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Sample records for chlorpromazine

  1. 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/chlorpromazin...e.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/chlorpromazin.../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 ...

  2. Chlorpromazine-induced corneal endothelial phototoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Hull, D.S.; Csukas, S.; Green, K.

    1982-04-01

    Chlorpromazine, which has been used extensively for the treatment of psychiatric disorders, is known to accumulate in the posterior corneal stroma, lens, and uveal tract. Because it is a phototoxic compound, the potential exists for it to cause cellular damage after light exposure. Specular microscopic perfusion of corneal endothelial cells in darkness with 0.5 mM chlorpromazine HCl resulted in a swelling rate of 18 +/- 2 micrometer/hr, whereas corneas exposed to long-wavelength ultraviolet light for 3 min in the presence of 0.5 mM chlorpromazine swelled at 37 +/- 9 micrometer/hr (p less than 0.01). Preirradiation of 0.5 mM chlorpromazine solution with ultraviolet light for 30 min and subsequent corneal perfusion with the solution resulted in a corneal swelling rate of 45 +/- 19 micrometer/hr. Cornea endothelial cells perfused with 0.5 mM chlorpromazine that was preirradiated with ultraviolet light showed marked swelling on scanning electron microscopic examination, whereas those perfused with nonirradiated chlorpromazine were flat and showed a normal mosaic pattern. Combining either 500 U/ml catalase or 290 U/ml superoxide dismutase with chlorpromazine did not alter photoinduction of corneal swelling. The data suggest that corneal endothelial chlorpromazine phototoxicity is secondary to cytotoxic products resulting from the photodynamically induced decomposition of chlorpromazine and is not caused by hydrogen peroxide or superoxide anion generated during the phototoxic reaction.

  3. Chlorpromazine

    Science.gov (United States)

    ... and that may cause changes in mood and personality) who take antipsychotics (medications for mental illness) such ... menstrual periods decreased sexual ability changes in skin color dry mouth stuffed nose difficulty urinating widening or ...

  4. Interaction of chlorpromazine with DNA.

    Science.gov (United States)

    Motohashi, N; Kamata, K; Meyer, R

    1990-01-01

    The mechanism of the potential anticancer agent chlorpromazine hydrochloride (CPZ) with DNA was investigated by the techniques of high-performance liquid chromatography (HPLC), viscosity and Raman spectroscopy. It has been suggested from HPLC work that DNA nucleotides (except nucleosides) from either a CPZ-DNA system or a CPZ-nucleotide system. Furthermore, the shear stress of the viscosity of the CPZ-DNA system and the CPZ-nucleotide systems ware shown to be apparently the higher increasing than that of DNA and nucleotide alone. These systems had non-Newtonian properties for the formation of the CPZ-DNA and the CPZ-nucleotide systems under experimental conditions. The Raman spectra showed a dramatic difference at 982 cm-1 due to the symmetric P-O stretching vibration of the PO4(2-) group between dGMP and the CPZ-dGMP system. PMID:2285233

  5. Chlorpromazine inhibits mitosis of mammalian cells.

    Science.gov (United States)

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

    OpenAIRE

    Carla Carnovale; Paolo Pellegrino; Silvia Beretta; Gian Vincenzo Zuccotti; Valentina Perrone; Stefania Antoniazzi; Marco Pozzi; Emilio Clementi; Sonia Radice

    2014-01-01

    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 n...

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

    Science.gov (United States)

    Carnovale, Carla; Pellegrino, Paolo; Beretta, Silvia; Zuccotti, Gian Vincenzo; Perrone, Valentina; Antoniazzi, Stefania; Pozzi, Marco; Clementi, Emilio; Radice, Sonia

    2014-01-01

    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. PMID:24799822

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

    Directory of Open Access Journals (Sweden)

    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. Chlorpromazine inhibits store-operated calcium entry and subsequent noradrenaline secretion in PC12 cells

    OpenAIRE

    Choi, Se-Young; Kim, Yong-Hyun; Lee, Yong-kyu; Kim, Kyong-Tai

    2001-01-01

    The effect of chlorpromazine on the store-operated Ca2+ entry activated via the phospholipase C signalling pathway was investigated in PC12 cells.Chlorpromazine inhibited the sustained increase after the initial peak in the intracellular Ca2+ concentration produced by bradykinin while having no effect on the initial transient response. The inhibition was lowered by the removal of extracellular free Ca2+. However, chlorpromazine did not inhibit bradykinin-induced inositol 1,4,5-trisphosphate p...

  10. Chlorpromazine distribution in hamsters and mice bearing transplantable melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Fairchild, R.G. (Brookhaven National Lab., Upton, NY); Greenberg, D.; Watts, K.P.; Packer, S.; Atkins, H.L.; Som, P.; Hannon, S.J.; Brill, A.B.; Fand, I.; McNally, W.P.

    1982-02-01

    Chlorpromazine (CPZ) distribution was measured in tissues of Syrian golden hamsters bearing Greene melanoma and in BALB/c mice bearing Harding-Passey melanoma. Distribution was evaluated as a function of time (0.5 to 14 days) and as a function of single and multiple doses (up to five) of from 5 to 50 mg CPZ per kg body weight. Routes of administration (i.p., i.v., p.o.) were compared. The physiological behavior of CPZ is of interest as it is used extensively as a tranquilizing drug (Thorazine). Further, since CPZ binds to the pigment melanin, the possibility exists of using CPZ to transport diagnostic or therapeutic agents to melanoma. It was found that, at 2 days postinjection, tumor/tissue concentration ratios exceeded 10 for metabolizing organs, such as liver, and 100 for background tissues, such as blood and muscle. Absolute concentrations of CPZ in tumor exceeding 100 ..mu..g CPZ per g tumor were obtained with both single and multiple doses. This selective high concentration in tumor would make CPZ an ideal vehicle for the transport of boron to tumor for use in neutron capture therapy via the /sup 10/B(n,..cap alpha..)/sup 7/Li reaction.

  11. 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.

  12. Thermal responses to 5. 6-GHz radiofrequency radiation in anesthetized rats. Effect of chlorpromazine

    Energy Technology Data Exchange (ETDEWEB)

    Jauchem, J.R.; Frei, M.R.; Heinmets, F.

    1988-01-01

    Anesthetized rats were exposed to 5.6-GHz continuous-wave radiofrequency radiation (RFR) at an average power density of 60 mW/Sq. cm (average specific absorption rate 12 W/kg). Exposure was performed to raise colonic temperature from 38.5 to 39.5C. Following acute administration of chlorpromazine, body temperature exhibited a faster return to baseline temperature when exposure was discontinued. When exposure was initiated at 38.5C and continued until lethal temperature resulted, chlorpromazine-treated animals exhibited significantly shorter survival times than saline-treated animals. Thus, although chlorpromazine enhanced thermoregulatory efficiency at colonic temperature below 39.5 deg C, the drug caused increased susceptibility to terminal RFR. The present results, when compared with previous studies of irradiation at 2.8 GHz, indicate that the effects of chlorpromazine on thermal response to RFR during intermittent and terminal exposure are similar at both 2.8 and 5.6 GHz.

  13. 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

  14. Comparative effects of Rauwolfia vomitoria and chlorpromazine on social behaviour and pain

    Directory of Open Access Journals (Sweden)

    Sunday Bisong

    2011-01-01

    Full Text Available Background : Rauwolfia vomitoria has been used in Nigeria to manage psychiatric disorders despite orthodox medicine. Aims : This research was therefore aimed at comparing the effects of R. vomitoria, chlorpromazine and reserpine on social behaviour and pain in mice. Materials and Methods : Ninety male CD-1 mice (32 - 38g body weight were grouped into 3 with 5 subgroups (n=6 each. Mice were given chlorpromazine (0.0, 0.25, 1.0, 2.0, 4.0 mg/kg i.p., 30 minutes before testing and R. vomitoria (0.0, 0.25, 1.0, 2.0, 4.0 mg/kg, i.p. and reserpine (0.0, 0.1, 0.4, 0.8, 1.6 mg/kg, i.p 24 hours before testing. Nesting score assessed social behaviour while the tail flick and hot plate analgesiometers assessed pain. Results : Chlorpromazine dose-dependently decreased nesting score (F 4,25 = 5.5660; p< 0.01, indicating decreased social behaviour (social loss in the mice. Although R. vomitoria did not affect nesting score, reserpine decreased the nesting score (social loss. In the pain test, chlorpromazine did not alter tail flick latency but decreased hind paw lick latency in the hot plate at 2.0 and 4.0 mg/kg (p< 0.01, indicating increased pain sensitivity at these doses which may indirectly increase social withdrawal and thus aggravating depression. R. vomitoria however, increased tail flick and hind paw lick latencies in the hot plate test (p< 0.05 indicating decreased pain sensitivity. Reserpine, like R. vomitoria, increased latency of hind paw lick in the hot plate. Conclusion : R. vomitoria has a high potential as an antipsychotic and may have advantage over chlorpromazine; it is not necessary to isolate active components from this herb.

  15. Protective Effects of Agmatine against Chlorpromazine- Induced Toxicity in the Liver of Wistar Rats

    OpenAIRE

    Dejanović Bratislav; Stevanović Ivana; Ninković Milica; Stojanović Ivana; Lavrnja Irena; Radičević Tatjana

    2016-01-01

    The metabolic pathways of chlorpromazine (CPZ) toxicity were tracked by assessing oxidative/nitrosative stress markers. The main objective of the study was to test the hypothesis that agmatine (AGM) prevents oxidative/nitrosative stress in the liver of Wistar rats 15 days after administration of CPZ. All tested substances were administered intraperitoneally (i.p.) for 15 consecutive days. The rats were divided into four groups: the control group (C, 0.9 % saline solution), the CPZ group (CPZ,...

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

    Directory of Open Access Journals (Sweden)

    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.

  17. 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.

  18. Agmatine protection against chlorpromazine-induced forebrain cortex injury in rats.

    Science.gov (United States)

    Dejanovic, Bratislav; Stevanovic, Ivana; Ninkovic, Milica; Stojanovic, Ivana; Lavrnja, Irena; Radicevic, Tatjana; Pavlovic, Milos

    2016-03-01

    This study was conducted to investigate whether agmatine (AGM) provides protection against oxidative stress induced by treatment with chlorpromazine (CPZ) in Wistar rats. In addition, the role of reactive oxygen species and efficiency of antioxidant protection in the brain homogenates of forebrain cortexes prepared 48 h after treatment were investigated. Chlorpromazine was applied intraperitoneally (i.p.) in single dose of 38.7 mg/kg body weight (BW) The second group was treated with both CPZ and AGM (75 mg/kg BW). The control group was treated with 0.9% saline solution in the same manner. All tested compounds were administered i.p. in a single dose. Rats were sacrificed by decapitation 48 h after treatment Treatment with AGM significantly attenuated the oxidative stress parameters and restored antioxidant capacity in the forebrain cortex. The data indicated that i.p. administered AGM exerted antioxidant action in CPZ-treated animals. Moreover, reactive astrocytes and microglia may contribute to secondary nerve-cell damage and participate in the balance of destructive vs. protective actions involved in the pathogenesis after poisoning. PMID:27051340

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

    Science.gov (United States)

    Ficarra, Silvana; Russo, Annamaria; Barreca, Davide; Giunta, Elena; Galtieri, Antonio; Tellone, Ester

    2016-01-01

    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. PMID:27579150

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Therapeutic and hypothermic properties of diazepam altered by a diazepam-chlorpromazine association.

    Science.gov (United States)

    Taukulis, H K; Brake, L D

    1989-09-01

    Rats were injected (IP) with diazepam (2.5 mg/kg) and chlorpromazine (10.0 mg/kg) with a 30-min interval between the two injections. After 10-12 repeated drug pairings of this type, the thermic, muscle relaxant, and anxiolytic responses of the animals to diazepam alone were tested. These tests revealed: 1) an enhanced hypothermia (rectal temperature), 2) an attenuated muscle relaxant effect (inclined plane test), and 3) a potentiated anxiolytic effect (plus-maze test). Although various interdrug associations have previously been demonstrated using other measures of conditioning, this is the first instance in which changes in the therapeutic effects of a drug (in this case, muscle relaxation and anxiety reduction) have been obtained with this procedure. PMID:2626441

  2. Protective Effects of Agmatine against Chlorpromazine- Induced Toxicity in the Liver of Wistar Rats

    Directory of Open Access Journals (Sweden)

    Dejanović Bratislav

    2016-03-01

    Full Text Available The metabolic pathways of chlorpromazine (CPZ toxicity were tracked by assessing oxidative/nitrosative stress markers. The main objective of the study was to test the hypothesis that agmatine (AGM prevents oxidative/nitrosative stress in the liver of Wistar rats 15 days after administration of CPZ. All tested substances were administered intraperitoneally (i.p. for 15 consecutive days. The rats were divided into four groups: the control group (C, 0.9 % saline solution, the CPZ group (CPZ, 38.7 mg/kg b.w., the CPZ+AGM group (AGM, 75 mg/kg b.w. immediately after CPZ, 38.7 mg/kg b.w. i.p. and the AGM group (AGM, 75 mg/kg b.w..

  3. 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

  4. Probable Case of Neuroleptic Malignant Syndrome Following Administration of Antituberculotic Drugs in a Chlorpromazine-Treated Patient

    OpenAIRE

    Shim, Geumsook; Kang, Do-Hyung; Kwon, Jun Soo

    2008-01-01

    Neuroleptic malignant syndrome (NMS), a potentially fatal adverse reaction to neuroleptics, is known to occur more often in the initial stage of antipsychotic treatment. We describe a patient with chronic schizophrenia who, in a few days after the addition of antituberculotic drugs to his antipsychotic regimen, developed probable NMS without pyrexia. We reasoned that rifampin, a strong hepatic enzyme inducer, decreased the plasma chlorpromazine concentration of the patient, with the result of...

  5. 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.

  6. 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.

  7. 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.

  8. Study of inclusion complex formation between chlorpromazine hydrochloride, as an antiemetic drug, and β-cyclodextrin, using conductometric technique

    International Nuclear Information System (INIS)

    The behavior of micellization of chlorpromazine hydrochloride (CPH) as an antiemetic drug and its inclusion complex formation with β-cyclodextrin (β-CD) was studied using conductometric technique. The binding or association constant of the complexation equilibrium is evaluated from conductometric measurements by using a nonlinear regression method. The resulting K values for micellization as well as complexation are analyzed. The experiments were carried out at different temperatures. It has been found that CPH form only the 1:1 complex. The association constant values are used for evaluation of thermodynamic parameters of complexation, such as ΔGcomplexo, ΔHcomplexo and ΔScomplexo.

  9. 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

    Tamoxifen resistance is a major clinical problem in the treatment of estrogen receptor a-positive breast tumors. It is, at present, unclear what exactly causes tamoxifen resistance. For decades, chlorpromazine has been used for treating psychotic diseases, such as schizophrenia. However......, the compound is now also recognized as a multitargeting drug with diverse potential applications, for example, it has antiproliferative properties and it can reverse resistance toward antibiotics in bacteria. Furthermore, chlorpromazine can reverse multidrug resistance caused by overexpression of P......-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...

  10. 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

  11. Renographic evaluation of kidney preservation with chlorpromazine. [In vitro and in vivo studies with /sup 125/I-Hippuran in rabbit kidneys

    Energy Technology Data Exchange (ETDEWEB)

    Dahlager, J.I.; Bilde, T.

    1979-01-01

    The effect of chlorpromazine pretreatment of kidneys then damaged by warm ischemia was investigated. The ischemia was inflicted on rabbit kidneys by renal arterial occlusion of 1 1/2 and 3 hours' duration after contralateral nephrectomy. Pretreatment with chlorpromazine, 3.5 mg/kg, was given intravenously before arterial clamping. I-125 Hippuran renography was performed before clamping, immediately after clamp release, and at 2, 4, 6, and 14 days later. Serum creatinine and survival rate were followed. Comparison with untreated control groups was made. The effect on tubular function was investigated by measuring I-125 Hippuran uptake in pretreated slices of renal cortex (compared with untreated contralateral kidney) 48 hr after circulation was restored to the ischemic kidney. Chlorpromazine pretreatment improved recovery from ischemic damage: the renograms showed improved Hippuran uptake after clamp removal, and return to normal was faster. Survival rate after 3 hr of ischemia increased from 1/10 to 6/10 in the pretreated group, and serum creatinine recovered earlier. Hippuran uptake in slices of cortex showed no significant improvement because of pretreatment. It is concluded that the beneficial effect of chlorpromazine pretreatment must be because of decreased vascular resistance, leading to long-lasting increased postischemic renal blood flow.

  12. Enhancement of chlorpromazine antitumor activity by Pluronics F127/L81 nanostructured system against human multidrug resistant leukemia.

    Science.gov (United States)

    Mello, Joyce C de; Moraes, Vivian Wr; Watashi, Carolina M; da Silva, Deyse C; Cavalcanti, Leide P; Franco, Margareth Kkd; Yokaichiya, Fabiano; de Araujo, Daniele R; Rodrigues, Tiago

    2016-09-01

    The development of specific tyrosine kinase inhibitors (TKIs) revolutionized the treatment of chronic myeloid leukemia (CML). However, chemoresistance of tumor cells to TKIs has already been described, and several mechanisms account for the multidrug resistance (MDR) phenotypes, including the overexpression of P-glycoprotein (P-gp). This decreases the rate of healing and complete tumor remission. Nanotechnological tools have been studied to allow advances in this field. Poloxamers (Pluronics(®)) have been proposed as drug carriers to improve therapeutic efficacy and decrease side effects, even in cancer therapy, due to their ability to inhibit P-gp. Antipsychotic phenothiazines have been described as potent cytotoxic drugs against several types of tumor cells in vitro. Here, we show that nanostructured micellar systems containing the phenothiazine derivative chlorpromazine (CPZ) potentiated the cytotoxicity of free CPZ and increased the selectivity against CML tumor cells, demonstrating the pharmacological potential of these poloxamer-based nanostructured systems containing CPZ in cancer therapy. PMID:27265114

  13. Nanostructured biocompatible thermal/electrical stimuli-responsive biopolymer-doped polypyrrole for controlled release of chlorpromazine: kinetics studies.

    Science.gov (United States)

    Shamaeli, Ehsan; Alizadeh, Naader

    2014-09-10

    Biocompatible nanostructured conductive heparin-doped polypyrrole film was fabricated and employed as a high-capacity cation exchanger for programmable release of neuroleptic drug, chlorpromazine (CPZ) with thermally and electrical dual-stimulation. Releasing behavior were studied at different applied potentials and temperatures by in-situ monitoring of UV absorbance measurements. Three mathematical models (Higuchi, Power, and Avrami equation) were employed to investigate kinetics of the release. Based on the obtained results, the Avrami model found to be more comprehensive than two other ones for mathematical description of electro-stimulated release of CPZ. A quantitative relationship between activation energy parameters (Ea, ΔG(≠), ΔH(≠), and ΔS(≠)) and release conditions (applied potential and temperature) has been developed and established to predict release rate constants at various applied conditions. PMID:24969668

  14. 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.

  15. Association studies of genomic variants with treatment response to risperidone, clozapine, quetiapine and chlorpromazine in the Chinese Han population.

    Science.gov (United States)

    Xu, Q; Wu, X; Li, M; Huang, H; Minica, C; Yi, Z; Wang, G; Shen, L; Xing, Q; Shi, Y; He, L; Qin, S

    2016-08-01

    Schizophrenia is a widespread mental disease with a prevalence of about 1% in the world population. Continuous long-term treatment is required to maintain social functioning and prevent symptom relapse of schizophrenia patients. However, there are considerable individual differences in response to the antipsychotic drugs. There is a pressing need to identify more drug-response-related markers. But most pharmacogenomics of schizophrenia have typically focused on a few candidate genes in small sample size. In this study, 995 subjects were selected for discovering the drug-response-related markers. A total of 77 single-nucleotide polymorphisms of 25 genes have been investigated for four commonly used antipsychotic drugs in China: risperidone, clozapine, quetiapine, and chlorpromazine. Significant associations with treatment response for several genes, such as CYP2D6, CYP2C19, COMT, ABCB1, DRD3 and HTR2C have been verified in our study. Also, we found several new candidate genes (TNIK, RELN, NOTCH4 and SLC6A2) and combinations (haplotype rs1544325-rs5993883-rs6269-rs4818 in COMT) that are associated with treatment response to the four drugs. Also, multivariate interactions analysis demonstrated the combination of rs6269 in COMT and rs3813929 in HTR2C may work as a predictor to improve the clinical antipsychotic response. So our study is of great significance to improve current knowledge on the pharmacogenomics of schizophrenia, thus promoting the implementation of personalized medicine in schizophrenia.The Pharmacogenomics Journal advance online publication, 18 August 2015; doi:10.1038/tpj.2015.61. PMID:26282453

  16. Inhibitory effect of chlorpromazine on the syndrome of hyperactivity produced by L-tryptophan or 5-methoxy-N,N-dimethyltryptamine in rats treated with a monoamine oxidase inhibitor

    Science.gov (United States)

    Grahame-Smith, D. G.

    1971-01-01

    1. The hyperactivity and hyperpyrexia produced by L-tryptophan in rats treated with a monoamine oxidase inhibitor was inhibited by chlorpromazine. 2. Chlorpromazine did not inhibit the increased rate of synthesis of brain 5-hydroxytryptamine (5-HT) produced by tryptophan loading. 3. Hyperactivity and hyperpyrexia were also produced by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) in rats. Pretreatment with a monoamine oxidase inhibitor potentiated the hyperactivity response. Pretreatment of rats with p-chlorophenylalanine did not inhibit hyperactivity produced by 5-MeODMT. 4. Chlorpromazine inhibits hyperactivity caused by tryptophan or 5-MeODMT after monoamine oxidase inhibition either by competition with 5-HT or 5-MeODMT, respectively, at receptor sites or by physiological antagonism. PMID:4261561

  17. 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.

  18. Predicting steady -state plasma concentration of chlorpromazine using radial basis function neural networks%用径向基神经网络预测氯丙嗪的稳态血药浓度

    Institute of Scientific and Technical Information of China (English)

    刘朝晖; 黄榕波; 陈庆强; 温预关; 李明亚

    2012-01-01

    目的 评价用径向基(RBF)神经网络所建立的预测氯丙嗪稳态血药浓度模型的预测性能.方法 将数据分为训练集、校验集和测试集,来建立获取输出变量(37项参数)与输出变量(氯丙嗪稳态血药浓度)两者间关系的RBF网络模型,并评价其预测性能.结果 当扩展速度(SP)值为2.8时,所建立的RBF网络模型,预测奋乃静稳态血药浓度的效果和泛化能力较好.结论 RBF网络用于预测氯丙嗪稳态血药浓度是可行的和有效的.%Objective To evaluate the performance of a model for predicting the steady - state plasma concentration of chlorpromazine established by using radial basis function (RBF) neural network. Methods The data was divided into training set, validation set and test set to establish the RBF neural network model which had captured the relationships between the input variables (37 parametes) and the output variable ( steady - state plasma concentration of chlorpromazine) and evaluate predictive performance of the model. Results When the SPREAD (SP) value was 2. 8, the RBF neural network model had the better effect on predicting the steady - state plasma concentration of chlorpromazine and better generalization. Conclusion It is practical and valid for RBF neural network model to be applied to the study of steady - state plasma concentration prediction of chlorpromazine.

  19. 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

  20. 奥氮平与氯丙嗪对精神分裂症患者认知功能的影响%The impact of olanzapine and chlorpromazine on cognitive function of schizophrenia patient

    Institute of Scientific and Technical Information of China (English)

    赵虎; 陈平

    2014-01-01

    Objective To compare the impact between olanzapine and chlorpromazine on cognitive func-tions of schizophrenia patients .Methods Ninety-six schizophrenics were randomly assigned to olanzapine (n=48) and chlorpromazine group (n=48) taking orally olanzapine or chlorpromazine for 8 weeks .Cogni-tive functions were assessed with the Wisconsin Card Sorting Test (WCST ) ,Wechsler Memory Scale (WMS) and Tower of Hanoi (TOH) before and after treatment .Results At the end of 8 week treatment WCST categories achieved ,correct ,percent conceptual-level and perseverative responses as well as WMS score heightened more significantly compared with pre-treatment in olanzapine group (P<0 .01) and were significantly higher than those in chlorpromazine group (P< 0 .05 or 0 .01);perseverative errors ,TOH completion time and moving times of both groups lowered more significantly compared with pre-treatment (P<0 .01) ,so did those in olanzapine than in chlorpromazine group (P<0 .01) .Conclusion Olanzapine could improve cognitive function of schizophrenia patient compared with chlorpromazine .%目的:比较奥氮平与氯丙嗪对精神分裂症患者认知功能的影响。方法将96例精神分裂症患者随机分为奥氮平组和氯丙嗪组,每组48例,分别口服奥氮平和氯丙嗪治疗,观察8周。于治疗前后采用威斯康星卡片分类测验、韦氏记忆测验及河内塔测验对两组患者的认知功能进行测评分析。结果治疗8周末,奥氮平组威斯康星卡片分类测验完成分类数、正确应答数、概念化水平百分数及持续性应答数和韦氏记忆测验评分均较治疗前显著升高(P<0.01),奥氮平组显著高于氯丙嗪组( P<0.05或0.01);两组持续性错误数和河内塔测验的完成时间和移动次数均较治疗前显著降低(P<0.01),奥氮平组显著低于氯丙嗪组(P<0.01)。结论奥氮平能显著改善精神分裂症患者的认知功能,优于氯丙嗪。

  1. 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.

  2. 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 .

  3. Impact of Chlorpromazine Taken for Long Term on Blood Sugar of Schizophrenia Patients.%长期服用氯丙嗪对精神分裂症患者血糖的影响

    Institute of Scientific and Technical Information of China (English)

    卢智慧; 卢自祥

    2011-01-01

    Objective To know about the impact of taking chlorpromazine long term on the blood sugar of the schizophrenia patients. Methods A total of 106 cases were surveyed in our mental home for long term, including 9 female patients and 97 male patients. Then after a year, the blood sugar of the patients without eating food was compared with that when they registered in our mental home for treatment. Results Among 106 patients, the number of the patients whose blood sugar levels rose was 30, that was 28. 30%. Compared with the average(2. 5%), the difference was significant (P < 0. 05). Conclusion The patients with schizophrenia who take chlorpromazine long term will have their blood sugar levels increased, reaching 28. 30%, which is significantly higher than the normal people,and is also related to the increase of body mass index.%目的 了解长期服用氯丙嗪对精神分裂症患者血糖的影响.方法 对我院长期住院的精神分裂症患者106例,其中女9例,男97例进行观察.对入院时及住院1年后患者的空腹血糖进行比较.结果 106例中.伴发空腹血糖增高者30例,占28.30%.与普通人群2.5%比较.差异有显著性(P<0.05).结论 长期服用氯丙嗪治疗这1年的精神分裂症患者,空腹血糖增高的发生率为28.30%,显著高于普通人群,且与体质量指数增加有关.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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、

  10. Chlorpromazine--a specific effect on breathlessness?

    OpenAIRE

    O'Neill, P A; Morton, P B; Stark, R D

    1985-01-01

    Previous work has left unresolved questions on whether promethazine reduces the sensation of breathlessness. This study was designed to provide a definitive answer and to determine the contributions from promethazine's major pharmacological actions. Twelve healthy subjects participated in a double-blind, within-subject comparison of promethazine and placebo each given acutely by mouth. Breathlessness was assessed with visual analogue scales during a progressive exercise test and was related t...

  11. 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

  12. 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

  13. 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.

  14. 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...

  15. 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

  16. 大鼠体内恩丹西酮与氯丙嗪的药动学相互作用研究%Study on Pharmacokinetic Interaction of ondansetron and Chlorpromazine in Rat

    Institute of Scientific and Technical Information of China (English)

    沈于兰; 冯芳

    2008-01-01

    目的 建立同时测定大鼠血浆中恩丹西酮、氯丙嗪的HPLC-UV分析方法,探索恩丹西酮与氯丙嗪在大鼠体内药动学的相互作用,并进行高蛋白食物对2种药物药动学影响的研究.方法 以替米沙坦为内标,乙酸乙酯提取,HPLC-UV分离、分析.色谱系统:C8柱(4.6 mm×250 mm,5 μm),甲醇-水(70:30)为流动相,流速1.0mL·min-1,柱温30℃.以大鼠为研究对象,分别在禁食和服用高蛋白食物状态下给以恩丹西酮、氯丙嗪或联合使用2种药物.用建立的血药浓度测定方法测定,计算其药动学参数并进行t检验.结果 联合用药后,恩丹西酮的pmax,tt/2,MRT,AUC0→t,AUC0→∞与单独用药时相比显著性增加.氯丙嗪单独用药和联合用药时的pmax,t1/2,MRT,AUC0→s,AUC0→∞无显著性差异.高蛋白食物能使恩丹西酮的pmax,AUC0→s,AUC0→∞明显增加,使氯丙嗪的tmax延长,pmax,AUC0→t,AUC0→∞降低.结论 恩丹西酮和氯丙嗪联合使用时,恩丹西酮的药动学过程会受到显著性影响;食用高蛋白食物后,恩丹西酮和氯丙嗪的药动学参数均会发生明显的改变,应在临床使用中注意这些问题,适当调整药物剂量.

  17. 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.

  18. 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.

  19. 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.

  20. 男性精神分裂症患者服用氯丙嗪、利培酮及喹硫平影响下丘脑-垂体-性腺轴及性功能的比较%Comparison of the effects of chlorpromazine, risperidone and quetiapine on hypothalamic-pituitary-gonadal axis and sexual function in male patients with schizophrenia

    Institute of Scientific and Technical Information of China (English)

    曹栋; 谢世平; 陈启豹; 袁勇贵; 方群

    2005-01-01

    目的:抗精神病药物引起的性功能障碍可能与下丘脑-垂体-性腺轴激素水平变化有关.探讨喹硫平、利培酮及氯丙嗪对男性精神分裂症患者下丘脑-垂体-性腺轴激素水平及性功能影响的差异.方法:选择2003-10/2004-10在南京医科大学附属脑科医院住院的精神分裂症患者75例,随机分为喹硫平组、利培酮组及氯丙嗪组,每组25例,各组患者在年龄、文化程度、病程、经济状况、夫妻关系及基线阳性与阴性症状量表评分等方面基线值均无明显差异.患者法定监护人知情同意.喹硫平组、利培酮组和氯丙嗪组分别予以喹硫平(200mg/片)、利培酮(1 mg/片)和氯丙嗪(25 mg/片)进行干预.应用放免法检测各组患者治疗前、治疗后4周及8周血清促卯泡素、黄体生成素、催乳素、睾酮水平.治疗前由配偶提供患者基线性功能资料,待患者精神症状缓解后可进一步完善评估.利用自制男性性功能量表评估疗前、治疗后8,12及16周的性功能状况(量表分为性欲、性唤起、性高潮及性满意度4项因子分,性功能总体因子分为上述4项分值总和).结果:进入结果分析氯丙嗪组、利培酮组及喹硫平组分别为17,19和19例.①血清催乳素水平:氯丙嗪组治疗8周后显著高于基线值(F=3.120,P=0.05);利培酮组在治疗4周及8周后均显著高于基线值(F=23.770,P<0.01);喹硫平组在治疗4周及8周后与基线值差异均无显著性意义(P>0.05).②血清睾酮及黄体生成素水平:利培酮组在治疗8周后显著低于基线值(F=2.560,8.340,P<0.05~0.01);喹硫平组在治疗4周及8周后与基线值差异均无显著性意义(P>0.05).③性欲减退发生率:喹硫平组在人组8周后显著低于氯丙嗪组及利培酮组[21.1%,58.8%,63.2%,(F=5.386,6.909,P<0.05)].④性唤起困难发生率:喹硫平在人组后的8,12及16周显著低于氯丙嗪组[(21.1%,21.1%,15.8%),(64.7%,70.6%,70.6%),(F=7.034,8.916,11.085,P<0.05~0.01)],在第8及16周显著低于利培酮组[63.2%,57.9%,(F=6.909,7.238,P<0.05)].结论:利培酮和氯丙嗪均能引起较明显的催乳素水平升高,对性欲及性唤起也有不同程度的影响.服用利培酮后,还可能出现黄体生成素及睾酮水平下降.而喹硫平对血清催乳素水平及性功能的影响较小.

  1. 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.

  2. 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 ...

  3. 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

  4. 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)

  5. An autopsy case of multiple psychotropic drug poisoning.

    Science.gov (United States)

    Tanaka, Naoko; Kinoshita, Hiroshi; Nishiguchi, Minori; Jamal, Mostofa; Kumihashi, Mitsuru; Takahashi, Motonori; Nishio, Hajime; Ameno, Kiyoshi

    2011-07-01

    A fatal poisoning case involving etizolam, phenobarbital, promethazine and chlorpromazine is presented. Quantitative toxicological analysis showed that the concentrations of etizolam, phenobarbital, promethazine and chlorpromazine in the femoral blood were 86 ng/ml, 5082 microg/ml, 0.107 microg/ml and 0.144 microg/ml, respectively, and large amounts of drugs were also detected in the stomach contents. We conclude that the cause of death was due to the interaction of multiple psychotropic drugs. PMID:21887897

  6. 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.

  7. Effects of filaricidal drugs on longevity and enzyme activities of the microfilariae of Setaria cervi in white rats

    Institute of Scientific and Technical Information of China (English)

    Haytham Ahmed Zakai; Wajihullah Khan

    2015-01-01

    To analyse the efficacy of diethylcarbamazine (DEC), tetramisole and chlorpromazine on the longevity and activity of glucose-6-phosphatase and succinate dehydrogenase in the microfilariae recovered from the peripheral circulation of the rats before and after the treatment. Methods: Setaria cervi worms were implanted in white rats via laparotomy and microfilaraemic rats were divided into 4 groups. Groups 1, 2 and 3 were treated with DEC, tetramisole and chlorpromazine respectively, while Group 4 served as infected control. Longevity of microfilariae and differential leucocyte counts were recorded till the disappearance of microfilariae from peripheral blood. Glucose-6-phosphatase and succinate dehydrogenase enzymes were localized in the microfilariae recovered from normal and treated rats. Results: The microfilariae survived for 48 days in untreated rats while survival was reduced to 15, 21 and 27 days after treatment with DEC, tetramisole and chlorpromazine, respectively. Eosinophils and neutrophils increased during 2nd and 3rd weeks, whereas the lymphocytes increased during 4-7 weeks. DEC treatment resulted in slight decrease in the localization of succinate dehydrogenase but not in glucose-6-phosphatase. Tetramisole and chlorpromazine treatment did not show any appreciable change in the localization of both the above enzymes. Conclusions: DEC proved the most effective drug which cleared the microfilaraemia within 15 days and reduced the activity of succinate dehydrogenase to some extent followed by tetramisole and chlorpromazine which took more time for the clearance of microfilariae and had no effect on the localization of both glucose-6-phosphatase and succinate dehydrogenase.

  8. Amphipaths Differentially Modulate Membrane Surface Deformation in Rat Peritoneal Mast Cells During Exocytosis

    Directory of Open Access Journals (Sweden)

    Itsuro Kazama

    2013-04-01

    Full Text Available Background/Aims: Salicylate and chlorpromazine exert differential effects on the chemokine release from mast cells. Since these drugs are amphiphilic and preferentially partitioned into the lipid bilayers of the plasma membranes, they would induce some morphological changes in mast cells and thus affect the process of exocytosis. Methods: Employing the standard patch-clamp whole-cell recording technique, we examined the effects of salicylate and chlorpromazine on the membrane capacitance (Cm during exocytosis in rat peritoneal mast cells. Using confocal imaging of a water-soluble fluorescent dye, lucifer yellow, we also examined their effects on plasma membrane deformation of the cells. Results: Salicylate dramatically accelerated the GTP-γ-S-induced increase in the Cm immediately after its application, whereas chlorpromazine significantly suppressed the increase. Treatment with salicylate increased the trapping of the dye on the cell surface, while treatment with chlorpromazine completely washed it out, indicating that both drugs induced membrane surface deformation in mast cells. Conclusion: This study demonstrated for the first time that membrane amphipaths, such as salicylate and chlorpromazine, may oppositely modulate the process of exocytosis in mast cells, as detected by the changes in the Cm. The plasma membrane deformation induced by the drugs was thought to be responsible for their differential effects.

  9. Modulators of membrane drug transporters potentiate the activity of the DMI fungicide oxpoconazole against Botrytis cinerea

    NARCIS (Netherlands)

    Hayashi, K.; Schoonbeek, H.; Waard, de M.A.

    2003-01-01

    Modulators known to reduce multidrug resistance in tumour cells were tested for their potency to synergize the fungitoxic activity of the fungicide oxpoconazole, a sterol demethylation inhibitor (DMI), against Botrytis cinerea Pers. Chlorpromazine, a phenothiazine compound known as a calmodulin anta

  10. Effects of fi laricidal drugs on longevity and enzyme activities of the microfilariae of Setaria cervi in white rats

    Institute of Scientific and Technical Information of China (English)

    Haytham; Ahmed; Zakai; Wajihullah; Khan

    2015-01-01

    Objective: To analyse the efficacy of diethylcarbamazine(DEC), tetramisole and chlorpromazine on the longevity and activity of glucose-6-phosphatase and succinate dehydrogenase in the microi lariae recovered from the peripheral circulation of the rats before and after the treatment.Methods: Setaria cer vi worms were implanted in white rats via laparotomy and microfilaraemic rats were divided into 4 groups. Groups 1, 2 and 3 were treated with DEC, tetramisole and chlorpromazine respectively, while Group 4 served as infected control. Longevity of microi lariae and dif erential leucocyte counts were recorded till the disappearance of microi lariae from peripheral blood. Glucose-6-phosphatase and succinate dehydrogenase enzymes were localized in the microi lariae recovered from normal and treated rats.Results: The microi lariae survived for 48 days in untreated rats while survival was reduced to 15, 21 and 27 days after treatment with DEC, tetramisole and chlorpromazine, respectively. Eosinophils and neutrophils increased during 2nd and 3rd weeks, whereas the lymphocytes increased during 4-7 weeks. DEC treatment resulted in slight decrease in the localization of succinate dehydrogenase but not in glucose-6-phosphatase. Tetramisole and chlorpromazine treatment did not show any appreciable change in the localization of both the above enzymes. Conclusions: DEC proved the most ef ective drug which cleared the microi laraemia within 15 days and reduced the activity of succinate dehydrogenase to some extent followed by tetramisole and chlorpromazine which took more time for the clearance of microi lariae and had no ef ect on the localization of both glucose-6-phosphatase and succinate dehydrogenase.

  11. 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.

  12. Regional blockade by neuroleptic drugs of in vivo /sup 3/H-spiperone binding in the rat brain. Relation to blockade of apomorphine induced hyperactivity and stereotypies

    Energy Technology Data Exchange (ETDEWEB)

    Koehler, C.; Haglund, L.; Oegren, S.O.; Aengeby, T. (Astra Lackemedel AB, Soedertaelje (Sweden). Dept. of Pharmacology)

    1981-01-01

    The regional prevention by neuroleptic drugs of specific in vivo /sup 3/H-spiperone binding was studied in the rat brain. L-sulpiride, thioridazine and clozapine were found to reduce the /sup 3/H-spiperone bindings selectively in the olfactory tubercle, septum, substantia nigra and frontal cortex but not the striatum at dose levels which preferentially block apomorphine (APO) induced hyperactivity. The maximal prevention of specific /sup 3/H-spiperone binding by l-sulpiride and clozapine reached 60-80% in the former structures while the displacement of striatal /sup 3/H-spiperone binding did not exceed 40%. In contrast to l-sulpiride, thioridazine and clozapine both chlorpromazine and haloperidol reduced the /sup 3/H-spiperone binding to the same extent in all regions studied. Chlorpromazine and haloperidol were potent in prevention of striatal /sup 3/H-spiperone binding in vivo which reached 60-80% in this structure.

  13. 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. PMID:624603

  14. Interaction between rocuronium bromide and some drugs used during anaesthesia.

    Science.gov (United States)

    Muir, A W; Anderson, K A; Pow, E

    1994-01-01

    In cats anaesthetized with i.p. chloralose and pentobarbitone, neuromuscular blockade produced by various doses of rocuronium was measured and dose response curves constructed in the presence of halothane, enflurane, nitrous oxide, propofol, alfentanil, thiopentone, ketamine, diazepam, chlorpromazine, morphine or streptomycin. In general, when a shift in the dose response curve was produced, it was a parallel shift to the left, indicating potentiation. Both halothane and enflurane produced a left shift and a small increase in the time from maximum block to 90% recovery. Nitrous oxide had no effect on the depth of block but delayed recovery. Thiopentone and ketamine potentiated the blocking effect of rocuronium but propofol and alfentanil had no effect. Chlorpromazine and morphine caused potentiation which took 1-1.5 h to develop. Streptomycin had a potentiating effect in four cats but not in two others. Diazepam displaced the dose-response curve to the right in four cats. Prior treatment with suxamethonium had no effect. PMID:7925217

  15. 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.

  16. 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.

  17. Selective modulation of P-glycoprotein-mediated drug resistance

    OpenAIRE

    Bebawy, M; Morris, M B; Roufogalis, B. D.

    2001-01-01

    Multidrug resistance associated with the overexpression of the multidrug transporter P-glycoprotein is a serious impediment to successful cancer treatment. We found that verapamil reversed resistance of CEM/VLB 100 cells to vinblastine and fluorescein-colchicine, but not to colchicine. Chlorpromazine reversed resistance to vinblastine but not to fluorescein-colchicine, and it increased resistance to colchicine. Initial influx rates of fluorescein-colchicine were similar in resistant and paren...

  18. 23Na and 1H NMR studies on melittin channels activated by tricyclic tranquilizers.

    OpenAIRE

    Tanaka, H.; Matsunaga, K.; Kawazura, H

    1992-01-01

    A dynamic 23Na nuclear magnetic resonance (NMR) technique was applied to the exchange system of Na+ ions present inside and outside large unilamellar vesicles at an equivalent concentration. Addition of melittin to phosphatidylcholine vesicles did not induce any detectable Na+ transport across the membrane but subsequent addition of a trace of chlorpromazine or imipramine did induce Na+ transport. Because the formation of a drug-melittin adduct in a solution was detected by 1H NMR, the activa...

  19. Radiosensitization of hypoxic bacterial cells and animal tumours by membrane active drugs and hyperthermia

    International Nuclear Information System (INIS)

    The present report deals with the results on phenothiazine derivatives such as promethazine (PMZ), trimeprazine (TMZ), trifluoperazine (TFP) and prochlorperazine (PCP) and their comparison with that of chlorpromazine (CPZ). Their efficiency in combination with hyperthermia, radiation and other anti-cancer drugs in treating murine tumors has also been presented herein. In addition, results on bacterial cells dealing with their mechanistic aspects are also included. (author). 57 refs., 27 figures, 13 tables

  20. Effects of Three Different Fibrates on Intrahepatic Cholestasis Experimentally Induced in Rats

    OpenAIRE

    Alaa El-Sisi; Sahar Hegazy; Eman El-Khateeb

    2013-01-01

    Background. Activation of PPAR α modulates cholesterol metabolism and suppresses bile acid synthesis. This study aims to evaluate the effect of PPAR α agonists, fenofibrate, bezafibrate, and gemfibrozil, on acute cholestasis induced by ethinylestradiol (EE) plus chlorpromazine (CPZ) in rats. Method. 100 male albino rats (150–200 gm) were divided randomly into 10 equal groups. Control group received 1% methylcellulose vehicle; disease group received CPZ plus EE for 5 consecutive days; four gro...

  1. Antipsychotic-like effect of minocycline in a rat model

    OpenAIRE

    Dokuyucu, Recep; Kokacya, Hanifi; Inanir, Sema; Copoglu, Umit Sertan; Erbas, Oytun

    2014-01-01

    Objectives: Tetracycline antibiotic drug minocycline has strongly neuroprotective and anti-inflammatory effects. Minocycline has also remarkable brain tissue penetration, is clinically entirely tolerated and properly absorbed when taken orally. In our study, we class with the effects of minocycline and chlorpromazine, a conventional antipsychotic drug, by evaluating the novelty-induced rearing, apomorphine-induced stereotypic behavior, and brain MDA levels in rats. Materials and Methods: Four...

  2. 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.

  3. Migraine.

    OpenAIRE

    Edmeads, J. G.

    1988-01-01

    Recent advances in migraine therapy include the recognition of analgesic or ergotamine abuse as a cause of chronic daily migraine, the introduction of effective non-narcotic drugs such as chlorpromazine, dihydroergotamine and corticosteroids for the treatment of intractable migraine attacks, the increased number of beta-blockers now recognized as effective prophylactic agents and the introduction of calcium-channel blockers for prophylaxis. There is a sufficient variety of antimigraine drugs,...

  4. Effects of serotonin on the internal anal sphincter: in vivo manometric study in rats.

    OpenAIRE

    Goldberg, M; Hanani, M.; Nissan, S

    1986-01-01

    The effects of serotonin (5-hydroxytryptamine, 5-HT) on the internal anal sphincter were studied in anaesthesized rats. Serotonin induced a dose dependent relaxation of the internal anal sphincter. Methysergide blocked this relaxation, but did not affect the rectoanal reflex. Methysergide did not antagonise the actions of cholinergic and adrenergic agonists on the internal anal sphincter. Other 5-HT antagonists such as cyproheptadine, ketanserin, chlorpromazine, amitriptyline and ergotamine f...

  5. Bovine Viral Diarrhea Virus Entry Is Dependent on Clathrin-Mediated Endocytosis

    OpenAIRE

    Lecot, Steve; Belouzard, Sandrine; Dubuisson, Jean; Rouillé, Yves

    2005-01-01

    Cellular mechanisms of bovine viral diarrhea virus (BVDV) entry in MDBK cells were investigated. Chloroquine, bafilomycin A1, or ammonium chloride inhibited BVDV infection, indicating that an acidic endosomal pH is required for BVDV entry. The tyrosine kinase inhibitor genistein partially inhibited BVDV infection at a postentry step, whereas BVDV entry was strongly inhibited by chlorpromazine or by the overexpression of a dominant-negative form of EPS15, a protein essential for the formation ...

  6. Toxicity study in blood and tumor cells of laser produced medicines for application in fabrics.

    Science.gov (United States)

    Morán, M Carmen; Tozar, Tatiana; Simon, Agota; Dinache, Andra; Smarandache, Adriana; Andrei, Ionut Relu; Boni, Mihai; Pascu, Mihail Lucian; Cirisano, Francesca; Ferrari, Michele

    2016-01-01

    Phenothiazine derivatives are non-antibiotics with antimicrobial, fungistatic and fungicidal effects. We exposed to a high energy UV laser beam phenothiazines solutions in water at 20mg/mL concentration to increase antibacterial activity of resulting mixtures. Compared to previous results obtained on bacteria, more research is needed about UV laser irradiated phenothiazines applications on cancer cell cultures to evidence possible anticancerous properties. Evaluation of the safety of the newly obtained photoproducts in view of use on humans is also needed. Due to expensive animal testing in toxicology and pressure from general public and governments to develop alternatives to in vivo testing, in vitro cell-based models are attractive for preliminary testing of new materials. Cytotoxicity screening reported here shows that laser irradiated (4h exposure time length) chlorpromazine and promazine are more efficient against some cell cultures. Interaction of laser irradiated phenothiazines with fabrics show that promethazine and chlorpromazine have improved wetting properties. Correlation of these two groups of properties shows that chlorpromazine appears to be more recommended for applications on tissues using fabrics as transport vectors. The reported results concern stability study of phenothiazines water solutions to know the time limits within which they are stable and may be used. PMID:26187648

  7. 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.

  8. 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.

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

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    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

  10. Neuroleptics Affect Neuropeptide S and NPSR mRNA Levels in the Rat Brain.

    Science.gov (United States)

    Pałasz, Artur; Rojczyk, Ewa

    2015-11-01

    Neuropeptide S (NPS) has a multidirectional regulatory activity, especially when considered as a potent endogenous anxiolytic factor. Accumulating data suggests that neuroleptics affect peptidergic signaling in various brain structures. However, there is no information regarding the influence of treatment with antipsychotics on brain NPS expression. In the current study, we assessed the NPS and NPS receptor (NPSR) mRNA levels in the brains of rats shortly and chronically treated with chlorpromazine and olanzapine using quantitative real-time PCR. Both single-dose and long-term (4 months) olanzapine treatment led to the upregulation of NPS expression in the rat hypothalamus. It supports the hypothesis that NPS is involved in the dopamine-dependent anxiolytic actions of selected neuroleptics and possibly also in the pathophysiology of mental disorders. On the other hand, NPSR expression decreased after single-dose and chronic chlorpromazine administration in the hypothalamus, as well as after chronic olanzapine and chlorpromazine administration in the striatum and hippocampus. These results cast a new light on the pharmacology of antipsychotics and contribute to a better understanding of the mechanisms responsible for their action. Furthermore, our findings underline the complex nature of potential interactions between dopamine receptors and brain peptidergic pathways, which has potential clinical applications. PMID:26227793

  11. 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

  12. 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.

  13. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, J.; Neff, N.H.

    1982-05-01

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

  15. 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)

  16. Molar ratios of therapeutic water-soluble phenothiazine⋅water-insoluble phospholipid adducts reveal a Fibonacci correlation and a putative link for structure–activity relationships

    DEFF Research Database (Denmark)

    Keyzer, Hendrik; Fey, S. J.; Thornton, Barry;

    2015-01-01

    the changes in the membrane proportions found in eukaryotic cells proceeding from the plasma membrane to the endoplasmic reticulum. The same order was found when hydrogen ion concentration was increased [ΔiH+] when plotted against the MR for each separate diacyl series. The [ΔiH+] of the PTH/PL was always...... lipids. Micro-gravimetric titrations were performed on aqueous suspensions of promethazine (PMTZ), promazine (PMZ), triflupromazine (TFM), chlorpromazine (CPZ), prochlorperazine⋅HCl (PClP⋅HCl), trifluoperazine⋅HCl (TFP⋅HCl), prochlorperazine⋅2HC1 (PClP⋅2HCl), trifluoperazine⋅2HCl (TFP⋅2HCl) and synthetic...

  17. Evidence for an inhibitory presynaptic component of neuroleptic drug action.

    OpenAIRE

    de Belleroche, J. S.; Bradford, H. F.

    1981-01-01

    1 The action of five neuroleptic drugs (haloperidol, cis-flupenthixol, chlorpromazine, fluphenazine and thioridazine) was studied on the synthesis and release of dopamine from rat striatal synaptosomes. 2. In vitro application of the drugs induced an inhibition of synthesis of [14C]-dopamine from L-[U-14C]-tyrosine and a decrease in the tissue content of [14-C]-dopamine, with IC50 values for the latter effect ranging from 3.6 x 10(-7) to 5.9 x 10(-5) M. The rank of their potency was similar t...

  18. 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.

  19. Effect of cholera toxin on cAMP levels and Na/sup +/ influx in isolated intestinal epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Hyun, C.S.; Kimmich, G.A.

    1982-09-01

    Freshly isolated chicken intestinal cells contain approximately 20 pmol adenosine 3',5'-cyclic monophosphate (cAMP)/mg cellular protein. Incubation with 3 ..mu..g/ml cholera toxin (CT) at 37/sup 0/C induces an elevation of cellular cAMP beginning 10-15 min after initial exposure. The response is linear with time for 40-50 min and causes a six- to eightfold increase over control levels at steady state. Dibutyryl cAMP and agents that increase cAMP production inhibit Na/sup +/ influx into the isolated enterocytes. Chlorpromazine completely abolishes the toxin-induced elevation of cAMP in the isolated cells and also reverses the effect on Na/sup +/ entry. The data provide evidence for a cAMP-mediated control of intestinal cell Na/sup +/ uptake, which may represent the mechanistic basis for the antiabsorptive effect of CT on Na/sup +/ during induction of intestinal secretory activity. Studies on the time-dependent effects of chlorpromazine on both intracellular cAMP concentration and Na/sup +/ influx suggest that the reactivation of the Na/sup +/ transport system after cAMP-induced inhibition is slow relative to the disappearance of cAMP.

  20. Antipsychotic-Like Effect of Trimetazidine in a Rodent Model

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    Oytun Erbaş

    2013-01-01

    Full Text Available Trimetazidine (TMZ has been used as an anti-ischemic agent for angina pectoris, chorioretinal disturbances, and vertigo. Also, it can induce extrapyramidal type adverse reaction such as parkinsonism, gait disorder, and tremor via blockade of D2 receptors. In the present study, we evaluated the effect of TMZ on novelty-induced rearing behavior and apomorphine-induced stereotypy behavior in male rats. Four groups of rat ( were administrated with TMZ (10 and 20 mg/kg, i.p., chlorpromazine (1 mg/kg, i.p., or isotonic saline. One hour later, apomorphine (2 mg/kg, s.c. was administrated to each rat. Our results showed that both doses of TMZ significantly decreased the rearing behavior in rats, whereas the decrease with chlorpromazine was higher. TMZ also decreased the stereotypy scores in a dose-dependent manner. We concluded that TMZ has beneficial effects on rearing behavior and stereotypy, which are accepted to be indicators of antipsychotic effect. Taken together, with its antioxidative and cytoprotective properties, TMZ is worthy of being investigated for its anti-psychotic effects as a primary or an adjunctive drug.

  1. 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.

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

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    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.

  3. 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.

  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. Blood to brain iron uptake in one rhesus monkey using [Fe-52]-citrate and positron emission tomography (PET): influence of haloperidol.

    Science.gov (United States)

    Leenders, K L; Antonini, A; Schwarzbach, R; Smith-Jones, P; Reist, H; Ben-Shachar, D; Youdim, M; Henn, V

    1994-01-01

    Iron is highly concentrated in the basal ganglia of the brain. The involvement of cerebral iron and its handling systems in neurodegenerative brain diseases like Parkinson's disease and tardive dyskinesia is currently under close investigation. There is evidence from animal studies that neuroleptics can increase iron uptake into brain. This effect appeared to be due to alteration of blood-brain barrier transport by the neuroleptics, particularly chlorpromazine and haloperidol, but not clozapine. We have investigated one Rhesus monkey using positron emission tomography (PET) and [Fe-52]-citrate before and during haloperidol administration. After drug withdrawal during a period of 1.5 year the investigation procedure was repeated. The results show that in the investigated monkey haloperidol induces a reversible marked increase of iron transport across the blood brain barrier concomitant with a large increase in elimination rate of the tracer from the blood. PMID:7884394

  6. 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

  7. A double-suicide autopsy case of potassium poisoning by intravenous administration of potassium aspartate after intake of some psychopharmaceuticals.

    Science.gov (United States)

    Watanabe, K; Hasegawa, K; Suzuki, O

    2011-07-01

    We report a curious double-suicide autopsy case of both male and female who died of potassium poisoning by intravenous administration of concentrated potassium aspartate solution. The plasma concentrations of potassium of the male and female subjects were as high as 49.7 and 62.8 mEq/L, respectively. In addition to the high concentrations of potassium, toxic levels of phenobarbital, promethazine and chlorpromazine, and relatively low levels of etizolam and brotizolam were also detected from whole blood and urine specimens of both cadavers. Twenty empty plastic bottles (10-mL capacity) labeled 'ASPARA® Potassium Injection 10 mEq' were found at the suicide spot. To our knowledge, this is the first description for suicidal death by potassium aspartate; in all of the previous literature, they used potassium chloride intravenously or per os. PMID:20670988

  8. The role of brain biogenic amines in the control of pituitary-adrenocortical activity

    Science.gov (United States)

    Maickel, R. P.

    1975-01-01

    It was found that pretreatment of animals with desmethyl imipramine antagonized the reserpine-induced sedation without preventing the decline in brain amines or the hypersecretion of adrenocorticotropic hormone (ACTH). The antagonism of reserpine-induced ACTH hypersecretion by the monoamine oxidose (MAO) inhibitor pargyline (MO 911, N-methyl-N-benzyl-2-propynylamine) was studied. Evidence is presented that this antagonism is related to the level of brain biogenic amines maintained during the course of action of the drug. Pretreatment with MAO inhibitors does not affect the ACTH hypersecretion evoked by exposure to cold or chlorpromazine, lending further support to the hypothesis that reserpine-induced ACTH hypersecretion is related to brain amine changes.

  9. 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.

  10. 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.

  11. 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.

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

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    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.

  13. 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

  14. Interaction of injectable neurotropic drugs with the red cell membrane.

    Science.gov (United States)

    Reinhart, Walter H; Lubszky, Szabina; Thöny, Sandra; Schulzki, Thomas

    2014-10-01

    The normal red blood cell (RBC) shape is a biconcave discocyte. An intercalation of a drug in the outer half of the membrane lipid bilayer leads to echinocytosis, an intercalation in the inner half to stomatocytosis. We have used the shape transforming capacity of RBCs as a model to analyse the membrane interaction potential of various neurotropic drugs. Chlorpromazine, clomipramine, citalopram, clonazepam, and diazepam induced a reversible stomatocytosis, phenytoin induced echinocytosis, while the anticonvulsants levetiracetam, valproic acid and phenobarbital had no effect. This diversity of RBC shape transformations suggests that the pharmacological action is not linked to the membrane interaction. We conclude that this simple RBC shape transformation assay could be a useful tool to screen for potential drug interactions with cell membranes. PMID:24997296

  15. Pulse radiolysis and stopped-flow studies into the mechanism of radiosensitizing action or organic nitro-compounds. Part of a coordinated programme on improvement in radiotherapy of cancer using modifiers of radiosensitivity of cells

    International Nuclear Information System (INIS)

    The formation of long-lived radical-cations on reaction of chlorpromazine with hydroxyl radicals could account for the radiosensitising effect of the drug (Shenoy et al 1975). It may also account for the observed cytotoxic action of the drug on hypoxic cells. An analogous reaction to the observed reaction of the phenothiazine radical cation from promethazine with cysteamine may similarly account for the protective effect of the sulphydryl compounds dithiothreitol or glutathione in these systems. (Shenoy et al, 1978). The reduction in induced mutation frequency when bacteria are incubated with metronidazole and cysteamine indicates that cysteamine may act not only by scavenging short lived toxic species but also by repairing long-lived damage to vital molecules

  16. Pathogenesis of drug induced acneform eruptions

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    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.

  17. Radiolytic reductions and oxidations in dimethyl sulfoxide solutions. Solvent effects on reactivity of halogen atom complexes

    International Nuclear Information System (INIS)

    Radiolysis of dimethyl sulfoxide (DMSO) solutions containing various additives was used to achieve clean one-electron reduction or oxidation of solutes. Pulse radiolysis of benzoquinone in DMSO solutions containing acetone and triethylamine permitted conversion of all primary radicals into reducing species. The total yield of reduction in the γ-radiolysis of methyl viologen solutions was found to be 0.37 μmol/J. In the pulse radiolysis of TMPD and triphenylamine in aerated DMSO containing LiCl and/or CCl4, all the primary radicals were converted into oxidizing species and gave a maximum yield of 0.39 μmol/J. In the latter systems, oxidation, was partly by halogen atom complexes. The reactivity of complexes of DMSO (DMSO-Cl DMSO-Br) and of halide ions (Br2sm-bullet-, I2sm-bullet-) was examined for several organic compounds. DMSO-Cl oxidizes chlorpromazine triphenylamine, and zinc porphyrin with rate constants of the order of 107-108 M-1s-1, and the rates increase upon addition of CH2Cl2 as well as upon addition of water and formamide. DMSO-Cl also reacts with olefins by addition of Cl to the double bond; the rate constants increase upon increasing the electron-donating properties of the substituents on the double bond. The rate constants for oxidation of chlorpromazine by Br2sm-bullet- and I2sm-bullet- increase by more than 2 orders of magnitude upon changing the solvent from DMSO gradually to water. The change was less with acetonitrile/water mixtures, and the difference is probably due to differences in ion solvation. 28 refs., 3 figs., 4 tabs

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

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    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.

  19. 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.

  20. 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

  1. 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.

  2. Uniform procedure of (1)H NMR analysis of rat urine and toxicometabonomics Part II: comparison of NMR profiles for classification of hepatotoxicity.

    Science.gov (United States)

    Schoonen, Willem G E J; Kloks, Cathelijne P A M; Ploemen, Jan-Peter H T M; Smit, Martin J; Zandberg, Pieter; Horbach, G Jean; Mellema, Jan-Remt; Thijssen-Vanzuylen, Carol; Tas, Albert C; van Nesselrooij, Joop H J; Vogels, Jack T W E

    2007-07-01

    A procedure of nuclear magnetic resonance (NMR) urinalysis using pattern recognition is proposed for early detection of toxicity of investigational compounds in rats. The method is applied to detect toxicity upon administration of 13 toxic reference compounds and one nontoxic control compound (mianserine) in rats. The toxic compounds are expected to induce necrosis (bromobenzene, paracetamol, carbon tetrachloride, iproniazid, isoniazid, thioacetamide), cholestasis (alpha-naphthylisothiocyanate (ANIT), chlorpromazine, ethinylestradiol, methyltestosterone, ibuprofen), or steatosis (phenobarbital, tetracycline). Animals were treated daily for 2 or 4 days except for paracetamol and bromobenzene (1 and 2 days) and carbon tetrachloride (1 day only). Urine was collected 24 h after the first and second treatment. The animals were sacrificed 24 h after the last treatment, and NMR data were compared with liver histopathology as well as blood and urine biochemistry. Pathology and biochemistry showed marked toxicity in the liver at high doses of bromobenzene, paracetamol, carbon tetrachloride, ANIT, and ibuprofen. Thioacetamide and chlorpromazine showed less extensive changes, while the influences of iproniazid, isoniazid, phenobarbital, ethinylestradiol, and tetracycline on the toxic parameters were marginal or for methyltestosterone and mianserine negligible. NMR spectroscopy revealed significant changes upon dosing in 88 NMR biomarker signals preselected with the Procrustus Rotation method on principal component discriminant analysis (PCDA) plots. Further evaluation of the specific changes led to the identification of biomarker patterns for the specific types of liver toxicity. Comparison of our rat NMR PCDA data with histopathological changes reported in humans and/or rats suggests that rat NMR urinalysis can be used to predict hepatotoxicity. PMID:17420222

  3. 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. PMID:26152524

  4. 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.

  5. 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.

  6. Natural products from the termite Nasutitermes corniger lowers aminoglycoside minimum inhibitory concentrations

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    Henrique D.M Coutinho

    2010-01-01

    Full Text Available Bacterial infectious agents present a risk to populations, as they are responsible for high morbidity and mortality. For combating these pathogens, our main line of defense is the use of antibiotics. However, indiscriminate use of these drugs develops resistant strains to these same drugs. The present study has tested the antibacterial and modifying antibiotic activity of natural products from Nasutitermes corniger (Termitidae (Motschulsky, a termite used in folk medicine in Northeast Brazil, by the microdilution and checkerboard methods, respectively. In this study, the aqueous extract from the nest of N. corniger (ANCE was prepared and tested with chlorpromazine (CPZ for its antimicrobial activity, using the microdilution method. CPZ and ANCE were used independently and also in combination with aminoglycosides, against a strain of Escherichia coli resistant to these antibiotics, to determine the participation of efflux systems in resistance mechanisms. The fractional inhibitory concentration (FIC index was calculated and evaluated for the occurrence of synergism, using the checkerboard method. The minimum inhibitory concentrations (MIC and minimum bactericidal concentrations (MBC values were ≥ 2048 µg/mL for both strains of E. coli assayed, indicating low antibacterial activity. However, synergism was observed with kanamycin when the decoction was used, but when chlorpromazine was used, synergism was observed with kanamycin, amikacin, and neomycin. This synergism with CPZ indicated the involvement of an efflux system in the resistance to these aminoglycosides. Therefore, it was suggested that the natural products from N. corniger could be used as a source of zoo-derived natural products with kanamycin-modifying activity, resulting in a new approach against bacterial resistance to antibiotics.

  7. 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.

  8. A new model of obese mice%一种新型小鼠肥胖模型的建立

    Institute of Scientific and Technical Information of China (English)

    田辉; 王玉婷; 陶莉; 丁虹

    2013-01-01

    目的 建立新型腹型肥胖实验动物模型.方法 30只小鼠随机分为空白对照组、模型组、食量控制组.空白对照组一次性注射生理盐水并自由饮食;模型组一次性注射氯丙嗪4 mg·kg-1并自由饮食;食量控制组一次性注射氯丙嗪4 mg·kg-1并控制食量同空白对照组,3组均喂饲基础饲料,共15 d.测定小鼠体重、Lee's指数、内脏脂肪湿重、血糖和血脂水平,病理切片观察脂肪组织形态学差异.结果 模型组、食量控制组小鼠均表现出内脏脂肪大量堆积,形成腹型肥胖,并出现GLU、TG、TC升高和HDL-C降低的糖脂代谢紊乱.结论 一次性注射氯丙嗪的小鼠具有与中老年人腹型肥胖相似的临床特征,可作为中老年腹型肥胖相关药物研究的筛选模型.%Aim To establish a new model of obese mice. Methods 30 mice were randomly divided into control group, model group, diet controlling group. The mice of control group were given one-time injection of normal saline and free diet. Those of model group were given one-time injection of chlor-promazine and free diet. Those of diet controlling group were given one-time injection of chlorpromazine with the same food intake as the control group. Three groups were all fed with standard diet, a total of 15d. The indices of experiments were body weight, Lee' s index, wet weight of visceral adipose tissue and testicular, blood lipid and glucose level. And the difference in morphology of adipose tissue was observed. Results Model group and diet controlling group both showed a large accumulation of visceral adipose, and formed abdominal obesity. GLU, TG and TC significantly increased( P < 0. 01 ) but HDL-C de-creased( P < 0. 05 ). Conclusion One-time injection of chlorpromazine in mice which has the similar clinical features with elderly abdominal obesity can be used as screening model of elderly abdominal obesity related drug.

  9. 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

  10. 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.

  11. Chemokine Transfer by Liver Sinusoidal Endothelial Cells Contributes to the Recruitment of CD4+ T Cells into the Murine Liver.

    Directory of Open Access Journals (Sweden)

    Katrin Neumann

    Full Text Available Leukocyte adhesion and transmigration are central features governing immune surveillance and inflammatory reactions in body tissues. Within the liver sinusoids, chemokines initiate the first crucial step of T-cell migration into the hepatic tissue. We studied molecular mechanisms involved in endothelial chemokine supply during hepatic immune surveillance and liver inflammation and their impact on the recruitment of CD4(+ T cells into the liver. In the murine model of Concanavalin A-induced T cell-mediated hepatitis, we showed that hepatic expression of the inflammatory CXC chemokine ligands (CXCL9 and CXCL10 strongly increased whereas homeostatic CXCL12 significantly decreased. Consistently, CD4(+ T cells expressing the CXC chemokine receptor (CXCR3 accumulated within the inflamed liver tissue. In histology, CXCL9 was associated with liver sinusoidal endothelial cells (LSEC which represent the first contact site for T-cell immigration into the liver. LSEC actively transferred basolaterally internalized CXCL12, CXCL9 and CXCL10 via clathrin-coated vesicles to CD4(+ T cells leading to enhanced transmigration of CXCR4(+ total CD4(+ T cells and CXCR3(+ effector/memory CD4(+ T cells, respectively in vitro. LSEC-expressed CXCR4 mediated CXCL12 transport and blockage of endothelial CXCR4 inhibited CXCL12-dependent CD4(+ T-cell transmigration. In contrast, CXCR3 was not involved in the endothelial transport of its ligands CXCL9 and CXCL10. The clathrin-specific inhibitor chlorpromazine blocked endothelial chemokine internalization and CD4(+ T-cell transmigration in vitro as well as migration of CD4(+ T cells into the inflamed liver in vivo. Moreover, hepatic accumulation of CXCR3(+ CD4(+ T cells during T cell-mediated hepatitis was strongly reduced after administration of chlorpromazine. These data demonstrate that LSEC actively provide perivascularly expressed homeostatic and inflammatory chemokines by CXCR4- and clathrin-dependent intracellular

  12. 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

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

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    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

  14. 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

  15. 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.

  16. Farnesol, a Potential Efflux Pump Inhibitor in Mycobacterium smegmatis

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    Jing Jin

    2010-10-01

    Full Text Available The active multidrug efflux pump (EP has been described as one of the mechanisms involved in the natural drug resistance of bacteria, such as mycobacteria. As a result, the development of efflux pumps inhibitors (EPIs is an important topic. In this study, a checkerboard synergy assay indicated that farnesol both decreased the minimum inhibitory concentration (MIC of ethidium bromide (EtBr 8-fold against Mycobacterium smegmatis (M. smegmatis mc2155 ATCC 700084 when incorporated at a concentration of 32 μg/mL (FICI = 0.625 and decreased MIC 4-fold at 16 μg/mL (FICI = 0.375. Farnesol also showed synergism when combined with rifampicin. A real-time 96-well plate fluorometric method was used to assess the ability of farnesol to inhibit EPs in comparison withfour positive EPIs: chlorpromazine, reserpine, verapamil, and carbonyl cyanide m-chlorophenylhydrazone (CCCP. Farnesol significantly enhanced the accumulation of EtBr and decreased the efflux of EtBr in M. smegmatis; these results suggest that farnesol acts as an inhibitor of mycobacterial efflux pumps.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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.

  19. 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.

  20. Olfactory bulb ablation in the rat: behavioural changes and their reversal by antidepressant drugs.

    Science.gov (United States)

    van Riezen, H; Schnieden, H; Wren, A F

    1977-01-01

    1. The effects of bilateral olfactory bulbectomy, sham-operation and inducement of peripheral anosmia were studied on locomotor activity, passive avoidance acquisition and irritability. 2. Bulbectomized rats were hyperactive, deficient at learning a step-down passive avoidance response and hyperirritable. Peripheral anosmia, induced by intranasal infusion of ZnSO4 solution resulted in no behavioural changes. 3. Chronic pretreatment with amitriptyline (3 and 10 mg/kg) and a tetracyclic antidepressant mianserin (Org GB 94, 5 and 15 mg/kg) reversed the hyperactivity and reduced the learning deficit of bulbectomized rats. These drugs had no significant effects on sham-operated animals. 4. Neither amitriptyline nor mianserin reduced the exaggerated responses of bulbectomized rats to external stimuli. 5. (+)-Amphetamine (1 and 3 mg/kg) accelerated the acquisition of the passive avoidance response, greatly enhanced the locomotor activity and slightly increased the irritability score of both sham-operated and bulbectomized rats. 6. Chlorpromazine (1 and 3 mg/kg) and chlordiazepoxide (10 mg/kg) significantly reduced the acquisition, locomotor activity and irritability of experimental and control rats. 7. Lithium sulphate (1 and 3 mg/kg) had no effect on activity or irritability but produced a small impairment in acquistion of bulbectomized rats. 8. It is concluded that the reversal by antidepressant drugs of the behavioural syndrome seen after olfactory bulb ablation could constitute a new model for the detection of this group of centrally acting compounds. PMID:907867

  1. 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.

  2. Chlorotoxin-Fc Fusion Inhibits Release of MMP-2 from Pancreatic Cancer Cells

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    Samah El-Ghlban

    2014-01-01

    Full Text Available Chlorotoxin (CTX is a 36-amino acid peptide derived from Leiurus quinquestriatus (scorpion venom, which inhibits low-conductance chloride channels in colonic epithelial cells. It has been reported that CTX also binds to matrix metalloproteinase-2 (MMP-2, membrane type-1 MMP, and tissue inhibitor of metalloproteinase-2, as well as CLC-3 chloride ion channels and other proteins. Pancreatic cancer cells require the activation of MMP-2 during invasion and migration. In this study, the fusion protein was generated by joining the CTX peptide to the amino terminus of the human IgG-Fc domain without a hinge domain, the monomeric form of chlorotoxin (M-CTX-Fc. The resulting fusion protein was then used to target pancreatic cancer cells (PANC-1 in vitro. M-CTX-Fc decreased MMP-2 release into the media of PANC-1 cells in a dose-dependent manner. M-CTX-Fc internalization into PANC-1 cells was observed. When the cells were treated with chlorpromazine (CPZ, the internalization of the fusion protein was reduced, implicating a clathrin-dependent internalization mechanism of M-CTX-Fc in PANC-1 cells. Furthermore, M-CTX-Fc clearly exhibited the inhibition of the migration depending on the concentration, but human IgG, as negative control of Fc, was not affected. The M-CTX-Fc may be an effective instrument for targeting pancreatic cancer.

  3. 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.

  4. 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 (R2 = 0.947 and Adj-R2 = 0.906, R2 = 0.977 and Adj-R2 = 0.960 and R2 = 0.982 and Adj-R2 = 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.

  5. Synthesis and Characterization of Mercuric Bromide-Phenothiazine Complexes

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    Vidisha A. Alwani

    2014-12-01

    Full Text Available N-alkylphenothiazines (NAPTZs are biologically active heterocyclic compounds that find extensive applications in the field of medicine. In the pharmaceutical industry, they are used as psychotherapeutic, antiemetic, and antihistaminic drugs. In this study, complexation reactions of mercuric bromide with NAPTZs as principal ligands have been investigated in MeOH medium. Five mercuric bromide complexes of the NAPTZ ligands namely, chlorpromazine hydrochloride (CP.HCl, promethazine hydrochloride (PM.HCl, ethopropazine hydrochloride (EP.HCl, trifluoperazine dihydrochloride (TF.2HCl and thioridazine hydrochloride (TR.HCl have been synthesized. These complexes were subjected to elemental analysis, solubility, molar conductance and magnetic susceptibility, U.V-Vis, I.R, and NMR spectroscopy. The molecular formulations of the complexes have been found to be: [HgBr2(CP2].4H2O; [HgBr2(PM2].2H2O; [HgBr2(EP2]; [HgBr2(TF2].2H2O and [HgBr2(TR2]. Tentative molecular structures have been proposed and presented.

  6. Binding of anti-prion agents to glycosaminoglycans: Evidence from electronic absorption and circular dichroism spectroscopy

    International Nuclear Information System (INIS)

    The polyanionic glycosaminoglycans (GAGs) are intimately involved in the pathogenesis of protein conformational disorders such as amyloidosis and prion diseases. Several cationic agents are known to exhibit anti-prion activity but their mechanism of action is poorly understood. In this study, UV absorption and circular dichroism (CD) spectroscopic techniques were used to investigate the interaction between heparin and chondroitin-6-sulfate and anti-prion drugs including acridine, quinoline, and phenothiazine derivatives. UV band hypochromism of (±)-quinacrine, (±)-primaquine, tacrine, quinidine, chlorpromazine, and induced CD spectra of (±)-quinacrine upon addition of GAGs provided evidence for the GAG binding of these compounds. The association constants (∼106-107 M-1) estimated from the UV titration curves show high-affinity drug-heparin interactions. Ionic strength-dependence of the absorption spectra suggested that the interaction between GAGs and the cationic drugs is principally electrostatic in nature. Drug binding differences of heparin and chondroitin-6-sulfate were attributed to their different negative charge density. These results call the attention to the alteration of GAG-prion/GAG-amyloid interactions by which these compounds might exert their anti-prion/anti-amyloidogenic activities

  7. 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.

  8. 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.

  9. Most drugs that reverse multidrug resistance also inhibit photoaffinity labeling of P-glycoprotein by a vinblastine analog

    Energy Technology Data Exchange (ETDEWEB)

    Akiyama, S.; Cornwell, M.M.; Kuwano, M.; Pastan, I.; Gottesman, M.M.

    1988-02-01

    Multidrug-resistant human KB carcinoma cells express a 170,000-dalton membrane glycoprotein (P-glycoprotein) that can be photoaffinity labeled with the vinblastine analog N-(p-azido-(3-/sup 125/I)salicyl)-N'-(beta-aminoethyl)vindesine. Several agents that suppress the multidrug-resistant phenotype, including N-solanesyl-N,N'-bis(3,4-dimethylbenzyl)ethylenediamine, cepharanthine, quinidine, and reserpine, were found to inhibit photolabeling of P-glycoprotein at doses comparable to those that reverse multidrug resistance. However, the phenothiazines chlorpromazine and trifluoperazine, which also effectively reverse multidrug resistance, were poor inhibitors of the photoaffinity labeling of P-glycoprotein. Chloroquine, propranolol, or atropine, which only partially reversed the drug resistance, also did not inhibit photolabeling. Naphthalene sulfonamide calmodulin inhibitors, W7 and W5, as well as many other drugs that did not circumvent multidrug resistance, did not inhibit photolabeling. These studies suggest that most, but not all, agents that phenotypically suppress multidrug resistance also inhibit drug binding to a site on P-glycoprotein with which a photoaffinity analog of vinblastine interacts.

  10. 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.

  11. Genetic analysis of ryanodine receptor 1 gene and carnitine palmitoyltransferase II gene: an autopsy case of neuroleptic malignant syndrome related to vegetamin.

    Science.gov (United States)

    Matsusue, Aya; Hara, Kenji; Kageura, Mitsuyoshi; Kashiwagi, Masayuki; Lu, Wang; Ishigami, Akiko; Gotohda, Takako; Tokunaga, Itsuo; Nisimura, Akiyoshi; Sugimura, Tomoko; Kubo, Shin-ichi

    2009-04-01

    We report an autopsy case of a man in his forties who died 2 days after taking an overdose of vegetamin. The autopsy findings were as follows: externally, the upper epidermis of some parts of the body had become loosened. The epidermis was easily detached from the dermis using the fingers. Viscous fluid adhered around the nose and mouth. The brain was edematous and weighed 1520 g. Skeletal muscle was discolored. The urine was a slightly red-tinged yellow. The organs showed congestion. Urine tests: urea nitrogen: 1.95 g/day; creatinine: 0.66 g/day; urine myoglobin: 1100 ng/mL. Blood level of drugs: phenobarbital: 38.2 microg/ml; promethazine: 2.22 microg/ml; chlorpromazine: 0.96 microg/ml. Immunohistochemistry identified myoglobin in the kidney. From these findings, his cause of death was considered to be vegetamin-induced neuroleptic malignant syndrome and rhabdomyolysis. Mutation of the ryanodine receptor 1 gene is associated with malignant hyperthermia. However, there was no mutation which causes amino acid substitution in the three hot-spot regions of the ryanodine receptor 1 gene. Partial deficiency of carnitine palmitoyltransferase II is the commonest cause of recurrent rhabdomyolysis in adults. The subject was found to be heterozygous for an amino acid exchange in exon 4, (1203)G-->A causing a (368)Val-->Ile amino acid substitution. It is necessary to examine other candidate gene mutations. PMID:19269221

  12. 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.

  13. 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.

  14. 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. PMID:22344494

  15. 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. PMID:20873698

  16. 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. PMID:26559224

  17. Effects of Three Different Fibrates on Intrahepatic Cholestasis Experimentally Induced in Rats

    Directory of Open Access Journals (Sweden)

    Alaa El-Sisi

    2013-01-01

    Full Text Available Background. Activation of PPARα modulates cholesterol metabolism and suppresses bile acid synthesis. This study aims to evaluate the effect of PPARα agonists, fenofibrate, bezafibrate, and gemfibrozil, on acute cholestasis induced by ethinylestradiol (EE plus chlorpromazine (CPZ in rats. Method. 100 male albino rats (150–200 gm were divided randomly into 10 equal groups. Control group received 1% methylcellulose vehicle; disease group received CPZ plus EE for 5 consecutive days; four groups received either ursodeoxycholic acid, fenofibrate, bezafibrate, or gemfibrozil for 7 days; 2 days before EE + CPZ, three other groups received one of the three fibrates after GW6471, a selective PPARα antagonist in addition to EE + CPZ. The final group received GW6471 alone. Results. The three fibrates showed marked reduction ( in serum levels of ALP, GGT, ALT, AST, total bile acids, bilirubin, TNFα, and IL-1β and in hepatic malondialdehyde level as well as a significant increase in bile flow rate ( in addition to improvements in histopathological parameters compared to diseased group. In groups which received GW6471, these effects were completely abolished with fenofibrate and partially blocked with bezafibrate and gemfibrozil. Conclusion. Short-term administration of fibrates to EE/CPZ-induced intrahepatic cholestatic rats exerted beneficial effects on hepatocellular damage and apoptosis. Fenofibrate anticholestatic effect was solely PPARα dependent while other mechanisms played part in bezafibrate and gemfibrozil actions.

  18. 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.

  19. 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.

  20. Dosimetric implications of new compounds for neutron capture therapy (NCT)

    Energy Technology Data Exchange (ETDEWEB)

    Fairchild, R.G.

    1982-01-01

    Systemic application of radiolabeled or cytotoxic agents should allow targeting of primary and metastatic neoplasms on a cellular level. In fact, drug uptake in non-target cell pools often exceeds toxic levels before sufficient amounts are delivered to tumor. In addition, at the large concentration of molecules necessary for therapy, effects of saturation are often found. Application of NCT can circumvent problems associated with high uptake in competing non-target cell pools, as the /sup 10/B(n,..cap alpha..)/sup 7/Li reaction is activated only within the radiation field. A comparison with other modes of particle therapy indicated that NCT provides significant advantages. It is however, difficult to obtain vehicles for boron transport which demonstrate both the tumor specificity and concentration requisite for NCT. A number of biomolecules have been investigated which show both the necessary concentration and specificity. These include chlorpromazine, thiouracil, porphyrins, amino acids, and nucleosides. However, these analogs have yet to be made available for NCT. Dosimetric implications of binding sites are considered, as well as alternate neutron sources. (ERB)

  1. Phenothiazines inhibit copper and endothelial cell-induced peroxidation of low density lipoprotein. A comparative study with probucol, butylated hydroxytoluene and vitamin E.

    Science.gov (United States)

    Breugnot, C; Mazière, C; Salmon, S; Auclair, M; Santus, R; Morlière, P; Lenaers, A; Mazière, J C

    1990-11-01

    The effect of two phenothiazines, chlorpromazine (CPZ) and trifluoperazine (TFP) on the copper and endothelial cell-induced peroxidation of low density lipoprotein (LDL) has been studied and compared to that of drugs previously shown to protect LDL against peroxidation: probucol (PBC) and butylated hydroxytoluene (BHT). Incubation with CPZ or TFP inhibited in a dose-dependent manner LDL peroxidation induced either by copper ions or by cultured endothelial cells. Both the electrophoretic mobility and the thiobarbituric reactive substance content of LDL returned to almost normal values in the presence of 50 microM CPZ or TFP. The two studied phenothiazines also strongly inhibited the hydrolysis of LDL phosphatidylcholine which accompanies copper or endothelial cell-induced peroxidation of the particle. CPZ and TFP were as effective as PBC and BHT in inhibiting the LDL peroxidation. Whereas copper or endothelial cell-oxidized LDL were recognized and rapidly catabolized by mouse peritoneal macrophages, CPZ- or TFP-, as well as PBC- or BHT-treated LDL were not. Moreover, it was found that, in contrast to vitamin E, neither CPZ nor PBC reacted with model peroxy radicals formed by gamma irradiation of aerated ethanol. The possible mechanisms underlying this protective effect of phenothiazines against LDL oxidative modification are discussed. PMID:2242028

  2. [A case of acute renal failure in neuroleptic malignant syndrome associated with rhabdomyolysis--possible contributing role of hyperreninemia].

    Science.gov (United States)

    Fujisawa, K; Maruyama, Y; Nakamura, K; Nagase, M

    1994-10-01

    A schizophrenic woman, aged 45, was admitted complaining of high fever, oliguria, blackish urine, muscle swelling and pain. She had been treated for the past 3 years with haloperidol (8 mg), levomepromazine (150 mg), chlorpromazine (75 mg), lithium carbonate (600 mg), bromocriptine mesilate (7.5 mg), etizolam (1 mg), and flunitrazepam (2 mg), Physical examination revealed her to be an obese and uncommunicatable woman with swelling and weakness of the extremities and abdominal distension without borborygmus. Urine was dark brown and (+) for protein and occult blood. Blood chemistry analysis revealed BUN 71 mg/dl, creatinine 6.8 mg/dl, CPK 143,850 IU and myoglobin 3,980 ng/ml. PRA on the 11th hospital day was 96 ng/ml/hour. This patient fulfilled the Levenson's diagnostic criteria for manifestations of neuroleptic malignant syndrome (NMS). High PRA did not decrease after cessation of the diuretics. After treatment with dantrolene sodium and 10 treatments with hemodialysis, azotemia disappeared with the start of diuresis. The PRA also decreased to the normal level. Characteristic acceleration of the central sympathetic stimuli in NMS seemed to have induced hyperreninemia, which together with rhabdomyolysis, might have contributed to the development of acute renal failure. PMID:7815749

  3. Effects of psychotropic drugs on the rage responses induced by electrical stimulation of the medial hypothalamus in cats.

    Science.gov (United States)

    Fukuda, T; Tsumagari, T

    1983-08-01

    Effects of psychotropic drugs on the rage responses induced by electrical stimulation were investigated in cats with electrodes chronically implanted in the medial hypothalamus. Diazepam produced marked elevation in the threshold for directed attack and slight elevation in that for hissing. The inhibitory effect of etizolam on hissing was about 6 times as potent as that of diazepam. Anti-anxiety drugs such as diazepam, nitrazepam, lorazepam, clotiazepam and etizolam produced marked elevation in the directed attack threshold dose-dependently. The effect of chlorpromazine on directed attack was far less potent than that of anti-anxiety drugs. The anti-anxiety drugs used in this experiment had anti-pentetrazol activity in mice as well as muscle relaxant activity in cats. There were close correlations between the directed attack inhibition produced by the anti-anxiety drugs and both anti-pentetrazol activity and muscle relaxant activity. These results indicate that the above anti-anxiety drugs have a more potent inhibitory effect on the function of the medial hypothalamus than neuroleptic drugs. The inhibitory effect of anti-anxiety drugs on directed attack may be considered to correlate with clinical anti-anxiety effects. PMID:6632385

  4. [Effects of psychotropic drugs on lateral hypothalamic self-stimulation behavior in rats: correlation between self-stimulation behavior inhibition and striatal dopaminergic blockade by neuroleptic drugs].

    Science.gov (United States)

    Fukuda, T; Tsumagari, T

    1984-06-01

    The effects of neuroleptic drugs on self-stimulation behavior were investigated in rats with electrodes chronically implanted in the lateral hypothalamus. Except for sulpiride and carpipramine, the neuroleptic drugs chlorpromazine, thioridazine, perphenazine, haloperidol, floropipamide, pimozide, clocapramine and oxypertine all suppressed self-stimulation behavior dose-dependently. The anti-anxiety drugs chlordiazepoxide, diazepam, clotiazepam and etizolam facilitated this behavior. The antidepressant drugs imipramine and amitriptyline suppressed this behavior slightly at the dose of 40 mg/kg. The alpha-antagonist phenoxybenzamine also suppressed this behavior, but the slope of its dose-response curve was gentle compared with those of the neuroleptic drugs. The inhibition produced by the neuroleptic drugs is considered to be mediated primarily at the dopaminergic receptors. Turning behavior induced by methamphetamine in rats with unilateral 6-hydroxydopamine lesions of the caudate nucleus was used to assess the striatal dopaminergic blocking potency of the neuroleptic drugs. No correlation was found between the ED50 values for the turning behavior inhibition and the ED50 values for the self-stimulation behavior inhibition produced by these drugs, so the dopaminergic receptors in the striatum are apparently not involved in the mediation of self-stimulation behavior. PMID:6149172

  5. Egg drop syndrome virus enters duck embryonic fibroblast cells via clathrin-mediated endocytosis.

    Science.gov (United States)

    Huang, Jingjing; Tan, Dan; Wang, Yang; Liu, Caihong; Xu, Jiamin; Wang, Jingyu

    2015-12-01

    Previous studies of egg drop syndrome virus (EDSV) is restricted to serological surveys, disease diagnostics, and complete viral genome analysis. Consequently, the infection characteristics and entry routes of EDSV are poorly understood. Therefore, we aimed to explore the entry pathway of EDSV into duck embryonic fibroblast (DEF) cells as well as the infection characteristics and proliferation of EDSV in primary DEF and primary chicken embryo liver (CEL) cells. Transmission electron microscopy revealed that the virus triggered DEF cell membrane invagination as early as 10 min post-infection and that integrated endocytic vesicles formed at 20 min post-infection. The virus yield in EDSV-infected DEF cells treated with chlorpromazine (CPZ), sucrose, methyl-β-cyclodextrin (MβCD), or NH4Cl was measured by quantitative real-time PCR. Compared with the mock treatment, CPZ and sucrose greatly inhibited the production of viral progeny in a dose-dependent manner, while MβCD treatment did not result in a significant difference. Furthermore, NH4Cl had a strong inhibitory effect on the production of EDSV progeny. In addition, indirect immunofluorescence demonstrated that virus particles clustered on the surface of DEF cells treated with CPZ or sucrose. These results indicate that EDSV enters DEF cells through clathrin-mediated endocytosis followed by a pH-dependent step, which is similar to the mechanism of entry of human adenovirus types 2 and 5. PMID:26200954

  6. Assay for the detection of non-lethal changes that are expressed as a proliferative disadvantage in mouse (Mus musculus) embryo aggregation chimberas

    International Nuclear Information System (INIS)

    This study demonstrates the potential utility of the chimera embryo assay in measuring the effects of a variety of non-lethal, potentially hazardous environmental agents on normal mammalian embryonic cells. The two major findings to have emerged from this investigation are, (1) relative cellular contribution per embryo in chimeras was found to depend on the strain of the partner embryo and this relationship apparently does not require cell to cell contact between the partner embryos of the chimera and is already apparent after only two cell cycles; and (2) within the same outbred strain, exposure of one partner embryo in the chimera to either X-irradiation or chlorpromazine, at dose levels that were lower than those previously found to be embryotoxic; such toxicity was revealed as a proliferative disadvantage that was also evident after only 2 cell cycles. Partner embryos in the chimera were distinguished by labelling one of them with the fluorescent dye, fluorescein isothiocyanate (FITC), which was shown to have no detrimental effects on the proliferation rate of the labelled embryos

  7. [Chemotherapies of negative schizophrenia].

    Science.gov (United States)

    Petit, M; Dollfus, S

    1991-01-01

    Five years ago, Goldberg claimed that negative symptoms of schizophrenia do respond to neuroleptics. This apparent discovery is, in fact, a very common way of thinking for European schools of psychiatry, specially the French one guided by Delay and Deniker. Initially focused on reserpine and some alerting phenothiazines such as thioproperazine, this opinion has been extended to benzamides in the 1970s. The analysis of the publications devoted to this point indicates that several drugs are actually considered as potent disinhibitors (i.e. active on negative symptoms of schizophrenia): Phenothiazines: As shown in the controlled studies by Itil (1971), Poirier-Littré (1988), fluphenazine and pipotiazine improve the BPRS anergia factor and the SANS score. Butyrophenones: The first description of the "imipramine like" effect of trifluperidol by Janssen (1959) initiated the studies by Gallant (1960), Fox (1963). They compared trifluperidol at low doses versus haloperidol and chlorpromazine at medium and high doses, BPRS anergia factor improved only at low doses. Diphenylbutylpiperidines (DPBP): Meltzer's review (1986) concluded to the efficacy of such drugs on negative symptoms appearing as a specific biochemical relationship effect. A definite analysis about doses leads to a very different interpretation: DPBP low doses and only low doses improved negative symptoms as much as some low doses of phenothiazines. On the opposite, DPBP, phenothiazines and butyrophenones high doses are inefficient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1683624

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

    International Nuclear Information System (INIS)

    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.

  9. Molecular characterization of a rat α2B-adrenergic receptor

    International Nuclear Information System (INIS)

    α2-Adrenergic receptors comprise a heterogeneous population based on pharmacologic and molecular evidence. The authors have isolated a cDNA clone (pRNGα2) encoding a rat α2-adrenergic receptor. A rat kidney cDNA library was screened with an oligonucleotide complementary to a highly conserved region found in all biogenic amine receptors described to date. The deduced amino acid sequence displays many features of guanyl nucleotide-binding protein-coupled receptors except it does not have a consensus N-linked glycosylation site near the amino terminus. Membranes prepared from COS cells transfected with pRNGα2 DNA display high affinity an saturable binding to [3H]rauwolscine. Competition curve data analysis shows that RNGα2 protein binds to a variety of adrenergic drugs with the following rank order of potency: yohimbine ≥ chlorpromazine > prazosin ≥ clonidine > norepinephrine ≥ oxymetazoline. RNGα2 RNA accumulates in both rat kidney and neonatal rat lung. When a cysteine residue (Cys-169) that is conserved among all members of the seven-transmembrane-region superfamily is changed to phenylalanine, the RNGα2 protein fails to bind [3H]rauwolscine after expression in COS cells. They conclude that pRNGα2 likely represents a cDNA for a rat α2B-adrenergic receptor

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. [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.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Gene expression profiling in rat liver treated with compounds inducing phospholipidosis

    International Nuclear Information System (INIS)

    We have constructed a large-scale transcriptome database of rat liver treated with various drugs. In an effort to identify a biomarker for diagnosis of hepatic phospholipidosis, we extracted 78 probe sets of rat hepatic genes from data of 5 drugs, amiodarone, amitriptyline, clomipramine, imipramine, and ketoconazole, which actually induced this phenotype. Principal component analysis (PCA) using these probes clearly separated dose- and time-dependent clusters of treated groups from their controls. Moreover, 6 drugs (chloramphenicol, chlorpromazine, gentamicin, perhexiline, promethazine, and tamoxifen), which were reported to cause phospholipidosis but judged as negative by histopathological examination, were designated as positive by PCA using these probe sets. Eight drugs (carbon tetrachloride, coumarin, tetracycline, metformin, hydroxyzine, diltiazem, 2-bromoethylamine, and ethionamide), which showed phospholipidosis-like vacuolar formation in the histopathology, could be distinguished from the typical drugs causing phospholipidosis. Moreover, the possible induction of phospholipidosis was predictable by the expression of these genes 24 h after single administration in some of the drugs. We conclude that these identified 78 probe sets could be useful for diagnosis of phospholipidosis, and that toxicogenomics would be a promising approach for prediction of this type of toxicity

  15. Gene expression profiling in rat liver treated with compounds inducing phospholipidosis.

    Science.gov (United States)

    Hirode, Mitsuhiro; Ono, Atsushi; Miyagishima, Toshikazu; Nagao, Taku; Ohno, Yasuo; Urushidani, Tetsuro

    2008-06-15

    We have constructed a large-scale transcriptome database of rat liver treated with various drugs. In an effort to identify a biomarker for diagnosis of hepatic phospholipidosis, we extracted 78 probe sets of rat hepatic genes from data of 5 drugs, amiodarone, amitriptyline, clomipramine, imipramine, and ketoconazole, which actually induced this phenotype. Principal component analysis (PCA) using these probes clearly separated dose- and time-dependent clusters of treated groups from their controls. Moreover, 6 drugs (chloramphenicol, chlorpromazine, gentamicin, perhexiline, promethazine, and tamoxifen), which were reported to cause phospholipidosis but judged as negative by histopathological examination, were designated as positive by PCA using these probe sets. Eight drugs (carbon tetrachloride, coumarin, tetracycline, metformin, hydroxyzine, diltiazem, 2-bromoethylamine, and ethionamide), which showed phospholipidosis-like vacuolar formation in the histopathology, could be distinguished from the typical drugs causing phospholipidosis. Moreover, the possible induction of phospholipidosis was predictable by the expression of these genes 24 h after single administration in some of the drugs. We conclude that these identified 78 probe sets could be useful for diagnosis of phospholipidosis, and that toxicogenomics would be a promising approach for prediction of this type of toxicity. PMID:18355885

  16. Formation and reactivity of phenylperoxyl radicals in aqueous solutions

    International Nuclear Information System (INIS)

    The reaction of phenyl radicals with oxygen, to produce phenylperoxyl radicals, and the reactions of several phenylperoxyl radicals with a number of organic compounds in aqueous solutions have been studied by pulse radiolysis. Phenyl radicals were produced by reduction of aryl halides with hydrated electrons. The rate constant for the reaction of 4-carboxyphenyl with O2 was determined from the rate of buildup of the peroxyl radical absorption at 520 nm as a function of [O2] and found to be 1.6 x 109 L mol-1 s-1. Phenyl radicals react with 2-PrOH by H abstraction; a rate constants of 4 x 106 L mol-1 s-1 was determined for 4-carboxyphenyl by competition with the reaction of this radical with O2. Phenylperoxyl radicals react with 4-methoxyphenolate ions, trolox C(6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), ascorbate ions, chlorpromazine, and ABTS [2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate ion)] by one-electron oxidation. The rate constants for such reactions, determined from the rate of formation of the one-electron oxidation product as a function of substrate concentration, were found to be near 108-109 L mol-1 s-1. 24 refs., 4 figs., 1 tab

  17. Drug-induced hepatotoxicity in a tertiary care hospital in Rural South India

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    Heethal Jaiprakash

    2012-01-01

    Full Text Available Background: Liver is the main organ for metabolism of drugs and hepatotoxicity is a potential adverse effect for most drugs. Aims: This study was to study the frequency of drug-induced hepatotoxicity and to find the common drugs causing hepatotoxicity. Materials and Methods: The study was conducted at a tertiary care hospital in rural India. It is a study based on case series analysis. All patients with an abnormal liver function report, between July 2006 and July 2007, were included in the study. Results : The study included 411 patients. Among them 141 patients were females and 270 males. The common cause for abnormal liver function was alcoholic liver disease (30.4% followed by drug-induced hepatotoxicity (15.8% and malaria (15.3%. Drug-induced hepatotoxicity was seen in 65 patients. It was common in males (55% compared to females (44%. The mean age of the patients with drug-induced hepatotoxicity was 43±15.9. Antitubercular drugs were the commonly encountered drugs (44% causing hepatotoxicity followed by lipid lowering agents (41%. The others drugs included antiretroviral drugs (6%,steroids (5% and chlorpromazine (2%. Conclusion : A thorough history of drug intake must be taken in all patients presenting with abnormal hepatic function.

  18. Effects of certain muscarinic antagonists on the actions of anticholinesterases on cat skeletal muscle.

    Science.gov (United States)

    Brimblecombe, R W; French, M C; Webb, S N

    1979-04-01

    1. The effects of some muscarinic antagonists, namely, N-ethyl-2-pyrrolidylmethyl-cyclopentylphenyl glycollate (PMCG), N-methyl-4-piperidyl-phenylcyclohexyl glycollate (PPCG, racemate and R and S enantiomers) and 4'-N-methyl-piperidyl-1-phenyl-cyclopentane carboxylate (G3063) on organophosphate (sarin, soman)- and carbamate (neostigmine)-induced twitch augmentation have been studied in cat soleus muscle. 2. The results of a preliminary study comparing the potency of sarin and soman in inhibiting the acetylcholinesterase activity of muscle in relation to the effect on the maximal twitch response indicated that there is not a simple relationship between degree of enzyme inhibition by these drugs and alteration of muscle function. 3. The muscarinic antagonists studied were capable of preventing or reversing sarin-, soman- or neostigmine-induced twitch augmentation. Doses sufficient to give complete protection from the effects of the anticholinesterase agents had little or no effect on the twitch response of normal muscle. 4. The protective action of these muscarinic antagonists is dose-dependent but independent of known antagonist actions at muscarinic receptors. 5. The effects of some local anaesthetics (lignocaine, prilocaine, cinchocaine, procaine) and other membrane stabilizers (quinine, ketamine, chlorpromazine, triflupromazine) were compared with those of the muscarinic antagonists in an attempt to elucidate the mode of action of these acetylcholine antagonists. The evidence is insufficient to exclude the involvement of a membrane stabilizing action. PMID:435681

  19. 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.

  20. 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).

  1. The effect of estrogen administration on the level of various binding proteins in animal plasma and their use in radioassays

    International Nuclear Information System (INIS)

    The main goal of the work carried out was to check if it will be possible to use in the radioassay of thyroxine the animal serum as a source of thyroxine binding proteins. The results of experimental studies showed that the human and animal sera treated with Merthiolate, ANS, Salicylate, Diphenylhydantoin, Chlorpromazine, Trifluoroperazine, Phenylbutazone, and Urea behave in different ways. For example, Merthiolate in concentration 1.73 x 10-3M reduced the thyroxine binding capacity of human serum by 2.4% and of sheep serum by 17.5% of their original level. Knowing that, it was possible to prepare the standard curve using sheep serum and increasing quantities of thyroxine. The author observed also that urea in various concentrations and pH caused irreversible denaturation of human serum thyroxine binding proteins and this denaturation could be controlled. On the basis of this finding it was possible to develop a normalized thyroxine assay in which no extraction step is needed

  2. Cost prediction of antipsychotic medication of psychiatric disorder using artificial neural network model

    Directory of Open Access Journals (Sweden)

    Arash Mirabzadeh

    2013-01-01

    Full Text Available Background: Antipsychotic monotherapy or polypharmacy (concurrent use of two or more antipsychotics are used for treating patients with psychiatric disorders (PDs. Usually, antipsychotic monotherapy has a lower cost than polypharmacy. This study aimed to predict the cost of antipsychotic medications (AM of psychiatric patients in Iran. Materials and Methods: For this purpose, 790 patients with PDs who were discharged between June and September 2010 were selected from Razi Psychiatric Hospital, Tehran, Iran. For cost prediction of AM of PD, neural network (NN and multiple linear regression (MLR models were used. Analysis of data was performed with R 2.15.1 software. Results: Mean ± standard deviation (SD of the duration of hospitalization (days in patients who were on monotherapy and polypharmacy was 31.19 ± 15.55 and 36.69 ± 15.93, respectively (P < 0.001. Mean and median costs of medication for monotherapy (n = 507 were $8.25 and $6.23 and for polypharmacy (n =192 were $13.30 and $9.48, respectively (P = 0.001. The important variables for cost prediction of AM were duration of hospitalization, type of treatment, and type of psychiatric ward in the MLR model, and duration of hospitalization, type of diagnosed disorder, type of treatment, age, Chlorpromazine dosage, and duration of disorder in the NN model. Conclusion: Our findings showed that the artificial NN (ANN model can be used as a flexible model for cost prediction of AM.

  3. Determination of Drugs in Plasma Samples by High-Performance Liquid Chromatography-Tandem Mass Spectrometry for Therapeutic Drug Monitoring of Schizophrenic Patients.

    Science.gov (United States)

    Domingues, Diego Soares; Pinto, Mônia Aparecida Lemos; de Souza, Israel Donizeti; Hallak, Jaime Eduardo Cecilio; Crippa, José Alexandre de Souza; Queiroz, Maria Eugênia Costa

    2016-01-01

    This work describes the development of a simple, sensitive and selective method based on high-performance liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) to determine antipsychotics (olanzapine, quetiapine, clozapine, haloperidol and chlorpromazine) along with antidepressants (mirtazapine, paroxetine, citalopram, sertraline, imipramine, clomipramine and fluoxetine), anticonvulsants (carbamazepine and lamotrigine) and anxiolytics (diazepam and clonazepam) in plasma samples obtained from schizophrenic patients. The samples were prepared by protein precipitation. The target drugs were separated on an XSelect SCH C18 column (100 mm × 2.1 mm × 2.5 µm) within 8.0 min by means of gradient elution. The drugs were then detected on a quadrupole tandem mass spectrometer equipped with an electrospray ionization source, operating in the multiple reactions monitoring mode and in the positive ionization mode. The LC-MS-MS method was linear range from subtherapeutic to toxic concentrations with lower limit of quantification values ranged from 0.2 to 5.0 ng mL(-1), precision with coefficient of variation values lower than 12%, and accuracy ranged from 90 to 108%. The developed method enabled successful analysis of the target drugs in plasma samples obtained from 51 schizophrenic patients. Therapeutic drug monitoring revealed that many of the evaluated schizophrenic patients presented altered plasma concentrations of the analyzed drugs. These altered concentrations resulted from pharmacokinetic interactions among the medications prescribed to treat schizophrenia. PMID:26333987

  4. 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. PMID:25627815

  5. Antipsychotic drug-induced hematologic disorders

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    Theocharis Kyziridis

    2014-01-01

    Full Text Available Over half a century after the discovery of chlorpromazine and haloperidol, antipsychotic drugs showed a true evolutionary revolution. The knowledge of their adverse effects is of outmost importance as it may contribute to the prevention of unwanted sequelae, to the decrease of the duration and cost of hospitalization, it may improve the quality of life of patients, minimize the problems and maximize the therapeutic gain. Aim: The aim of this review was the presentation of the hematologic side-effects of antipsychotic drugs, and most particularly their frequency and association with the different classes of these drugs, their clinical picture and their pathophysiologic mechanisms. Material-method: This paper is a review of the literature (mainly articles from journals, PubMed, as well as books and monographs of the period 1978-2012. Key-words used included antipsychotics, hematologic adverse effects, drug-induced adverse effects. Results: Antipsychotic-drug induced hematologic side-effects are not particularly highly prevalent, while many of them are found in case reports. For this reason they have not drawn much of attention. These hematologic dyscrasias may concern all the blood cell series as well as the coagulation mechanism. Excluded from this rule is the case of clozapine-induced agranulocytosis, which demands increased clinical vigilance. In fact, agranulocytosis was the reason why the drug was drawn away from circulation approximately 35 years ago. Conclusions: In any case the appearance of a hematologic disorder in a patient receiving antipsychotic medications should prompt careful evaluation.

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

    Directory of Open Access Journals (Sweden)

    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

  7. 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.

  8. Patch photopatch test at Manipal

    Directory of Open Access Journals (Sweden)

    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.

  9. 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.

  10. 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.

  11. 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.

  12. Synthesis and cellular uptake of folic acid-conjugated cellulose nanocrystals for cancer targeting.

    Science.gov (United States)

    Dong, Shuping; Cho, Hyung Joon; Lee, Yong Woo; Roman, Maren

    2014-05-12

    Elongated nanoparticles have recently been shown to have distinct advantages over spherical ones in targeted drug delivery applications. In addition to their oblong geometry, their lack of cytotoxicity and numerous surface hydroxyl groups make cellulose nanocrystals (CNCs) promising drug delivery vectors. Herein we report the synthesis of folic acid-conjugated CNCs for the targeted delivery of chemotherapeutic agents to folate receptor-positive cancer cells. Folate receptor-mediated cellular binding/uptake of the conjugate was demonstrated on human (DBTRG-05MG, H4) and rat (C6) brain tumor cells. Folate receptor expression of the cells was verified by immunofluorescence staining. Cellular binding/uptake of the conjugate by DBTRG-05MG, H4, and C6 cells was 1452, 975, and 46 times higher, respectively, than that of nontargeted CNCs. The uptake mechanism was determined by preincubation of the cells with the uptake inhibitors chlorpromazine or genistein. DBTRG-05MG and C6 cells internalized the conjugate primarily via caveolae-mediated endocytosis, whereas H4 cells internalized the conjugate primarily via clathrin-mediated endocytosis. PMID:24716601

  13. Cllmodulin in tip-growing plant cells, visualized by fluorescing calmodulin-binding phenothiazines.

    Science.gov (United States)

    Haußer, I; Herth, W; Reiss, H D

    1984-09-01

    Calmodulin (CaM) was visualized light-microscopically by the fluorescent CaM inhibitors fluphenazine and chlorpromazine, both phenothiazines, during polar tip growth of pollen tubes of Lilium longiflorum, root hairs of Lepidium sativum, moss caulonema of Funaria hygrometrica, fungal hyphae of Achlya spec. and in the alga Acetabularia mediterranea, as well as during multipolar tip growth in Micrasterias denticulata. Young pollen tubes and root hairs showed tip fluorescence; at later stages and in the growing parts of the other subjects the fluorescence was almost uniform. After treatment with cytochalasin B, punctuate fluorescence occurred in the clear zone adjacent to the tip of pollen tubes. The observations indicate that there is CaM in all our tested systems detectable with this method. It may play a key role in starting polar growth. As in pollen tubes, CaM might be in part associated with the microfilament network at the tip, and thus regulate vesicle transport and cytoplasmic streaming. PMID:24253945

  14. The role of pharmacotherapy in anorexia nervosa and bulimia.

    Science.gov (United States)

    Tolstoi, L G

    1989-11-01

    The purpose of this article is to review the basic pharmacology and the role of drugs that are used to treat anorexia nervosa and bulimia. The pharmacological treatment of eating disorders is based upon theoretical principles. The theoretical models include: (a) an illness secondary to other psychiatric disorders, (b) a disorder in the hypothalamic control of food intake, (c) a disorder of hypothalamic endocrine regulation, (d) a syndrome secondary to depressive illness, and (e) a disorder in the hypothalamic regulation of food intake. Theoretical models a, b, and c govern the choice of drug therapy for anorexia nervosa, and models d and e govern the choice of drug therapy for bulimia. Drugs used to treat anorexia nervosa and bulimia include tricyclic antidepressants and lithium carbonate. Chlorpromazine, metoclopramide, cyproheptadine, and clomiphene citrate have also been prescribed for the treatment of anorexia nervosa. Monoamine oxidase inhibitors are commonly prescribed to treat bulimia. Fenfluramine has the potential to be of therapeutic value in patients with bulimia. Although drug therapy plays a limited role in the treatment of eating disorders, drugs are commonly prescribed. Therefore, the nutritionist should be familiar with the basic pharmacology and the side effects related to drug therapy. PMID:2572619

  15. 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.

  16. Modulation of visceral nociception, inflammation and gastric mucosal injury by cinnarizine.

    Science.gov (United States)

    Abdel-Salam, Omar M E

    2007-01-01

    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 (K(ATP)) 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-inflammatory, antinociceptive and gastric protective properties. The mechanism by which cinnarizine modulates pain transmission is likely to involve adenosine receptors and K(ATP) channels. PMID:21901060

  17. Pharmacokinetics and interactions of headache medications, part I: introduction, pharmacokinetics, metabolism and acute treatments.

    Science.gov (United States)

    Sternieri, Emilio; Coccia, Ciro Pio Rosario; Pinetti, Diego; Ferrari, Anna

    2006-12-01

    Recent progress in the treatment of primary headaches has made available specific, effective and safe medications for these disorders, which are widely spread among the general population. One of the negative consequences of this undoubtedly positive progress is the risk of drug-drug interactions. This review is the first in a two-part series on pharmacokinetic drug-drug interactions of headache medications. Part I addresses acute treatments. Part II focuses on prophylactic treatments. The overall aim of this series is to increase the awareness of physicians, either primary care providers or specialists, regarding this topic. Pharmacokinetic drug-drug interactions of major severity involving acute medications are a minority among those reported in literature. The main drug combinations to avoid are: i) NSAIDs plus drugs with a narrow therapeutic range (i.e., digoxin, methotrexate, etc.); ii) sumatriptan, rizatriptan or zolmitriptan plus monoamine oxidase inhibitors; iii) substrates and inhibitors of CYP2D6 (i.e., chlorpromazine, metoclopramide, etc.) and -3A4 (i.e., ergot derivatives, eletriptan, etc.), as well as other substrates or inhibitors of the same CYP isoenzymes. The risk of having clinically significant pharmacokinetic drug-drug interactions seems to be limited in patients with low frequency headaches, but could be higher in chronic headache sufferers with medication overuse. PMID:17125411

  18. 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.

  19. 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.

  20. Common solvent toxicity: autoxidation of respiratory redox-cyclers enforced by membrane derangement

    Energy Technology Data Exchange (ETDEWEB)

    Garbe, T.R.; Yukawa, H. [Research Inst. of Innovative Technology for the Earth (RITE), Kyoto (Japan)

    2001-08-01

    Unspecific biological effects of chemically diverse solvents strikingly reveal the unifying motif of oxidant toxicity both in higher organisms and in aerobic bacteria. In a few spectacular cases, solvent metabolites with oxidant properties were demonstrated, which however cannot explain extrahepatic toxicity, e.g. in muscle and nerve cells. A common source of solvent-inducible oxidants, by contrast, is suggested to be located in mitochondria or, more general, in membranes where the respiratory chain operates. Orderly respiration depends on membrane integrity, which is invariably compromised by exposure to most solvents and many other lipophils. In rat mitochondria, toluene-induced membrane derangement has been directly implicated with superoxide production, resulting from autoxidation of the membrane-located respiratory redox-cycler ubisemiquinone. A related mechanism may occur in bacteria: Exposure of Escherichia coli to lipophils such as ethanol, tetralin, indole, chlorpromazine and procaine, or to heat shock, induces anti-oxidant proteins, which are reliable indicators of increased oxidant levels. Although many molecular details remain to be elucidated, this review documents that oxidant toxicity of lipophilic compounds is a common physiological phenomenon correlated with derangement of membranes where respiratory processes take place. Subjective consequences of acute oxidant injury are probably the hangover from alcohol and nicotine consumption, and the sudden death from recreational solvent abuse. Suggestions concerning oxidants as major contributors to ageing remain unchallenged. (orig.)

  1. 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.

  2. Characterization of transport of calcium by microsomal membranes from roots maize

    Energy Technology Data Exchange (ETDEWEB)

    Vaughan, M.A.

    1985-01-01

    This study investigates calcium transport by membranes of roots of maize isolated by differential centrifugation. The preparation was determined to be enriched in plasma membrane using market enzyme and electron microscopy. Using the /sup 45/Ca filtration technique and liquid scintillation counting, vesicular calcium uptake was shown to be stimulated by added calmodulin and specific for and dependent on ATP. Conditions for maximal calcium accumulation were found to be 30 min incubation in the presence of 5 mM ATP, 5 mM MgCl/sub 2/, 50 ..mu..M CaCl/sub 2/, at 23/sup 0/C, and at pH 6.5. Calcium uptake was inhibited by the ionophores A23187, X-537A, and ionomycin. Sodium fluoride, ruthenium red, and p-chloromercuribenzoate completely inhibited transport: diamide and vanadate produced slight inhibition; caffeine, caffeic acid, oligomycin, and ouabain produced little or no inhibition. Chlorpromazine, W7, trifluoperazine, and R 24 571 inhibit calcium uptake irrespective of added calmodulin, while W5 showed little effect on uptake. Verapamil, nifedipine, cinnarizine, flunarizine, lidoflazine, and diltiazem decreased calcium uptake by 17%-50%. Electron microscopic localization of calcium by pyroantimonate showed vesicles incubated with calmodulin and ATP showed the greatest amount of precipitate. These results suggest that these vesicles accumulate calcium in an ATP-dependent, calmodulin-stimulated manner.

  3. 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.

  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. 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

  6. 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

  7. 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

  8. Endocytosis‒Mediated Invasion and Pathogenicity of Streptococcus agalactiae in Rat Cardiomyocyte (H9C2.

    Directory of Open Access Journals (Sweden)

    Sharma Pooja

    Full Text Available Streptococcus agalactiae infection causes high mortality in cardiovascular disease (CVD patients, especially in case of setting prosthetic valve during cardiac surgery. However, the pathogenesis mechanism of S. agalactiae associate with CVD has not been well studied. Here, we have demonstrated the pathogenicity of S. agalactiae in rat cardiomyocytes (H9C2. Interestingly, both live and dead cells of S. agalactiae were uptaken by H9C2 cells. To further dissect the process of S. agalactiae internalization, we chemically inhibited discrete parts of cellular uptake system in H9C2 cells using genistein, chlorpromazine, nocodazole and cytochalasin B. Chemical inhibition of microtubule and actin formation by nocodazole and cytochalasin B impaired S. agalactiae internalization into H9C2 cells. Consistently, reverse‒ transcription PCR (RT‒PCR and quantitative real time‒PCR (RT-qPCR analyses also detected higher levels of transcripts for cytoskeleton forming genes, Acta1 and Tubb5 in S. agalactiae‒infected H9C2 cells, suggesting the requirement of functional cytoskeleton in pathogenesis. Host survival assay demonstrated that S. agalactiae internalization induced cytotoxicity in H9C2 cells. S. agalactiae cells grown with benzyl penicillin reduced its ability to internalize and induce cytotoxicity in H9C2 cells, which could be attributed with the removal of surface lipoteichoic acid (LTA from S. agalactiae. Further, the LTA extracted from S. agalactiae also exhibited dose‒dependent cytotoxicity in H9C2 cells. Taken together, our data suggest that S. agalactiae cells internalized H9C2 cells through energy‒dependent endocytic processes and the LTA of S. agalactiae play major role in host cell internalization and cytotoxicity induction.

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

    Science.gov (United States)

    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

  10. An ATP- and Ca/sup 2 +/-regulated Na/sup +/ channel in isolated intestinal epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Kimmich, G.A.; Randles, J.

    1982-09-01

    When isolated intestinal epithelial cells are treated with 2 mM ATP, the undirectional influx of Na/sup +/ to those cells increases from values near 50 to rates over 200 nmol.min/sup -1/.mg protein/sup -1/. Calcium influx increases from 1 to 40 nmol.min/sup -1/.mg protein/sup -1/. Within 2 min, the total cell Na/sup +/ increases two- to threefold, and total Ca/sup +/ increases about fivefold. The cells lose a major part of their capability for accumulating sugars during this interval. About 2 min after the time of ATP addition the normal permeability for Na/sup +/ and Ca/sup 2 +/ is restored, at which time the previously accumulated ions are rapidly extruded on a net basis until control levels are attained and the cells regain their usual sugar transport capability. The ''repair'' process requires Ca/sup 2 +/ in the incubation medium and is dependent on cellular uptake of Ca/sup 2 +/. Chlorpromazine (0.5 mM) blocks the Ca/sup 2 +/ entry route and the restoration of normal Na/sup +/ permeability. The Na/sup +/ entry route is selectively blocked by 4-acetamido-4'-isocyanostilbene-2,2'-disulfonic acid. The data show that ATP induces the influx of Na/sup +/ and Ca/sup 2 +/ by two different routes, which can be selectively inhibited. These ion flux routes may be involved in the events that allow intestinal tissue to convert from an absorptive state to a state in which net ion secretion occurs.

  11. Electronic micropipettor: A versatile fluid propulsion and injection device for micro-flow analysis

    International Nuclear Information System (INIS)

    The shortage of ready to use small sized liquid propulsion and switching devices for microfluidic cells (μ-cell) is a bottleneck in the dissemination of micro-flow analysis (μ-FA), now that microfluidic electrochemical cells can be designed and assembled in any laboratory by thermal transfer of laser printed masks and CD-Rs. Microprocessor-controlled electronic pipettors, commercially available with minimum capacity of 10 μL, represent a compromise solution between oversized peristaltic pumps and tiny 'on a chip' micropumps and valves. The versatility of the electronic pipette coupled with the μ-cell (13-μm deep longitudinal channel) was demonstrated in three operation modes: SIA like, FIA like and direct injection analysis (DIA). Injections of 100 nL K4Fe(China)6 (0.1 mol L-1 KCl) define a linear analytical curve (r = 0.999) in the range of 5 x 10-7 to 1.0 x 10-3 mol L-1 for flow amperometry at a gold electrode potentiostated at 0.4 V versus Ag/AgCl. Methods for the amperometric μ-flow determination of promethazine (FIA like), dipyrone (SIA like) and chlorpromazine (DIA) in pharmaceutical formulations were developed and applied to real samples. Excellent linearity of analytical curves and high repeatability (R.S.D. < 3.0%) at the low picomole range was obtained and all results for real samples were in agreement with reference methods. The results reflect the stability and the reliability of the setups envisioned for the electronic pipette coupled with amperometric μ-cell and the validity of the μ-FA methods

  12. Impacts and concerns for vCJD in blood transfusion: current status.

    Science.gov (United States)

    MacGregor, I R; Prowse, C V

    2004-06-01

    The impact of vCJD upon blood transfusion practice hinges on its lymphoreticular involvement. B lymphocytes play a key supporting role for the capture and replication of infectivity by follicular dendritic cells of the lymphoid tissue in animal models of transmissible spongiform encephalopathies (TSE) and tonsils, spleen and appendix in man can harbour vCJD infectivity, a situation not seen with the other human TSEs. Leucodepletion of blood donations in the UK was implemented to reduce possible vCJD transmission and preliminary data suggests that white cell associated infectivity will be effectively removed although plasma infectivity will not. Blood screening assays are under development but none yet are ready for application. The conformation dependant immunoassay, based on differences in secondary and tertiary structure between normal and TSE-associated abnormal prion protein, has a sensitivity now approaching the best bioassay. Even so further development is needed to detect the fg/ml levels likely in the event that vCJD blood does contain abnormal prion, which is as yet unproven. Surrogate assays, such as for erythroid associated factor, may provide additional means of identifying donors harbouring vCJD. Validation of clearance of TSEs from pooled plasma products consistently demonstrates effective removal of the agents in downscaled systems and studies comparing vCJD, BSE and scrapie agents yield similar results. Many approaches to therapy are under investigation, in cell culture and animal models, targeted to normal or abnormal prion metabolism, including chemical and immunological interventions. Efficacy of quinacrine/chlorpromazine and pentosan polysulphate in a clinical setting, and agents yet to be used, will be more accurately known following recent agreement of clinical drug evaluation protocols. PMID:15354867

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

    Directory of Open Access Journals (Sweden)

    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.

  14. 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

    Directory of Open Access Journals (Sweden)

    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.

  15. Blocking the PI3K/AKT pathway enhances mammalian reovirus replication by repressing IFN-stimulated genes

    Science.gov (United States)

    Tian, Jin; Zhang, Xiaozhan; Wu, Hongxia; Liu, Chunguo; Li, Zhijie; Hu, Xiaoliang; Su, Shuo; Wang, Lin-Fa; Qu, Liandong

    2015-01-01

    Many host cellular signaling pathways were activated and exploited by virus infection for more efficient replication. The PI3K/Akt pathway has recently attracted considerable interest due to its role in regulating virus replication. This study demonstrated for the first time that the mammalian reovirus strains Masked Palm Civet/China/2004 (MPC/04) and Bat/China/2003 (B/03) can induce transient activation of the PI3K/Akt pathway early in infection in vitro. When UV-treated, both viruses activated PI3K/Akt signaling, indicating that the virus/receptor interaction was sufficient to activate PI3K/Akt. Reovirus virions can use both clathrin- and caveolae-mediated endocytosis, but only chlorpromazine, a specific inhibitor of clathrin-mediated endocytosis, or siRNA targeting clathrin suppressed Akt phosphorylation. We also identified the upstream molecules of the PI3K pathway. Virus infection induced phosphorylation of focal adhesion kinase (FAK) but not Gab1, and blockage of FAK phosphorylation suppressed Akt phosphorylation. Blockage of PI3K/Akt activation increased virus RNA synthesis and viral yield. We also found that reovirus infection activated the IFN-stimulated response element (ISRE) in an interferon-independent manner and up-regulated IFN-stimulated genes (ISGs) via the PI3K/Akt/EMSY pathway. Suppression of PI3K/Akt activation impaired the induction of ISRE and down-regulated the expression of ISGs. Overexpression of ISG15 and Viperin inhibited virus replication, and knockdown of either enhanced virus replication. Collectively, these results demonstrate that PI3K/Akt activated by mammalian reovirus serves as a pathway for sensing and then inhibiting virus replication/infection. PMID:26388843

  16. Antipsychotic Drug-Induced Somnolence: Incidence, Mechanisms, and Management.

    Science.gov (United States)

    Fang, Fang; Sun, Hongwei; Wang, Zuowei; Ren, Ming; Calabrese, Joseph R; Gao, Keming

    2016-09-01

    Somnolence is a common side effect of antipsychotics. To assess the incidence of this side effect, we performed a MEDLINE search for randomized, double-blinded, placebo- or active-controlled studies of adult patients treated with antipsychotics for schizophrenia, mania, bipolar depression, or bipolar disorder. We extracted rates of somnolence from original publications and pooled them based on the dose of each antipsychotic in the same psychiatric condition, then estimated the absolute risk increase (ARI) and the number needed to harm (NNH) of an antipsychotic relative to placebo or an active comparator in the same psychiatric condition. According to the ARI in acute schizophrenia, bipolar mania, and bipolar depression, antipsychotics can be classified as high somnolence (clozapine), moderate somnolence (olanzapine, perphenazine, quetiapine, risperidone, ziprasidone), and low somnolence (aripiprazole, asenapine, haloperidol, lurasidone, paliperidone, cariprazine). The risk of somnolence with blonanserin, brexpiprazole, chlorpromazine, iloperidone, sertindole, and zotepine needs further investigation. The rates of somnolence were positively correlated to dose and duration for some antipsychotics, but not for others. Many factors, including antipsychotic per se, the method used to measure somnolence, patient population, study design, and dosing schedule, might affect the incidence of antipsychotic-induced somnolence. The mechanisms of antipsychotic-induced somnolence are likely multifactorial, although the blockade of histamine 1 receptors and α1 receptors may play a major role. The management of antipsychotic-induced somnolence should include sleep hygiene education, choosing an antipsychotic with a lower risk for somnolence, starting at a lower dose with a slower titration based on psychiatric diagnoses, adjusting doses when necessary, and minimizing concurrent somnolence-prone agents. Since most cases of somnolence were mild to moderate, allowing tolerance to

  17. Expression and characterization of human cytochrome P450 4F11: Putative role in the metabolism of therapeutic drugs and eicosanoids

    International Nuclear Information System (INIS)

    We previously reported the cDNA cloning of a new CYP4F isoform, CYP4F11. In the present study, we have expressed CYP4F11 in Saccharomyces cerevisiae and examined its catalytic properties towards endogenous eicosanoids as well as some clinically relevant drugs. CYP4F3A, also known as a leukotriene B4 ω-hydroxylase, was expressed in parallel for comparative purposes. Our results show that CYP4F11 has a very different substrate profile than CYP4F3A. CYP4F3A metabolized leukotriene B4, lipoxins A4 and B4, and hydroxyeicosatetraenoic acids (HETEs) much more efficiently than CYP4F11. On the other hand, CYP4F11 was a better catalyst than CYP4F3A for many drugs such as erythromycin, benzphetamine, ethylmorphine, chlorpromazine, and imipramine. Erythromycin was the most efficient substrate for CYP4F11, with a Km of 125 μM and Vmax of 830 pmol min-1 nmol-1 P450. Structural homology modeling of the two proteins revealed some interesting differences in the substrate access channel including substrate recognition site 2 (SRS2). The model of CYP4F11 presents a more open access channel that may explain the ability to metabolize large molecules like erythromycin. Also, some wide variations in residue size, charge, and hydrophobicity in the FG loop region may contribute to differences in substrate specificity and activity between CYP4F3A and CYP4F11

  18. 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.

  19. 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

  20. Action of cholera toxin in the intestinal epithelial cells

    International Nuclear Information System (INIS)

    The primary event in the action of cholera toxin on the isolated chick intestinal epithelial cell is its interaction with a large number of high affinity binding sites in the cell membrane. Binding of 125I-labeled toxin is rapid, temperature-dependent, reversible, and saturable over a wide range of concentrations and includes only a small contribution from nonspecific sites. A characteristic lag phase of 10 min occurs following the complete binding of toxin before any increase in cellular cAMP levels can be detected. The response (elevation of cellular cAMP) is linear with time for 40 to 50 min and causes a six- to eight-fold increase over control levels (10 to 15 picomole cAMP/mg cellular protein) at steady state. cAMP and agents that increase cAMP production inhibit Cl--independent Na+ influx into the isolated enterocytes whereas chlorpromazine (CPZ) which completely abolishes toxin-induced elevation of cAMP both reverses and prevents the cAMP-mediated inhibition of Na+ entry. Correlation between cellular cAMP levels and the magnitude of Na+ influx provides evidence for a cAMP-mediated control of intestinal Na+ uptake, which may represent the mechanistic basis for the antiabsorptive effect of CT on Na+ during induction of intestinal secretion. The effect of cAMP on Na+ but not Cl- influx preparations can be partially explained in terms of a cAMP-regulated Na+/H+ neutral exchange system. Data on the coupling relationship between Na+ transport and the intra- and extracellular pH in the enterocytes show that an amiloride-sensitive electroneutral Na+/H+ exchange process occurs. This coupling between Na+ and H+ is partially inhibited by CT and dbcAMP, suggesting that the Na+/H+ exchange may be a cAMP-regulated process. 31 references, 32 figures, 5 tables

  1. Development of HepG2-derived cells expressing cytochrome P450s for assessing metabolism-associated drug-induced liver toxicity.

    Science.gov (United States)

    Xuan, Jiekun; Chen, Si; Ning, Baitang; Tolleson, William H; Guo, Lei

    2016-08-01

    The generation of reactive metabolites from therapeutic agents is one of the major mechanisms of drug-induced liver injury (DILI). In order to evaluate metabolism-related toxicity and improve drug efficacy and safety, we generated a battery of HepG2-derived cell lines that express 14 cytochrome P450s (CYPs) (1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 3A4, 3A5 and 3A7) individually using a lentiviral expression system. The expression/production of a specific CYP in each cell line was confirmed by an increased abundance of the CYP at both mRNA and protein levels. Moreover, the enzymatic activities of representative CYPs in the corresponding cell lines were also measured. Using our CYP-expressed HepG2 cells, the toxicity of three drugs that could induce DILI (amiodarone, chlorpromazine and primaquine) was assessed, and all of them showed altered (increased or decreased) toxicity compared to the toxicity in drug-treated wild-type HepG2 cells. CYP-mediated drug toxicity examined in our cell system is consistent with previous reports, demonstrating the potential of these cells for assessing metabolism-related drug toxicity. This cell system provides a practical in vitro approach for drug metabolism screening and for early detection of drug toxicity. It is also a surrogate enzyme source for the enzymatic characterization of a particular CYP that contributes to drug-induced liver toxicity. PMID:26477383

  2. 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

  3. 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

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  6. Psychiatric morbidity, phenomenology and management in hospitalized female foreign domestic workers in Lebanon.

    Science.gov (United States)

    Zahreddine, Nada; Hady, Rima Talaat; Chammai, Rabih; Kazour, François; Hachem, Dory; Richa, Sami

    2014-07-01

    40 million female domestic workers worldwide experience the inhumane conditions associated with this unregulated occupation, a situation that induces psychiatric morbidities in many. The case in Lebanon is not any better where it is estimated that one foreign domestic worker (FDW) commits suicide weekly. 33 female FDW and 14 female Lebanese (control group, CG) were enrolled. Brief Psychotic Rating Scale (BPRS) and Clinical Global Impression (CGI) scales were administered on admission and discharge and socio-demographic, living conditions, mental health care data and phenomenological observations were collected. Sexual, physical, and verbal abuses were detected in FDW (12.5, 37.5, and 50.0 %. respectively). 66.7 % of them were diagnosed with brief psychotic episode. The mean duration of hospital stay (13.1 days) was significantly lower in the FDW group. The mean cumulative antipsychotic dose of the FDW was 337.1 mg of chlorpromazine equivalent and the mean BPRS total pre-score of FDW was 66.4 with a much improved state on the CGI global improvement scale, all of which were nonsignificantly different from the CG. Striking phenomenological findings among FDW were acute anorexia (39.4 %), nudity (30.3 %), catatonic features (21.2 %), and delusion of pregnancy (12.1 %). Inpatient FDW are more diagnosed with psychotic than affective disorders and receive approximately similar treatment as controls in spite of the trend to rapidly discharge and deport the worker to limit the costs. Both groups presented with similar severity, although the FDW had peculiar phenomenological observations. PMID:24370752

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  10. 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

  11. 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.

  12. Ethidium bromide transport across Mycobacterium smegmatis cell-wall: correlation with antibiotic resistance

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    Couto Isabel

    2011-02-01

    Full Text Available Abstract Background Active efflux systems and reduced cell-wall permeability are considered to be the main causes of mycobacterial intrinsic resistance to many antimicrobials. In this study, we have compared the Mycobacterium smegmatis wild-type strain mc2155 with knockout mutants for porins MspA (the main porin of M. smegmatis and MspC, the efflux pump LfrA (the main efflux pump system of M. smegmatis and its repressor LfrR for their ability to transport ethidium bromide (EtBr on a real-time basis. This information was then correlated with minimum inhibitory concentrations (MICs of several antibiotics in the presence or absence of the efflux inhibitors chlorpromazine, thioridazine and verapamil. Results In the absence of porins MspA and MspC, accumulation of ethidium bromide decreased and the cells became more resistant to several antibiotics, whereas the knockout mutant for the LfrA pump showed increased accumulation of EtBr and increased susceptibility to EtBr, rifampicin, ethambutol and ciprofloxacin. Moreover, the efflux inhibitors caused a reduction of the MICs of streptomycin, rifampicin, amikacin, ciprofloxacin, clarithromycin and erythromycin in most of the strains tested. Conclusions The methodology used in this study demonstrated that porin MspA plays an important role in the influx of quaternary ammonium compounds and antibiotics and that efflux via the LfrA pump is involved in low-level resistance to several antimicrobial drugs in M. smegmatis. The results obtained with this non-pathogenic mycobacterium will be used in future studies as a model for the evaluation of the activity of the same efflux inhibitors on the susceptibility of multidrug resistant strains of Mycobacterium tuberculosis to isoniazid and rifampicin.

  13. 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".

  14. Mechanisms of DRA recycling in intestinal epithelial cells: effect of enteropathogenic E. coli.

    Science.gov (United States)

    Gujral, Tarunmeet; Kumar, Anoop; Priyamvada, Shubha; Saksena, Seema; Gill, Ravinder K; Hodges, Kim; Alrefai, Waddah A; Hecht, Gail A; Dudeja, Pradeep K

    2015-12-15

    Enteropathogenic Escherichia coli (EPEC) is a food-borne pathogen that causes infantile diarrhea worldwide. EPEC decreases the activity and surface expression of the key intestinal Cl(-)/HCO3(-) exchanger SLC26A3 [downregulated in adenoma (DRA)], contributing to the pathophysiology of early diarrhea. Little is known about the mechanisms governing membrane recycling of DRA. In the current study, Caco-2 cells were used to investigate DRA trafficking under basal conditions and in response to EPEC. Apical Cl(-)/HCO3(-) exchange activity was measured as DIDS-sensitive (125)I(-) uptake. Cell surface biotinylation was performed to assess DRA endocytosis and exocytosis. Inhibition of clathrin-mediated endocytosis by chlorpromazine (60 μM) increased apical Cl(-)/HCO3(-) exchange activity. Dynasore, a dynamin inhibitor, also increased function and surface levels of DRA via decreased endocytosis. Perturbation of microtubules by nocodazole revealed that intact microtubules are essential for basal exocytic (but not endocytic) DRA recycling. Mice treated with colchicine showed a decrease in DRA surface levels as visualized by confocal microscopy. In response to EPEC infection, DRA surface expression was reduced partly via an increase in DRA endocytosis and a decrease in exocytosis. These effects were dependent on the EPEC virulence genes espG1 and espG2. Intriguingly, the EPEC-induced decrease in DRA function was unaltered in the presence of dynasore, suggesting a clathrin-independent internalization of surface DRA. In conclusion, these studies establish the role of clathrin-mediated endocytosis and microtubules in the basal surface expression of DRA and demonstrate that the EPEC-mediated decrease in DRA function and apical expression in Caco-2 cells involves decreased exocytosis.

  15. 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.

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

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    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.

  17. 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.

  18. [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.

  19. Interaction and uptake of exosomes by ovarian cancer cells

    International Nuclear Information System (INIS)

    Exosomes consist of membrane vesicles that are secreted by several cell types, including tumors and have been found in biological fluids. Exosomes interact with other cells and may serve as vehicles for the transfer of protein and RNA among cells. SKOV3 exosomes were labelled with carboxyfluoresceine diacetate succinimidyl-ester and collected by ultracentrifugation. Uptake of these vesicles, under different conditions, by the same cells from where they originated was monitored by immunofluorescence microscopy and flow cytometry analysis. Lectin analysis was performed to investigate the glycosylation properties of proteins from exosomes and cellular extracts. In this work, the ovarian carcinoma SKOV3 cell line has been shown to internalize exosomes from the same cells via several endocytic pathways that were strongly inhibited at 4°C, indicating their energy dependence. Partial colocalization with the endosome marker EEA1 and inhibition by chlorpromazine suggested the involvement of clathrin-dependent endocytosis. Furthermore, uptake inhibition in the presence of 5-ethyl-N-isopropyl amiloride, cytochalasin D and methyl-beta-cyclodextrin suggested the involvement of additional endocytic pathways. The uptake required proteins from the exosomes and from the cells since it was inhibited after proteinase K treatments. The exosomes were found to be enriched in specific mannose- and sialic acid-containing glycoproteins. Sialic acid removal caused a small but non-significant increase in uptake. Furthermore, the monosaccharides D-galactose, α-L-fucose, α-D-mannose, D-N-acetylglucosamine and the disaccharide β-lactose reduced exosomes uptake to a comparable extent as the control D-glucose. In conclusion, exosomes are internalized by ovarian tumor cells via various endocytic pathways and proteins from exosomes and cells are required for uptake. On the other hand, exosomes are enriched in specific glycoproteins that may constitute exosome markers. This work contributes to

  20. [Intractable vomiting, convulsions and megaloblastic anemia: anamnesis, key to diagnosis].

    Science.gov (United States)

    Schlaeppi, M; Humair, L; de Torrenté, A

    1999-07-01

    In July 1996 a 43-year-old illiterate Hispanic woman presented with uncontrollable vomiting, palpitations and confusion. In 1994, despite several hospitalisations in other medical centres where a cerebral CT-scan, oesogastroduodenoscopy, colonoscopy and abdominal ultrasound were performed, no satisfactory diagnosis could be found. A psychiatric origin was finally considered. On admission, the laboratory findings showed severe metabolic alkalosis with associated hypokalaemia, confirmatory evidence of vomiting. The ECG showed tremendous P waves (5 mV) in the standard derivations, which can be explained by the hypokalaemia, with multiple supraventricular extrasystoles. Echocardiography and pulmonary scintigraphy ruled out pulmonary hypertension and a pulmonary embolus. After additional discussion with her daughter we discovered that the patient had been treating chronic headaches for years with 4-5 Cafergot-PB suppositories per day. This drug contains 2 mg ergotamine tartrate, 100 mg butalbital, 100 mg caffeine and 0.25 mg belladona alkaloids. As is known, vomiting is a classical symptom of ergotamine intoxication. After rehydration we discovered a megaloblastic anaemia with a folate deficiency compatible with chronic barbiturate intoxication. Folate and iron supplementation allowed a rapid normalisation of the haemoglobin values. Five months after having stopped the Cafergot-PB, the patient was well and did not vomit anymore. The headaches were treated with chlorpromazine with a good result. Despite sophisticated technical means, the diagnosis could only be established after a thorough history taking. This message should be heard in times when high tech medicine tends to obscure the place of a good history taking! PMID:10431323

  1. 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

  2. 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.

  3. Gene expression-based chemical genomics identifies potential therapeutic drugs in hepatocellular carcinoma.

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    Ming-Huang Chen

    Full Text Available Hepatocellular carcinoma (HCC is an aggressive tumor with a poor prognosis. Currently, only sorafenib is approved by the FDA for advanced HCC treatment; therefore, there is an urgent need to discover candidate therapeutic drugs for HCC. We hypothesized that if a drug signature could reverse, at least in part, the gene expression signature of HCC, it might have the potential to inhibit HCC-related pathways and thereby treat HCC. To test this hypothesis, we first built an integrative platform, the "Encyclopedia of Hepatocellular Carcinoma genes Online 2", dubbed EHCO2, to systematically collect, organize and compare the publicly available data from HCC studies. The resulting collection includes a total of 4,020 genes. To systematically query the Connectivity Map (CMap, which includes 6,100 drug-mediated expression profiles, we further designed various gene signature selection and enrichment methods, including a randomization technique, majority vote, and clique analysis. Subsequently, 28 out of 50 prioritized drugs, including tanespimycin, trichostatin A, thioguanosine, and several anti-psychotic drugs with anti-tumor activities, were validated via MTT cell viability assays and clonogenic assays in HCC cell lines. To accelerate their future clinical use, possibly through drug-repurposing, we selected two well-established drugs to test in mice, chlorpromazine and trifluoperazine. Both drugs inhibited orthotopic liver tumor growth. In conclusion, we successfully discovered and validated existing drugs for potential HCC therapeutic use with the pipeline of Connectivity Map analysis and lab verification, thereby suggesting the usefulness of this procedure to accelerate drug repurposing for HCC treatment.

  4. 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

  5. 21例精神科老年病人猝死的现况及原因分析%ANALYSIS THE STATE AND CAUSES OF 21 GERIATRIC PSYCHIATRIC PATIENTS SUFFERED FROM SUDDEN DEATH

    Institute of Scientific and Technical Information of China (English)

    张燕

    2011-01-01

    [Objective] To elaborate the 21 geriatric psychiatric patients who suffered from sudden death, to reduce the incidence of sudden death in psychiatric hospital. [Methods] Retrospectively analyzed cases of sudden death occurred during recent 11 years in our hospital. [Results] The incidence of sudden death was 0.17%. In autumn and winter, 04: 00-07: 59 was the peak time of sudden death. 98.48% psychiatric patients accompanied with physical diseases. Patients taking clozapine, chlorpromazine, perphenazine or haloperidol in sudden death cases accounted for a higher proportion, and cases with combinations of drugs were more. [Conclusion] In sudden death cases, most of patients accompany with physical diseases, so such patients should be carefully given antipsychotic drugs.%[目的]描述精神科21例老年住院患者猝死的现况,为降低精神病住院患者猝死发生率提供依据.[方法]对近11年来在某院住院期间发生猝死病例的临床资料进行回顾性调查分析.[结果]11年内猝死发生率0.17%.冬、秋季,04:00~07:59时间段为猝死高峰期.98.48%伴有躯体疾病.服用氯氮平、氯丙嗪、奋乃静、氟哌啶醇者在猝死病例中占较高比例,且联合用药者较多.[结论]精神科猝死病例中伴有躯体疾病者较多,对此类患者应谨慎应用抗精神病药物.

  6. Triolein-based polycation lipid nanocarrier for efficient gene delivery: characteristics and mechanism

    Directory of Open Access Journals (Sweden)

    Zhang ZW

    2011-10-01

    Full Text Available Zhiwen Zhang1,2, Xiaoling Fang1, Junguo Hao1, Yajuan Li1, Xianyi Sha1 1Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, People’s Republic of China; 2Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China Abstract: We proposed to develop a polycation lipid nanocarrier (PLN with higher transfection efficiency than our previously described polycation nanostrucutred lipid nanocarrier (PNLC. PLN was composed of triolein, cetylated low-molecular-weight polyethylenimine, and dioleoyl phosphatidylethanolamine. The physicochemical properties of PLN and the PLN/DNA complexes (PDC were characterized. The in vitro transfection was performed in human lung adenocarcinoma (SPC-A1 cells, and the intracellular mechanism was investigated as well. The measurements indicated that PLN and PDC are homogenous nanometer-sized particles with a positive charge. The transfection efficiency of PDC significantly increased with the content of triolein and was higher than that of PNLC and commercial LipofectamineTM 2000. In particular, the transfection of PLN in the presence of 10% serum was more effective than that in its absence. With the help of specific inhibitors of chlorpromazine and filipin, the clathrin-dependent endocytosis pathway was determined to be the main contributor to the successful transfection mediated by PLN in SPC-A1 cells. The captured images verified that the fluorescent PDC was localized in the lysosomes and nuclei after endocytosis. Thus, PLN represents a novel efficient nonviral gene delivery vector. Keywords: triolein, dioleoyl phosphatidylethanolalmine, polyethylenimine, lipid nanocarrier, mechanism

  7. 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

  8. Síndrome neuroléptica maligna: relato de caso com recorrência associada ao uso de olanzapina Neuroleptic malignant syndrome: case report of a recurrence related to olanzapine

    Directory of Open Access Journals (Sweden)

    RICARDO A. HANEL

    1998-12-01

    Full Text Available A síndrome neuroléptica maligna (SNM consiste em reação idiossincrática a neurolépticos, provavelmente relacionada a bloqueio dos receptores dopaminérgicos nos gânglios da base, sendo por isso também conhecida como síndrome da deficiência aguda de dopamina.A SNM é caracterizada por hiperpirexia, alteração do nível de consciência, hipertonia, disfunção autonômica e insuficiência respiratória, podendo ainda ser encontrados rabdomiólise e leucocitose. O haloperidol é a droga mais frequentemente associada à síndrome. Relatamos o caso de um paciente de 30 anos que apresentou SNM em duas ocasiões diferentes, a primeira delas relacionada ao uso de haloperidol e clorpromazina e a segunda relacionada ao uso de olanzapina, fato este sem menção anterior na literatura indexada.The neuroleptic malignant syndrome (NMS consists in an idiosyncratic reaction to neuroleptic drugs, probably related to a blockage of dopamine receptors in basal ganglia. Research criteria for diagnosing NMS from DSM-IV require severe rigidity and fever accompanied by 2 of 10 minor features including diaphoresis, dysphagia, tremor, incontinence, altered mentation, mutism, tachycardia, elevated or labile blood pressure, leukocytosis and elevation of creatine phosphokinase. From a clinical point of view, the NMS may range a large spectrum of presentations. Haloperidol is the most frequent drug associated with this syndrome. We report the case of a 30 year-old man who developed NMS at two different occasions, the first related to haloperidol and chlorpromazine and the second related to olanzapine, to our knowledge without previous mention in the indexed literature.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  10. Bioactivation of myelotoxic xenobiotics by human neutrophil myeloperoxidase

    International Nuclear Information System (INIS)

    Many environmental pollutants and drugs are toxic to the bone marrow. Some of these xenobiotics may initiate toxicity after undergoing bioactivation to free radicals and/or other reactive electrophiles. Peroxidases are a group of enzymes that catalyze the one-electron oxidative bioactivation of a variety of xenobiotics in vitro. Myeloperoxidase (MPO) is a peroxidative enzyme found in very high concentration in the neutrophils of human bone marrow. In this study, human MPO was evaluated to determine its ability to catalyze the in vitro bioactivation of known bone marrow toxicants that contain the aromatic hydroxyl (Ar-OH), aromatic amine (Ar-N-R2), or heterocyclic tertiary amine (double-bond N-R) moieties. The formation of free radical metabolites during the MPO-catalyzed bioactivation of hydroquinone and catechol (benzene metabolites), mitoxantrone and ametantrone (antitumor drugs), and chlorpromazine and promazine (antipsychotic drugs) was demonstrated by EPR spectroscopy. The reactivity of the products formed during the MPO catalyzed bioactivation of [14C]hydroquinone and [14C]catechol was shown by their covalent binding to protein and DNA in vitro. The covalently binding metabolite in each case is postulated to be the quinone form of the xenobiotic. In addition, both GSH and NADH were oxidized by the reactive intermediate(s) formed during the MPO-catalyzed bioactivation of many of the bone marrow toxicants tested. It was also shown that p,p-biphenol stimulated the MPO catalyzed bioactivation of both hydroquinone and catechol, while p-cresol stimulated the MPO-catalyzed bioactivation of catechol

  11. 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.

  12. 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. PMID:14642968

  13. Mechanisms regulating expression of the HPV 31 L1 and L2 capsid proteins and pseudovirion entry

    Directory of Open Access Journals (Sweden)

    Hindmarsh Patrick L

    2007-02-01

    Full Text Available Abstract Human papillomaviruses (HPV infect stratified epithelia and restrict expression of late capsid genes to highly differentiated cells. In order to begin to understand the processes regulating HPV 31 infection we examined the synthesis of the HPV 31 capsid proteins, L1 and L2, using heterologous expression systems. Similar to studies in HPV 16, expression of wild type HPV 31 L1 and L2 from heterologous promoters resulted in very low levels of synthesis. In contrast, modification of the codons in the capsid genes to ones more commonly used in cellular genes resulted in high-level synthesis. Through the use of chimeric proteins that fused fragments of wild type L1 to Green Fluorescent Protein (GFP coding sequences, a short region was identified that was sufficient to inhibit high level synthesis and similar elements were detected in L2. One element was localized to the 3' end of the L1 gene while a series of elements were localized at the 3' end of the L2 coding sequences. These observations are most consistent with negative RNA regulatory elements controlling the levels of L1 and L2 synthesis that are distinct from those identified in HPV 16. Expression vectors for the codon modified HPV 31 capsid proteins were then transfected together with GFP reporter plasmids to generate HPV 31 pseudoviruses. Infection of cells with HPV 31 pseudoviruses in the presence of the inhibitors, chlorpromazine, nystatin or methyl-beta-cyclodextrin, demonstrated that HPV 31, like HPV 16, enters human and monkey cells through a clathrin-mediated pathway rather than through caveolae as previously reported. This suggests that high-risk HPV types may enter cells through common mechanisms.

  14. 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

  15. Research Resource: A Reference Transcriptome for Constitutive Androstane Receptor and Pregnane X Receptor Xenobiotic Signaling.

    Science.gov (United States)

    Ochsner, Scott A; Tsimelzon, Anna; Dong, Jianrong; Coarfa, Cristian; McKenna, Neil J

    2016-08-01

    The pregnane X receptor (PXR) (PXR/NR1I3) and constitutive androstane receptor (CAR) (CAR/NR1I2) members of the nuclear receptor (NR) superfamily of ligand-regulated transcription factors are well-characterized mediators of xenobiotic and endocrine-disrupting chemical signaling. The Nuclear Receptor Signaling Atlas maintains a growing library of transcriptomic datasets involving perturbations of NR signaling pathways, many of which involve perturbations relevant to PXR and CAR xenobiotic signaling. Here, we generated a reference transcriptome based on the frequency of differential expression of genes across 159 experiments compiled from 22 datasets involving perturbations of CAR and PXR signaling pathways. In addition to the anticipated overrepresentation in the reference transcriptome of genes encoding components of the xenobiotic stress response, the ranking of genes involved in carbohydrate metabolism and gonadotropin action sheds mechanistic light on the suspected role of xenobiotics in metabolic syndrome and reproductive disorders. Gene Set Enrichment Analysis showed that although acetaminophen, chlorpromazine, and phenobarbital impacted many similar gene sets, differences in direction of regulation were evident in a variety of processes. Strikingly, gene sets representing genes linked to Parkinson's, Huntington's, and Alzheimer's diseases were enriched in all 3 transcriptomes. The reference xenobiotic transcriptome will be supplemented with additional future datasets to provide the community with a continually updated reference transcriptomic dataset for CAR- and PXR-mediated xenobiotic signaling. Our study demonstrates how aggregating and annotating transcriptomic datasets, and making them available for routine data mining, facilitates research into the mechanisms by which xenobiotics and endocrine-disrupting chemicals subvert conventional NR signaling modalities. PMID:27409825

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  18. Mutation of Rv2887, a marR-like gene, confers Mycobacterium tuberculosis resistance to an imidazopyridine-based agent.

    Science.gov (United States)

    Winglee, Kathryn; Lun, Shichun; Pieroni, Marco; Kozikowski, Alan; Bishai, William

    2015-11-01

    Drug resistance is a major problem in Mycobacterium tuberculosis control, and it is critical to identify novel drug targets and new antimycobacterial compounds. We have previously identified an imidazo[1,2-a]pyridine-4-carbonitrile-based agent, MP-III-71, with strong activity against M. tuberculosis. In this study, we evaluated mechanisms of resistance to MP-III-71. We derived three independent M. tuberculosis mutants resistant to MP-III-71 and conducted whole-genome sequencing of these mutants. Loss-of-function mutations in Rv2887 were common to all three MP-III-71-resistant mutants, and we confirmed the role of Rv2887 as a gene required for MP-III-71 susceptibility using complementation. The Rv2887 protein was previously unannotated, but domain and homology analyses suggested it to be a transcriptional regulator in the MarR (multiple antibiotic resistance repressor) family, a group of proteins first identified in Escherichia coli to negatively regulate efflux pumps and other mechanisms of multidrug resistance. We found that two efflux pump inhibitors, verapamil and chlorpromazine, potentiate the action of MP-III-71 and that mutation of Rv2887 abrogates their activity. We also used transcriptome sequencing (RNA-seq) to identify genes which are differentially expressed in the presence and absence of a functional Rv2887 protein. We found that genes involved in benzoquinone and menaquinone biosynthesis were repressed by functional Rv2887. Thus, inactivating mutations of Rv2887, encoding a putative MarR-like transcriptional regulator, confer resistance to MP-III-71, an effective antimycobacterial compound that shows no cross-resistance to existing antituberculosis drugs. The mechanism of resistance of M. tuberculosis Rv2887 mutants may involve efflux pump upregulation and also drug methylation. PMID:26303802

  19. 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.

  20. Longitudinal changes in total brain volume in schizophrenia: relation to symptom severity, cognition and antipsychotic medication.

    Directory of Open Access Journals (Sweden)

    Juha Veijola

    Full Text Available Studies show evidence of longitudinal brain volume decreases in schizophrenia. We studied brain volume changes and their relation to symptom severity, level of function, cognition, and antipsychotic medication in participants with schizophrenia and control participants from a general population based birth cohort sample in a relatively long follow-up period of almost a decade. All members of the Northern Finland Birth Cohort 1966 with any psychotic disorder and a random sample not having psychosis were invited for a MRI brain scan, and clinical and cognitive assessment during 1999-2001 at the age of 33-35 years. A follow-up was conducted 9 years later during 2008-2010. Brain scans at both time points were obtained from 33 participants with schizophrenia and 71 control participants. Regression models were used to examine whether brain volume changes predicted clinical and cognitive changes over time, and whether antipsychotic medication predicted brain volume changes. The mean annual whole brain volume reduction was 0.69% in schizophrenia, and 0.49% in controls (p = 0.003, adjusted for gender, educational level, alcohol use and weight gain. The brain volume reduction in schizophrenia patients was found especially in the temporal lobe and periventricular area. Symptom severity, functioning level, and decline in cognition were not associated with brain volume reduction in schizophrenia. The amount of antipsychotic medication (dose years of equivalent to 100 mg daily chlorpromazine over the follow-up period predicted brain volume loss (p = 0.003 adjusted for symptom level, alcohol use and weight gain. In this population based sample, brain volume reduction continues in schizophrenia patients after the onset of illness, and antipsychotic medications may contribute to these reductions.

  1. Longitudinal Changes in Total Brain Volume in Schizophrenia: Relation to Symptom Severity, Cognition and Antipsychotic Medication

    Science.gov (United States)

    Veijola, Juha; Guo, Joyce Y.; Moilanen, Jani S.; Jääskeläinen, Erika; Miettunen, Jouko; Kyllönen, Merja; Haapea, Marianne; Huhtaniska, Sanna; Alaräisänen, Antti; Mäki, Pirjo; Kiviniemi, Vesa; Nikkinen, Juha; Starck, Tuomo; Remes, Jukka J.; Tanskanen, Päivikki; Tervonen, Osmo; Wink, Alle-Meije; Kehagia, Angie; Suckling, John; Kobayashi, Hiroyuki; Barnett, Jennifer H.; Barnes, Anna; Koponen, Hannu J.; Jones, Peter B.; Isohanni, Matti; Murray, Graham K.

    2014-01-01

    Studies show evidence of longitudinal brain volume decreases in schizophrenia. We studied brain volume changes and their relation to symptom severity, level of function, cognition, and antipsychotic medication in participants with schizophrenia and control participants from a general population based birth cohort sample in a relatively long follow-up period of almost a decade. All members of the Northern Finland Birth Cohort 1966 with any psychotic disorder and a random sample not having psychosis were invited for a MRI brain scan, and clinical and cognitive assessment during 1999–2001 at the age of 33–35 years. A follow-up was conducted 9 years later during 2008–2010. Brain scans at both time points were obtained from 33 participants with schizophrenia and 71 control participants. Regression models were used to examine whether brain volume changes predicted clinical and cognitive changes over time, and whether antipsychotic medication predicted brain volume changes. The mean annual whole brain volume reduction was 0.69% in schizophrenia, and 0.49% in controls (p = 0.003, adjusted for gender, educational level, alcohol use and weight gain). The brain volume reduction in schizophrenia patients was found especially in the temporal lobe and periventricular area. Symptom severity, functioning level, and decline in cognition were not associated with brain volume reduction in schizophrenia. The amount of antipsychotic medication (dose years of equivalent to 100 mg daily chlorpromazine) over the follow-up period predicted brain volume loss (p = 0.003 adjusted for symptom level, alcohol use and weight gain). In this population based sample, brain volume reduction continues in schizophrenia patients after the onset of illness, and antipsychotic medications may contribute to these reductions. PMID:25036617

  2. Differences in the tumor microenvironment between African-American and European-American breast cancer patients.

    Directory of Open Access Journals (Sweden)

    Damali N Martin

    Full Text Available BACKGROUND: African-American breast cancer patients experience higher mortality rates than European-American patients despite having a lower incidence of the disease. We tested the hypothesis that intrinsic differences in the tumor biology may contribute to this cancer health disparity. METHODS AND RESULTS: Using laser capture microdissection, we examined genome-wide mRNA expression specific to tumor epithelium and tumor stroma in 18 African-American and 17 European-American patients. Numerous genes were differentially expressed between these two patient groups and a two-gene signature in the tumor epithelium distinguished between them. To identify the biological processes in tumors that are different by race/ethnicity, Gene Ontology and disease association analyses were performed. Several biological processes were identified which may contribute to enhanced disease aggressiveness in African-American patients, including angiogenesis and chemotaxis. African-American tumors also contained a prominent interferon signature. The role of angiogenesis in the tumor biology of African-Americans was further investigated by examining the extent of vascularization and macrophage infiltration in an expanded set of 248 breast tumors. Immunohistochemistry revealed that microvessel density and macrophage infiltration is higher in tumors of African-Americans than in tumors of European-Americans. Lastly, using an in silico approach, we explored the potential of tailored treatment options for African-American patients based on their gene expression profile. This exploratory approach generated lists of therapeutics that may have specific antagonistic activity against tumors of African-American patients, e.g., sirolimus, resveratrol, and chlorpromazine in estrogen receptor-negative tumors. CONCLUSIONS: The gene expression profiles of breast tumors indicate that differences in tumor biology may exist between African-American and European-American patients beyond the

  3. Dual chitosan/albumin-coated alginate/dextran sulfate nanoparticles for enhanced oral delivery of insulin.

    Science.gov (United States)

    Lopes, Marlene; Shrestha, Neha; Correia, Alexandra; Shahbazi, Mohammad-Ali; Sarmento, Bruno; Hirvonen, Jouni; Veiga, Francisco; Seiça, Raquel; Ribeiro, António; Santos, Hélder A

    2016-06-28

    The potential of nanoparticles (NPs) to overcome the barriers for oral delivery of protein drugs have led to the development of platforms capable of improving their bioavailability. However, despite the progresses in drug delivery technologies, the success of oral delivery of insulin remains elusive and the disclosure of insulin mechanisms of absorption remains to be clarified. To overcome multiple barriers faced by oral insulin and to enhance the insulin permeability across the intestinal epithelium, here insulin-loaded alginate/dextran sulfate (ADS)-NPs were formulated and dual-coated with chitosan (CS) and albumin (ALB). The nanosystem was characterized by its pH-sensitivity and mucoadhesivity, which enabled to prevent 70% of in vitro insulin release in simulated gastric conditions and allowed a sustained insulin release following the passage to simulated intestinal conditions. The pH and time-dependent morphology of the NPs was correlated to the release and permeation profile of insulin. Dual CS/ALB coating of the ADS-NPs demonstrated augmented intestinal interactions with the intestinal cells in comparison to the uncoated-NPs, resulting in a higher permeability of insulin across Caco-2/HT29-MTX/Raji B cell monolayers. The permeability of the insulin-loaded ALB-NPs was reduced after the temperature was decreased and after co-incubation with chlorpromazine, suggesting an active insulin transport by clathrin-mediated endocytosis. Moreover, the permeability inhibition with the pre-treatment with sodium chlorate suggested that the interaction between glycocalix and the NPs was critical for insulin permeation. Overall, the developed nanosystem has clinical potential for the oral delivery of insulin and therapy of type 1 diabetes mellitus. PMID:27074369

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

    Directory of Open Access Journals (Sweden)

    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

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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

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

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    Machado, Diana; Pires, David; Perdigão, João; Couto, Isabel; Portugal, Isabel; Martins, Marta; Amaral, Leonard; Anes, Elsa; Viveiros, Miguel

    2016-01-01

    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 irrespective of their

  11. Calcium affecting protein expression in longan under simulated acid rain stress.

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    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. PMID:25893616

  12. [Compliance in schizophrenia: predictive factors, therapeutical considerations and research implications].

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    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

  13. Talidomida: indicações em Dermatologia Thalidomide: indications in Dermatology

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    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.

  14. 早、晚发性精神分裂症临床对照分析%Early,Late Onset Schizophrenia Clinical Analysis

    Institute of Scientific and Technical Information of China (English)

    刘娜

    2015-01-01

    Objective To compare the clinical characteristics, the difference between early and late-onset schizophrenia.MethodsSchizophrenia were randomly selected to early, late onset schizophrenia patients from each 100 cases in our hospital spirit, retrospective clinical analysis of their. ResultsAnalysis of the clinical data of two groups: early, that has significant difference in late-onset schizophrenia, affective disorder in the language barrier, behavior disorder, thought disorder, etc. (P<0.01), in the etiology of evoked, positive family history, using a potion (equivalent to chlorpromazine potency differences) and the amount of the effect rate of treatment and so on also has significant (P<0.05). Conclusion Early onset schizophrenia psychiatric symptoms significantly more than late-onset schizophrenia, late age of onset of primary light, and acute onset; early, late onset schizophrenia patients both on psychiatric symptoms, family history of Su, disease induced factors, therapeutic effect and prognosis, difference.%目的:比较早、晚发性精神分裂症的临床特征的区别。方法从我院收治的精神分裂症病人中随机抽取早、晚发性精神分裂症患者各100例,回顾性对照分析他们的临床资料。结果分析两组的临床资料得出:早、晚发性精神分裂症在情感障碍、语言障碍、行为障碍、思维障碍、等方面的差异具有显著性意义(P<0.01),在病因诱发、阳性家族史,使用药剂(折合氯丙嗪效价)量及治疗显效率等方面的差异也具有显著性意义(P<0.05)。结论早发性精神分裂症精神症状显著多于晚发性精神分裂症,发病年龄较晚发性轻,且起病急;早、晚发精神分裂症忠者在精神症状、家族史、诱病因素、治疗效果、和预后等方面均有差异。

  15. 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.

  16. Adherence to depot versus oral antipsychotic medication in schizophrenic patients during the long-term therapy

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    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

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

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    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

  18. 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

  19. Cytotoxicity of CdTe quantum dots in human umbilical vein endothelial cells: the involvement of cellular uptake and induction of pro-apoptotic endoplasmic reticulum stress.

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    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

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

    Directory of Open Access Journals (Sweden)

    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

  1. 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

  2. Clinical analysis of 56 cases of chronic alcoholic psychosis%慢性酒精中毒性精神障碍56例临床分析

    Institute of Scientific and Technical Information of China (English)

    赵长银; 王瑜; 王方昀

    2016-01-01

    目的:探讨慢性酒精中毒性精神障碍的治疗方法及治疗效果。方法:收治慢性酒精中毒性精神障碍患者56例,随机分成观察组和对照组。对照组给予氯丙嗪治疗,观察组给予安定治疗,比较两组治疗前后精神症状、认知功能及生活质量。结果:两组治疗后随机错误数、持续错误数、正确次数、完成分类数、PANSS、总测验比较,差异具有统计学意义(P<0.05)。两组治疗后生理领域评分、心理领域评分、社会关系领域评分、环境领域评分和综合评分比较,差异具有统计学意义(P<0.05)。结论:苯二氮卓类药物对慢性酒精中毒性精神障碍的治疗效果显著。%Objective:To explore the treatment methods and therapeutic effect of chronic alcoholic psychosis.Methods:56 cases of patients with chronic alcoholic psychosis were divided into the observation group and the control group randomly.The control group was treated with chlorpromazine,and the observation group was treated with diazepam.The psychiatric symptoms,cognitive function and quality of life in the two groups before and after treatment were compared.Results:After treatment,there were statistically significant differences of the number of random errors,number of persistent errors,correct times,complete classification number,PANSS,total test between groups (P<0.05).After treatment,there were statistically significant differences of physical scores,psychological scores,social relationship scores,environment scores and comprehensive scores between groups (P<0.05).Conclusion:Benzodiazepines in the treatment of chronic alcoholic psychosis had remarkable therapeutic effect.

  3. 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

  4. Gel filtration chromatographic study on the self-association of surfactants and related compounds.

    Science.gov (United States)

    Funasaki, N

    1993-01-25

    After a brief survey of gel filtration chromatography (GFC) and the self-association equilibrium, it is shown that GFC is a unique tool for investigating the self-association of many substances, such as surfactants, chlorpromazine hydrochloride (CPZ), Methylene Blue (MB) and a sulfobetaine derivative (CHAPS) of cholic acid. The hydrodynamic radius of an aggregate can be estimated with the gel of large pore size, such as Sephadex G-200. This method is utilized for the study of the sphere-rod transition of surfactant micelles. A precise value of monomer concentration can be determined from the centroid elution volume of a frontal chromatogram on Sephadex G-10. This important parameter in self-associating systems allows us to determine the micellar aggregation number as a function of the total surfactant concentration. The derivative chromatogram can be used to detect slight changes in self-association. From these results, it is found that nonionic surfactants form premicelles including dimer and that multiple equilibrium model for micelle formation is more appropriate than mass-action model. The Tanford theory with some modifications appears to fit the concentration dependence of the aggregation properties of surfactants forming small globular micelles and allows us to estimate the stepwise aggregation constant and the micelle size distribution function. The pronounced cooperativity in the self-association of surfactants forms the basis of mass action model and the concept of the cmc, though they are actually approximations even for surfactants. They would be more inadequate, though often used, for the self-association of drugs and bile salts. The stepwise aggregation constant of MB is almost independent of aggregation numbers, which may be expected from the stacking mode of aggregation. The main aggregates of CPZ in 154 mM sodium chloride solution are dimer and 38-mer and its dimerization constant is smaller than that of MB and larger than those of surfactants. The

  5. 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

  6. 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

  7. 根管治疗后疾病中粪肠球菌的致病性和检测及清除%Pathogenicity, detection, and elimination ofEnterococcus faecalis in post-treatment endodontic disease

    Institute of Scientific and Technical Information of China (English)

    张瑞瑞; 孙克勤

    2015-01-01

    Enterococcus faecalis(E.faecalis) is the most commonly detected bacteria in post-treatment endodontic disease, with a detection rate that ranges from 24% to 77% in reinfected root canal. The pathogenicity of E.faecalis is highly correlated with the formation of biofilms and presents a complex relationship to drug resistance. This association is the key factor in chronic infections in the root canal. Primary methods, including bacterial culture and PCR, are used to detect E.faecalis. PCR is more sensitive to E.faecalisin the infected root canals than bacterial culture. Methods on removal of E.faecalis in post-treatment endodontic disease vary and provide different results, particularly inhibition rate. The use of 2% chlorhexidine gel results in 100% inhibition of bacterial growth compared with using 10% chlorpromazine(88.8%), 4% lignocaine gel(76.4%), and 5% amiloride hydrochloride(71.4%). Moreover, mixture-tetracycline-isomer-acid-detergent, QMiX, and NaClO are more effective than 2% chlorhexidine. In addition, erbium: yttrium-aluminum-garnet laser can eliminate E.faecalis biofilm. This article reviewed different correlation studies regarding pathogenicity, detection, and elimination of E.faecalis in post-treatment endodontic disease.%粪肠球菌是根管治疗后疾病最常见的细菌,在再感染根管内的检出率为24%~77%。粪肠球菌的致病性与其形成的生物膜高度相关,而其耐药性也与其致病性密不可分,是引发根管内慢性感染的关键。粪肠球菌的检测以细菌培养和聚合酶链反应(PCR)为主,而PCR用于检测感染根管内粪肠球菌较细菌培养更为敏感。根管治疗后疾

  8. 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

  9. Situation analysis and nursing countermeasure of 15 years psychiatric inpatients with sudden death%精神科住院病人15年猝死情况分析与护理对策

    Institute of Scientific and Technical Information of China (English)

    冯春杰; 安春梅

    2012-01-01

    Objective: Nursing perspectives on the causes of sudden death of mental patients and care requirements of hospitalized psychiatric patients to reduce mortality measures. Methods; A retrospective medical record reading method. Cases of sudden death, one by one according to the survey with self -registration of medical information, and univariate statistical analysis. Results: 22 cases of sudden death in 6 patients with physical illness, clozapine , chlorpromazine, perphenazme in the high proportion of patients with sudden death, and the combination of drugs more. In addition to the body of patients with sudden death related to the situation, the various types of anti - psychiatric drugs on sudden death also has a direct or indirect relationship. Conclusion : All hospitalized patients receiving anttpsychotics in the treatment of early stage should be closely observed. Especially for young adutts for the first time hospitalized, frail, suffering from cardiovascular disease, high dose or two of the joint use of antipsychotics in patients, should be attached great importance to the nursing work closely observed changes, strengthen the sense of responsibility , to step up inspection and timely detection of problems and timely treatment.%目的:从护理角度了解精神病病人猝死的原因及护理要求,探讨降低精神病病人住院猝死率的措施.方法:采用回顾阅读病历的方法,对猝死病例,用自制调查表逐一按照病历登记的有关资料进行统计分析.结果:22例猝死者中6例伴有躯体疾病,猝死病人除与躯体状况有关外,各类抗精神病药物对猝死也有直接或间接的关系.服用氯氮平、氯丙嗪、奋乃静者在猝死病人中占较高比例,且合用药物者较多.结论:对所有住院接受抗精神病药物治疗的病人,在治疗早期都应进行严密观察.特别是对青壮年首次住院、年老体弱、患有心脑血管疾病、用药剂量偏离或两种抗精

  10. 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.

  11. 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.

  12. 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

  13. 非药物整体调序疗法治疗精神分裂症的机理、疗效、安全性及性能特征%Mechanism ,Efficacy ,Safety ,and Performance Characteristics of Non-drug Overall Modulating-order Therapy in the Treatment of Schizophrenia

    Institute of Scientific and Technical Information of China (English)

    彭宗禹; 彭睿; 朱二龙

    2013-01-01

    有非常显著性差异(t=9.59,P<0.01),乙、丙两组的显效率做组间对照,也达到了非常显著性差异(t=7.4,P<0.01);⑨对乙组用TESS量表进行治疗前后不良反应对照,治疗后毒副反应发生率明显低于治疗前,且所降低的副反应具有广泛性特征;⑩乙组失眠发生率治疗前为20.3%,治疗后降为零;(11)乙组治疗前有明显的认知功能障碍,治疗后5项认知功能障碍全部有改善,改善率最低为75%,最高达95%;(12)对甲A组进行TESS不良反应评价,结果显示:调序治疗仪无副作用.结论 中枢神经细胞信号转导可被体外调控,非药物整体调序疗法是当前精神分裂症临床治疗中一种创新的、具有独特性能特征的非药物治疗技术.其治疗机理用“整体调序”取代了药物治疗的“受体阻断”,且对精神分裂症有显著的治疗效果,本身无副作用,并具有降低药物的副作用、改善睡眠、改善和提高认知功能等性能特征.%Objective To explore the pathogenesis of schizophrenia,and the treatment mechanism,efficacy,safety of modulat-ing-crder therapeutic apparatus in the treatment of schizophrenia and its performance characteristics of reducing drugs' side effects, improving sleep disorder and cognitive function. Methods A total of 189 patients treated by modulating-order therapeutic apparatus were collected, including 64 patients(Jia A group)treated by simple application of modulating-order therapeutic apparatus; 64 cases of false treatment by sequencing therapy(Jia B group) ; 61 cases(Yi group)were treated by modulating-order therapeutic apparatus + drug treatment (mainly chlorpromazine);and references to relevant data of chlorpromazine in the treatment of psychiatric observation such as Chen Jindong's schizophrenia as a reference control(Bing Group). The basic study took ET,using the positive and negative symptom scale(PANSS)to assess efficacy,using TESS to assess side effects,according to the clinical symptoms

  14. 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

  15. A cross-sectional study on treatment patterns of bipolar disorders in China in 2006%2006年我国十省市双相障碍患者药物使用的横断面调查

    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

    2012-01-01

    Objective To understand the treatment patterns for bipolar disorders in China in 2006.Methods Based on the economic level,760 out- and in-patients,aged 16 -65 years and meeting the ICD-10 criteria for bipolar disorder were selected from 41 hospitals in 10 provinces and municipalities using the convenient sampling.The investigation was conducted during 22th -28th May,2006,using the retested and revised self-made modified questionnaires.Results ( 1 ) Totally 760 cases including 329 (43.3% ) outpatients and 431 (56.7 % ) inpatients ( male:female =436:318,missing value was 6 ) were recruited in the study.(2) Two thirds of patients experienced elation (n =481,63.3% ),flight of thought (n =436,57.4% ) and hyperactivity ( n =513,67.5% ),and 21.3% patients ( n =162) were bipolar depression.And 7.9% ( n =60) of patients experienced psychotic symptoms,and 6.3% of them ( n =48) manifested suicide idea or behaviors.More inpatients were severe and in the acute phase than outpatients.(3) 88.3% of the patients were treated with mood stabilizer,most frequently prescribed were lithium and valproate.The antipsychotics were used in 78% of all the patients,with the most five medications being clozapine,risperidone,chlorpromazine,quetiapine and haloperidone.18.7% (n =142) of the patients were prescribed antidepressants,the first-line drugs were SSRIs. (4) More inpatients were treated with the antipsychotics and more outpatients with antidepressants.(5) 79.8% of patients (n =606) were treated with two or more kinds of medications,with first-line strategy of combination of antipsychotics and mood stabilizers.(6) Results from the logistic analysis showed that the clinical profile,including experiencing psychotic symptoms,depressive or manic moods played the important role in using the antipsychotics,mood stabilizers or antidepressants treatment.Conclusion The polypharmacy is the mainstream in treatment of bipolar disorder,with the combination of antipsychotics and

  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.