2+)-uptake in intact TRPV1(+) cells, and suggests an extracellular site of inhibition. TRPV1(+), inflammatory pain-conferring nociceptive neurons from sensory ganglia, were blocked by various anti-psychotic and anti-calmodulin drugs. Among them, calmidazolium, the most effective calmodulin agonist, blocked Ca(2+)-entry by a non-competitive kinetics, affecting the TRPV1 at a different site than the vanilloid binding pocket. Data suggest that various calmodulin antagonists dock to an extracellular site, not found in other Ca(2+)-channels. Calmodulin antagonist-evoked inhibition of TRPV1 and NMDA receptors/Ca(2+)-channels was validated by microiontophoresis of calmidazolium to laminectomised rat monitored with extracellular single unit recordings in vivo. These unexpected findings may explain empirically noted efficacy of clinical pain adjuvant therapy that justify efforts to develop hits into painkillers, selective to sensory Ca(2

  8. Anti-calmodulins and tricyclic adjuvants in pain therapy block the TRPV1 channel.

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    Zoltán Oláh

    Full Text Available Ca(2+-loaded calmodulin normally inhibits multiple Ca(2+-channels upon dangerous elevation of intracellular Ca(2+ and protects cells from Ca(2+-cytotoxicity, so blocking of calmodulin should theoretically lead to uncontrolled elevation of intracellular Ca(2+. Paradoxically, classical anti-psychotic, anti-calmodulin drugs were noted here to inhibit Ca(2+-uptake via the vanilloid inducible Ca(2+-channel/inflamatory pain receptor 1 (TRPV1, which suggests that calmodulin inhibitors may block pore formation and Ca(2+ entry. Functional assays on TRPV1 expressing cells support direct, dose-dependent inhibition of vanilloid-induced (45Ca(2+-uptake at microM concentrations: calmidazolium (broad range > or = trifluoperazine (narrow range chlorpromazine/amitriptyline>fluphenazine>>W-7 and W-13 (only partially. Most likely a short acidic domain at the pore loop of the channel orifice functions as binding site either for Ca(2+ or anti-calmodulin drugs. Camstatin, a selective peptide blocker of calmodulin, inhibits vanilloid-induced Ca(2+-uptake in intact TRPV1(+ cells, and suggests an extracellular site of inhibition. TRPV1(+, inflammatory pain-conferring nociceptive neurons from sensory ganglia, were blocked by various anti-psychotic and anti-calmodulin drugs. Among them, calmidazolium, the most effective calmodulin agonist, blocked Ca(2+-entry by a non-competitive kinetics, affecting the TRPV1 at a different site than the vanilloid binding pocket. Data suggest that various calmodulin antagonists dock to an extracellular site, not found in other Ca(2+-channels. Calmodulin antagonist-evoked inhibition of TRPV1 and NMDA receptors/Ca(2+-channels was validated by microiontophoresis of calmidazolium to laminectomised rat monitored with extracellular single unit recordings in vivo. These unexpected findings may explain empirically noted efficacy of clinical pain adjuvant therapy that justify efforts to develop hits into painkillers, selective to sensory Ca(2

  9. The inhibitory effects in vitro of phenothiazines and other drugs on lipid-peroxidation systems in rat liver microsomes, and their relationship to the liver necrosis produced by carbon tetrachloride

    Science.gov (United States)

    Slater, T. F.

    1968-01-01

    1. The effects of several phenothiazine derivatives on lipid-peroxidation systems in rat liver microsomes were studied and the results are considered in relation to the hepatotoxic action of carbon tetrachloride. 2. The lipid-peroxidation system coupled to NADPH2 oxidation and stimulated by an ADP–Fe2+ mixture is strongly inhibited in vitro by promethazine (50% inhibition at 29μm). Chlorpromazine and Stelazine also inhibit the peroxidation system but are less effective than promethazine. 3. The effects of promethazine on three other systems involving oxygen uptake (sulphite oxidation, orcinol oxidation and mitochondrial succinate oxidation) were also studied. Promethazine does not inhibit these systems to the same extent as it does the NADPH2–ADP–Fe2+ lipid-peroxidation system. 4. Promethazine also produces an inhibition of the NADPH2–ADP–Fe2+ system in liver microsomes after administration in vivo. It is concluded that the inhibition involves the interaction of the drug (or a metabolite of it) with the microsomal electron-transport chain. 5. Several other compounds known to protect the rat against liver necrosis after the administration of carbon tetrachloride were tested for inhibitory action on the NADPH2–ADP–Fe2+ system. No clear correlation was observed between effectiveness in vivo as a protective agent and inhibitory effects on the NADPH2–ADP–Fe2+ system in vitro. 6. Promethazine was found to inhibit the stimulation of lipid peroxidation produced in rat liver microsomes by low concentrations of carbon tetrachloride. This effect occurs at a concentration similar to that observed in vivo after administration of a normal clinical dose. PMID:4388686

  10. Evaluation of (iodine-125)N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3- propanediamine lung uptake using an isolated-perfused lung model

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    Slosman, D.O.; Brill, A.B.; Polla, B.S.; Alderson, P.O.

    1987-02-01

    Lung uptake of N,N,N'-trimethyl-N'-(2-Hydroxy-3-methyl-5-iodobenzyl)-1,3- propanediamine (HIPDM) has been reported, but the mechanism of this process has not yet been established. Thus, single-pass (/sup 125/I)HIPDM accumulation was studied in rat lungs perfused with a Krebs-Ringer bicarbonate buffer containing 4.5% bovine albumin. Iodine-125 HIPDM lung accumulation was monitored by the percent of extraction per gram of lung tissue. Iodine-125 HIPDM lung uptake did not appear to occur by simple diffusion. As the time of perfusion was increased from 2 to 15 min, the rate of uptake of 2 microM (/sup 125/I)HIPDM decreased by 40%. During a 2-min perfusion, 98.6% +/- 6.7 (n = 8) extraction was observed with 2 microM (/sup 125/I)HIPDM, but only 38% +/- 2.0 (n = 3) was extracted when the (/sup 125/I)HIPDM concentration was 1 mM. The addition of 1 mM chlorpromazine, propranolol or imipramine also decreased (/sup 125/I)HIPDM lung uptake to 43.0% +/- 1.5, 51.4% +/- 2.2, and 49.8% +/- 0.8, respectively, (each n = 4 - 6, p less than 0.001). Cold (4 degrees C) had little effect on pulmonary accumulation (77.7% +/- 7.4, n = 5, p less than 0.01), and the addition of ouabain or the use of sodium-free medium had no effect. Thus, pulmonary (/sup 125/I)HIPDM accumulation does not appear to occur by sodium-dependent active transport. Rather, its uptake appears to be similar to the uptake of other basic amines, such as propranolol and imipramine, which are known to bind by physico-chemical interactions to pulmonary endothelial cell membranes and reflect pulmonary vascular surface area.

  11. Treatment of patients with painful blind eye using stellate ganglion block

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    Tatiana Vaz Horta Xavier

    2016-02-01

    Full Text Available BACKGROUND AND OBJECTIVES: management of pain in painful blind eyes is still a challenge. Corticosteroids and hypotensive agents, as well as evisceration and enucleation, are some of the strategies employed so far that are not always effective and, depending on the strategy, cause a deep emotional shock to the patient. Given these issues, the aim of this case report is to demonstrate a new and viable option for the management of such pain by treating the painful blind eye with the stellate ganglion block technique, a procedure that has never been described in the literature for this purpose. CASE REPORT: six patients with painful blind eye, all caused by glaucoma, were treated; in these patients, VAS (visual analogue scale for pain assessment, in which 0 is the absence of pain and 10 is the worst pain ever experienced ranged from 7 to 10. We opted for weekly sessions of stellate ganglion block with 4 mL of bupivacaine (0.5% without vasoconstrictor and clonidine 1 mcg/kg. Four patients had excellent results at VAS, ranging between 0 and 3, and two remained asymptomatic (VAS = 0, without the need for additional medication. The other two used gabapentin 300 mg every 12 h. CONCLUSION: currently, there are several therapeutic options for the treatment of painful blind eye, among which stand out the retrobulbar blocks with chlorpromazine, alcohol and phenol. However, an effective strategy with low rate of serious complications, which is non-mutilating and improves the quality of life of the patient, is essential. Then, stellate ganglion block arises as a demonstrably viable and promising option to meet this demand.

  12. Megalin/cubilin-mediated uptake of FITC-labeled IgG by OK kidney epithelial cells.

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    Nagai, Junya; Sato, Koya; Yumoto, Ryoko; Takano, Mikihisa

    2011-01-01

    In this paper, we characterize the uptake mechanism of fluorescein isothiocyanate-labeled human immunoglobulin G (FITC-hIgG) in opossum kidney (OK) epithelial cells, which have been shown to express megalin and cubilin. Confocal immunofluorescence microscopy showed the punctate expression of the neonatal Fc receptor FcRn in the cytoplasm, but not on the cell surface membrane. Temperature- and energy-dependent uptake of FITC-hIgG was observed at pH 7.4 but not at pH 6.0, indicating that the internalization of FITC-hIgG might not be due to FcRn, which has a binding affinity for IgG under acidic conditions. Under physiological pH conditions, human and bovine serum γ-globulin decreased FITC-hIgG uptake in a concentration-dependent manner. In addition, FITC-hIgG uptake was inhibited by various megalin and/or cubilin ligands including albumin, cytochrome c, transferrin and gentamicin. Endosomal acidification inhibitors (bafilomycin A(1) and chloroquine) significantly decreased the uptake of FITC-hIgG. Clathrin-dependent endocytosis inhibitors (phenylarsine oxide and chlorpromazine) decreased FITC-hIgG uptake. Potassium depletion and hypertonicity, conditions known to inhibit clathrin-dependent endocytosis, also decreased FITC-hIgG uptake. In contrast, caveolin-dependent endocytosis inhibitors (nystatin and methyl-β-cyclodextrin) did not decrease, but rather increased the uptake of FITC-hIgG. These observations suggest that the internalization of FITC-hIgG in OK cells might be, at least in part, due to megalin/cubilin-mediated, clathrin-dependent endocytosis.

  13. The PI3K/Akt pathway is involved in early infection of some exogenous avian leukosis viruses.

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    Feng, Shao-zhen; Cao, Wei-sheng; Liao, Ming

    2011-07-01

    Avian leukosis virus (ALV) is an enveloped and oncogenic retrovirus. Avian leukosis caused by the members of ALV subgroups A, B and J has become one of the major problems challenging the poultry industry in China. However, the cellular factors such as signal transduction pathways involved in ALV infection are not well defined. In this study, our data demonstrated that ALV-J strain NX0101 infection in primary chicken embryo fibroblasts or DF-1 cells was correlated with the activity and phosphorylation of Akt. Akt activation was initiated at a very early stage of infection independently of NX0101 replication. The specific phosphatidylinositol 3-kinase (PI3K) inhibitors LY294002 or wortmannin could suppress Akt phosphorylation, indicating that NX0101-induced Akt phosphorylation is PI3K-dependent. ALV-A strain GD08 or ALV-B strain CD08 infection also demonstrated a similar profile of PI3K/Akt activation. Treatment of DF-1 cells with the drug 5-(N, N-hexamethylene) amiloride that inhibits the activity of chicken Na(+)/H(+) exchanger type 1 significantly reduced Akt activation induced by NX0101, but not by GD08 and CD08. Akt activation triggered by GD08 or CD08 was abolished by clathrin-mediated endocytosis inhibitor chlorpromazine. Receptor-mediated endocytosis inhibitor dansylcadaverine had a negligible effect on all ALV-induced Akt phosphorylation. Moreover, viral replication of ALV was suppressed by LY294002 in a dose-dependent manner, which was due to the inhibition of virus infection by LY294002. These data suggest that the activation of the PI3K/Akt signalling pathway by exogenous ALV infection plays an important role in viral entry, yet the precise mechanism remains under further investigation.

  14. Associations of Adverse Clinical Course and Ingested Substances among Patients with Deliberate Drug Poisoning: A Cohort Study from an Intensive Care Unit in Japan

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    Ichikura, Kanako; Takeuchi, Takashi

    2016-01-01

    Objectives Some patients with deliberate drug poisoning subsequently have an adverse clinical course. The present study aimed to examine whether the type of drugs ingested and psychiatric diagnoses were related to an adverse clinical course. Methods We conducted a cohort study of patients with deliberate drug poisoning admitted to the intensive care unit of a university hospital located in Tokyo, Japan, between September 2006 and June 2013. Intensive care unit (ICU) stay of ≥4 days was used as a primary outcome measure, while the incidence of aspiration pneumonitis was used as a secondary outcome measure. Ingested substances and psychiatric diagnoses were used as explanatory variables. Results Of the 676 patients with deliberate drug poisoning, 88% had a history of psychiatric treatment and 82% had ingested psychotropic drugs. Chlorpromazine-promethazine-phenobarbital combination drug (Vegetamin®) ranked fifth among the most frequently ingested substances in cases of deliberate drug poisoning and had the highest incidence of prolonged ICU stay (20%) and aspiration pneumonitis (29%). The top three major classes consisted of benzodiazepines (79%), new-generation antidepressants (25%), and barbiturates/non-barbiturates (23%). Barbiturate overdose was independently associated with increased odds of both prolonged ICU stay (8% vs. 17%; odds ratio [OR], 2.97; 95% confidence interval [CI], 1.60–5.55) and aspiration pneumonitis (8% vs. 24%; OR, 3.83; 95% CI, 2.18–6.79) relative to those associated with overdose of only other sedative-hypnotics (i.e., benzodiazepines). Conclusion These results suggest that judicious prescribing of barbiturates by psychiatrists could reduce the risk of an adverse clinical course when a patient attempts an overdose. PMID:27560966

  15. Small interference RNA profiling reveals the essential role of human membrane trafficking genes in mediating the infectious entry of dengue virus

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    Chu Justin

    2010-02-01

    Full Text Available Abstract Background Dengue virus (DENV is the causative agent of Dengue fever and the life-threatening Dengue Haemorrhagic fever or Dengue shock syndrome. In the absence of anti-viral agents or vaccine, there is an urgent need to develop an effective anti-viral strategy against this medically important viral pathogen. The initial interplay between DENV and the host cells may represent one of the potential anti-viral targeting sites. Currently the involvements of human membrane trafficking host genes or factors that mediate the infectious cellular entry of dengue virus are not well defined. Results In this study, we have used a targeted small interfering RNA (siRNA library to identify and profile key cellular genes involved in processes of endocytosis, cytoskeletal dynamics and endosome trafficking that are important and essential for DENV infection. The infectious entry of DENV into Huh7 cells was shown to be potently inhibited by siRNAs targeting genes associated with clathrin-mediated endocytosis. The important role of clathrin-mediated endocytosis was confirmed by the expression of well-characterized dominant-negative mutants of genes in this pathway and by using the clathrin endocytosis inhibitor chlorpromazine. Furthermore, DENV infection was shown to be sensitive to the disruption of human genes in regulating the early to late endosomal trafficking as well as the endosomal acidic pH. The importance and involvement of both actin and microtubule dynamics in mediating the infectious entry of DENV was also revealed in this study. Conclusions Together, the findings from this study have provided a detail profiling of the human membrane trafficking cellular genes and the mechanistic insight into the interplay of these host genes with DENV to initiate an infection, hence broadening our understanding on the entry pathway of this medically important viral pathogen. These data may also provide a new potential avenue for development of anti

  16. Choking risk among psychiatric inpatients

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    Nagamine T

    2011-06-01

    Full Text Available Takahiko Nagamine1Division of Psychiatric Internal Medicine, Seiwakai-Kitsunan Hospital, Suzenji, JapanChoking is a life-threatening and not infrequent occurrence in psychiatric hospitals. There is, however, little information available about the risk factors or methods to prevent choking. We conducted a retrospective analysis of the 8 patients who had a cardiopulmonary arrest due to choking and received resuscitation at our hospital during the 6-year period from April 2005 to March 2011. The study involved 6 males and females, all of whom were patients with schizophrenia taking antipsychotics orally. They were aged from 56 to 79 (mean ± SD: 69.0 ± 7.5 years, with the duration of illness from 28 to 54 years (39.9 ± 7.9 years. In 6 of the 8 cases, choking was diagnosed immediately on the basis of the situation at the time of cardiopulmonary arrest. In the remaining 2 cases, cardiopulmonary arrest was initially unexplained, and choking was only diagnosed subsequently. Choking was caused by bread in all cases. Tracheal intubation was carried out in all cases and resulted in successful resuscitation, causing no subsequent change in functions compared with the prechoking condition. All 8 patients had been receiving multiple antipsychotics before the event (mean number of drugs used 2.5 ± 0.7, with a total dose level ranging from 600 to 1800 mg/day chlorpromazine equivalents (mean 1113 ± 341 mg/day. Seven of the 8 patients had mild to moderate involuntary movements, and 5 patients were diagnosed with antipsychotic-induced tardive dyskinesia. During the 5-year period before the choking event, 7 of the 8 patients had at least 1 treatment interruption, and some patients had up to 4 interruptions.

  17. The availability of essential medicines for mental healthcare in Sofala, Mozambique

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    Bradley H. Wagenaar

    2015-06-01

    Full Text Available Objective: We assessed the availability of essential medicines for mental healthcare (MH across levels of the public healthcare system to aid in future systems planning. Design: Non-expired MH medications were assessed in 24 public health facilities and 13 district warehouses across Sofala Province, Mozambique, from July to August 2014. Medication categories included: antipsychotics, antidepressants, benzodiazepines, antiepileptics and mood stabilizers, and anticholinergics and antihistamines. Results: Only 7 of 12 (58.3% district warehouses, 11 of 24 (45.8% of all health facilities, and 10 of 12 (83.3% of facilities with trained MH staff had availability of at least one medication of each category. Thioridazine was the most commonly available antipsychotic across all facilities (9 of 24, 37.5%, while chlorpromazine and thioridazine were most common at facilities providing MH care (8 of 12, 66.7%. The atypical antipsychotic risperidone was not available at any facility or district warehouse. Amitriptyline was the most commonly available antidepressant (10 of 12 districts; 12 of 24 overall facilities; 9 or 12 MH facilities. Despite being on the national essential drug list, fluoxetine was only available at one quaternary-level facility and no district warehouses. Conclusions: Essential psychotropic medicines are routinely unavailable at public health facilities. Current essential drug lists include six typical but no atypical antipsychotics, which is concerning given the side-effect profiles of typical antipsychotics. Ensuring consistent availability of at least one selective serotonin reuptake inhibitor should also be a priority, as they are essential for the treatment of individuals with underlying cardiovascular disease and/or suicidal ideation. Similar to successful task-sharing approaches used for HIV/AIDS, mid-level providers could be retrained and certified to prescribe and monitor first-line psychotropic regimens.

  18. Oxidative stress/reactive metabolite gene expression signature in rat liver detects idiosyncratic hepatotoxicants

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    Leone, Angelique; Nie, Alex; Brandon Parker, J.; Sawant, Sharmilee; Piechta, Leigh-Anne; Kelley, Michael F., E-mail: mkelley2@its.jnj.com; Mark Kao, L.; Jim Proctor, S.; Verheyen, Geert; Johnson, Mark D.; Lord, Peter G.; McMillian, Michael K.

    2014-03-15

    Previously we reported a gene expression signature in rat liver for detecting a specific type of oxidative stress (OS) related to reactive metabolites (RM). High doses of the drugs disulfiram, ethinyl estradiol and nimesulide were used with another dozen paradigm OS/RM compounds, and three other drugs flutamide, phenacetin and sulindac were identified by this signature. In a second study, antiepileptic drugs were compared for covalent binding and their effects on OS/RM; felbamate, carbamazepine, and phenobarbital produced robust OS/RM gene expression. In the present study, liver RNA samples from drug-treated rats from more recent experiments were examined for statistical fit to the OS/RM signature. Of all 97 drugs examined, in addition to the nine drugs noted above, 19 more were identified as OS/RM-producing compounds—chlorpromazine, clozapine, cyproterone acetate, dantrolene, dipyridamole, glibenclamide, isoniazid, ketoconazole, methapyrilene, naltrexone, nifedipine, sulfamethoxazole, tamoxifen, coumarin, ritonavir, amitriptyline, valproic acid, enalapril, and chloramphenicol. Importantly, all of the OS/RM drugs listed above have been linked to idiosyncratic hepatotoxicity, excepting chloramphenicol, which does not have a package label for hepatotoxicity, but does have a black box warning for idiosyncratic bone marrow suppression. Most of these drugs are not acutely toxic in the rat. The OS/RM signature should be useful to avoid idiosyncratic hepatotoxicity of drug candidates. - Highlights: • 28 of 97 drugs gave a positive OS/RM gene expression signature in rat liver. • The specificity of the signature for human idiosyncratic hepatotoxicants was 98%. • The sensitivity of the signature for human idiosyncratic hepatotoxicants was 75%. • The signature can help eliminate hepatotoxicants from drug development.

  19. Recruitment of endocytosis in sonopermeabilization-mediated drug delivery: a real-time study.

    Science.gov (United States)

    Derieppe, Marc; Rojek, Katarzyna; Escoffre, Jean-Michel; de Senneville, Baudouin Denis; Moonen, Chrit; Bos, Clemens

    2015-06-29

    Microbubbles (MBs) in combination with ultrasound (US) can enhance cell membrane permeability, and have the potential to facilitate the cellular uptake of hydrophilic molecules. However, the exact mechanism behind US- and MB-mediated intracellular delivery still remains to be fully understood. Among the proposed mechanisms are formation of transient pores and endocytosis stimulation. In our study, we investigated whether endocytosis is involved in US- and MB-mediated delivery of small molecules. Dynamic fluorescence microscopy was used to investigate the effects of endocytosis inhibitors on the pharmacokinetic parameters of US- and MB-mediated uptake of SYTOX Green, a 600 Da hydrophilic model drug. C6 rat glioma cells, together with SonoVue(®) MBs, were exposed to 1.4 MHz US waves at 0.2 MPa peak-negative pressure. Collection of the signal intensity in each individual nucleus was monitored during and after US exposure by a fibered confocal fluorescence microscope designed for real-time imaging. Exposed to US waves, C6 cells pretreated with chlorpromazine, an inhibitor of clathrin-mediated endocytosis, showed up to a 2.5-fold significant increase of the uptake time constant, and a 1.1-fold increase with genistein, an inhibitor of caveolae-mediated endocytosis. Both inhibitors slowed down the US-mediated uptake of SYTOX Green. With C6 cells and our experimental settings, these quantitative data indicate that endocytosis plays a role in sonopermeabilization-mediated delivery of small molecules with a more predominant contribution of clathrin-mediated endocytosis.

  20. Mechanisms of nanoparticle internalization and transport across an intestinal epithelial cell model: effect of size and surface charge.

    Science.gov (United States)

    Bannunah, Azzah M; Vllasaliu, Driton; Lord, Jennie; Stolnik, Snjezana

    2014-12-01

    This study investigated the effect of nanoparticle size (50 and 100 nm) and surface charge on their interaction with Caco-2 monolayers as a model of the intestinal epithelium, including cell internalization pathways and the level of transepithelial transport. Initially, toxicity assays showed that cell viability and cell membrane integrity were dependent on the surface charge and applied mass, number, and total surface area of nanoparticles, as tested in two epithelial cell lines, colon carcinoma Caco-2 and airway Calu-3. This also identified suitable nanoparticle concentrations for subsequent cell uptake experiments. Nanoparticle application at doses below half maximal effective concentration (EC₅₀) revealed that the transport efficiency (ratio of transport to cell uptake) across Caco-2 cell monolayers is significantly higher for negatively charged nanoparticles compared to their positively charged counterparts (of similar size), despite the higher level of internalization of positively charged systems. Cell internalization pathways were hence probed using a panel of pharmacological inhibitors aiming to establish whether the discrepancy in transport efficiency is due to different uptake and transport pathways. Vesicular trans-monolayer transport for both positively and negatively charged nanoparticles was confirmed via inhibition of dynamin (by dynasore) and microtubule network (via nocodazole), which significantly reduced the transport of both nanoparticle systems. For positively charged nanoparticles a significant decrease in internalization and transport (46% and 37%, respectively) occurred in the presence of a clathrin pathway inhibitor (chlorpromazine), macropinocytosis inhibition (42%; achieved by 5-(N-ethyl-N-isopropyi)-amiloride), and under cholesterol depletion (38%; via methyl-β-cyclodextrin), but remained unaffected by the inhibition of lipid raft associated uptake (caveolae) by genistein. On the contrary, the most prominent reduction in

  1. Purification and characterization of a casein kinase 2-type protein kinase from pea nuclei

    Science.gov (United States)

    Li, H.; Roux, S. J.

    1992-01-01

    Almost all the polyamine-stimulated protein kinase activity associated with the chromatin fraction of nuclei purified from etiolated pea (Pisum sativum L.) plumules is present in a single enzyme that can be extracted from chromatin by 0.35 molar NaCl. This protein kinase can be further purified over 2000-fold by salt fractionation and anion-exchange and casein-agarose column chromatography, after which it is more than 90% pure. The purified kinase has a specific activity of about 650 nanomoles per minute per milligram protein in the absence of polyamines, with either ATP or GTP as phosphoryl donor. Spermidine can stimulate its activity fourfold, with half-maximal activation at about 2 millimolar. Spermine and putrescine also stimulate activity, although somewhat less effectively. This kinase has a tetrameric alpha 2 beta 2 structure with a native molecular weight of 130,000, and subunit molecular weights of 36,000 for the catalytic subunit (alpha) and 29,000 for the regulatory subunit (beta). In western blot analyses, only the alpha subunit reacts strongly with polyclonal antibodies to a Drosophila casein kinase II. The pea kinase can use casein and phosvitin as artificial substrates, phosphorylating both the serine and threonine residues of casein. It has a pH optimum near 8.0, a Vmax of 1.5 micromoles per minute per milligram protein, and a Km for ATP of approximately 75 micromolar. Its activity can be almost completely inhibited by heparin at 5 micrograms per milliliter, but is relatively insensitive to concentrations of staurosporine, K252a, and chlorpromazine that strongly antagonize Ca(2+) -regulated protein kinases. These results are discussed in relation to recent findings that casein kinase 2-type kinases may phosphorylate trans-acting factors that bind to light-regulated promoters in plants.

  2. An Observational Study to Evaluate the Prevalence of Erectile Dysfunction (ED) and Prescribing Pattern of Drugs in Patients with ED Visiting an Andrology Specialty Clinic, Mumbai: 2012-14

    Science.gov (United States)

    Kulkarni, Vijay R.; Bhagat, Sagar B.; Beldar, Amit S.; Patel, Sadiq B.

    2015-01-01

    Introduction: Erectile dysfunction (ED) is a common occurrence and its incidence is expected to increase significantly along with the increase in various lifestyle diseases. The drug utilization for ED is very low. Also, studies describing the prescription pattern in ED are lacking. Materials and Methods: We conducted a retrospective cross-sectional observational study, including a drug utilization analysis, of 606 prescriptions as per the standard guidelines (WHO and STROBE). Results: Out of 606, 249 (41%) were from the age group of 30-39 years. Addictions were present in 388 (64%). Out of 606, 186 had urological, 154 had cardiovascular and 102 had psychological co-morbid disorders. Out of 348, 201 were prescribed Tadalafil (low dose) on a once daily basis. Out of 172, 121 were prescribed Sildenafil (high dose) on an ‘as and when required’ basis. Nutritional/ herbal supplements were prescribed in 126/606. The ratio of ‘Prescribed Daily Dose’ to ‘Defined Daily Dose’ of Tadalafil, Sildenafil, and Dapoxetine were 1.1, 1.3 and 1.5 respectively. Conclusion: Measures for de-addiction play an important role in the overall management of ED. The most common co-morbid disorders were urological, like BPH, LUTS, etc, followed by cardiovascular, psychological and diabetes. Overall, rational pharmacotherapy was observed. Tadalafil was the most commonly prescribed drug for ED. The main factor in the selection of a particular PDE5 inhibitor was its pharmacokinetics and cost. Udenafil, being the costliest, was the least prescribed. Dapoxetine was used in a significant number of individuals primarily for PE with ED. The combination of Papaverine, Chlorpromazine ± Alprostadil was used as intracavernosal injection in patients not responding to oral drugs. PMID:26393163

  3. Acute inhibition of corticosteroidogenesis by inhibitors of calmodulin action.

    Science.gov (United States)

    Carsia, R V; Moyle, W R; Wolff, D J; Malamed, S

    1982-11-01

    To identify the possible role of calmodulin in ACTH function, we tested the ability of chlorpromazine (CP) and other calmodulin antagonists to inhibit steroidogenesis of isolated adrenocortical cells of the rat. CP reversibly inhibited maximal ACTH-induced corticosterone (B) production. The presence of the drug did not alter the ED50 of ACTH stimulation (3.2 X 10(3) pg/ml), suggesting that it inhibited ACTH-induced steroidogenesis in a noncompetitive manner. The CP concentration required for half-maximal inhibition was 8.2 microM, a value close to the dissociation constant of the CP-calmodulin complex (5.3 microM). Concentrations greater than 40 microM resulted in complete inhibition. Similar concentrations of CP inhibited ACTH-induced cAMP accumulation in a dose-dependent manner, indicating an effect of the drug on early events in ACTH action. In addition, CP also apparently acted at a site distal to the point of cAMP formation, as shown by the finding that it inhibited cAMP-induced B production. CP inhibition of ACTH-induced B production was independent of the Ca2+ concentration, suggesting that the drug did not compete with Ca2+ directly. Concentrations of CP greater than 20 microM inhibited protein synthesis as measured by leucine incorporation into cellular proteins. Thus, although the inhibitory effect of high concentrations of CP on steroidogenesis might be explained by an effect on protein synthesis, the inhibition seen at 10 microM appeared to be independent of protein synthesis. Other antagonists of calmodulin action inhibited maximal ACTH-induced B production with the following relative potencies: trifluoperazine greater than CP greater than haloperidol greater than chlordiazepoxide. This order is similar to that reported for inhibition of calmodulin-activated phosphodiesterase and for binding to calmodulin. These findings suggest that calmodulin may modulate the effect of ACTH on steroidogenesis at multiple sites.

  4. Hepatocyte-based in vitro model for assessment of drug-induced cholestasis

    Energy Technology Data Exchange (ETDEWEB)

    Chatterjee, Sagnik, E-mail: Sagnik.Chatterjee@pharm.kuleuven.be [Drug Delivery and Disposition, KU Leuven Department of Pharmaceutical and Pharmacological Sciences, O and N2, Herestraat 49 — bus 921, 3000 Leuven (Belgium); Richert, Lysiane, E-mail: l.richert@kaly-cell.com [KaLy-Cell, 20A rue du Général Leclerc, 67115 Plobsheim (France); Augustijns, Patrick, E-mail: Patrick.Augustijns@pharm.kuleuven.be [Drug Delivery and Disposition, KU Leuven Department of Pharmaceutical and Pharmacological Sciences, O and N2, Herestraat 49 — bus 921, 3000 Leuven (Belgium); Annaert, Pieter, E-mail: Pieter.Annaert@pharm.kuleuven.be [Drug Delivery and Disposition, KU Leuven Department of Pharmaceutical and Pharmacological Sciences, O and N2, Herestraat 49 — bus 921, 3000 Leuven (Belgium)

    2014-01-01

    Early detection of drug-induced cholestasis remains a challenge during drug development. We have developed and validated a biorelevant sandwich-cultured hepatocytes- (SCH) based model that can identify compounds causing cholestasis by altering bile acid disposition. Human and rat SCH were exposed (24–48 h) to known cholestatic and/or hepatotoxic compounds, in the presence or in the absence of a concentrated mixture of bile acids (BAs). Urea assay was used to assess (compromised) hepatocyte functionality at the end of the incubations. The cholestatic potential of the compounds was expressed by calculating a drug-induced cholestasis index (DICI), reflecting the relative residual urea formation by hepatocytes co-incubated with BAs and test compound as compared to hepatocytes treated with test compound alone. Compounds with clinical reports of cholestasis, including cyclosporin A, troglitazone, chlorpromazine, bosentan, ticlopidine, ritonavir, and midecamycin showed enhanced toxicity in the presence of BAs (DICI ≤ 0.8) for at least one of the tested concentrations. In contrast, the in vitro toxicity of compounds causing hepatotoxicity by other mechanisms (including diclofenac, valproic acid, amiodarone and acetaminophen), remained unchanged in the presence of BAs. A safety margin (SM) for drug-induced cholestasis was calculated as the ratio of lowest in vitro concentration for which was DICI ≤ 0.8, to the reported mean peak therapeutic plasma concentration. SM values obtained in human SCH correlated well with reported % incidence of clinical drug-induced cholestasis, while no correlation was observed in rat SCH. This in vitro model enables early identification of drug candidates causing cholestasis by disturbed BA handling. - Highlights: • Novel in vitro assay to detect drug-induced cholestasis • Rat and human sandwich-cultured hepatocytes (SCH) as in vitro models • Cholestatic compounds sensitize SCH to toxic effects of accumulating bile acids • Drug

  5. Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture.

    Science.gov (United States)

    de Wilde, Adriaan H; Jochmans, Dirk; Posthuma, Clara C; Zevenhoven-Dobbe, Jessika C; van Nieuwkoop, Stefan; Bestebroer, Theo M; van den Hoogen, Bernadette G; Neyts, Johan; Snijder, Eric J

    2014-08-01

    Coronaviruses can cause respiratory and enteric disease in a wide variety of human and animal hosts. The 2003 outbreak of severe acute respiratory syndrome (SARS) first demonstrated the potentially lethal consequences of zoonotic coronavirus infections in humans. In 2012, a similar previously unknown coronavirus emerged, Middle East respiratory syndrome coronavirus (MERS-CoV), thus far causing over 650 laboratory-confirmed infections, with an unexplained steep rise in the number of cases being recorded over recent months. The human MERS fatality rate of ∼ 30% is alarmingly high, even though many deaths were associated with underlying medical conditions. Registered therapeutics for the treatment of coronavirus infections are not available. Moreover, the pace of drug development and registration for human use is generally incompatible with strategies to combat emerging infectious diseases. Therefore, we have screened a library of 348 FDA-approved drugs for anti-MERS-CoV activity in cell culture. If such compounds proved sufficiently potent, their efficacy might be directly assessed in MERS patients. We identified four compounds (chloroquine, chlorpromazine, loperamide, and lopinavir) inhibiting MERS-CoV replication in the low-micromolar range (50% effective concentrations [EC(50)s], 3 to 8 μM). Moreover, these compounds also inhibit the replication of SARS coronavirus and human coronavirus 229E. Although their protective activity (alone or in combination) remains to be assessed in animal models, our findings may offer a starting point for treatment of patients infected with zoonotic coronaviruses like MERS-CoV. Although they may not necessarily reduce viral replication to very low levels, a moderate viral load reduction may create a window during which to mount a protective immune response.

  6. The uptake of soluble and particulate antigens by epithelial cells in the mouse small intestine.

    Directory of Open Access Journals (Sweden)

    Savannah E Howe

    Full Text Available Intestinal epithelial cells (IECs overlying the villi play a prominent role in absorption of digested nutrients and establish a barrier that separates the internal milieu from potentially harmful microbial antigens. Several mechanisms by which antigens of dietary and microbial origin enter the body have been identified; however whether IECs play a role in antigen uptake is not known. Using in vivo imaging of the mouse small intestine, we investigated whether epithelial cells (enterocytes play an active role in the uptake (sampling of lumen antigens. We found that small molecular weight antigens such as chicken ovalbumin, dextran, and bacterial LPS enter the lamina propria, the loose connective tissue which lies beneath the epithelium via goblet cell associated passageways. However, epithelial cells overlying the villi can internalize particulate antigens such as bacterial cell debris and inert nanoparticles (NPs, which are then found co-localizing with the CD11c+ dendritic cells in the lamina propria. The extent of NP uptake by IECs depends on their size: 20-40 nm NPs are taken up readily, while NPs larger than 100 nm are taken up mainly by the epithelial cells overlying Peyer's patches. Blocking NPs with small proteins or conjugating them with ovalbumin does not inhibit their uptake. However, the uptake of 40 nm NPs can be inhibited when they are administered with an endocytosis inhibitor (chlorpromazine. Delineating the mechanisms of antigen uptake in the gut is essential for understanding how tolerance and immunity to lumen antigens are generated, and for the development of mucosal vaccines and therapies.

  7. Higher cerebral oxygen saturation may provide higher urinary output during continuous regional cerebral perfusion

    Directory of Open Access Journals (Sweden)

    Tomoyasu Takahiro

    2008-10-01

    Full Text Available Abstract Objective We examined the hypothesis that higher cerebral oxygen saturation (rSO2 during RCP is correlated with urinary output. Methods Between December 2002 and August 2006, 12 patients aged 3 to 61 days and weighing 2.6 to 3.4 kg underwent aortic arch repair with RCP. Urinary output and rSO2 were analyzed retrospectively. Data were assigned to either of 2 groups according to their corresponding rSO2: Group A (rSO2 ≦ 75% and Group B (rSO2 Results Seven and 5 patients were assigned to Group A and Group B, respectively. Group A was characterized by mean radial arterial pressure (37.9 ± 9.6 vs 45.8 ± 7.8 mmHg; P = 0.14 and femoral arterial pressure (6.7 ± 6.1 vs 20.8 ± 14.6 mmHg; P = 0.09 compared to Group B. However, higher urinary output during CPB (1.03 ± 1.18 vs 0.10 ± 0.15 ml·kg-1·h-1; P = 0.03. Furthermore our results indicate that a higher dose of Chlorpromazine was used in Group A (2.9 ± 1.4 vs 1.7 ± 1.0 mg/kg; P = 0.03. Conclusion Higher cerebral oxygenation may provide higher urinary output due to higher renal blood flow through collateral circulation.

  8. Clathrin-mediated endocytosis in living host cells visualized through quantum dot labeling of infectious hematopoietic necrosis virus.

    Science.gov (United States)

    Liu, Haibin; Liu, Yi; Liu, Shulin; Pang, Dai-Wen; Xiao, Gengfu

    2011-07-01

    Infectious hematopoietic necrosis virus (IHNV) is an important fish pathogen that infects both wild and cultured salmonids. As a species of the genus Novirhabdovirus, IHNV is a valuable model system for exploring the host entry mechanisms of rhabdoviruses. In this study, quantum dots (QDs) were used as fluorescent labels for sensitive, long-term tracking of IHNV entry. Using live-cell fluorescence microscopy, we found that IHNV is internalized through clathrin-coated pits after the virus binds to host cell membranes. Pretreatment of host cells with chlorpromazine, a drug that blocks clathrin-mediated endocytosis, and clathrin light chain (LCa) depletion using RNA interference both resulted in a marked reduction in viral entry. We also visualized transport of the virus via the cytoskeleton (i.e., actin filaments and microtubules) in real time. Actin polymerization is involved in the transport of endocytic vesicles into the cytosol, whereas microtubules are required for the trafficking of clathrin-coated vesicles to early endosomes, late endosomes, and lysosomes. Disrupting the host cell cytoskeleton with cytochalasin D or nocodazole significantly impaired IHNV infectivity. Furthermore, infection was significantly affected by pretreating the host cells with bafilomycin A1, a compound that inhibits the acidification of endosomes and lysosomes. Strong colocalizations of IHNV with endosomes indicated that the virus is internalized into these membrane-bound compartments. This is the first report in which QD labeling is used to visualize the dynamic interactions between viruses and endocytic structures; the results presented demonstrate that IHNV enters host cells via clathrin-mediated endocytic, cytoskeleton-dependent, and low-pH-dependent pathways.

  9. Cell uptake mechanisms of PAMAM G4-FITC dendrimer in human myometrial cells

    Energy Technology Data Exchange (ETDEWEB)

    Oddone, Natalia; Zambrana, Ana I.; Tassano, Marcos [Instituto de Investigaciones Biologicas Clemente Estable, Laboratorio de Senalizacion Celular y Nanobiologia (Uruguay); Porcal, Williams [Universidad de la Republica, Grupo de Quimica Medicinal, Instituto de Quimica Biologica, Facultad de Ciencias-Facultad de Quimica (Uruguay); Cabral, Pablo [Universidad de la Republica, Laboratorio de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias (Uruguay); Benech, Juan C., E-mail: benech@iibce.edu.uy [Instituto de Investigaciones Biologicas Clemente Estable, Laboratorio de Senalizacion Celular y Nanobiologia (Uruguay)

    2013-07-15

    The high incidence and severity of diseases which involve smooth muscle dysfunction dictates the need of continued search for novel therapeutic strategies to treat these conditions. Dendrimers are branched macromolecules with multiple end-groups that can be functionalized for applications which include drug delivery. There is no data regarding the cellular uptake mechanisms used by dendrimers in smooth muscle human myometrial cells (HMC). Polyamidoamine G4 dendrimers were conjugated with fluorescein isothiocyanate (FITC) and the resulting conjugate (G4-FITC) was characterized using high-performance liquid chromatography, nuclear magnetic resonance, and atomic force microscopy. G4-FITC showed to have no significant effect on the primary culture HMC viability up to 48 h. HMC incubated with G4-FITC were analyzed by laser confocal microscopy. Peri-nuclear fluorescence distribution was observed at 5 h of incubation or more (24, 36, and 48 h). At 24 h, G4-FITC partially co-localized with lysotracker. Uptake of G4-FITC by HMC was slightly inhibited by filipin (8.0 {+-} 3.9 %) and significantly inhibited by chlorpromazine (63.5 {+-} 3.7 %). In non-electroporated HMC, G4-FITC was never observed inside the cell nucleus. Interestingly, we detected G4-FITC inside the nuclear domain of some electroporated cells. Thus, electroporation changed intracellular G4-FITC localization. Isolated nuclei of HMC incubated with G4-FITC showed fluorescence signal inside the nuclear domain. The results suggest that in HMC, G4-FITC is taken up by clathrin-mediated endocytosis with endosomal and lysosomal localization at 24 h. The combination of electroporation and dendrimers could be an interesting technology to electrotransfer drugs into smooth muscle cells cytosol and nuclei.

  10. Effects of Scopolamine on Blood Vessels in Rabbit Ear after Sympathetic and Sensory Denervation

    Institute of Scientific and Technical Information of China (English)

    刘书勤; 臧伟进; 成亮; 李增利; 于晓江; 李宝平

    2004-01-01

    Objectives To investigate the effects and involved mechanisms of scopolamine (Scop) on rabbit ear blood vessels. Methods Rabbit ear blood vessels were desympathetic and desensory innervation with surgical operation. Diameters of dorsal auricular arterial trunks in vivo were measured with a pair of compasses and the ruler in a dissecting microscope, and effluents from isolated ear under constant perfusion pressure were recorded with a digital drop-recorder. Results Intramuscular injection of Scop 0.1 mg/kg made the diameter of denerved dorsal auricular arterial trunks, as well as that of innerved ones, significantly increased. Scop by itself, at the maximal concentration (Cmax) of 3 μM, 30 μM and 300 μM, did not alter the effluent flow from the isolated denervated rabbit ear, but chlorpromazine (CPZ), at Cmax of 1 μM, acetylcholine (ACh), 0.25μM, all significantly increased the effluent flow, and norepinephrine (NE), 0.1μM, significantly decreased the effluent. Scop, 3 μM, did not affect ACh (0.25μM)-induced the increase of effluent flow, but Scop,30μM, alleviated the increase. Scop, 3μM, did not affect NE (0.1 μM)-induced the decrease of effluent flow, but Scop, 10, 30 and 100 μM, significantly alleviated the decrease. Conclusions The study suggests that Scop has no direct vasodilator effect. The vasodilator effect of Scop is not due to the blockade of muscarinic receptor. However, Scop can dilate blood vessels contracted by α1-adrenoceptor activation.

  11. The FMCA-GM assays, high throughput non-clonogenic alternatives to CFU-GM in preclinical hematotoxicity testing.

    Science.gov (United States)

    Haglund, Caroline; Aleskog, Anna; Håkansson, Lena Douhan; Höglund, Martin; Jacobsson, Stefan; Larsson, Rolf; Lindhagen, Elin

    2010-05-04

    One of the most common dose limiting adverse effects in cancer treatment is myelotoxicity. The aim of this study was to develop an in vitro method for measuring potential myelotoxic properties of a drug candidate in a high throughput setting. Human CD34(+) progenitor cells from umbilical cord blood were plated in 384-well microplates with drugs in liquid culture, supplemented with specific cytokines for the granulocytopoietic-macrophage lineage. After 7 or 14 days of proliferation and differentiation the cells were analyzed using the automated non-clonogenic fluorometric microculture cytotoxicity assay (FMCA). Two types of assays setups were evaluated, the FMCA-GM7 where cells were exposed to drugs directly after thawing and cytotoxicity measured on day 7 in contrast to the FMCA-GM14 where the cells were cultured 7 days prior to plating and drug exposure, with viability analysis on day 14 of differentiation. Drug sensitivity was similar in both assays and method validation was performed using 24 drugs with known myelotoxic profile (acyclovir, bortezomib, busulfan, carboplatin, chloramphenicol, chlorpromazine, cisplatin, cytarabine, clozapine, doxorubicin, erlotinib, etoposide, 5-fluorouracil, fludarabine, gefitinib, gemcitabine, hydroxyurea, imatinib, lomustine, melphalan, sorafenib, sunitinib, taxol and 6-thioguanine). The 50% inhibitory concentrations (IC(50)) from the FMCA-GM7 and the FMCA-GM14 correlated highly (r = 0.83) and (r = 0.82), respectively, with IC(50) from the established clonogenic assay (CFU-GM), obtained from the literature. The current data suggests that the FMCA-GM could offer a simple and robust alternative to the CFU-GM assay in preclinical hematotoxicity studies.

  12. Anti-Lipid IgG Antibodies Are Produced via Germinal Centers in a Murine Model Resembling Human Lupus

    Science.gov (United States)

    Wong-Baeza, Carlos; Reséndiz-Mora, Albany; Donis-Maturano, Luis; Wong-Baeza, Isabel; Zárate-Neira, Luz; Yam-Puc, Juan Carlos; Calderón-Amador, Juana; Medina, Yolanda; Wong, Carlos; Baeza, Isabel; Flores-Romo, Leopoldo

    2016-01-01

    Anti-lipid IgG antibodies are produced in some mycobacterial infections and in certain autoimmune diseases [such as anti-phospholipid syndrome, systemic lupus erythematosus (SLE)]. However, few studies have addressed the B cell responses underlying the production of these immunoglobulins. Anti-lipid IgG antibodies are consistently found in a murine model resembling human lupus induced by chlorpromazine-stabilized non-bilayer phospholipid arrangements (NPA). NPA are transitory lipid associations found in the membranes of most cells; when NPA are stabilized they can become immunogenic and induce specific IgG antibodies, which appear to be involved in the development of the mouse model of lupus. Of note, anti-NPA antibodies are also detected in patients with SLE and leprosy. We used this model of lupus to investigate in vivo the cellular mechanisms that lead to the production of anti-lipid, class-switched IgG antibodies. In this murine lupus model, we found plasma cells (Gr1−, CD19−, CD138+) producing NPA-specific IgGs in the draining lymph nodes, the spleen, and the bone marrow. We also found a significant number of germinal center B cells (IgD−, CD19+, PNA+) specific for NPA in the draining lymph nodes and the spleen, and we identified in situ the presence of NPA in these germinal centers. By contrast, very few NPA-specific, extrafollicular reaction B cells (B220+, Blimp1+) were found. Moreover, when assessing the anti-NPA IgG antibodies produced during the experimental protocol, we found that the affinity of these antibodies progressively increased over time. Altogether, our data indicate that, in this murine model resembling human lupus, B cells produce anti-NPA IgG antibodies mainly via germinal centers. PMID:27746783

  13. Changes in clinical trials methodology over time: a systematic review of six decades of research in psychopharmacology.

    Directory of Open Access Journals (Sweden)

    André R Brunoni

    Full Text Available BACKGROUND: There have been many changes in clinical trials methodology since the introduction of lithium and the beginning of the modern era of psychopharmacology in 1949. The nature and importance of these changes have not been fully addressed to date. As methodological flaws in trials can lead to false-negative or false-positive results, the objective of our study was to evaluate the impact of methodological changes in psychopharmacology clinical research over the past 60 years. METHODOLOGY/PRINCIPAL FINDINGS: We performed a systematic review from 1949 to 2009 on MEDLINE and Web of Science electronic databases, and a hand search of high impact journals on studies of seven major drugs (chlorpromazine, clozapine, risperidone, lithium, fluoxetine and lamotrigine. All controlled studies published 100 months after the first trial were included. Ninety-one studies met our inclusion criteria. We analyzed the major changes in abstract reporting, study design, participants' assessment and enrollment, methodology and statistical analysis. Our results showed that the methodology of psychiatric clinical trials changed substantially, with quality gains in abstract reporting, results reporting, and statistical methodology. Recent trials use more informed consent, periods of washout, intention-to-treat approach and parametric tests. Placebo use remains high and unchanged over time. CONCLUSIONS/SIGNIFICANCE: Clinical trial quality of psychopharmacological studies has changed significantly in most of the aspects we analyzed. There was significant improvement in quality reporting and internal validity. These changes have increased study efficiency; however, there is room for improvement in some aspects such as rating scales, diagnostic criteria and better trial reporting. Therefore, despite the advancements observed, there are still several areas that can be improved in psychopharmacology clinical trials.

  14. Calcium Signaling is Involved in Negative Phototropism of Rice Seminal Roots

    Institute of Scientific and Technical Information of China (English)

    CHEN Juan; MO Yi-wei; XU Hua-wei

    2014-01-01

    Calcium ions (Ca2+) act as an intracellular second messenger and affect nearly all aspects of cellular life. They are functioned by interacting with polar auxin transport, and the negative phototropism of plant roots is caused by the transport of auxin from the irradiated side to the shaded side of the roots. To clarify the role of calcium signaling in the modulation of rice root negative phototropism, as well as the relationship between polar auxin transport and calcium signaling, calcium signaling reagents were used to treat rice seminal roots which were cultivated in hydroculture and unilaterally illuminated at an intensity of 100-200μmol/(m2·s) for 24 h. Negative phototropism curvature and growth rate of rice roots were both promoted by exogenous CaCl2 lower than 100 μmol/L, but inhibited by calcium channel blockers (verapamil and LaCl3), calcineurin inhibitor (chlorpromazine, CPZ), and polar auxin transport inhibitor (N-1-naphthylphthalamic acid, NPA). Roots stopped growing and negative phototropism disappeared when the concentrations increased to 100μmol/L verapamil, 12.500μmol/L LaCl3, 60μmol/L CPZ, and 6μmol/L NPA. Moreover, 100 μmol/L CaCl2 could relieve the inhibition of LaCl3, verapamil and NPA. The enhanced negative phototropism curvature was caused by the transportation of more auxin from the irradiated side to the shaded side in the presence of exogenous Ca2+. Calcium signaling plays a key role as a second messenger in the process of light signal regulation of rice root growth and negative phototropism.

  15. Influences of Chloropazine, Nimodipine and Their Combination on the Toxic Effects of Cadmium in Liver and Kidney of Mice

    Institute of Scientific and Technical Information of China (English)

    TANG LING-FANG; YANG YONG-NIAN; CHEN YAN-MENG; ZHANG ZHEN-LING; SONG LING; FENG ZHU-YING

    1999-01-01

    The influences of the calmodulin antagonist chlorpromazine (CPZ), and calcium chanmel blocker nimodipine (NLMO) and their combination on cadmium (Cd) poisoning of mice were studied.A series of biochemical parameters including urinary enzyme activities, blood and urine Cd levels, metallothionein (MT) contents in liver and kidney, hepatic ultrastructure and Ca2+ -Mg2- AT Pase activitv in erythrocyte membrane were determined. Animal models for Cd poisoning were established by peritoneal injection of 1/5 LD50 CdCl2. The experimental groups were protected by administration of CPZ, NIMO and CPZ and NIMO in combination I h before the injection of CdCl2. Five days later, samples were collected for analysis. The data showed that CPZ could protect kidney tissue against Cd-induced damage, as the urinary y-glutamyl-traspeptidase (γ-GT) and N-acetyl-β-D-glucosaminidase (NAG) activities were reduced significantly. There was neither evidence of the protective effect of NIMO on kidney tissue nor an indication of a synergistic effecf of CPZ and NIMO.Both CPZ and NIMO showed a considerable protective effect against the decrease in Ca2+ -Mg2+ AT-Pase activity, and a synergistic action was observed. Cd content in blood was reduced significantly by CPZ or the combination of CPZ and NIMO, but elevated by NIMO. Both CPZ and NIMO considerably increased MT contents in livers and kidneys and ameliorated damaged to the hepatic ultrastructures caused by Cd. The results indicated that these inhibitors could protect mice against the toxic effects of Cd in liver and kidney tissues, while CPZ was more efficient than NIMO. The combination of CPZ and NIMO excrted a synergistic action. The protective action of these two drugs might be relevent to the function of MT.

  16. Characterization of a β-adrenergic-like octopamine receptor from the rice stem borer (Chilo suppressalis).

    Science.gov (United States)

    Wu, Shun-Fan; Yao, Yao; Huang, Jia; Ye, Gong-Yin

    2012-08-01

    Octopamine, the invertebrate counterpart of adrenaline and noradrenaline, plays a key role in regulation of many physiological and behavioral processes in insects. It modulates these functions through binding to specific octopamine receptors, which are typical rhodopsin-like G-protein coupled receptors. A cDNA encoding a seven-transmembrane receptor was cloned from the nerve cord of the rice stem borer, Chilo suppressalis, viz. CsOA2B2, which shares high sequence similarity to CG6989, a Drosophila β-adrenergic-like octopamine receptor (DmOctβ2R). We generated an HEK-293 cell line that stably expresses CsOA2B2 in order to examine the functional and pharmacological properties of this receptor. Activation of CsOA2B2 by octopamine increased the production of cAMP in a dose-dependent manner (EC(50)=2.33 nmol l(-1)), with a maximum response at 100 nmol l(-1). Tyramine also activated the receptor but with much less potency than octopamine. Dopamine and serotonin had marginal effects on cAMP production. Using a series of known agonists and antagonists for octopamine receptors, we observed a rather unique pharmacological profile for CsOA2B2 through measurements of cAMP. The rank order of potency of the agonists was naphazoline > clonidine. The activated effect of octopamine is abolished by co-incubation with phentolamine, mianserin or chlorpromazine. Using in vivo pharmacology, CsOA2B2 antagonists mianserin and phentolamine impaired the motor ability of individual rice stem borers. The results of the present study are important for a better functional understanding of this receptor as well as for practical applications in the development of environmentally sustainable pesticides.

  17. Temporal and spatial transcriptional fingerprints by antipsychotic or propsychotic drugs in mouse brain.

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    Kensuke Sakuma

    Full Text Available Various types of antipsychotics have been developed for the treatment of schizophrenia since the accidental discovery of the antipsychotic activity of chlorpromazine. Although all clinically effective antipsychotic agents have common properties to interact with the dopamine D2 receptor (D2R activation, their precise mechanisms of action remain elusive. Antipsychotics are well known to induce transcriptional changes of immediate early genes (IEGs, raising the possibility that gene expressions play an essential role to improve psychiatric symptoms. Here, we report that while different classes of antipsychotics have complex pharmacological profiles against D2R, they share common transcriptome fingerprint (TFP profile of IEGs in the murine brain in vivo by quantitative real-time PCR (qPCR. Our data showed that various types of antipsychotics with a profound interaction of D2R including haloperidol (antagonist, olanzapine (antagonist, and aripiprazole (partial agonist all share common spatial TFPs closely homologous to those of D2R antagonist sulpiride, and elicited greater transcriptional responses in the striatum than in the nucleus accumbens. Meanwhile, D2R agonist quinpirole and propsychotic NMDA antagonists such as MK-801 and phencyclidine (PCP exhibited the contrasting TFP profiles. Clozapine and propsychotic drug methamphetamine (MAP displayed peculiar TFPs that reflect their unique pharmacological property. Our results suggest that transcriptional responses are conserved across various types of antipsychotics clinically effective in positive symptoms of schizophrenia and also show that temporal and spatial TFPs may reflect the pharmacological features of the drugs. Thus, we propose that a TFP approach is beneficial to evaluate novel drug candidates for antipsychotic development.

  18. Tracking the virus-like particles of Macrobrachium rosenbergii nodavirus in insect cells

    Science.gov (United States)

    Hanapi, Ummi Fairuz; Yong, Chean Yeah; Goh, Zee Hong; Alitheen, Noorjahan Banu; Yeap, Swee Keong

    2017-01-01

    Macrobrachium rosenbergii nodavirus (MrNv) poses a major threat to the prawn industry. Currently, no effective vaccine and treatment are available to prevent the spread of MrNv. Its infection mechanism and localisation in a host cell are also not well characterised. The MrNv capsid protein (MrNvc) produced in Escherichia coli self-assembled into virus-like particles (VLPs) resembling the native virus. Thus, fluorescein labelled MrNvc VLPs were employed as a model to study the virus entry and localisation in Spodoptera frugiperda, Sf9 cells. Through fluorescence microscopy and sub-cellular fractionation, the MrNvc was shown to enter Sf9 cells, and eventually arrived at the nucleus. The presence of MrNvc within the cytoplasm and nucleus of Sf9 cells was further confirmed by the Z-stack imaging. The presence of ammonium chloride (NH4Cl), genistein, methyl-β-cyclodextrin or chlorpromazine (CPZ) inhibited the entry of MrNvc into Sf9 cells, but cytochalasin D did not inhibit this process. This suggests that the internalisation of MrNvc VLPs is facilitated by caveolae- and clathrin-mediated endocytosis. The whole internalisation process of MrNvc VLPs into a Sf9 cell was recorded with live cell imaging. We have also identified a potential nuclear localisation signal (NLS) of MrNvc through deletion mutagenesis and verified by classical-NLS mapping. Overall, this study provides an insight into the journey of MrNvc VLPs in insect cells. PMID:28194311

  19. Tracking the virus-like particles of Macrobrachium rosenbergii nodavirus in insect cells

    Directory of Open Access Journals (Sweden)

    Ummi Fairuz Hanapi

    2017-02-01

    Full Text Available Macrobrachium rosenbergii nodavirus (MrNv poses a major threat to the prawn industry. Currently, no effective vaccine and treatment are available to prevent the spread of MrNv. Its infection mechanism and localisation in a host cell are also not well characterised. The MrNv capsid protein (MrNvc produced in Escherichia coli self-assembled into virus-like particles (VLPs resembling the native virus. Thus, fluorescein labelled MrNvc VLPs were employed as a model to study the virus entry and localisation in Spodoptera frugiperda, Sf9 cells. Through fluorescence microscopy and sub-cellular fractionation, the MrNvc was shown to enter Sf9 cells, and eventually arrived at the nucleus. The presence of MrNvc within the cytoplasm and nucleus of Sf9 cells was further confirmed by the Z-stack imaging. The presence of ammonium chloride (NH4Cl, genistein, methyl-β-cyclodextrin or chlorpromazine (CPZ inhibited the entry of MrNvc into Sf9 cells, but cytochalasin D did not inhibit this process. This suggests that the internalisation of MrNvc VLPs is facilitated by caveolae- and clathrin-mediated endocytosis. The whole internalisation process of MrNvc VLPs into a Sf9 cell was recorded with live cell imaging. We have also identified a potential nuclear localisation signal (NLS of MrNvc through deletion mutagenesis and verified by classical-NLS mapping. Overall, this study provides an insight into the journey of MrNvc VLPs in insect cells.

  20. Effect of short and long-term treatment with antipsychotics on orexigenic/anorexigenic neuropeptides expression in the rat hypothalamus.

    Science.gov (United States)

    Rojczyk, Ewa; Pałasz, Artur; Wiaderkiewicz, Ryszard

    2015-06-01

    Among numerous side effects of antipsychotic drugs (neuroleptics), one of the leading problems is a significant weight gain caused by disturbances in energy homeostasis. The hypothalamus is considered an important target for neuroleptics and contains some neuronal circuits responsible for food intake regulation, so we decided to study which hypothalamic signaling pathways connected with energy balance control are modified by antipsychotic drugs of different generations. We created an expression profile of different neuropeptides after single-dose and chronic neuroleptic administration. Experiments were carried out on adult male Sprague-Dawley rats injected intraperitoneally for 1 day or for 28 days by three neuroleptics: olanzapine, chlorpromazine and haloperidol. Hypothalami were isolated in order to perform PCR reactions and also whole brains were sliced for immunohistochemical analysis. We assessed the expression of orexigenic/anorexigenic neuropeptides and their receptors--neuropeptide Y (NPY), NPY receptor type 1 (Y1R), preproorexin (PPOX), orexin A, orexin receptor type 1 (OX1R) and 2 (OX2R), nucleobindin 2 (NUCB2), nesfatin-1, proopiomelanocortin (POMC), alpha-melanotropin (α-MSH) and melanocortin receptor type 4 (MC4R)--both on the mRNA and protein levels. We have shown that antipsychotics of different generations administered chronically have the ability to upregulate PPOX, orexin A and Y1R expression with little or no effect on orexigenic receptors (OX1R, OX2R) and NPY. Interestingly, antipsychotics also increased the level of some anorexigenic factors (POMC, α-MSH and MC4R), but at the same time strongly downregulated NUCB2 and nesfatin-1 signaling--a newly discovered neuropeptide known as a food-intake inhibiting factor. Our results may contribute to a better understanding of mechanisms responsible for antipsychotics' side effects. They also underline the complex nature of interactions between classical monoamine receptors and hypothalamic peptidergic

  1. Antipsychotics--history of development and field of indication, new wine--old glassess.

    Science.gov (United States)

    Jašović-Gašić, Miroslava; Vuković, Olivera; Pantović, Maja; Cvetić, Tijana; Marić-Bojović, Nadja

    2012-10-01

    More than half a century ago, Delay and colleagues have discovered, quite accidentally, that antihistamine (chlorpromazine) relieves psychotic symptoms. This discovery prompted further investigation through a series of performed experiments aimed to elucidate the antipsychotic mechanism of action. Initial results have shown that antipsychotic drugs in experimental animals lead to "neuroleptic effect" (indifference). However, not until the end of 1960s, it becomes clear that all previously known antipsychotics block dopamine receptors, particularly postsynaptic D2 receptors. The next three decades marked the development and application of these so-called classic neuroleptics in the treatment of psychotic patients. During the nineteen nineties, as a result of ongoing efforts to achieve greater efficiency and reduce the scope of side effects, novel antipsychotics were synthesized (second generation antipsychotics--SGA). As a result the notion of serotonin-dopamine antagonist (SDA) was formulated. According to one of the hypothesis, "new", so called atypical antipsychotic drugs strongly block the serotonin (5-HT2), and weakly block the dopamine (D2) receptors. Yet, there is still a debate as to the molecular basis of atypicality, whether it is in dopaminergic and serotonergic antagonism of neurotransmission or it lays exclusively in the modulation of dopaminergic system and dissociation rate at the level of D2 receptors in specific brain regions. Although the synthesis and use of antipsychotics in clinical practice have radically changed not only the basic approach to the patient, but also the quality of life of millions of people, the question remains whether this is just "old wine in new glasses".

  2. Suicide for survival--death of infected erythrocytes as a host mechanism to survive malaria.

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    Föller, Michael; Bobbala, Diwakar; Koka, Saisudha; Huber, Stephan M; Gulbins, Erich; Lang, Florian

    2009-01-01

    The pathogen of malaria, Plasmodium, enters erythrocytes and thus escapes recognition by the immune system. The pathogen induces oxidative stress to the host erythrocyte, which triggers eryptosis, the suicidal death of erythrocytes. Eryptosis is characterized by cell shrinkage, membrane blebbing and cell membrane phospholipid scrambling with phosphatidylserine exposure at the cell surface. Phosphatidylserine-exposing erythrocytes are identified by macrophages which engulf and degrade the eryptotic cells. To the extent that infected erythrocytes undergo eryptosis prior to exit of Plasmodiaand subsequent infection of other erythrocytes, the premature eryptosis may protect against malaria. Accordingly, any therapeutical intervention accelerating suicidal death of infected erythrocytes has the potential to foster elimination of infected erythrocytes, delay the development of parasitemia and favorably influence the course of malaria. Eryptosis is stimulated by a wide variety of triggers including osmotic shock, oxidative stress, energy depletion and a wide variety of xenobiotics. Diseases associated with accelerated eryptosis include sepsis, haemolytic uremic syndrome, malaria, sickle-cell anemia, beta-thalassemia, glucose-6-phosphate dehydrogenase (G6PD)-deficiency, phosphate depletion, iron deficiency and Wilson's disease. Among the known stimulators of eryptosis, paclitaxel, chlorpromazine, cyclosporine, curcumin, PGE2 and lead have indeed been shown to favourably influence the course of malaria. Moreover, sickle-cell trait, beta-thalassemia trait, glucose-6-phosphate dehydrogenase (G6PD)-deficiency and iron deficiency confer some protection against a severe course of malaria. Importantly, counteracting Plasmodia by inducing eryptosis is not expected to generate resistance of the pathogen, as the proteins involved in suicidal death of the host cell are not encoded by the pathogen and thus cannot be modified by mutations of its genes.

  3. Enhancement of antibiotic activity by efflux inhibitors against multidrug resistant Mycobacterium tuberculosis clinical isolates from Brazil

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    Tatiane eCoelho

    2015-04-01

    Full Text Available Drug resistant tuberculosis continues to increase and new approaches for its treatment are necessary. The identification of M. tuberculosis clinical isolates presenting efflux as part of their resistant phenotype has a major impact in tuberculosis treatment. In this work, we used a checkerboard procedure combined with the tetrazolium microplate-based assay (TEMA to study single combinations between antituberculosis drugs and efflux inhibitors (EIs against multidrug resistant M. tuberculosis clinical isolates using the fully susceptible strain H37Rv as reference. Efflux activity was studied on a real-time basis by a fluorometric method that uses ethidium bromide as efflux substrate. Quantification of efflux pump genes mRNA transcriptional levels were performed by RT-qPCR. The fractional inhibitory concentrations (FIC indicated synergistic activity for the interactions between isoniazid, rifampicin, amikacin, ofloxacin, and ethidium bromide plus the EIs verapamil, thioridazine and chlorpromazine. The FICs ranged from 0.25, indicating a four-fold reduction on the MICs, to 0.015, 64-fold reduction. The detection of active efflux by real-time fluorometry showed that all strains presented intrinsic efflux activity that contributes to the overall resistance which can be inhibited in the presence of the EIs. The quantification of the mRNA levels of the most important efflux pump genes on these strains shows that they are intrinsically predisposed to expel toxic compounds as the exposure to subinhibitory concentrations of antibiotics were not necessary to increase the pump mRNA levels when compared with the non-exposed counterpart. The results obtained in this study confirm that the intrinsic efflux activity contributes to the overall resistance in multidrug resistant clinical isolates of M. tuberculosis and that the inhibition of efflux pumps by the EIs can enhance the clinical effect of antibiotics that are their substrates.

  4. Body composition in patients with schizophrenia: Comparison with healthy controls

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    Sugawara Norio

    2012-05-01

    Full Text Available Abstract Background Recently, a relationship between obesity and schizophrenia has been reported. Although fat- mass and fat free mass have been shown to be more predictive of health risk than body mass index, there are limited findings about body composition among patients suffering from schizophrenia. The aim of this study is to compare the body composition of schizophrenia patients with that of healthy subjects in Japan. Methods We recruited patients (n = 204, aged 41.3 ± 13.8 (mean ± SD years old with the DSM-IV diagnosis of schizophrenia who were admitted to psychiatric hospital using a cross-sectional design. Subjects' anthropometric measurements including weight, height, body mass index (BMI, and medications were also collected. Body fat, percent (% body fat, fat- free mass, muscle mass, and body water were measured using the bioelectrical impedance analysis (BIA method. Comparative analysis was performed with schizophrenic subjects and 204 healthy control individuals. Results In a multiple regression model with age, body mass index, and dose in chlorpromazine equivalents, schizophrenia was a significantly linked with more body fat, higher % body fat, lower fat- free mass, lower muscle mass, and lower body water among males. In females, schizophrenia had a significant association with lower % body fat, higher fat- free mass, higher muscle mass, and higher body water. Conclusions Our data demonstrate gender differences with regard to changes in body composition in association with schizophrenia. These results indicate that intervention programs designed to fight obesity among schizophrenic patients should be individualized according to gender.

  5. Conventional and atypical antipsychotics in the elderly : a review.

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    Gareri, Pietro; De Fazio, Pasquale; Stilo, Mariagrazia; Ferreri, Guido; De Sarro, Giovambattista

    2003-01-01

    Psychoses are major mental disorders marked by derangement of personality and loss of contact with reality, and are common in the elderly. Various hypotheses suggest the pivotal role of abnormal neurotransmitter and neuropeptide systems in psychotic patients, the most studied of which are the dopaminergic, serotonergic and glutamatergic systems. In particular, long-term treatment with antagonists at dopamine (D) and serotonin (5-hydroxytryptamine; 5-HT) receptors and agonists at glutamate receptors may improve symptoms. Treatment with antipsychotics is very common in the elderly and often indispensable. However, for successful treatment it is essential to have an adequate multidimensional assessment of the geriatric patient and of his or her polypathology and polypharmacy, together with knowledge of age-dependent pharmacokinetics and pharmacodynamic changes and drug-drug interactions.Conventional antipsychotics such as haloperidol, chlorpromazine, promazine, tiapride and zuclopenthixol are D(2)-receptor antagonists and inhibit dopaminergic neurotransmission in a dose-related manner. They decrease the intensity of all psychotic symptoms, although not necessarily to the same extent and with the same time course. Negative symptoms may persist to a much more striking extent than delusions, hallucinations and thought disorders, and there is a dose-related incidence of extrapyramidal side effects (EPS). Newer antipsychotics, such as clozapine, olanzapine, risperidone, quetiapine and ziprasidone, have a different receptor-binding profile, interacting with both D and 5-HT receptors; they less frequently cause EPS and are better tolerated in the elderly. Their use is advantageous because they are effective both on positive and negative symptoms of schizophrenia and may also be used in the treatment of behavioural disturbances in elderly and/or demented individuals. The use of clozapine is limited by the onset of agranulocytosis, whereas olanzapine, risperidone, quetiapine

  6. Pré-condicionamento precoce da medula espinal isquêmica: pesquisa em coelhos

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    Albert Amin SADER

    1998-04-01

    entre os resultados dos grupos III e IV, e quando ambos foram comparados com o grupo I. Não foi significativa a diferença entre os grupos V e VI, mas foi significativa quando ambos foram comparados com o grupo I (pEarly preconditioning of the spinal cord was investigated in rabbits, as an eventual protection mechanism, immediately before a 30 min ischemic period. Eight-seven New Zealand rabbits divided into 6 groups were assigned to the study. Ischemia of the spinal cord was induced by crossclamping (C the abdominal aorta distal to the emergence of the left renal artery. Preconditioning was stimulated by short and sometimes repetitive ischemic periods, underlined in the text, and followed by different periods of reperfusion. Group I - Control: In 20 animals the aorta was crossclamped for 30 min. In two of them (10% motricity and sensitivity of the hind-legs and tail were entirely restored; the other 18(90% became paraplegic. Group II - Sham operation: 10 animals were operated as the ones in the previous group except for the fact that the aorta was not clamped. All of them (100% had their sensitive and motor functions entirely restored. Group III - Preconditioning: 10 animals - (C 1 min ® 15 min® (C 30 min ® final reperfusion. All animals became paraplegic. Group IV - Preconditioning: 6 animals - (C 1 min ® 5 min® (C 2 min ® 5 min ® (C 2 min ® 5 min ® (C 30 min final reperfusion. Five rabgbits (83,33% became paraplegic and 1 (16,66% became monoplegic. Group V - Chlorpromazine: 20 animals were given chlorpromazine, intravenously, 2 mg/kg, 10 min before aortic crossclamping. Eleven animals (55% had their sensitive and motor functions reestablished and 9 (45% became paraplegic. Group VI - Clorpromazine + preconditioning: 21 animals were given chlorpromazine as those of group V and were preconditioned as follows: (C 1 min ® 5 min ® (C 1 min ® 5 min ® (C 30 min ® final reperfusion. Nine animals (32.8% recovered the sensitive and motor functions and 2

  7. Doença de Creutzfeldt-Jakob forma Heidenhain: relato de caso com achados de ressonância magnética e DWI Creutzfeldt-Jakob disease, Heidenhain variant: case report with MRI (DWI findings

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    Walter Oleschko Arruda

    2004-06-01

    -old white woman, was admitted in our service with a month history of progressive, bilateral cortical blindness. After admission, she developed right partial motor seizures( right facial, upper and lower limbs, she became progressively aphasic( mixed aphasia. Seizures were controlled with phenytoin, but she developed choreoathetotic movements on her right dimidium, with partial control after introduction of chlorpromazine 25 mg q/d. She could no longer stand up or walk due to severe ataxia. The first EEG (October, 2001 showed left hemisphere severe seizure activity (status epilepticus partialis. She was delivered home with enteral nutrition, phenytoin , chlorpromazine and mepacrine 100 mg qd. The following laboratorial tests were negative or normal: blood series, platelets, ESR, kidney and liver function, copper, ceruloplasmin, VDRL, HIV, HTLV-1, lactate, and cerebral DSA (performed in other service.A spinal tap with normal opening pressure was perform and CSF examination was normal. CSF 14-3-3 protein was positive, CSF specific neuronal enolase 7.5 ng/ml(normal. Genetic study of PRNP gene did not disclosed any known mutation. A MRI (October, 2001 showed areas of hyperintense signal (T2 and FLAIR without Gd-enhancement on T1, in the left temporal lobe and in both occipital lobes; basal ganglia have a normal appearance. DWI imaging showed bright areas at the same sites. An EEG (March, 2002 disclosed a periodical sharp triphasic waves pattern, suggestive of CJD. A second MRI (April, 2002 showed mild generalized atrophy, no ventricular dilatation, and the hyperintense sites disappeared. She remained clinically stable and under use of chlorpromazine and mepacrine until she died due to pulmonary complications on April, 2003.

  8. Treatment of schizophrenia with antipsychotics in Norwegian emergency wards, a cross-sectional national study

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    Wentzel-Larsen Tore

    2009-05-01

    Full Text Available Abstract Background Surveys on prescription patterns for antipsychotics in the Scandinavian public health system are scarce despite the prevalent use of these drugs. The clinical differences between antipsychotic drugs are mainly in the areas of safety and tolerability, and international guidelines for the treatment of schizophrenia offer rational strategies to minimize the burden of side effects related to antipsychotic treatment. The implementation of treatment guidelines in clinical practice have proven difficult to achieve, as reflected by major variations in the prescription patterns of antipsychotics between different comparable regions and countries. The objective of this study was to evaluate the practice of treatment of schizophrenic patients with antipsychotics at discharge from acute inpatient settings at a national level. Methods Data from 486 discharges of patients from emergency inpatient treatment of schizophrenia were collected during a three-month period in 2005; the data were collected in a large national study that covered 75% of Norwegian hospitals receiving inpatients for acute treatment. Antipsychotic treatment, demographic variables, scores from the Global Assessment of Functioning and Health of the Nation Outcome Scales and information about comorbid conditions and prior treatment were analyzed to seek predictors for nonadherence to guidelines. Results In 7.6% of the discharges no antipsychotic treatment was given; of the remaining discharges, 35.6% were prescribed antipsychotic polypharmacy and 41.9% were prescribed at least one first-generation antipsychotic (FGA. The mean chlorpromazine equivalent dose was 450 (SD 347, range 25–2800. In the multivariate regression analyses, younger age, previous inpatient treatment in the previous 12 months before index hospitalization, and a comorbid diagnosis of personality disorder or mental retardation predicted antipsychotic polypharmacy, while previous inpatient treatment in

  9. Treatment of schizophrenia with antipsychotics in Norwegian emergency wards, a cross-sectional national study

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    Kroken, Rune A; Johnsen, Erik; Ruud, Torleif; Wentzel-Larsen, Tore; Jørgensen, Hugo A

    2009-01-01

    Background Surveys on prescription patterns for antipsychotics in the Scandinavian public health system are scarce despite the prevalent use of these drugs. The clinical differences between antipsychotic drugs are mainly in the areas of safety and tolerability, and international guidelines for the treatment of schizophrenia offer rational strategies to minimize the burden of side effects related to antipsychotic treatment. The implementation of treatment guidelines in clinical practice have proven difficult to achieve, as reflected by major variations in the prescription patterns of antipsychotics between different comparable regions and countries. The objective of this study was to evaluate the practice of treatment of schizophrenic patients with antipsychotics at discharge from acute inpatient settings at a national level. Methods Data from 486 discharges of patients from emergency inpatient treatment of schizophrenia were collected during a three-month period in 2005; the data were collected in a large national study that covered 75% of Norwegian hospitals receiving inpatients for acute treatment. Antipsychotic treatment, demographic variables, scores from the Global Assessment of Functioning and Health of the Nation Outcome Scales and information about comorbid conditions and prior treatment were analyzed to seek predictors for nonadherence to guidelines. Results In 7.6% of the discharges no antipsychotic treatment was given; of the remaining discharges, 35.6% were prescribed antipsychotic polypharmacy and 41.9% were prescribed at least one first-generation antipsychotic (FGA). The mean chlorpromazine equivalent dose was 450 (SD 347, range 25–2800). In the multivariate regression analyses, younger age, previous inpatient treatment in the previous 12 months before index hospitalization, and a comorbid diagnosis of personality disorder or mental retardation predicted antipsychotic polypharmacy, while previous inpatient treatment in the previous 12 months also

  10. A mixed MDPV and benzodiazepine intoxication in a chronic drug abuser: determination of MDPV metabolites by LC-HRMS and discussion of the case.

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    Bertol, Elisabetta; Mari, Francesco; Boscolo Berto, Rafael; Mannaioni, Guido; Vaiano, Fabio; Favretto, Donata

    2014-10-01

    We report on a case of repeated MDPV consumptions that resulted in severe psychosis and agitation prompting the concomitant abuse of benzodiazepines. A 27-year-old man was found irresponsive in his apartment and was brought to the emergency department (ED) of a local hospital. When in ED, he rapidly recovered and self-reported to have recently injected some doses of MDPV that he had bought in the Internet. He left the hospital without medical cares. 15 days after, he was again admitted to the same ED due to severe agitation, delirium and hallucinations, and reported the use of MDPV and pharmaceutical drugs during the preceding week. He was sedated with diazepam and chlorpromazine. Urine samples collected in both occasions were sent for testing using liquid chromatography-high resolution mass spectrometry (LC-HRMS) and liquid chromatography-high resolution multiple mass spectrometry (LC-HRMS/MS) on an Orbitrap. The LC-HRMS analysis revealed the presence of MDPV and its phase I and phase II metabolites (demethylenyl-MDPV, demethylenyl-methyl-MDPV, demethylenyl-methyl-oxo-MDPV, demethylenyl-hydroxy-alkyl-MDPV, demethylenyl-methyl-hydroxy alkyl-MDPV, demethylenyl-oxo-MDPV and their corresponding glucuronides), alprazolam and alprazolam metabolite at the first ED admission; at the time of the second ED access, the same MDPV metabolites, alprazolam, temazepam, and chlordiazepoxide were detected together with diazepam and metabolites. LC-HRMS/MS was use to determine the following concentrations, respectively on his first and second admission: MDPV 55ng/mL, alprazolam 114ng/mL, α-hydroxyalprazolam 104ng/mL; MDPV 35ng/mL, alprazolam 10.4ng/mL, α -hydroxyalprazolam 13ng/mL; chlordiazepoxide 13ng/mL, temazepam 170ng/mL, diazepam 1.3ng/mL, nordiazepam 61.5, oxazepam 115ng/mL. The toxicological findings corroborated the referred concomitant use of multiple pharmaceutical drugs and benzodiazepines. Confirmation of previous hypothesis on human metabolism of MDPV could be

  11. Survey of methadone-drug interactions among patients of methadone maintenance treatment program in Taiwan

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    Lee Hsin-Ya

    2012-03-01

    Full Text Available Abstract Background Although methadone has been used for the maintenance treatment of opioid dependence for decades, it was not introduced in China or Taiwan until 2000s. Methadone-drug interactions (MDIs have been shown to cause many adverse effects. However, such effects have not been scrutinized in the ethnic Chinese community. Methods The study was performed in two major hospitals in southern Taiwan. A total of 178 non-HIV patients aged ≥ 20 years who had participated in the Methadone Maintenance Treatment Program (MMTP ≥ 1 month were recruited. An MDI is defined as concurrent use of drug(s with methadone that may result in an increase or decrease of effectiveness and/or adverse effect of methadone. To determine the prevalence and clinical characteristics of MDIs, credible data sources, including the National Health Insurance (NHI database, face-to-face interviews, medical records, and methadone computer databases, were linked for analysis. Socio-demographic and clinical factors associated with MDIs and co-medications were also examined. Results 128 (72% MMTP patients took at least one medication. Clinically significant MDIs included withdrawal symptoms, which were found among MMTP patients co-administered with buprenorphine or tramadol; severe QTc prolongation effect, which might be associated with use of haloperidol or droperidol; and additive CNS and respiratory depression, which could result from use of methadone in combination with chlorpromazine or thioridazine. Past amphetamine use, co-infection with hepatitis C, and a longer retention in the MMTP were associated with increased odds of co-medication. Among patients with co-medication use, significant correlates of MDIs included the male gender and length of co-medication in the MMTP. Conclusions The results demonstrate clinical evidence of significant MDIs among MMTP patients. Clinicians should check the past medical history of MMTP clients carefully before prescribing medicines

  12. ABC gene-ranking for prediction of drug-induced cholestasis in rats

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    Yauheniya Cherkas

    2016-01-01

    drugs that behaved very differently, and were distinct from both non-cholestatic and cholestatic drugs (ketoconazole, dipyridamole, cyproheptadine and aniline, and many postulated human cholestatic drugs that in rat showed no evidence of cholestasis (chlorpromazine, erythromycin, niacin, captopril, dapsone, rifampicin, glibenclamide, simvastatin, furosemide, tamoxifen, and sulfamethoxazole. Most of these latter drugs were noted previously by other groups as showing cholestasis only in humans. The results of this work suggest that the ABC procedure and similar statistical approaches can be instrumental in combining data to compare toxicants across toxicogenomics databases, extract similarities among responses and reduce unexplained data varation.

  13. Ion Channel Blockers as Antimicrobial Agents, Efflux Inhibitors, and Enhancers of Macrophage Killing Activity against Drug Resistant Mycobacterium tuberculosis.

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    Diana Machado

    Full Text Available Given the ability of M. tuberculosis to survive as an intracellular pathogen and its propensity to develop resistance to the existing antituberculosis drugs, its treatment requires new approaches. Here the antimycobacterial properties of verapamil, thioridazine, chlorpromazine, flupenthixol and haloperidol were investigated against a panel of drug resistant M. tuberculosis strains, both in vitro and on human-infected macrophages. These compounds are efflux inhibitors that share among them the characteristic of being ion channel blockers. In vitro, all compounds exhibited synergistic inhibitory activities when combined with isoniazid and rifampicin, and were able to inhibit active efflux, demonstrating their role as efflux inhibitors. Gene expression analysis showed that M. tuberculosis efflux genes were overexpressed in response to antibiotic exposure, in vitro and within macrophages, irrespective of their resistance pattern. These compounds displayed a rapid and high killing activity against M. tuberculosis, associated with a decrease in intracellular ATP levels demonstrating that the bactericidal action of the ion channel blockers against M. tuberculosis clinical strains is associated with their interference with energy metabolism. The compounds led to a decrease in the intracellular mycobacterial load by increasing phagosome acidification and activating lysosomal hydrolases. The results presented in this study enable us to propose the following mechanism of action for these compounds: a in the bacteria, the compounds generate a cascade of events involving the inhibition of the respiratory chain complexes and energy production for efflux activity. Indirectly, this reduce the resistance level to antituberculosis drugs potentiating their activity; b on the host cell, the treatment with the ion channel blockers increases phagosome acidification and induces the expression of phagosomal hydrolases, leading to bacterial growth restriction

  14. Functional potencies of dopamine agonists and antagonists at human dopamine D₂ and D₃ receptors.

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    Tadori, Yoshihiro; Forbes, Robert A; McQuade, Robert D; Kikuchi, Tetsuro

    2011-09-01

    We measured the functional agonist potencies of dopamine agonists including antiparkinson drugs, and functional antagonist potencies of antipsychotics at human dopamine D(2) and D(3) receptors. In vitro pharmacological assessment included inhibition of forskolin-stimulated cAMP accumulation and the reversal of dopamine-induced inhibition in clonal Chinese hamster ovary cells expressing low and high densities of human dopamine D(2L) and D(2S) receptors (hD(2L)-Low, hD(2L)-High, hD(2S)-Low and hD(2S)-High, respectively) and human dopamine D(3) Ser-9 and D(3) Gly-9 receptors (hD(3)-Ser-9 and hD(3)-Gly-9, respectively). Cabergoline, bromocriptine, pergolide, (±)-7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT), talipexole, pramipexole, R-(+)-trans-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano[4,3-b]-1,4-oxazin-9-olhydrochloride (PD128907) and ropinirole behaved as dopamine D(2) and D(3) receptor full agonists and showed higher potencies in hD(2L)-High and hD(2S)-High compared to hD(2L)-Low and hD(2S)-Low. In hD(3)-Ser-9 and hD(3)-Gly-9 compared to hD(2L)-Low and hD(2S)-Low, dopamine, ropinirole, PD128907, and pramipexole potencies were clearly higher; talipexole and 7-OH-DPAT showed slightly higher potencies; pergolide showed slightly lower potency; and, cabergoline and bromocriptine potencies were lower. Aripiprazole acted as an antagonist in hD(2L)-Low; a low intrinsic activity partial agonist in hD(2S)-Low; a moderate partial agonist in hD(3)-Ser-9 and hD(3)-Gly-9; a robust partial agonist in hD(2L)-High; and a full agonist in hD(2S)-High. Amisulpride, sulpiride and perphenazine behaved as preferential antagonists; and chlorpromazine and asenapine behaved as modest preferential antagonists; whereas fluphenazine, haloperidol, and blonanserin behaved as non-preferential antagonists in hD(2S)-Low and hD(2S)-High compared to hD(3)-Ser-9 and hD(3)-Gly-9. These findings may help to elucidate the basis of therapeutic benefit observed with these drugs, with

  15. Measuring the bioactivity and molecular conformation of typically globular proteins with phenothiazine-derived methylene blue in solid and in solution: A comparative study using photochemistry and computational chemistry.

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    Ding, Fei; Xie, Yong; Peng, Wei; Peng, Yu-Kui

    2016-05-01

    Methylene blue is a phenothiazine agent, that possesses a diversity of biomedical and biological therapeutic purpose, and it has also become the lead compound for the exploitation of other pharmaceuticals such as chlorpromazine and the tricyclic antidepressants. However, the U.S. Food and Drug Administration has acquired cases of detrimental effects of methylene blue toxicities such as hemolytic anemia, methemoglobinemia and phototoxicity. In this work, the molecular recognition of methylene blue by two globular proteins, hemoglobin and lysozyme was characterized by employing fluorescence, circular dichroism (CD) along with molecular modeling at the molecular scale. The recognition of methylene blue with proteins appears fluorescence quenching via static type, this phenomenon does cohere with time-resolved fluorescence lifetime decay that nonfluorescent protein-drug conjugate formation has a strength of 10(4)M(-1), and the primary noncovalent bonds, that is hydrogen bonds, π-conjugated effects and hydrophobic interactions were operated and remained adduct stable. Meantime, the results of far-UV CD and synchronous fluorescence suggest that the α-helix of hemoglobin/lysozyme decreases from 78.2%/34.7% (free) to 58.7%/23.8% (complex), this elucidation agrees well with the elaborate description of three-dimensional fluorescence showing the polypeptide chain of proteins partially destabilized upon conjugation with methylene blue. Furthermore, both extrinsic fluorescent indicator and molecular modeling clearly exhibit methylene blue is situated within the cavity constituted by α1, β2 and α2 subunits of hemoglobin, while it was located at the deep fissure on the lysozyme surface and Trp-62 and Trp-63 residues are nearby. With the aid of computational analyses and combining the wet experiments, it can evidently be found that the recognition ability of proteins for methylene blue is patterned upon the following sequence: lysozyme

  16. Torsadogenic risk of antipsychotics: combining adverse event reports with drug utilization data across Europe.

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    Emanuel Raschi

    Full Text Available BACKGROUND: Antipsychotics (APs have been associated with risk of torsade de Pointes (TdP. This has important public health implications. Therefore, (a we exploited the public FDA Adverse Event Reporting System (FAERS to characterize their torsadogenic profile; (b we collected drug utilization data from 12 European Countries to assess the population exposure over the 2005-2010 period. METHODS: FAERS data (2004-2010 were analyzed based on the following criteria: (1 ≥ 4 cases of TdP/QT abnormalities; (2 Significant Reporting Odds Ratio, ROR [Lower Limit of the 95% confidence interval>1], for TdP/QT abnormalities, adjusted and stratified (Arizona CERT drugs as effect modifiers; (3 ≥ 4 cases of ventricular arrhythmia/sudden cardiac death (VA/SCD; (4 Significant ROR for VA/SCD; (5 Significant ROR, combined by aggregating TdP/QT abnormalities with VA and SCD. Torsadogenic signals were characterized in terms of signal strength: from Group A (very strong torsadogenic signal: all criteria fulfilled to group E (unclear/uncertain signal: only 2/5 criteria. Consumption data were retrieved from 12 European Countries and expressed as defined daily doses per 1,000 inhabitants per day (DID. RESULTS: Thirty-five antipsychotics met at least one criterium: 9 agents were classified in Group A (amisulpride, chlorpromazine, clozapine, cyamemazine, haloperidol, olanzapine, quetiapine, risperidone, ziprasidone. In 2010, the overall exposure to antipsychotics varied from 5.94 DID (Estonia to 13.99 (France, 2009. Considerable increment of Group A agents was found in several Countries (+3.47 in France: the exposure to olanzapine increased across all Countries (+1.84 in France and peaked 2.96 in Norway; cyamemazine was typically used only in France (2.81 in 2009. Among Group B drugs, levomepromazine peaked 3.78 (Serbia; fluphenazine 1.61 (Slovenia. CONCLUSIONS: This parallel approach through spontaneous reporting and drug utilization analyses highlighted drug- and

  17. Fenton process on single and mixture components of phenothiazine pharmaceuticals: Assessment of intermediaries, fate, and preliminary ecotoxicity.

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    Wilde, Marcelo L; Schneider, Mandy; Kümmerer, Klaus

    2017-04-01

    Pharmaceuticals do not occur isolated in the environment but in multi-component mixtures and may exhibit antagonist, synergistic or additive behavior. Knowledge on this is still scarce. The situation is even more complicated if effluents or potable water is treated by oxidative processes or such transformations occur in the environment. Thus, determining the fate and effects of parent compounds, metabolites and transformation products (TPs) formed by transformation and degradation processes in the environment is needed. This study investigated the fate and preliminary ecotoxicity of the phenothiazine pharmaceuticals, Promazine (PRO), Promethazine (PRM), Chlorpromazine (CPR), and Thioridazine (THI) as single and as components of the resulting mixtures obtained from their treatment by Fenton process. The Fenton process was carried out at pH7 and by using 0.5-2mgL(-1) of [Fe(2+)]0 and 1-12.5mgL(-1) of [H2O2]0 at the fixed ratio [Fe(2+)]0:[H2O2]0 of 1:10 (w:w). No complete mineralization was achieved. Constitutional isomers and some metabolite-like TPs formed were suggested based on their UHPLC-HRMS(n) data. A degradation pathway was proposed considering interconnected mechanisms such as sulfoxidation, hydroxylation, N-dealkylation, and dechlorination steps. Aerobic biodegradation tests (OECD 301 D and OECD 301 F) were applied to the parent compounds separately, to the mixture of parent compounds, and for the cocktail of TPs present after the treatment by Fenton process. The samples were not readily biodegradable. However, LC-MS analysis revealed that abiotic transformations, such hydrolysis, and autocatalytic transformations occurred. The initial ecotoxicity tested towards Vibrio fischeri as individual compounds featured a reduction in toxicity of PRM and CPR by the treatment process, whereas PRO showed an increase in acute luminescence inhibition and THI a stable luminescence inhibition. Concerning effects of the mixture components, reduction in toxicity by the

  18. Prescribing pattern of antipsychotic drugs in the outpatient department of psychiatry in Silchar Medical College and Hospital, Assam

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    Pinaki Chakravarty

    2016-01-01

    Full Text Available Objective: To study the prescribing pattern of antipsychotic drugs in the outpatient department of psychiatry in Silchar Medical College and Hospital (SMCH of Assam. Methods: It is a prospective cross-sectional study which was carried out for three months from August to November 2015 in the outpatient department of psychiatry. All patients irrespective of their ages and sexes were included in this study. Inpatients, referred patients, patients not willing to give consent, patients of epilepsy as well as those cases where diagnoses were not certain were excluded from the study. The prescription patterns of antipsychotic drugs and the occurrences of various psychiatric diseases on both the sexes were studied after taking permission from the Institutional Ethical Committee (SMCH. Results: A total of 112 prescriptions were analysed. The most common disease was found to be schizophrenia. Total drugs prescribed were 265 and average number of drugs per prescription was 2.36. It was seen that out of the 112 prescriptions, monotherapy was practiced in 19.64% (22 compared to polytherapy in 80.35% (90. Out of 265 prescribed drugs atypical antipsychotics were 112 (42.26%, typical antipsychotics 12 (4.52%, antiepileptics 57 (21.50%, antidepressants 29 (10.94%, antiparkinsonian 29 (10.94%, and others 26 (9.81%. Antipsychotics given orally were 122 of which olanzapine was 54 (44.26%, risperidone 40 (32.78%, chlorpromazine ten (8.19%, quetiapine eight (6.55%, aripiprazole five (4.09%, amisulpiride five (4.09% were seen. Injectable antipsychotics were two, of which only haloperidol two (100%. Antipsychotics in combination prescription with same groups were 14 (12.5%, with antidepressants, antipileptics, antiparkinsonian were 88 (78.57% and other agents were ten (8.92%, which included pantoprazole, multivitamins, and benfotiamine. Conclusion: This study shows that atypical antipsychotics are the most common drugs prescribed in patients with psychotic illness and

  19. A randomised, blinded, placebo-controlled trial in dementia patients continuing or stopping neuroleptics (the DART-AD trial.

    Directory of Open Access Journals (Sweden)

    Clive Ballard

    2008-04-01

    Full Text Available BACKGROUND: There have been increasing concerns regarding the safety and efficacy of neuroleptics in people with dementia, but there are very few long-term trials to inform clinical practice. The aim of this study was to determine the impact of long-term treatment with neuroleptic agents upon global cognitive decline and neuropsychiatric symptoms in patients with Alzheimer disease. METHODS AND FINDINGS: DESIGN: Randomised, blinded, placebo-controlled parallel two-group treatment discontinuation trial. SETTING: Oxfordshire, Newcastle and Gateshead, London and Edinburgh, United Kingdom. PARTICIPANTS: Patients currently prescribed the neuroleptics thioridazine, chlorpromazine, haloperidol trifluoperazine or risperidone for behavioural or psychiatric disturbance in dementia for at least 3 mo. INTERVENTIONS: Continue neuroleptic treatment for 12 mo or switch to an identical placebo. OUTCOME MEASURES: Primary outcome was total Severe Impairment Battery (SIB score. Neuropsychiatric symptoms were evaluated with the Neuropsychiatric Inventory (NPI. RESULTS: 165 patients were randomised (83 to continue treatment and 82 to placebo, i.e., discontinue treatment, of whom 128 (78% commenced treatment (64 continue/64 placebo. Of those, 26 were lost to follow-up (13 per arm, resulting in 51 patients per arm analysed for the primary outcome. There was no significant difference between the continue treatment and placebo groups in the estimated mean change in SIB scores between baseline and 6 mo; estimated mean difference in deterioration (favouring placebo -0.4 (95% confidence interval [CI] -6.4 to 5.5, adjusted for baseline value (p = 0.9. For neuropsychiatric symptoms, there was no significant difference between the continue treatment and placebo groups (n = 56 and 53, respectively in the estimated mean change in NPI scores between baseline and 6 mo; estimated mean difference in deterioration (favouring continue treatment -2.4 (95% CI -8.2 to 3.5, adjusted for

  20. Sorption of structurally different ionized pharmaceutical and illicit drugs to a mixed-mode coated microsampler.

    Science.gov (United States)

    Peltenburg, Hester; Timmer, Niels; Bosman, Ingrid J; Hermens, Joop L M; Droge, Steven T J

    2016-05-20

    The mixed-mode (C18/strong cation exchange-SCX) solid-phase microextraction (SPME) fiber has recently been shown to have increased sensitivity for ionic compounds compared to more conventional sampler coatings such as polyacrylate and polydimethylsiloxane (PDMS). However, data for structurally diverse compounds to this (prototype) sampler coating are too limited to define its structural limitations. We determined C18/SCX fiber partitioning coefficients of nineteen cationic structures without hydrogen bonding capacity besides the charged group, stretching over a wide hydrophobicity range (including amphetamine, amitriptyline, promazine, chlorpromazine, triflupromazine, difenzoquat), and eight basic pharmaceutical and illicit drugs (pKa>8.86) with additional hydrogen bonding moieties (MDMA, atenolol, alprenolol, metoprolol, morphine, nicotine, tramadol, verapamil). In addition, sorption data for three neutral benzodiazepines (diazepam, temazepam, and oxazepam) and the anionic NSAID diclofenac were collected to determine the efficiency to sample non-basic drugs. All tested compounds showed nonlinear isotherms above 1mmol/L coating, and linear isotherms below 1mmol/L. The affinity for C18/SCX-SPME for tested organic cations without Hbond capacities increased with longer alkyl chains, ranging from logarithmic fiber-water distribution coefficients (log Dfw) of 1.8 (benzylamine) to 5.8 (triflupromazine). Amines smaller than benzylamine may thus have limited detection levels, while cationic surfactants with alkyl chain lengths >12 carbon atoms may sorb too strong to the C18/SCX sampler which hampers calibration of the fiber-water relationship in the linear range. The log Dfw for these simple cation structures closely correlates with the octanol-water partition coefficient of the neutral form (Kow,N), and decreases with increased branching and presence of multiple aromatic rings. Oxygen moieties in organic cations decreased the affinity for C18/SCX-SPME. Log Dfw values of

  1. Antipsychotic poisoning in young children: a systematic review.

    Science.gov (United States)

    Isbister, Geoffrey K; Balit, Corrine R; Kilham, Henry A

    2005-01-01

    The aim of this review was to determine the spectrum and severity of effects of unintentional antipsychotic poisoning in children. A computerised literature search of MEDLINE (1966 to February 2005) and EMBASE (1980 to February 2005) was undertaken. The Internet was searched using URL: www.google.com. The proceedings of the North American Congress of Clinical Toxicology (NACCT) and the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) were hand searched. All cases of unintentional antipsychotic (all classes) poisoning in children aged 0-6 years were included. The data extracted included the age, weight, antipsychotic, dose, clinical effects, treatment and outcomes. The toxic dose was estimated as the lowest dose causing objective adverse effects.Sixty-eight reports were identified. Few contained all of the required information. Most of the case series included multiple antipsychotics with limited information on individual drugs or all ages with limited paediatric information. For most antipsychotics the ingestion of one tablet caused symptoms that were sometimes severe and usually lasted from 1 to 3 days. Extrapyramidal symptoms (EPS) were often delayed for up to 12-24 hours. Chlorpromazine caused CNS depression, hypotension and miosis; EPS and cardiac effects were rare, and the toxic dose was estimated to be 15 mg/kg. Haloperidol caused drowsiness (rarely coma) and over one-half of patients had neuromuscular effects (mainly EPS), with a toxic dose estimated at 0.15 mg/kg. Thioridazine caused CNS depression and potentially cardiac effects, with a toxic dose of 1.4 mg/kg. Atypical antipsychotics caused significant CNS depression (except risperidone); EPS were less common. Toxic doses were clozapine 2.5 mg/kg, olanzapine 0.5 mg/kg and aripiprazole 3 mg/kg. EPS responded to anticholinergic drug treatment. In summary, unintentional antipsychotic ingestion in children can cause severe effects that last 1-3 days, often with one tablet. Children

  2. Purchase data analysis of antipsychotics medication in 2011 in 686 Program demonstration cities%“686项目”示范市(州)2011年抗精神病药物采购情况

    Institute of Scientific and Technical Information of China (English)

    张五芳; 马弘; 马宁; 管丽丽; 吴霞民; 王勋; 阎丹峰; 于欣

    2012-01-01

    Objective: Since 2004, the central government started a program to provide free medication for impoverished patients who were rated high on a risk assessment in China. This program is known as the " 686 Program". This paper was aimed to investigate the antipsychotic drug use patterns for treating mental illness in cities in 686 Program. Methods: The procurement of antipsychotic varieties and purchase cost data of 160 cities in 686 Program in 2011 year was surveyed and analyzed. Results: The total purchase amount of antipsychotics was 16. 5996 million Yuan. Second-generation antipsychotics accounted for 74. 46% of the total purchase amount, in which ris-peridone accounted for 46. 74%. The top six defined daily doses of antipsychotics were clozapine, sulpiride, chlor-promazine, risperidone, haloperidol decanoate and perphenazine. First-generation antipsychotics accounted for 62. 45% of total drug usage. Conclusion: It suggests that first-generation antipsychotics have higher proportion utilization than second-generation antipsychotics in the communities which are supported by the 686 Program.%目的:了解中央补助地方重性精神疾病管理治疗项目(686项目)示范市(州)2011年抗精神病药物采购种类和费用的特征.方法:对2011年“686项目”160个示范市(州)采购的抗精神病药品种、购药金额、用药频度进行统计分析.结果:2011年“686项目”160个示范市(州)采购的抗精神病药品总金额为1659.96万元.第二代抗精神病药采购金额占总金额的74.46%,其中利培酮占采购总金额的46.74%.用药频度排在前6位的为氯氮平、舒必利、氯丙嗪、利培酮、癸酸氟哌啶醇注射液和奋乃静.第一代抗精神病药物总用药频度占62.45%.结论:本项目主要支持的社区精神疾病患者中,第一代抗精神病药使用比例较高.

  3. Inhibiting the clathrin-mediated endocytosis pathway rescues K(IR)2.1 downregulation by pentamidine.

    Science.gov (United States)

    Varkevisser, Rosanne; Houtman, Marien J C; Waasdorp, Maaike; Man, Joyce C K; Heukers, Raimond; Takanari, Hiroki; Tieland, Ralph G; van Bergen En Henegouwen, Paul M P; Vos, Marc A; van der Heyden, Marcel A G

    2013-02-01

    Drug-induced ion channel trafficking disturbance can cause cardiac arrhythmias. We showed that the antiprotozoic pentamidine decreased K(IR)2.x carried I(K1) current and that inhibiting protein degradation in the lysosome increased intracellular K(IR)2.1 levels. In this study, we aim to identify and then inhibit preceding steps in clathrin-mediated endocytosis of K(IR)2.1 to further restore normal levels of functional K(IR)2.1 channels. K(IR)2.1 trafficking in HEK293 cells was studied by live cell imaging, immunofluorescence microscopy, and Western blot following pharmacological intervention with dynasore (Dyn), chlorpromazine (CPZ), bafilomycin A1 (Baf), or chloroquine (CQ). K(IR)2.1 function was determined by patch-clamp electrophysiology. CQ induced lysosomal build-up of full length (3.8 ± 0.8-fold) and N-terminal cleaved K(IR)2.1 protein. Baf induced late endosomal build-up of full length protein only (6.1 ± 1.6-fold). CPZ and Dyn increased plasma membrane-localized channel and protein levels (2.6 ± 0.4- and 4.2 ± 1.1-fold, respectively). Dyn increased I(K1) (at -60 mV) from 31 ± 6 to 55 ± 7 pA/pF (N = 9 and 13 respectively, p Pentamidine (10 μM, 48 h) reduced K(IR)2.1 levels to 0.6 ± 0.1-fold, which could be rescued by Baf (3.2 ± 0.9), CPZ (1.2 ± 0.3), or Dyn (1.2 ± 0.3). Taken together, the clathrin-mediated endocytosis pathway functions in K(IR)2.1 degradation. Pentamidine-induced downregulation of K(IR)2.1 can be rescued at the level of the plasma membrane, implying that acquired trafficking defects can be rescued.

  4. Mechanisms of pH-Sensitivity and Cellular Internalization of PEOz-b-PLA Micelles with Varied Hydrophilic/Hydrophobic Ratios and Intracellular Trafficking Routes and Fate of the Copolymer.

    Science.gov (United States)

    Wang, Dishi; Zhou, Yanxia; Li, Xinru; Qu, Xiaoyou; Deng, Yunqiang; Wang, Ziqi; He, Chuyu; Zou, Yang; Jin, Yiguang; Liu, Yan

    2017-03-01

    pH-responsive polymeric micelles have shown promise for the targeted and intracellular delivery of antitumor agents. The present study aimed to elucidate the possible mechanisms of pH-sensitivity and cellular internalization of PEOz-b-PLA micelles in detail, further unravel the effect of hydrophilic/hydrophobic ratio of the micelles on their cellular internalization, and examine the intracellular trafficking routes and fate of PEOz-b-PLA after internalization of the micelles. The results of variations in the size and Zeta potential of PEOz-b-PLA micelles and cross-sectional area of PEOz-b-PLA molecules with pH values suggested that electrostatic repulsion between PEOz chains resulting from ionization of the tertiary amide groups along PEOz chain at pH lower than its pKa was responsible for pH-sensitivity of PEOz-b-PLA micelles. Furthermore, the studies on internalization of PEOz-b-PLA micelles by MCF-7 cells revealed that the uptake of PEOz-b-PLA micelles was strongly influenced by their structural features, and showed that PEOz-b-PLA micelles with hydrophilic/hydrophobic ratio of 1.7-2.0 exhibited optimal cellular uptake. No evident alteration in cellular uptake of PEOz-b-PLA micelles was detected by flow cytometry upon the existence of EIPA and chlorpromazine. However, the intracellular uptake of the micelles in the presence of MβCD and genistein was effectively inhibited. Hence, the internalization of such micelles by MCF-7 cells appeared to proceed mainly through caveolae/lipid raft-mediated endocytosis without being influenced by their hydrophilic/hydrophobic ratio. Confocal micrographs revealed that late endosomes, mitochondria and endoplasmic reticulum were all involved in the intracellular trafficking of PEOz-b-PLA copolymers following their internalization via endocytosis, and then part of them was excreted from tumor cells to extracellular medium. These findings provided valuable information for developing desired PEOz-b-PLA micelles to improve their

  5. Roles of dopamine receptors in mediating acute modulation of immunological responses in Macrobrachium rosenbergii.

    Science.gov (United States)

    Chang, Zhong-Wen; Ke, Zhi-Han; Chang, Chin-Chyuan

    2016-02-01

    Dopamine (DA) was found to influence the immunological responses and resistance to pathogen infection in invertebrates. To clarify the possible modulation of DA through dopamine receptors (DAR) against acute environmental stress, the levels of DA, glucose and lactate in the haemolymph of Macrobrachium rosenbergii under hypo- and hyperthermal stresses were measured. The changes in immune parameters such as total haemocyte count (THC), differential haemocyte count (DHC), phenoloxidase (PO) activity, respiratory bursts (RBs), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities and phagocytic activity (PA) were evaluated in prawns which received DAR antagonists (SCH23390, SCH, D1 antagonist; domperidone, DOM, D2 antagonist; chlorpromazine, CH, D1+2 antagonist) followed by hypo- (15 °C) and hyperthermal (34 °C) stresses. In addition, pharmacological analysis of the effect DA modulation was studied in haemocytes incubated with DA and DAR antagonists. The results revealed a significant increase in haemolymph DA accompanied with upregulated levels of glucose and lactate in prawns exposed to both hypo- and hyperthermal stresses in 2 h. In addition, a significant decrease in RBs per haemocyte was noted in prawns which received DAR antagonists when they exposed to hyperthermal stress for 30 min. In in vitro test, antagonism on RBs, SOD and GPx activity of haemocytes were further evidenced through D1, D1, D1+D2 DARs, respectively, in the meantime, no significant difference in PO activity and PA was observed among the treatment groups. These results suggest that the upregulation of DA, glucose and lactate in haemolymph might be the response to acute thermal stress for the demand of energy, and the DAR occupied by its antagonistic action impart no effect on immunological responses except RBs in vivo even though the modulation mediated through D1 DAR was further evidenced in RBs, SOD and GPx activities in vitro. It is therefore concluded that thermal

  6. 老年患者腹腔镜手术后谵妄23例临床分析%Clinical analysis of postoperative delirium in elderly patients undergoing laparoscopic surgery: a report of 23 cases

    Institute of Scientific and Technical Information of China (English)

    潘孟; 赫军; 陆世锋; 左江伟; 李敏朋; 廖轲; 许斌; 范芳; 俞渊

    2013-01-01

    目的:探讨老年患者腹腔镜手术后发生谵妄的原因、处理及预防措施.方法:回顾分析2008年1月至2012年12月腹腔镜手术后出现谵妄症状的23例老年患者的临床资料.结果:23例患者中,19例症状较轻,经吸氧,使用氟哌啶醇、氟哌利多、奥氮平、氯丙嗪等药物对症治疗后24 h内好转;4例症状较重,予以改善脑循环及补充营养等支持疗法,并辅以心理治疗,1周内症状消失.无一例死亡.结论:老年患者行腹腔镜手术后发生的急性谵妄早期发现、诊断并治疗,对其术后早日康复具有重要意义.%Objective:To study the reason,treatment and prevention methods of postoperative delirium in elderly patients undergoing laparoscopic surgery.Methods:A retrospective analysis was made on clinical data of 23 elderly patients who suffered from postoperative delirium after laparoscopic surgery from Jan.2008 to Dec.2012.Results:Nineteen patients who had mild symptoms of postoperative delirium recovered in 24 h after oxygen inhalation and medical treatment,such as haloperidol,olanzapine,droperidol and chlorpromazine,and were discharged smoothly.4 patients with severe symptoms underwent supportive therapy (improving the cerebral circulation,nutritional supplement and so on) associated with psychotherapy,their symptoms disappeared in one week.No death occurred.Conclusions:Early detection,diagnosis and treatment has an important significance in speedy recovery of acute delirium in elderly patients after laparoscopic surgery.

  7. [Compliance in schizophrenia: predictive factors, therapeutical considerations and research implications].

    Science.gov (United States)

    Misdrahi, D; Llorca, P M; Lançon, C; Bayle, F J

    2002-01-01

    Compliance has been defined as the extent to which a person's behavior coincides with the medical advice given. Medication compliance is one of the foremost problems affecting neuroleptic efficacy in psychiatric patients. Since chlorpromazine introduction in 1952, antipsychotics are the principal element of schizophrenia treatment. Actually progress links to the use of new antipsychotics are conditioned by quality of compliance. The problem of nonadherence to medication could concern 50% of prescription. The reported incidence of non-compliance with antipsychotic medication ranges from 11 to 80%. In a two thirds of case rehospitalization is the result of complete or partial noncompliance. After one year of first hospitalisation, 40% of relapse results from non adherence to medication. Medication adherence problems increase hospitalisation, morbidity and mortality. Social consequences, professional problems and family troubles linked to hospitalisations lead to low quality of life for patients and high cost for society. There are three main methods of measuring compliance. These include patient and clinical self-report, pill counts, and biological measures. Self-report methods are generally the most cost-effective and time-efficient way of obtaining an indication of compliance. In psychiatric research, the most commonly used self-report measure of compliance is the Drug Attitude Inventory (DAI) originally devised by Hogan et al. On the basis of criticism concerning DAI reliability, a new questionnaire of medication compliance was proposed: the Medication Adherence Rating scale (MARS). The main goal of compliance evaluation is to quantify this phenomenon with accuracy and to find predictive factors of medication nonadherence. Three types of factors influencing compliance are identified: factors due to medications, factors linked to patients and factors depending on the therapeutic relation with the clinician. Tolerance is considered as the principal reason explaining

  8. Repurposing psychiatric medicines to target activated microglia in anxious mild cognitive impairment and early Parkinson’s disease

    Science.gov (United States)

    Lauterbach, Edward C

    2016-01-01

    Anxiety is common in the Mild Cognitive Impairment (MCI) stage of Alzheimer’s disease (AD) and the pre-motor stages of Parkinson’s disease (PD). A concomitant and possible cause of this anxiety is microglial activation, also considered a key promoter of neurodegeneration in MCI and early PD via inflammatory mechanisms and the generation of degenerative proinflammatory cytokines. Psychiatric disorders, prevalent in AD and PD, are often treated with psychiatric drugs (psychotropics), raising the question of whether psychotropics might therapeutically affect microglial activation, MCI, and PD. The literature of common psychotropics used in treating psychiatric disorders was reviewed for preclinical and clinical findings regarding microglial activation. Findings potentially compatible with reduced microglial activation or reduced microglial inflammogen release were evident for: antipsychotics including neuroleptics (chlorpromazine, thioridazine, loxapine) and atypicals (aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone); mood stabilizers (carbamazepine, valproate, lithium); antidepressants including tricyclics (amitriptyline, clomipramine, imipramine, nortriptyline), SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline), venlafaxine, and bupropion; benzodiazepine anxiolytics (clonazepam, diazepam); cognitive enhancers (donepezil, galantamine, memantine); and other drugs (dextromethorphan, quinidine, amantadine). In contrast, pramipexole and methylphenidate might promote microglial activation. The most promising replicated findings of reduced microglial activation are for quetiapine, valproate, lithium, fluoxetine, donepezil, and memantine but further study is needed and translation of their microglial effects to human disease still requires investigation. In AD-relevant models, risperidone, valproate, lithium, fluoxetine, bupropion, donepezil, and memantine have therapeutic microglial effects in need of replication. Limited

  9. 光敏性药疹68例临床分析%Clinical analysis of 68 patients with photosensitization drug eruption

    Institute of Scientific and Technical Information of China (English)

    朱敏刚; 魏盛; 王音; 胡晓波; 刘卫

    2015-01-01

    目的::明确光敏性药疹的临床特征及相关药物。方法:对我院门诊诊断为光敏性药疹患者的临床资料进行回顾性分析。结果:68例患者中,噻嗪类药物所致37例,喹诺酮类19例,多西环素3例,维胺酯、辛伐他丁及秋水仙碱各2例,氯丙嗪、地尔硫卓及乙胺碘呋酮各1例。皮损仅局限于曝光部位的62例,主要表现为水肿性红斑;皮损同时累及非曝光部位的有6例,表现为湿疹样皮损等多形性损害。患者停用可疑药物及避光,口服抗组胺药、烟酰胺或中小剂量糖皮质激素,外用炉甘石洗剂或糖皮质激素乳膏。65例患者皮损于4周内基本消退。结论:噻嗪类利尿剂及喹诺酮类是引起光敏性药疹最常见的药物。%Objective:To determine the types of drugs which caused photosensitization drug eruption and the clinical features of the patients. Methods: The data of patients with photosensitization drug eruption was analyzed retrospectively. Results: Out of 68 patients, 37 patients were caused by thiazine diuretics, 19 by quinolones, 3 by doxycycline, 2 by viaminate, 2 by Simvastatin, 2 by colchicine, 1 by chlorpromazine, 1 by diltiazem and 1 by amiodarone. The lesions were located on exposed area only and mainly manifested as edem-atous erythema in 62 patients. The lesions were located on both exposed and unexposed areas and manifested as various lesions in 6 patients. All patients stopped the suspicious drugs, kept away from the sun exposure and were given oral antihistamines, nicotinamide, low-medium doses of glucocorticoid and topical calamine lotion and corticosteroids cream. Six five patients were cured after the treatment of 4 weeks. Conclusion:Thia-zine diuretics and quinolones are the most common drugs inducing the photosensitization drug eruption in our patients.

  10. Rapid method for the determination of tranquilizers and a beta-blocker in porcine and bovine kidney by liquid chromatography with tandem mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Mitrowska, Kamila [National Veterinary Research Institute, Department of Pharmacology and Toxicology, al. Partyzantow 57, 24-100 Pulawy (Poland)], E-mail: kamitro@piwet.pulawy.pl; Posyniak, Andrzej; Zmudzki, Jan [National Veterinary Research Institute, Department of Pharmacology and Toxicology, al. Partyzantow 57, 24-100 Pulawy (Poland)

    2009-04-01

    A fast and simple liquid chromatography with tandem mass spectrometry method for detection and confirmation of tranquilizers (chlorpromazine, propionylpromazine, acepromazine, triflupromazine, promazine, azaperone and its metabolite, azaperol) and beta-blocker (carazolol) in porcine and bovine kidney has been presented. The method relies on the extraction with acetonitrile followed by centrifugation. After evaporation of acetonitrile, the residue was reconstituted in a mobile phase and filtrated. The separation of analytes was performed on a C18 column using a mobile phase of acetonitrile and ammonium formate buffer (0.05 M, pH 4.5) with gradient elution. The electrospray ionization was used to obtain the protonated molecules [M+H]{sup +} and two product ions were monitored for each compound. For quantification deutered internal standards were used. The whole method has been validated according to the European Union requirements. Specificity, decision limit (CC{alpha}), detection capability (CC{beta}), trueness and precision were determined. The results showed good trueness ranged from 73.2% to 110.6% with a good R.S.D., less than 13.0% under within-laboratory reproducibility conditions. The calculated critical concentrations of CC{alpha} for phenothiazines were between 5.8 and 6.6 {mu}g kg{sup -1} while for azaperone CC{alpha} was 105.5 {mu}g kg{sup -1} and for azaperol was 121.4 {mu}g kg{sup -1}. CC{alpha} for carazolol was 16.7 {mu}g kg{sup -1} in bovine and 21.9 {mu}g kg{sup -1} in porcine kidney. CC{beta} for phenothiazines were between 6.3 and 7.6 {mu}g kg{sup -1}, for azaperone was 119.0 {mu}g kg{sup -1} and for azaperol was 140.0 {mu}g kg{sup -1}. For carazolol in bovine kidney CC{beta} was 18.6 {mu}g kg{sup -1} whereas in porcine kidney was 24.4 {mu}g kg{sup -1}.

  11. Adherence to depot versus oral antipsychotic medication in schizophrenic patients during the long-term therapy

    Directory of Open Access Journals (Sweden)

    Stanković Žana

    2013-01-01

    Full Text Available Background/Aim. There is a high rate of schizophrenic patients who do not adhere to their prescribed therapy, despite the implementation of antipsychotic long-acting injections and the introduction of atypical antipsychotics. The aim of this study was to investigate the differences in sociodemographic, clinical and medication adherence variables between the two groups of schizophrenic patients on maintenance therapy with depot antipsychotic fluphenazine decanoate and oral antipsychotics only as well as a correlation between the medication adherence and other examined variables. Methods. A total of 56 patients of both genders, aged < 60 years, with the diagnosis of schizophrenia (F20 (ICD-10, 1992 clinically stable for at least 6 months were introduced in this cross-sectional study. The patients from the depot group (n = 19 were on classical depot antipsychotic fluphenazine decanoate administering intramuscularly every 4 weeks (with or without oral antipsychotic augmentation and the patients from the oral group (n = 37 were on oral therapy alone with classical or atypical antipsychotics, either as monotherapy or combined. The Positive and Negative Syndrome Scale (PANSS was used to assess symptom severity. Item G12 of the PANSS was used to assess insight into the illness. The patients completed the Medical Adherence Rating Scale (MARS was used to assess adherence to the therapy. A higher MARS score indicates behavior [Medical Adherence Questionnaire (MAQ subscale] and attitudes toward medication [Drug Attitude Inventory (DAI subscale] that are more consistent with treatment adherence. The exclusion criteria were determined. The Pearson's χ2 test was used to compare categorical variables, Student's t-test to compare continuous variables and Pearson's correlation to test the correlation significance; p = 0.05. Results. Significant betweengroup differences in age, illness duration, chlorpromazine equivalents, PANSS score and DAI subscore were found

  12. Decreases in nestlet shredding of mice by serotonin uptake inhibitors: comparison with marble burying.

    Science.gov (United States)

    Li, Xia; Morrow, Denise; Witkin, Jeffrey M

    2006-03-20

    Methods for detection of anxiolytic-like behavioral effects of serotonin uptake inhibitors are limited. The present study introduces a new quantitative method that permits dose-effect analysis of these compounds. Male NIH Swiss mice were given 60-min access to a piece of cotton gauze and the amount of material not torn into nesting material was weighed. Other groups of mice were individually placed in containers with 20 marbles resting on top of sawdust bedding. The number of marbles buried (2/3) by sawdust after 30 min was counted. Mice were first placed on a 6-rpm rotorod and the number of mice falling off twice in 2 min was measured. Serotonin uptake inhibitors (clomipramine, citalopram, fluoxetine, and venlafaxine) dose-dependently suppressed nestlet shredding and marble burying at doses that were generally without effect on rotorod performance. The amine-based antidepressant agents imipramine and desipramine as well as the selective norepinephrine transport inhibitor nisoxetine produced similar qualitative effects on these behaviors. Anxiolytics (chlordiazepoxide, bretazenil, buspirone, and pentobarbital) produced effects in the nestlet assay that were similar to those reported using another anxiolytic assay in mice (punished responding), whereas these compounds were not active at non-motor-impairing doses in the marble burying assay. The antipsychotic agents chlorpromazine and risperidone generally demonstrated suppression of nestlet shredding and marble burying at doses that impaired rotorod performance. Although d-amphetamine suppressed nestlet shredding and marble burying at doses without effect on the rotorod, d-amphetamine but not fluoxetine stimulated locomotor activity. Both nestlet shredding and marble burying behaviors were generally consistent across five consecutive experimental sessions and fluoxetine did not produce any systematic trends over repeated testing. The methods should have utility in defining pharmacological effects of these compounds

  13. Pharmacological treatment of schizophrenia: a critical review of the pharmacology and clinical effects of current and future therapeutic agents.

    Science.gov (United States)

    Miyamoto, S; Miyake, N; Jarskog, L F; Fleischhacker, W W; Lieberman, J A

    2012-12-01

    Since the introduction of chlorpromazine and throughout the development of the new-generation antipsychotic drugs (APDs) beginning with clozapine, the D(2) receptor has been the target for the development of APDs. Pharmacologic actions to reduce neurotransmission through the D(2) receptor have been the only proven therapeutic mechanism for psychoses. A number of novel non-D(2) mechanisms of action of APDs have been explored over the past 40 years but none has definitively been proven effective. At the same time, the effectiveness of treatments and range of outcomes for patients are far from satisfactory. The relative success of antipsychotics in treating positive symptoms is limited by the fact that a substantial number of patients are refractory to current medications and by their lack of efficacy for negative and cognitive symptoms, which often determine the level of functional impairment. In addition, while the newer antipsychotics produce fewer motor side effects, safety and tolerability concerns about weight gain and endocrinopathies have emerged. Consequently, there is an urgent need for more effective and better-tolerated antipsychotic agents, and to identify new molecular targets and develop mechanistically novel compounds that can address the various symptom dimensions of schizophrenia. In recent years, a variety of new experimental pharmacological approaches have emerged, including compounds acting on targets other than the dopamine D(2) receptor. However, there is still an ongoing debate as to whether drugs selective for singe molecular targets (that is, 'magic bullets') or drugs selectively non-selective for several molecular targets (that is, 'magic shotguns', 'multifunctional drugs' or 'intramolecular polypharmacy') will lead to more effective new medications for schizophrenia. In this context, current and future drug development strategies can be seen to fall into three categories: (1) refinement of precedented mechanisms of action to provide drugs

  14. Calcium affecting protein expression in longan under simulated acid rain stress.

    Science.gov (United States)

    Pan, Tengfei; Li, Yongyu; Ma, Cuilan; Qiu, Dongliang

    2015-08-01

    Longan (Dimocarpus longana Lour. cv. Wulongling) of uniform one-aged seedlings grown in pots were selected to study specific proteins expressed in leaves under simulated acid rain (SiAR) stress and exogenous Ca(2+) regulation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) results showed that there was a protein band specifically expressed under SiAR of pH 2.5 stress for 15 days with its molecular weight of about 23 kD. A 17 kD protein band specifically expressed after SiAR stress 5 days. Compared with pH 2.5, the pH 3.5 of SiAR made a less influence to protein expression. Two-dimensional electrophoresis (2-DE) results showed that six new specific proteins including C4 (20.2 kD pI 6.0), F (24 kD pI 6.35), B3 (22.3 kD pI 6.35), B4 (23.5 kD pI 6.5), C5 (21.8 kD pI 5.6), and C6 (20.2 kD pI 5.6) specifically expressed. C4 always expressed during SiAR stress. F expressed under the stress of pH 2.5 for 15 days and expressed in all pH SiAR stress for 20 days. The expression of proteins including B3, C5, and C6 was related to pH value and stress intensity of SiAR. The expression of B4 resulted from synergistic effects of SiAR and Ca. The expression of G1 (Mr 19.3 kD, pI 4.5), G2 (Mr 17.8 kD, pI 4.65), G3 (Mr 16.6 kD, pI 4.6), and G4 (Mr 14.7 kD, pI 4.4) enhanced under the treatment of 5 mM ethylene glycol tetraacetic acid (EGTA) and 2 mM chlorpromazine (CPZ). These proteins showed antagonistic effects and might be relative to the Ca-calmodulin (Ca-CaM) system of longan in response to SiAR stress.

  15. MetMaxStruct: a Tversky-similarity-based strategy for analysing the (substructural similarities of drugs and endogenous metabolites

    Directory of Open Access Journals (Sweden)

    Steve O'Hagan

    2016-08-01

    Full Text Available Background. Previous studies compared the molecular similarity of marketed drugs and endogenous human metabolites (endogenites, using a series of fingerprint-type encodings, variously ranked and clustered using the Tanimoto (Jaccard similarity coefficient (TS. Because this gives equal weight to all parts of the encoding (thence to different substructures in the molecule it may not be optimal, since in many cases not all parts of the molecule will bind to their macromolecular targets. Unsupervised methods cannot alone uncover this. We here explore the kinds of differences that may be observed when the TS is replaced – in a manner more equivalent to semi-supervised learning – by variants of the asymmetric Tversky (TV similarity, that includes  and  parameters. Results. Dramatic differences are observed in (i the drug-endogenite similarity heatmaps, (ii the cumulative ‘greatest similarity’ curves, and (iii the fraction of drugs with a Tversky similarity to a metabolite exceeding a given value when the Tversky  and  parameters are varied from their Tanimoto values. The same is true when the sum of the  and  parameters is varied. A clear trend towards increased endogenite-likeness of marketed drugs is observed when  or adopt values nearer the extremes of their range, and when their sum is smaller. The kinds of molecules exhibiting the greatest similarity to two interrogating drug molecules (chlorpromazine and clozapine also vary in both nature and the values of their similarity as  and  are varied. The same is true for the converse, when drugs are interrogated with an endogenite. The fraction of drugs with a Tversky similarity to a molecule in a library exceeding a given value depends on the contents of that library, and  and  may be ‘tuned’ accordingly, in a semi-supervised manner. At some values of  and  drug discovery library candidates or natural products can look much more like (i.e. have

  16. Cytotoxicity of CdTe quantum dots in human umbilical vein endothelial cells: the involvement of cellular uptake and induction of pro-apoptotic endoplasmic reticulum stress.

    Science.gov (United States)

    Yan, Ming; Zhang, Yun; Qin, Haiyan; Liu, Kezhou; Guo, Miao; Ge, Yakun; Xu, Mingen; Sun, Yonghong; Zheng, Xiaoxiang

    2016-01-01

    Cadmium telluride quantum dots (CdTe QDs) have been proposed to induce oxidative stress, which plays a crucial role in CdTe QDs-mediated mitochondrial-dependent apoptosis in human umbilical vein endothelial cells (HUVECs). However, the direct interactions of CdTe QDs with HUVECs and their potential impairment of other organelles like endoplasmic reticulum (ER) in HUVECs are poorly understood. In this study, we reported that the negatively charged CdTe QDs (-21.63±0.91 mV), with good dispersity and fluorescence stability, were rapidly internalized via endocytosis by HUVECs, as the notable internalization could be inhibited up to 95.52% by energy depletion (NaN3/deoxyglucose or low temperature). The endocytosis inhibitors (methyl-β-cyclodextrin, genistein, sucrose, chlorpromazine, and colchicine) dramatically decreased the uptake of CdTe QDs by HUVECs, suggesting that both caveolae/raft- and clathrin-mediated endocytosis were involved in the endothelial uptake of CdTe QDs. Using immunocytochemistry, a striking overlap of the internalized CdTe QDs and ER marker was observed, which indicates that QDs may be transported to ER. The CdTe QDs also caused remarkable ER stress responses in HUVECs, confirmed by significant dilatation of ER cisternae, upregulation of ER stress markers GRP78/GRP94, and activation of protein kinase RNA-like ER kinase-eIF2α-activating transcription factor 4 pathway (including phosphorylation of both protein kinase RNA-like ER kinase and eIF2α and elevated level of activating transcription factor 4). CdTe QDs further promoted an increased C/EBP homologous protein expression, phosphorylation of c-JUN NH2-terminal kinase, and cleavage of ER-resident caspase-4, while the specific inhibitor (SP600125, Z-LEVD-fmk, or salubrinal) significantly attenuated QDs-triggered apoptosis, indicating that all three ER stress-mediated apoptosis pathways were activated and the direct participation of ER in the CdTe QDs-caused apoptotic cell death in HUVECs. Our

  17. Talidomida: indicações em Dermatologia Thalidomide: indications in Dermatology

    Directory of Open Access Journals (Sweden)

    Rubem David Azulay

    2004-10-01

    mucous, pruritus, cutaneous eruption, weight gain, hypothyroidism, neutropenia, bradycardia or tachycardia, and hypotension. It interacts with other medicine: barbiturates, chlorpromazine, reserpine, alcohol, acetaminophen, histamine, serotonin and prostaglandin.

  18. The second cross-sectional study on antipsychotic drug patterns of schizophrenia in China%2006年我国十省市抗精神病药处方方式的现况调查

    Institute of Scientific and Technical Information of China (English)

    司天梅; 陈宪生; 梅其一; 栗克清; 舒良; 于欣; 马崔; 王高华; 白培深; 刘协和; 孙立忠; 师建国

    2010-01-01

    Objective To uncover the antipsychotic drug use patterns for treating schizophrenia in China in 2006, and the developing tendency from 2002 to 2006.Methods Based on the investigation in 2002, the same methods and same hospitals were selected, totally 41 hospitals from 10 provinces and cities.The investigation was conducted during 22th to 28th, May, 2006, using the revised self-made modified questionnaire.Results The total number of sample was 5898, including outpatients (46.0%) and inpatients (54.0% ) ( male: female = 51.6%: 47.4% ).The most common clinical characteristics were the personal and social dysfunction.Antipsychotic medication most frequently prescribed was clozapine (31.7%), subsequently were risperidone (30.5%), sulpiride (14.5%), chlorpromazine (10.8%),perphenazine (9.2%), quetiapine (7.2%) and haloperidol (5.8%) .The mean chlorpromazine equivalent dosage was higher in inpatients than outpatients.In all the patients, 75.6% were treated with mono-pharmacy, in which 72.7% with atypical antipsychotics (while 38.3% with typical drugs), and the percentage of patients with depot antipsychotics was 6.2%.24.4% of the patients were treated with 2 or more than 2 types of antipsychotics.The common concomitant medications were anticholinergic agents,benzodiazepine, β-receptor blockade, antidepressants and mood stabilizers, in order to control the adverse effects or augment the efficacy of antipsychotics.Conclusions Atypical drugs are the mainstream to treat schizophrenia in China, the tendency of antipsychotics prescription pattern matches the development of treatment outcome and treatment techniques for schizophrenia.%目的 调查2006年我国10省市抗精神病药处方方式;分析4年间我国抗精神病药处方方式的变化趋势.方法 按照作者2002年的调查方法,选择10省市41所精神疾病专科医院或综合医院精神科的5898例精神分裂症门诊和住院患者,于2006年5月22-28日使用自制修订的调查问卷进行精神

  19. Survey of antipsychotic druGs usinG status in patients with schizophrenia in Suzhou%苏州市精神分裂症患者抗精神病药物使用现况调查

    Institute of Scientific and Technical Information of China (English)

    杨勇; 盖海军; 王秀艳; 丁若水; 杨忠; 王新达; 杜向东; 梅其一; 吴爱勤

    2015-01-01

    Objective:To infestigate the status quo of antipsychotic drugs using in patients with schizo-phrenia in Suzhou. Method:The drugs using questionnaire was used to infestigate the drug using situation in 544 schizophrenic patients( including inpatients and outpatients)from 3 mental disease hospitals in Suzhou. Results:The first 6 drugs used frequently were clozapine( 25. 6%),risperidone( 16. 5%),olanzapine (13. 9%),quetiapine(11. 4%),aripiprazole(9. 1%)and chlorpromazine(6. 8%). The usage frequency of an-tipsychotic was significantly different between inpatients and outpatients(χ2 =37. 361,P=0. 003). Compared with inpatients,the dose of clozapine,risperidone,olanzapine,quetiapine,aripiprazole and chlorpromazine in outpatients were significantly lower,sulpiride,ziprasidone and haloperidol were significantly higher( all P ﹤0. 01). The rate of using single antipsychotic drug(54. 4%,293 cases)was higher than combination(45. 6%, 246 cases). Among the patients treated with single antipsychotic drug,84. 2%(247 cases)used the second gen-eration antipsychotics(SGAs);and among the patients treated with combination therapy,97. 8%(241 cases) main drug and 65. 0%(160 cases)secondary drugs were SGAs. The most common combinatife drugs were sed-atife hypnotics( 20. 2%),then mood stabilizers( 12. 2%),anticholinergics( 12. 1%),antidepressants (7. 8%)andβ-blockers(4. 3%). Conclusion:The major treatment model of schizophrenia in Suzhou is u-sing single antipsychotic drug and choosing SGAs.%目的:调查苏州市精神分裂症患者抗精神病药物使用现况。方法:采用患者药物使用调查表,对苏州市3家精神疾病专科医院的544例住院和门诊精神分裂症患者进行抗精神病药物使用情况调查。结果:使用居前6位的抗精神病药物分别是氯氮平(25.6%)、利培酮(16.5%)、奥氮平(13.9%)、奎硫平(11.4%)、阿立哌唑(9.1%)、氯丙嗪(6.8%)。门诊和住院

  20. The role of antipsychotics in the management of fibromyalgia.

    Science.gov (United States)

    Calandre, Elena P; Rico-Villademoros, Fernando

    2012-02-01

    amisulpride, have demonstrated antidepressant activity, with quetiapine approved for the treatment of bipolar depression and refractory major depression, and aripiprazole approved as an adjunctive treatment for major depressive disorder. Finally, several old and new antipsychotics, including promethazine, levopromazine, olanzapine, quetiapine and ziprasidone, have been shown to improve sleep parameters in healthy subjects. Each of these properties suggests that antipsychotics could represent a new potential alternative for the treatment of fibromyalgia syndrome. To date, most of the published studies on the use of antipsychotics in the treatment of fibromyalgia syndrome have been uncontrolled, either case reports or case series, dealing with olanzapine, quetiapine, ziprasidone, levopromazine and amisulpride. The studies on olanzapine and quetiapine have suggested therapeutic efficacy although, in the case of olanzapine, hampered by tolerability problems. A double-blind controlled trial, published in 1980, showed that chlorpromazine increased slow-wave sleep and improved pain and mood disturbances. More recently, four double-blind controlled studies have explored the efficacy of quetiapine, either alone or as an add-on treatment, in fibromyalgia management. None of these trials has yet been published, although two of them have been presented as congress communications, both of them suggesting that quetiapine could be a potential alternative treatment for fibromyalgia. In summary, the current available evidence suggests that at least some antipsychotics, specifically quetiapine, could be useful for the treatment of fibromyalgia and that further studies on the efficacy of these compounds are worth pursuing.

  1. Cytotoxicity of CdTe quantum dots in human umbilical vein endothelial cells: the involvement of cellular uptake and induction of pro-apoptotic endoplasmic reticulum stress

    Directory of Open Access Journals (Sweden)

    Yan M

    2016-02-01

    Full Text Available Ming Yan,1,* Yun Zhang,2,* Haiyan Qin,3 Kezhou Liu,1 Miao Guo,1 Yakun Ge,1 Mingen Xu,1 Yonghong Sun,4 Xiaoxiang Zheng4 1Department of Biomedical Engineering, College of Life Information Science and Instrument Engineering, Hangzhou Dianzi University, Hangzhou, 2Basic Medical Sciences, College of Medicine, Shaoxing University, Shaoxing, 3Department of Chemistry, Zhejiang University, 4Zhejiang Provincial Key Laboratory of Cardio-Cerebral Vascular Detection Technology and Medicinal Effectiveness Appraisal, Department of Biomedical Engineering, Zhejiang University, Hangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Cadmium telluride quantum dots (CdTe QDs have been proposed to induce oxidative stress, which plays a crucial role in CdTe QDs-mediated mitochondrial-dependent apoptosis in human umbilical vein endothelial cells (HUVECs. However, the direct interactions of CdTe QDs with HUVECs and their potential impairment of other organelles like endoplasmic reticulum (ER in HUVECs are poorly understood. In this study, we reported that the negatively charged CdTe QDs (–21.63±0.91 mV, with good dispersity and fluorescence stability, were rapidly internalized via endocytosis by HUVECs, as the notable internalization could be inhibited up to 95.52% by energy depletion (NaN3/deoxyglucose or low temperature. The endocytosis inhibitors (methyl-β-cyclodextrin, genistein, sucrose, chlorpromazine, and colchicine dramatically decreased the uptake of CdTe QDs by HUVECs, suggesting that both caveolae/raft- and clathrin-mediated endocytosis were involved in the endothelial uptake of CdTe QDs. Using immunocytochemistry, a striking overlap of the internalized CdTe QDs and ER marker was observed, which indicates that QDs may be transported to ER. The CdTe QDs also caused remarkable ER stress responses in HUVECs, confirmed by significant dilatation of ER cisternae, upregulation of ER stress markers GRP78/GRP94, and

  2. 20%的硫酸镁在成人重症破伤风中的治疗作用%The 20 % magnesium sulfate for the treatment of the adult severe tetanus

    Institute of Scientific and Technical Information of China (English)

    魏刚; 章希; 张必翔; 刘文; 陈孝平; 张应天

    2012-01-01

    目的 探讨20%的硫酸镁治疗成人重症破伤风的安全性及有效性.方法 对2005年4月- 2010年10月收治的27例成人重症破伤风住院病例行回顾性分析.结果 血镁超过4 mmol/L者2例(2/27,7.4%);气管切开者25例(25/27,92.6%),机械通气22例(22/25,88.0%),机械通气时间为4~16d,平均(7.5±3.7)d;肺部感染25例(25/27,92.6%);死亡4例(4/27,14.8%);治愈23例(23/27,85.2%),住院时间25~48 d,平均(32.2±18.8)d.结论 20%的硫酸镁治疗成人重症破伤风安全,可有效控制肌肉强直、抽搐和自律性不稳定,以减少安定和氯丙嗪等镇静药的用量,操作简单,价格便宜,易于在临床推广.%Objective To study the efficacy and safety magnesium sulfate for the treatment of adult severe tetanus.Methods Twenty-seven inpatients with adult severe tetanus during April 2005 - October 2010 were retrospectively analysed.Results The total serum magnesium more than 4 mmol/L was found in 2 patients ( 2/27,7.40% ).The tracheotomy was performed in 25 Patients (25/27,92.6%),22 of which (22/25,88.0%) run mechanical ventilation with the mean mechanical ventilation time (7.5 ± 3.7 ) days,(4 to 16 days).Pulmonary infection occurred in 25 cases (25/27,92.6%).Twenty-three of 27 (23/27,85.2% ) cases were cured except 4 cases died,and the mean hospital stay was (32.22 ± 18.78) days,(25to 48) days.Conclusions 20% magnesium sulfate is safe for treatment of the patients of adult severe tetanus.It can control not only muscle rigidity and spasms but also autonomic instability efficaciously,and lower the dosage of sedative such as diazepam and chlorpromazine.This method is worth popularizing in clinical practice for its easy operation and low cost.

  3. 长期住院男性精神分裂症患者血清催乳素水平调查%The investigation of serum prolactin level in the chronic male schizophrenia in patients

    Institute of Scientific and Technical Information of China (English)

    刘进文; 张晓斌; 储昕; 李继江; 董慧; 刘亚平; 秦捷

    2012-01-01

    目的:调查长期住院服用典型抗精神病药的男性精神分裂症患者血清催乳素(PRL)水平.方法:114例长期住院的男性精神分裂症患者(患者组)使用电化学发光免疫分析技术检测血清PRL水平,并与性别、年龄相匹配的57名正常男性(对照组)相比较. 结果:患者组的血清PRL水平平均(24.1±18.8) ng/ml显著高于对照组(10.6±5.5)ng/ml(t =7.06,P<0.01).患者组中吸烟精神分裂症患者血清PRL水平平均(21.2±15.4) ng/ml显著低于非吸烟精神分裂症患者(30.7±23.9) ng/ml(t=-2.17,P<0.05).精神分裂症患者血清PRL水平与患者年龄(r=0.003)、服药剂量(折算为氯丙嗪,r=-0.12)、服药时间(r=-0.18)以及体质量指数(r=-0.07)之间无明显相关性(P均>0.05).结论:长期服用典型抗精神病药可显著增高男性精神分裂症患者血清PRL水平,吸烟对血清PRL水平有一定的影响.%Objective: To investigate the serum prolactin levels in the chronic male schizophrenia inpa-tients who take the typical antipsychotics. Method; The serum prolactin levels in the chronic male schizophrenic group (n= 114) compared with the age and gender matched normal group (n = 57) were measured with electro-chemiluminescence immune assay instrument. Results;The serum prolactin levels in the schizophrenic group (24. 1 ±18. 8)ng/ml were significantly higher than the levels in the normal group (10. 6 ±5. 5) ng/ml (t =7. 06,P 0. 05 ) , drug dose ( conversions chlorpromazine, r = -0. 12, P> 0.05) , drug treatment time (r= -0. 18 ,P >0. 05) and the height and weight index (r = -0.07, P>0. 05). Conclusion; The typical antipsychotics treatment can significantly increase the serum prolactin levels in the male schizophrenic patients. Smoking status have the significantly effect on the serum prolactin levels in the schizophrenic patients.

  4. Immobilized Artificial Membrane HPLC Derived Parameters vs PAMPA-BBB Data in Estimating in Situ Measured Blood-Brain Barrier Permeation of Drugs.

    Science.gov (United States)

    Grumetto, Lucia; Russo, Giacomo; Barbato, Francesco

    2016-08-01

    ibuprofen and chlorpromazine, which behaved as moderate outliers (r(2) = 0.656 and r(2) = 0.757 for values achieved on IAM.PC.MG and IAM.PC.DD2, respectively). Since log P0(in situ) refer to the "intrinsic permeability" of the analytes regardless their ionization degree, no correction for ionization of Δlog kW(IAM) values was needed. Furthermore, log P0(in situ) were found roughly linearly related to log BB values (i.e., the logarithm of the ratio brain concentration/blood concentration measured in vivo) for all the analytes but those predominantly present at the experimental pH 7.4 as anions. These results suggest that, at least for the data set considered, Δlog kW(IAM) parameters are more effective than log P0(PAMPA-BBB) at predicting log P0(in situ) values for all the analytes. Furthermore, ionization appears to affect differently, and much more markedly, BBB passage of acids (yielding anions) than that of the other ionizable compounds.

  5. Interventional effects of different amino acids on schizophrenic BALB/C rats%不同氨基酸对精神分裂小鼠BALB/C干预作用研究

    Institute of Scientific and Technical Information of China (English)

    张程希; 吴晶; 翟寅

    2011-01-01

    Objective Study the interventional effects of different amino acids on schizophrenia through the schizophrenic BALB/C rats model. The possible psychophysiology mechanism is discussed. Methods The molded BALB/C rats were simulated with phosphoric acid codeine. Field experiment and the times of hole board tests are observed after the injection of L-glutamic acid, tyrosine,tryptophan,and glycine in molded BALB/C rats with the control medicine of chlorpromazine. Results Stereotyped behaviors time of high and low concentration of glutamate are (120. 67 ± 18. 23) s and (202. 33 ±48. 34) s,fast-moving times are (3.33 ± 0.58) times and (4.33 ±1.15) times,the hole board test are (26.00 ±2. 65) times and (22. 67 ±1.53)times; Stereotyped behaviors time of high and low concentration of tyrosine are ( 831.00 ± 41.62) s and (776.00 ± 9.17)s,fast-moving times are (49. 00 ±1.00) and (21.33 ±0. 58) times, the times of hole board test are (4.83 ±0.76) times and (7. 57 ±0. 51) times. Conclusion Amino acids have interventional effects on schizophrenia. Glutamate significantly alleviates the effect of schizophrenia, while tyrosine has a vital role in promoting schizophrenia.%目的 通过构建精神分裂小鼠BALB/C模型,研究不同种类氨基酸对模型的干预作用,初步探讨可能的精神分裂症生理学机制.方法 以氯丙嗪为对照,采用磷酸可待因构造小鼠BALB/C模型,用旷场实验、洞板实验观察L-谷氨酸、酪氨酸、色氨酸、甘氨酸对精神分裂小鼠BALB/C模型的作用.结果 L-谷氨酸高低剂量刻板行为时间分别为(120.67±18.23)s和(202.33±48.34)s,快速移动次数分别为(3.33±0.58)次和(4.33±1.15)次,洞板实验小鼠探洞次数(26.00±2.65)次和(22.67±1.53)次;酪氨酸高低剂量刻板行为时间分别为(831.00±41.62)s和(776.00±9.17)s,快速移动次数分别为(49.00±1.00)次和(21.33±0.58)次,洞板实验小鼠探洞次数分别为(4.83±0.76)次和(7.57±0.51)次.结论 氨基酸

  6. EPS profiles: the atypical antipsychotics are not all the same.

    Science.gov (United States)

    Weiden, Peter J

    2007-01-01

    Within the first few years after chlorpromazine began to be used to treat psychosis, it was observed that it could cause many kinds of neurologic reactions that resembled those seen in idiopathic Parkinson's disease. These reactions were termed "extrapyramidal side effects" (EPS) because of their resemblance to the signs of Parkinson's disease, which were associated with degeneration of the dopamine nerve tracks located in the extrapyramidal region of the central nervous system. Eventually this association of dopamine loss, antipsychotics, and parkinsonism became a central part of the dopamine hypothesis of schizophrenia. Unfortunately, this association was also used to support the hypothesis that EPS were absolutely necessary for antipsychotic efficacy--hence the term "neuroleptic" rather than "antipsychotic." This theory, now discredited, was used to justify the practice of inducing EPS as a means to gauge whether an antipsychotic would be effective. The demonstration that clozapine, an antipsychotic virtually devoid of EPS, has better efficacy for psychosis than any other "neuroleptic" disproved the theory that EPS were fundamentally linked to efficacy. Because the idea of a relationship between EPS and efficacy was so ingrained in clinical practice, clozapine was called "atypical." Our understanding of the relationship between EPS and antipsychotic response has come full circle. With the introduction of clozapine and other newer antipsychotics, it has become clear that EPS are harmful and serve no beneficial purpose. The availability of newer antipsychotics with a lower EPS burden means that, at least in theory, it is now possible to treat psychosis without EPS in the vast majority of patients. In practice, however, EPS remain a significant problem even in the era of atypical or second generation antipsychotics (SGAs). One limitation is that the concept of "atypicality," when used to denote antipsychotic efficacy without EPS, is a relative not an absolute

  7. Targeting Cells With MR Imaging Probes: Cellular Interaction And Intracellular Magnetic Iron Oxide Nanoparticles Uptake In Brain Capillary Endothelial and Choroidal Plexus Epithelial Cells

    Science.gov (United States)

    Cambianica, I.; Bossi, M.; Gasco, P.; Gonzalez, W.; Idee, J. M.; Miserocchi, G.; Rigolio, R.; Chanana, M.; Morjan, I.; Wang, D.; Sancini, G.

    2010-10-01

    microscopy and flow cytometry we studied the cell uptake of magnetic SLNs derivatized with a fluorescent reporter molecule and of L-DOPA-TRITC coated NPs. Inhibition of the caveolae-mediated pathway by preincubation with filipin and nystatin did not modify the cellular uptake of these NPs in both cell lines. Furthermore a mild decrease of the NPs cell uptake was obtained after chlorpromazine and NaN3 pretreatment, which interferes with clathrin and energy-dependent endocytosis, and cytochalasin and amiloride pretreatment which interfere with macropinocytosis. NPs particle size as such can strongly affect the efficiency of cellular uptake and the mode of endocytosis. Considering that our L-DOPA and magnetic SLNs display a medium hydrodynamic size of 120 nm with a polydispersity index of 0.3, we can assume that the cell uptake process of these NPs may develop, depending the particle size, both via clathrin mediated endocytosis and macropinocytosis and only to less extent via the pathway of caveolae-mediated endocytosis. Taken together these results let us to conclude that SLNs iron loaded and iron based L-DOPA coated NPs are internalized into brain endothelial and choroidal plexus epithelial cells and this might provide the first step of an intracellular trafficking to transport these NPs between blood and brain.

  8. Observation of Clinical Effects of Buspirone Combined with Antipsychotic Drugs in the Treatment of Schizophrenia with Psychopathology and Drug-induced Anxiety%丁螺环酮与抗精神病药物联用治疗精神分裂症患者病理性或药源性焦虑的疗效观察

    Institute of Scientific and Technical Information of China (English)

    周慧民; 韦德会

    2013-01-01

    目的:观察丁螺环酮与抗精神病药物联用治疗精神分裂症患者病理性或药源性焦虑的疗效.方法:将2008年2月-2012年2月在我院就诊的精神分裂症患者240例,按疾病类型的不同随机分为单用抗精神病药物组(A组)和抗精神病药物联用丁螺环酮组(B组).A组患者用药包括氯丙嗪、氯氮平、阿立哌唑、利培酮,B组患者为氯丙嗪、氯氮平、阿立哌唑、利培酮分别与丁螺环酮联用.然后进行各药物的单用和联用两两配对观察,共计4对、8小组,每小组纳入病例30例.采用汉密尔顿焦虑量表(HAMA)和阳性与阴性症状量表(PANSS)于入组前和入组后1、2、4、8、12周末各评定1次,对焦虑症状缓解程度及治疗效果进行比较.结果:各个时间点的HAMA和PANSS减分B组均快于A组(P<0.05或P<0.01),B组的抗精神病药物用量也少于A组(P<0.01),但总有效率两组比较差异无统计学意义(P>0.05).所有患者用药过程中均未见不良反应发生.结论:抗精神病药物与丁螺环酮联合使用可快速缓解精神病患者的精神症状,且可减少抗精神病药物的用量,安全性较好.%OBJECTIVE: To investigate therapeutic efficacies of buspirone combined with antipsychotic drugs in the treatment of schizophrenia with psychopathology and drug-induced anxiety. METHODS: 240 patients with schizophrenia were randomly divided into antipsychotic drugs alone group (group A) and antipsychotic drugs combined with buspirone (group B) in our hospital during Feb. 2008 -Feb. 2012. Group A received chlorpromazine, clozapine, aripiprazole and risperidone, and group B was given buspirone combined with clozapine, aripiprazole or risperidone. Therapy of single drug and two-drug were observed. A total of 4 pairs and 8 groups were formulated with 30 cases in each group. Therapeutic efficacy was evaluated with HAMA and PANSS before and 1, 2, 4, 8, 12 weeks of therapy. RESULTS: The reduction rates of HAMA and

  9. MnO_2纳米溶胶-甲醛化学发光体系及其分析应用研究%Chemiluminescence of Nano-Colloidal MnO2 with Formaldehyde and Its Analytical Application

    Institute of Scientific and Technical Information of China (English)

    杜建修; 王虹

    2012-01-01

    Water-soluble forms of colloidal MnO2 were prepared by the chemical reduction of KMnO4 with Na2S203 under neutral aqueous condition. The as-prepared colloidal MnO2 solution is dark-brown, trans- parent, stable, and possesses the maximum absorption peak at 375 nm and an average diameter of 40 nm. The as-prepared nano-colloidal MnO2 was found to react with formaldehyde to generate weak chemiluminescence (CL) under acidic condition. The effects of more than 30 pharmaceuticals on the nancolloidal MnO2-formaldehyde CL system were tested. Pharmaceuticals including phenothiazines and aminoethanethiols were observed to enhance the CL signal significantly. The experimental conditions were well optimized and the analytical figures for five phenothiazines and four aminoethanethiols were presented. The method was validated by the analysis of perphenazine in tablets and chlorpromazine hydrochloride in swine feed. The CL reaction mechanism was discussed by the study of CL spectra, fluorescence spectra, UV-vis absorption spectra, and other experiments. All of CL reactions had the same maximum emission wavelength about 640 nm, which suggested that the CL emitter was independent of analytes. The CL signal was inhibited obviously by single-state oxygen scavengers, sodium azide and 1,4-diazabicyclo[2,2,2]octane, indicating that single-state oxygen dimer was the potential CL emitter for the present CL reaction.%Na2S2O3在中性水溶液中还原KMnO4可制备得到暗棕色的可溶性MnO2溶胶.所制备的MnO2溶胶透明、稳定,最大吸收波长位于357 nm处,平均粒径约40 nm.研究发现,所制备的MnO2纳米溶胶在酸性介质中与甲醛反应可产生弱的化学发光.考察了近30种药物分子在MnO2纳米溶胶-甲醛体系中的化学发光行为.结果表明,吩噻嗪类药物、氨基硫醇类药物等对该体系的化学发光信号具有显著的增强作用.据此,建立了利用这一化学发光体系测定五种吩噻嗪类药物和四种氨基

  10. Renal ischemia and reperfusion injury: influence of chorpromazine on renal function and lipid peroxidation Lesão de isquemia e reperfusão renal: influência da clorpromazina na função renal e na peroxidação lipídica

    Directory of Open Access Journals (Sweden)

    Silvio Tucci Junior

    2008-01-01

    Full Text Available PURPOSE: To evaluate the influence of chlorpromazine (CPZ on renal function and lipid peroxidation in a rat model of kidney ischemia/reperfusion injury. METHODS: Forty eight Wistar rats underwent a laparotomy for hilar clamping of left kidney with a bulldog clamp for 60 minutes followed by organ reperfusion and contralateral nephrectomy. Of these, 26 received 3mg/kg of CPZ intravenously 15 minutes before renal ischemia (G-E while the remaining 22 were used as ischemic control group (G-C. Eleven rats of G-E and 8 of G-C were followed for blood urea nitrogen and creatinine determinations before renal ischemia and at 1st, 4th and 7th postoperative days. Samplings of left renal tissue were obtained at 5 minutes (5 rats from each group and 24 hours (9 G-C and 10 of G-E of reperfusion for malondialdehy (MDA content determination. Controls of renal MDA content were determined in kidneys harvested from 6 additional normal rats. RESULTS: Acute renal failure occurred in all animals but levels of BUN and creatinine were significantly lower in G-E (p0.05 and returned near to normal levels 24 hours later. CONCLUSION: CPZ conferred partial protection of renal function to kidneys submitted to ischemia/reperfusion injury that seems to be not dependent on inhibition of lipid peroxidation.OBJETIVO: avaliar a influência da clorpromazina (CPZ na função renal e na peroxidação lipídica num modelo de lesão de isquemia/reperfusão renal em ratos. MÉTODOS: 48 ratos Wistar foram submetidos à laparotomia para clampamento da artéria renal esquerda durante 60 minutos, seguido da reperfusão e nefrectomia contralateral. Destes animais, 26 receberam 3 mg/kg de CPZ intravenosa 15 minutos antes da isquemia renal (G-E, sendo os 22 animais restantes utilizados como grupo controle isquêmico (G-C. Em 11 ratos do G-E e 8 do G-C foi feita a dosagem de uréia e creatinina sérica antes da isquemia renal e no 1º, 4º e 7º dia pós-operatório. Amostras de tecido do rim

  11. 对内观疗法辅助治疗精神分裂症疗效的1年随访:一项单盲、随机对照研究%Single-blind, randomized controlled trial of effecitveness of Naikan therapy as an adjuncitve treatment for schizophrenia over a one-year follow-up period

    Institute of Scientific and Technical Information of China (English)

    张红; 李晨虎; 赵立宇; 占归来

    2015-01-01

    Background:Current treatments for schizophrenia are otfen only paritally effecitve. Aim:Assess the possible benefit of using adjunctive Naikan therapy, a cognitive approach based on self-relfeciton that originated in Japan for the treatment of schizophrenia. Methods:Atfer resoluiton of acute psychoitc symptoms, 235 psychiatric inpaitents with schizophrenia who had a middle school educaiton or higher were randomly assigned to a control group (n=112) that received routine medication and inpatient rehabilitative treatment or an intervention group (n=123) that also received adjunctive Naikan therapy for 2 hours daily, 5 days a week for 4 weeks. The patients were then discharged and followed up for 12 months. The Posiitve and Negaitve Syndrome Scale (PANSS), Personal and Social Performance scale (PSP), and Insight and Atttude Quesitonnaire (ITAQ) were used to assess paitents at enrollment, atfer the 1-month interveniton, and atfer the 12-month follow-up. Evaluators were blind to the group assignment of paitents. Results:Only 13(10.6%) of the interveniton group paritcipants relapsed over the 12-month follow-up, but 23 (20.5%)control group paritcipants relapsed (X2=4.50,p=0.034). Using a modiifed inteniton-to-treat analysis and a repeated measure analysis of variance, the PANSS, PSP, and ITAQ total scores all showed signiifcantly greater improvement over the 12-month follow-up in the Naikan group than in the control group. The drop in mean chlorpromazine-equivalent dosage from enrollment to the end of follow-up was signiifcantly different in the intervention group but not in the control group, though the change in dosage over time between groups was not staitsitcally signiifcant. Conclusions:This study provides robust support for the effecitveness of Naikan therapy as an adjuncitve treatment during the recovery period of schizophrenia. Compared to treatment as usually, adjuncitve Naikan therapy can sustain the improvement in psychotic symptoms achieved during acute

  12. 食管癌术后酒精戒断综合征的防治%Prevention and Treatment of Alcohol Withdrawal Syndrome after Esophageal Cancer Surgery

    Institute of Scientific and Technical Information of China (English)

    薛杨; 罗澍; 孙小康; 赵长明; 郭向东

    2012-01-01

    Objective To investigate the causes, prevention and treatment of alcohol withdrawal syndrome after esophageal cancer surgery. Methods From January 2000 to October 2011, 935 surgeries for esophageal cancer were performed, among which 16 patients had postoperative complications of alcohol withdrawal syndrome. All the 16 patients were male, aged between 41 to 67 years old, averaging at 54. Drinking histories ranged from 16 to 47 years with an average of 27.8 years. Daily liquor quantity ranged from 250 to 1 000 g, and the alcohol content was from 162 to 590 g, averaging 321.5 g. All patients were in accordance with the diagnosis standard of alcohol withdrawal syndrome in the Chinese Spirit Disease Classification and Diagnosis Standard Third Edition (CCMD-3). In addition to conventional treatment, based on the delirium, irritability, mental disorders, and coma of the patients, we administered B vitamins, naloxone, haloperidol, chlorpromazine, and diazepam to promote brain cell metabolism and energy of the patients, and when necessary, endotracheal intubation for assisted mechanical ventilation was used after sedation. Results The withdrawal symptoms totally disappeared after treatment. The treatment time varied from 2 to 10 days with an average of 3.5 days. Thirteen patients were followed up with a time period from 4 to 18 months. All of them achieved abstinence from alcohol. One patient died from acute myocardial infarction eight months after surgery. All the other twelve patients recovered well with complete abstinence from alcohol and no recurrence of withdrawal symptoms. Conclusions Reasonable and effective perioperative treatment can significantly lower the incidence of alcohol withdrawal syndrome. Detailed history of the patients, preoperative and postoperative active prevention and timely and effective treatment are the key to healing%目的 探讨食管癌术后酒精戒断综合征的原因及有效预防治疗措施.方法 2000年1月-2011年10

  13. [Cerebral hydatic cyst and psychiatric disorders. Two cases].

    Science.gov (United States)

    Asri, F; Tazi, I; Maaroufi, K; El Moudden, A; Ghannane, H; Ait Benali, S

    2007-01-01

    unconscious of his disorders. The patient has first been put under classical neuroleptic 9 mg/day of Haloperidol and 200 mg/day of chlorpromazine. The diagnosis of schizophrenia has been kept according to criteria of DSM IV. The PANSS (Positive and Negative Syndrome Scale) was to 137 (score on a positive scale was to 34, score on a negative scale was to 35 and the general psychopathologie scale was to 58). One week after his hospitalization, he developed headache with subconfusion, a cerebral scanning has been made in emergency and showed a voluminous cyst in oval foramen compressing the mesencephalon strongly. The cyst was well limited, hypodense, not taking the contrast, and without intracerebral oedema, the diagnosis of cerebral hydatic cyst has been made. The complementary exploration didn't show any other localizations, and biologic exam results didn't show any particular anomalies. The patient has been operated in neurosurgery. The immediate evolution was favorable with disappearance of confusion and absence of complications. The patient was lost of view. Six months after, the patient has been readmitted to the psychiatric emergency. He dropped his neuroleptic treatment. He was aggressive, raving, hallucinated and depersonalized. The global score to the PANSS was 63. He has been put back under neuroleptics. Three weeks after improvement and passage of the PANSS to 30, the patient went out. We couldn't have a cerebral scanner of control because the patient had no medical assurance and no money for cerebral scanner. Case 2 - Patient aged of 53 years, father of four children, uneducated, native and resident of Marrakech, confectioner as profession. He is in contact with dogs since 12 years. He has been brought to the psychiatric emergencies by his family after an agitation. The history of his illness seemed to go back at eight months ago, by the progressive apparition of an instability, sleep disorders, hostility, associated with an emotional lability. To the interview he

  14. Analysis of Food Safety Risk Surveillance of Kunming in 2012%2012年昆明市食品安全监测结果分析

    Institute of Scientific and Technical Information of China (English)

    王健芳; 黄文智; 林嘉; 赵俊丽

    2014-01-01

    Objective To understand the prevalence of food-borne pathogens and the status of chemical pollutants and harmful factors in food in Kunming in 2012, and provide the scientific support for the food safety assessment, and food safety standards’ amendment. Methods Using multistage stratified random sampling, a total of 334 samples were selected from local residents’ main purchasing places. The detection was in accordance with the handbook of food-borne pathogens and chemical pol utants and harmful factors. Results The pathogenic bacteria detection rate of samples reached to 5.7% and the Escherichia coli went to 20.8% , which was higher than the Staphylococcus aureus and mold. Bacil us cereus, Escherichia coli O157, Salmonel a Listeria monocytogenes and Shigel a had not been detected and there was no pathogen in the pickles vegetables, but fruits and vegetables had the highest detection rate. Among the 13 pork samples, six of them contained contraband chemicals including chlorpromazine, diazepam, corn gibberel ic enol, and olaquindox . More than 36.7% fried flour products was higher than the food standard of aluminium, and 35% wild mushrooms were over the standard in heavy metals as wel as 6.3% of pesticide residues in fresh vegetables. Conclusion Fruits and vegetables had a higher detection rate on Escherichia coli, and contraband chemicals had been detected in pork. Fried flour was higher in aluminium. And heavy metal was higher in wild mushrooms. Al of the above could be a sign to the authorities, which a series of measures should be taken in food supervising, transportation, distribution and other aspects.%目的了解2012年昆明市食品中食源性致病菌流行情况和化学污染物及有害因素污染状况,为食品安全评估、食品卫生标  准制修订提供科学依据。方法根据多级分层随机采样原则,选取当地居民的主要消费购买点,共采集样品997件。按照《食源性致病菌监测工作手册》及

  15. Protective effect of early application of lytic cocktail on small intestine of severely scalded rats%早期应用冬眠合剂对严重烫伤大鼠小肠的保护作用

    Institute of Scientific and Technical Information of China (English)

    邵庆波; 章雄; 陈雪莲; 刘琰; 张勤; 廖镇江

    2010-01-01

    .01);烫伤+冬眠合剂组各时相点IL-10水平均高于烫伤组,并在6、24 h时差异具有统计学意义(F值分别为8.668、19.634,P<0.05或P<0.01).结论 早期应用冬眠合剂可减轻严重烫伤大鼠小肠黏膜水肿和损害,该机制可能与其降低肠道ICAM-1的表达和血液炎症介质水平、减少肠道局部炎症细胞数量有关.%Objective To study the protective effect of early application of lytic cocktail on small intestine of severely scalded rats. Methods Sixty-six male SD rats were divided into sham injury group (SI, n =6) , scald group (S, n = 30) and scald + lytic cocktail group (SL, n =30) according to the random number table. After anesthesia, rats in the latter 2 groups were inflicted with 30% full-thickness scald, while rats in S group were sham scalded with 37 ℃ water. Resuscitation was carried out by intraperitoneal injection with 2 mL · kg-1 · %TBSA-1 lactated Ringer's solution in all rats; meanwhile 12 mL/kg lytic cocktail [ 1 mL pethidine (50 mg/mL) + 1 mL chlorpromazine (25 mg/mL) + 1 mL promethazine (25 mg/mL) + 125 mL saline] was hypodermically injected to rats in SL group, while 12 mL/kg saline was injected into rats in the other 2 groups. Samples of blood and small intestine were harvested from S and SL groups at post scald hour (PSH) 3, 6, 12, 24, 48 and from SI group at PSH 3, with 6 rats in each group at each time point. Pathological changes in intestine were observed, and the expression of intercellular adhesion molecule 1 (ICAM-1) and CD68 were determined with immunohistochemistry at PSH 24 for S and SL groups and at PSH 3 for SI group. Plasma levels of D-lactate, diamine oxidase (DAO) , IL-1β, TNF-α, IL-10 were determined with ELISA. Data were processed with one-way analysis of variance. Results (1) At PSH 24, mild hemorrhage, inflammatory cell infiltration and epithelial cell shedding were observed in small intestinal mucosa of rats in S group.Compared with S group, the intestinal villi of SL group

  16. Neuralgia do trigêmeo bilateral: relato de caso Neuralgia del trigémino bilateral: relato de caso Bilateral trigeminal neuralgia: case report

    Directory of Open Access Journals (Sweden)

    Caio Marcio Barros de Oliveira

    2009-08-01

    convencional.BACKGROUND AND OBJECTIVES: Trigeminal neuralgia is an extremely painful condition characterized by recurrent episodes of sudden, lancinating, shock-like pain lasting from a few seconds to two minutes usually unilateral. It has an annual incidence of approximately 4.3 in 100,000 in the general population and only 3% of those cases present bilateral manifestation. The objective of this report was to describe a rare case of bilateral trigeminal neuralgia. CASE REPORT: A 61 years old housewife from Maranhão, Brazil, married, with a history of hypertension, presented with a six-year history of severe pain in the left V2-V3 regions, lasting 5 to 10 seconds, in the lateral aspect of the nose and mandible, worsening by talking, chewing, and with a decrease in temperature. She had been treated with chlorpromazine (3 mg every eight hours and carbamazepine (200 mg every eight hours during six months without improvement. On physical exam, the patient presented thermal and mechanical allodynia in the V2-V3 regions. She was using gabapentin (1,200 mg/day with partial relief of the pain. The dose of gabapentin was increased to 1,500 mg/day and amitriptyline 12.5 mg at night was added to the therapeutic regimen. The patient evolved with mild and sporadical pain and a reduction in pain severity during 10 months; the dose of gabapentin was progressively reduced to 600 mg/day, and amitriptyline was maintained at 12.5 mg/day. After one year, the patient developed similar pain in the region of the right mandible, which improved with an increase in the dose of gabapentin to 900 mg/day. Head CT and MRI did not show any abnormalities. CONCLUSIONS: Carbamazepine is the first choice for the treatment of trigeminal neuralgia; however, the use of gabapentin as the first pharmacological choice or in cases refractory to conventional therapy has been increasing.

  17. Mild hypothermia treatment for acute respiratory distress syndrome in pigs%亚低温治疗急性呼吸窘迫综合征的实验研究

    Institute of Scientific and Technical Information of China (English)

    余方宇; 徐颖鹤; 林荣海; 蒋永泼; 郑贞苍

    2015-01-01

    (CI)及每搏量(SV)在1、2、3、4h时点比较差异均有统计学意义,亚低温保护组低于常温观察组,而两组间PVPI、EVLWI无统计学差异;炎症指标上:两组乳猪IL-6在2、3、4h时点的比较差异均有统计学意义,亚低温治疗组低于常温观察组;而IL-10在3h时两组间的差异有统计学意义,亚低温治疗组低于常温观察组;而两组间TNF-α在4个时点的差异均无统计学意义。ARDS乳猪的肺病理组织学检查表现不同,大体观察及光镜下均提示亚低温治疗组损伤轻。常温观察组:肺泡隔增宽、见纤维增生,终末细支气管壁及纤维间质中淋巴细胞、浆细胞浸润,部分间质见出血,小血管内皮损伤;亚低温治疗组:肺泡隔略增宽,少量淋巴细胞浸润。结论亚低温在早期ARDS猪模型中有治疗作用。%Objective To evaluate the effect of mild hypothermia on acute respiratory distress syndrome (ARDS) in piglets. Methods Twelve male piglets were randomly divided into normal temperature observation group (control group) and mild hypothermia treatment group(hypothermia group). ARDS was induced by injection of endotoxin 20μg/kg. After the ARDS was induced, the piglets in hypothermia group were treated with chlorpromazine and promethazine;and the blood temperature was kept round 34℃with temperature- control- blanket. The animals in control group received analgesic and sedation and the blood temperature was kept round 40℃. Respiratory mechanics, blood gases, the blood oxygen partial pressure/inhale oxygen volume fraction (PaO2/FiO2), hemodynamics, and plasma IL- 6, IL- 10, TNF- αwere measured at 0, 1, 2, 3, and 4h after the induction of ARDS and lung histology was evaluated after animals were sacrificed. Results After the ARDS was induced, animals in control group presented hypertension and high respiration rate, some even shivered;while the piglets in hypothermia group were calm and spontaneous breath was not obvious. There

  18. 亚低温物理技术并冬眠疗法对重度颅脑损伤患者血液生化学及血气变化的影响%Effect of mild hypothermia combined with hibernation on the homeostasis of patients with severe head injury

    Institute of Scientific and Technical Information of China (English)

    刘威; 安沂华; 刘恩重; 俞春江

    2005-01-01

    脉血氧分压和二氧化碳分压基本接近(P>0.05).③亚低温/冬眠联合治疗组的死亡率显著低于常温对照组(25.0%,66.6%,P<0.05).结论:亚低温/冬眠联合疗法能够有效地降低重度颅脑损伤患者的颅内压、肌酸磷酸激酶,对平均动脉压、血离子浓度、动脉血氧分压和二氧化碳分压无明显影响,但有降低患者造血功能的风险.%BACKGROUND: Both animal experiments and clinical practice have confirmed that mild or moderate hypothermia is effective in reducing secondary brain injury, but its effect on homeostasis is not very clear.OBJECTIVE: To investigate the effect of a combined therapy of mild hypothermia and hibernation on the homeostasis of patients with severe brain injury.DESIGN: A randomized controlled study.SETTING: Neurosurgical Institute of Beijing; Neurosurgical Department of the First Clinical Medical College Affiliated to Harbin Medical University;and Neurological Department of the Second Clinical Medical College Affiliated to Harbin Medical University.PARTICIPANTS: The study was conducted at the Department of Neurosurgery, the First Affiliated Hospital of Harbin Medical University, from June to December 2002. Totally 24 patients (aged 35-60 years) with severe cerebral hemorrhage or brain injury were randomly divided into combined therapy group and normothermia group. Their Glasgow Coma Scale scores ranged from 3 to 8. The subjects signed the informed consent.METHODS: Within 10 hours of their injury, patients in hypothermia and hibernation combination group were given half dosage of No. 1 hibernation cocktail (chlorpromazine 25 mg, pethidine hydrochloride 50 mg, and promethazine 25 mg), and were cooled by cooling blankets to make their body temperature dropped to 32-34 ℃ (rectal temperature). Their temperature was kept within this range for 5 days, at 35 ℃ for 24 hours, and then was slowly increased to their normal level. The body temperature of patients in normothermia group