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  1. Anticholinergic and blood pressure effects of mianserin, amitriptyline and placebo

    PubMed Central

    Kopera, H.

    1978-01-01

    1 Eighteen healthy male volunteers were treated at random in double-blind conditions with mianserin, amitriptyline, or placebo for 8 days. Measurements were made of various parameters indicative of anticholinergic and blood pressure effects. 2 Mianserin showed no significant anticholinergic effects on any of the measures used. Compared with placebo, mianserin significantly reduced pupil diameter and tended to increase salivary production and increase the distance of the near point. 3 Amitriptyline showed evidence of anticholinergic effects in that salivary production fell to a level significantly lower than that of the mianserin- or placebo-treated subjects. The distance of the near point tended to increase during amitriptyline treatment. Compared with placebo, amitriptyline also significantly reduced pupil diameter on some occasions. 4 Amitriptyline produced postural hypotension to a statistically significant degree, whereas this effect was not observed during mianserin treatment. 5 In conclusion, mianserin in doses of up to 60 mg daily given to healthy males seemed to lack the anticholinergic effects and postural hypotension associated with amitriptyline treatment. PMID:341941

  2. Specific radioimmunoassay of amitriptyline and nortriptyline.

    PubMed Central

    Brunswick, D J; Needelman, B; Mendels, J

    1979-01-01

    1 Antisera to nortriptyline were prepared by immunizing rabbits with N-succinylnortriptyline--bovine serum albumin conjugate. 2 A sensitive radioimmunoassay has been developed for the tricyclic antidepressants amitriptyline and nortriptyline. 3 amitriptyline and nortriptyline are separated from each other and from interfering metabolites before assay. 4 Using [3H]-imipramine and [3H]-succinylnortriptyline as tracers the radioimmunoassay can measure amitriptyline and nortriptyline levels down to 2--3 ng/ml using 0.05 ml plasma sample. 5 Agreement between the radioimmunoassay and a gas-chromatographic assay was excellent for both amitriptyline and nortriptyline. PMID:444353

  3. Repeated Administration of Amitriptyline in Neuropathic Pain: Modulation of the Noradrenergic Descending Inhibitory System.

    PubMed

    Hiroki, Tadanao; Suto, Takashi; Saito, Shigeru; Obata, Hideaki

    2017-10-01

    g). Additionally, 5 daily injections of amitriptyline increased the ratio of c-Fos-immunoreactive (IR) cells in noradrenergic LC neurons in SNL rats with or without DSP-4 pretreatment (P < .001, respectively). Five daily injections of amitriptyline increased DβH-IR in the LC and the spinal dorsal horn of SNL rats (P < .001, respectively). With DSP-4 pretreatment, DβH-IR was dramatically decreased with or without 5 daily injections of amitriptyline (P < .001). Five daily injections of amitriptyline produced antihyperalgesic effects against neuropathic pain despite suppression of noradrenergic descending inhibitory systems. Amitriptyline activated LC neurons and increased noradrenergic fibers density in SNL rats. These results suggest that amitriptyline could still produce analgesia under pathological dysfunction of the descending noradrenergic system. Amitriptyline may enhance the analgesic effect of drugs for neuropathic pain that require normal descending noradrenergic inhibition to produce analgesia, such as serotonin and noradrenaline reuptake inhibitors and gabapentinoids.

  4. Amitriptyline

    MedlinePlus

    ... is in a class of medications called tricyclic antidepressants. It works by increasing the amounts of certain ... Parkinson's disease, seizures, ulcers, or urinary problems; other antidepressants; phenobarbital (Bellatal, Solfoton); sedatives; selective serotonin reuptake inhibitors ( ...

  5. Caffeine reverses antinociception by amitriptyline in wild type mice but not in those lacking adenosine A1 receptors.

    PubMed

    Sawynok, Jana; Reid, Allison R; Fredholm, Bertil B

    2008-08-01

    Amitriptyline is used to treat neuropathic pain in humans. It produces antinociception in several animal models of pain, and this effect is blocked by methylxanthine adenosine receptor antagonists which implicates adenosine it its actions. Here, the antinociceptive effect of amitriptyline, and the ability of caffeine to reverse it, were examined using the formalin test (a model of persistent pain) in wild type mice and mice lacking the adenosine A(1) receptor (A1R). Amitriptyline produced dose-related suppression of flinching in wild type mice following both systemic and intraplantar drug administration; both of these effects were unaltered in A1R -/- mice. Following systemic administration, caffeine reversed the systemic effect of amitriptyline in wild type, but not A1R -/- mice; -/+ mice exhibited an intermediate effect. Intraplantar administration of caffeine also reversed the effect of intraplantar amitriptyline in A1R +/+, but not in -/- or +/- mice. These results indicate that adenosine A(1) receptors are not required in order for amitriptyline to cause antinociception in mice, but they are required to see caffeine reversal of this antinociceptive effect. When A1Rs are present, actions of amitriptyline may, however, partly depend on A1Rs.

  6. Interaction of desipramine and amitriptyline with adrenergic mechanisms in the human iris in vivo.

    PubMed

    Szabadi, E; Gaszner, P; Bradshaw, C M

    1981-01-01

    Mydriatic responses of the pupil were evoked by locally instilled noradrenaline and methoxamine in eight healthy volunteers. The effects of three single oral doses (25 mg, 50 mg and 100 mg) of amitriptyline and desipramine were compared on the mydriatic responses. Both antidepressants potentiated the mydriasis evoked by noradrenaline; desipramine appeared to be approximately four times more potent than amitriptyline. Both antidepressants antagonised the mydriasis evoked by noradrenaline; desipramine appeared to be approximately four times more potent than amitriptyline. Both antidepressants antagonised the mydriasis evoked by methoxamine, amitriptyline being approximately twice as potent as desipramine. It is suggested that the potentiation of the response to noradrenaline may reflect the blockade of the uptake of noradrenaline into adrenergic nerve terminals, whereas the antagonism of the response to methoxamine may reflect the blockade of postsynaptic alpha-adrenoceptors by the antidepressants. It is argued that the interaction of the antidepressants with adrenergic mechanisms could explain why amitriptyline, a potent anticholinergic agent, causes no significant change in resting pupil diameter, while desipramine, a relatively weaker anticholinergic agent, produces a significant mydriasis.

  7. Cytoprotective Effects of Melatonin Against Amitriptyline-Induced Toxicity in Isolated Rat Hepatocytes

    PubMed Central

    Taziki, Shohreh; Sattari, Mohammad Reza; Dastmalchi, Siavoush; Eghbal, Mohammad Ali

    2015-01-01

    Purpose: Amitriptyline, one of the commonly used tricyclic antidepressants, caused rare but severe hepatotoxicity in patients who received it continuously. Previous findings showed that the intermediate metabolites of amitriptyline produced by CYP450 are involved in hepatic injury. Melatonin is an antiaging and antioxidant hormone synthesized from pineal gland. The aim of present study was to evaluate the protective role of melatonin in an in vitro model of isolated rat hepatocytes. Methods: Markers such as cell viability, reactive oxygen species formation, lipid peroxidation, mitochondrial membrane potential, and hepatocytes glutathione content were evaluated every 60 minutes for 180 minutes. Results: Present results indicated that administration of 1mM of melatonin effectively reduced the cell death, ROS formation and lipid peroxidation, mitochondrial membrane potential collapse, and reduced cellular glutathione content caused by amitriptyline. Conclusion: Our results indicated that melatonin is an effective antioxidant in preventing amitriptyline-induced hepatotoxicity. We recommend further in vivo animal and clinical trial studies on the hepatoprotective effects of melatonin in patients receiving amitriptyline. PMID:26504754

  8. No antidotal effect of intravenous lipid emulsion in experimental amitriptyline intoxication despite significant entrapment of amitriptyline.

    PubMed

    Litonius, Erik; Niiya, Tomohisa; Neuvonen, Pertti J; Rosenberg, Per H

    2012-04-01

    Intravenous lipid emulsion has been used in the resuscitative treatment of intoxications caused by local anaesthetics and tricyclic antidepressants with seemingly beneficial results. We studied the effect of intravenous lipid emulsion on the plasma concentration of amitriptyline and haemodynamic recovery in a pig model of amitriptyline intoxication. Twenty pigs were anaesthetized (1% isoflurane in 21% O(2)) and given amitriptyline 15 mg/kg intravenously for 15 min. In random fashion immediately thereafter, either 20% lipid emulsion (ClinOleic(®), Lipid group) or Ringer's acetate (Control group) was infused for 30 min.; first 1.5 ml/kg for 1 min., followed by 0.25 ml/kg/min. for 29 min. The amitriptyline concentration in total and lipid-poor plasma and haemodynamic parameters were measured until 30 min. after the infusions. Lipid infusion prevented the decrease in plasma total amitriptyline concentration, resulting in a 90% higher (p < 0.001) total concentration and significantly (p = 0.014) lower free fraction of plasma amitriptyline in the Lipid group (1.1%) compared with the Control group (3.0%) at 30 min. Haemodynamic recovery from the intoxication as measured by heart rate, arterial pressure or cardiac output was similar in both groups. However, five pigs in the Lipid group and two pigs in the Control group died. In conclusion, a marked entrapment of amitriptyline by intravenous lipid emulsion was observed but this did not improve the pigs' haemodynamic recovery from severe amitriptyline intoxication. Care should be exercised in the antidotal use of lipid emulsion until controlled human studies indicate its efficacy and safety.

  9. Enhancement of Antinociceptive Effect by Co-administration of Amitriptyline and Crocus Sativus in a Rat Model of Neuropathic Pain

    PubMed Central

    Amin, Bahareh; Hosseini, Samira; Hosseinzadeh, Hossein

    2017-01-01

    The aim of this study was to evaluate the anti-nociceptive effects of a low, sub-effective dose of amitriptyline, in combination with the different doses of ethanolic and aqueous extracts of Crocus sativus following sciatic nerve chronic constriction injury (CCI) in rats. Amitriptyline (3, 10 and 30 mg/Kg, i.p.) and the extracts (25, 50 and 100 mg/Kg, i.p.), were separately administered at the time of CCI for 7 consecutive days. In combination therapy, the sub-antinociceptive dose of amitriptyline (3 mg/Kg) was given with the three different doses of extracts for seven days. Mechanical allodynia, thermal allodynia and thermal hyperalgesia were evaluated by von Frey, acetone and radiant heat tests, respectively, 1 day before and on days 3, 5 and 7 after surgery. Co-administration of amitriptyline (3 mg/Kg) with aqueous extract (50, 100 mg/Kg,) produced more potent cold anti-allodynic (P < 0.01 and P < 0.001, respectively) as well as thermal anti-hyperalgesic (P < 0.05) effects than that produced by each of them. Amitriptyline (3 mg/Kg) plus ethanolic extract (50, 100 mg/Kg) produced more potent cold anti-allodynic (P < 0.05 and P < 0.001, respectively) as well as thermal anti-hyperalgesic (P < 0.05) effects as compared with the sum effects produced by each of them. Mechanical anti-allodynia effect was only potentiated with the co-administration of amitriptyline with the high dose of aqueous extract (100 mg/Kg, P < 0.001). Our study supports the use of saffron as an adjunctive to amitriptyline to improve the therapeutic outcome in the management of neuropathic pain. PMID:28496474

  10. Minaprine in depression. A controlled trial with amitriptyline.

    PubMed

    Wheatley, D

    1992-07-01

    Minaprine (200 mg daily, either once or divided b.d.) was compared with amitriptyline (25-50 mg t.d.s.) over six weeks in 144 patients with major depression. Significant reductions in HRSD scores at the end of six weeks' treatment were recorded with both dose regimes of minaprine and with amitriptyline, with no significant differences between them. There was a significantly greater incidence of drowsiness and dry mouth with amitriptyline than with minaprine.

  11. Phase 1A safety assessment of intravenous amitriptyline

    PubMed Central

    Fridrich, Peter; Colvin, Hans Peter; Zizza, Anthony; Wasan, Ajay D.; Lukanich, Jean; Lirk, Philipp; Saria, Alois; Zernig, Gerald; Hamp, Thomas; Gerner, Peter

    2007-01-01

    The antidepressant amitriptyline is used as an adjuvant in the treatment of chronic pain. Among its many actions, amitriptyline blocks Na+ channels and nerves in several animal and human models. As perioperative intravenous lidocaine has been suggested to decrease post-operative pain, amitriptyline, because of its longer half-life time, might be more useful than lidocaine. However, the use of intravenous amitriptyline is not approved by the US Food and Drug Administration. We therefore investigated the adverse effects of preoperative intravenous amitriptyline in a typical phase 1A trial. After obtaining written Food and Drug Administration and institutional review board approval, we obtained written consent for preoperative infusion of amitriptyline in an open-label, dose-escalating design (25, 50, and 100 mg, n=5 per group). Plasma levels of amitriptyline/nortriptyline were determined, and adverse effects were recorded in a predetermined symptom list. Infusion of 25 and 50 mg amitriptyline appears to be well tolerated; however, the study was terminated when one subject in the 100-mg group developed severe bradycardia. Intravenous infusion of amitriptyline (25 - 50 mg over 1 hour) did not create side effects beyond dry mouth and drowsiness, or dizziness, in 2 of our 10 otherwise healthy participants receiving the 25-50 mg dose. An appropriately powered future trial is necessary to determine a potential role of amitriptyline in decreasing postoperative pain. Perspective Amitriptyline potently blocks the persistently open Na+ channels, which are known to be instrumental in various pain states. As this occurs at very low plasma concentrations, a single preoperative intravenous infusion of amitriptyline could provide long-lasting pain relief and decrease the incidence of chronic pain. PMID:17512256

  12. Spinal astrocytic c-Jun N-terminal kinase (JNK) activation as counteracting mechanism to the amitriptyline analgesic efficacy in painful peripheral neuropathies.

    PubMed

    Sanna, Maria Domenica; Ghelardini, Carla; Galeotti, Nicoletta

    2017-03-05

    Several drugs and agents are currently used for the treatment of neuropathic pain. Among them amitriptyline, a tricyclic antidepressant drug, represent a first line treatment. Despite its well-documented clinical efficacy, amitriptyline is ineffective in some animal models of neuropathic pain. The aim of this study was to investigate into amitriptyline poor efficacy in neuropathic pain and to determine the role of c-Jun N-terminal kinase (JNK) activation as counteracting mechanism to the analgesic effects of this drug. Experiments were performed in mice with painful peripheral neuropathies due to the antiretroviral agent 2,3-dideoxycytidine (ddC), and with the partial sciatic nerve injury produced in the spared nerve injury model (SNI). In mice subjected to SNI and antiretroviral treatment, amitriptyline did not attenuate mechanical allodynia and thermal hyperalgesia. Conversely, intrathecal injection of the JNK inhibitor SP600125 prevented SNI and ddC-induced nociceptive behavior and, its inactive dose co-administrated with amitriptyline induced an antinociceptive effect. Western blotting analysis showed an upregulation of p-JNK in the lumbar spinal cord of SNI and ddC-exposed mice, that was further enhanced after amitriptyline administration. Additionally, amitriptyline further promoted astrocyte activation in neuropathic mice, as illustrated by the increased expression of glial fibrillary acidic protein (GFAP), that was attenuated by intrathecal injection of the JNK inhibitor. These data indicate astrocyte JNK activation as counteracting pathway to amitriptyline analgesic response. Targeting the JNK pathway in spinal astroglia may present an efficient way to improve the analgesic efficacy of amitriptyline in the neuropathic pain treatment.

  13. [Amitriptyline-induced cardiac arrest : treatment with fat emulsion].

    PubMed

    Huge, V; Baschnegger, H; Moehnle, P; Peraud, A; Briegel, J

    2011-06-01

    A case of successful resuscitation of a patient with severe amitriptyline intoxication is reported. The measured amitriptyline serum levels far exceeded those assumed to be lethal according to the literature. Resuscitation was successful with the administration of intravenous fat emulsion and the patient recovered without any neurological sequelae.

  14. Amitriptyline effectively relieves neuropathic pain following treatment of breast cancer.

    PubMed

    Kalso, E; Tasmuth, T; Neuvonen, P J

    1996-02-01

    The effectiveness of amitriptyline in relieving neuropathic pain following treatment of breast cancer was studied in 15 patients in a randomised, double-blind placebo-controlled crossover study. The dose was escalated from 25 mg to 100 mg per day in 4 weeks. The placebo and amitriptyline phases were separated by a 2-week wash-out period. Visual analogue and verbal rating scales were used for the assessment of pain intensity and pain relief. Other measures included the number of daily activities disturbed by the pain, the Finnish McGill Pain Questionnaire, adverse effects, anxiety, depression, pressure threshold and grip strength. Amitriptyline significantly relieved neuropathic pain both in the arm and around the breast scar. Eight out of 15 patients had a more than 50% decrease in the pain intensity ('good responders') with a median dose of 50 mg of amitriptyline. The 7 patients who had a less than 50% effect had drug concentrations equaling those of the good responders. The 'poor responders' reported significantly more adverse effects with amitriptyline and placebo than the good responders. It is concluded that amitriptyline effectively reduced neuropathic pain following treatment of breast cancer. However, the adverse effects of amitriptyline put most of the patients off from using the drug regularly.

  15. Amitriptyline in the prevention of chemotherapy-induced neuropathic symptoms.

    PubMed

    Kautio, Anna-Liisa; Haanpää, Maija; Leminen, Arto; Kalso, Eija; Kautiainen, Hannu; Saarto, Tiina

    2009-07-01

    Neuropathy is a common adverse effect of chemotherapy. The tricyclic antidepressant, amitriptyline, is a gold standard in the treatment of neuropathic pain. This double-blind, randomized placebo-controlled trial assessed the efficacy of amitriptyline to prevent chemotherapy-induced neuropathic symptoms. Patients without previous neuropathy, who started chemotherapy with vinca alcaloids, platina derivatives or taxanes, were randomized to receive amitriptyline (target dose, 100 mg daily) or placebo for the duration of their chemotherapy. Chemotherapy-induced neuropathic symptoms were evaluated with a patient diary and after every third chemotherapy cycle with clinical examination. The diary data were transformed to a neuropathy score. A total of 114 patients fulfilling the inclusion criteria were randomly assigned to the treatment or control arm. There was no difference in the appearance of chemotherapy-induced neuropathic symptoms between the groups. In general, the intensity of neuropathic symptoms was mild. Amitriptyline does not prevent chemotherapy-induced neuropathy.

  16. Amitriptyline for the treatment of fibromyalgia: a comprehensive review.

    PubMed

    Rico-Villademoros, Fernando; Slim, Mahmoud; Calandre, Elena P

    2015-10-01

    Fibromyalgia is characterized by chronic generalized pain accompanied by a wide range of clinical manifestations. Most clinical practice guidelines recommend multidisciplinary treatment using a combination of pharmacological and non-pharmacological therapies. The tricyclic antidepressant amitriptyline has been most thoroughly studied in fibromyalgia. Amitriptyline has been evaluated in placebo-controlled studies, and it has served as an active comparator to other therapeutic interventions in the treatment of fibromyalgia. In addition, several systematic reviews and meta-analyses have evaluated its efficacy and safety for the treatment of fibromyalgia. Data from individual studies as well as from systematic reviews indicate that low doses (10-75 mg/day) of amitriptyline are effective for the treatment of fibromyalgia and, despite the limited quality of the data, they do not seem to be associated with relevant tolerability or safety issues. Consistent with some clinical guidelines, we believe amitriptyline in low doses should be considered a first-line drug for the treatment of fibromyalgia.

  17. AMITRIPTYLINE USAGE EXACERBATES THE IMMUNE SUPPRESSION FOLLOWING BURN INJURY

    PubMed Central

    Johnson, Bobby L.; Rice, Teresa C.; Xia, Brent T.; Boone, Kirsten I.; Green, Ellis A.; Gulbins, Erich; Caldwell, Charles C.

    2016-01-01

    Currently, over 10% of the US population is taking antidepressants. Numerous antidepressants such as amitriptyline are known to inhibit acid sphingomyelinase (Asm), an enzyme that is known to mediate leukocyte function and homeostasis. Severe burn injury can lead to an immunosuppressive state that is characterized by decreased leukocyte function and numbers as well as increased susceptibility to infection. Based upon the intersection of these facts, we hypothesized that amitriptyline-treated, scald-injured mice would have an altered immune response to injury as compared with untreated scald mice. Prior to burn, mice were pretreated with amitriptyline. Drug- or saline-treated mice were subjected full thickness dorsal scald- or sham-injury. Immune cells from spleen, thymus, and bone marrow were subsequently harvested and characterized. We first observed that amitriptyline prior to burn injury increased body mass loss and spleen contraction. Both amitriptylinetreatment and burn injury resulted in a 40% decrease of leukocyte Asm activity. Following scald injury, we demonstrate increased reduction of lymphocyte precursors in the bone marrow and thymus, as well as mature leukocytes in the spleen in mice that were treated with amitriptyline. We also demonstrate that amitriptyline treatment prior to injury reduced neutrophil accumulation following peptidoglycan stimulus in scald-injured mice. These data show that Asm alterations can play a significant role in mediating alterations to the immune system after injury. The data further suggest that those taking antidepressants may be at a higher risk for complications following burn injury. PMID:27172154

  18. Amitriptyline Usage Exacerbates the Immune Suppression Following Burn Injury.

    PubMed

    Johnson, Bobby L; Rice, Teresa C; Xia, Brent T; Boone, Kirsten I; Green, Ellis A; Gulbins, Erich; Caldwell, Charles C

    2016-11-01

    Currently, over 10% of the US population is taking antidepressants. Numerous antidepressants such as amitriptyline are known to inhibit acid sphingomyelinase (Asm), an enzyme that is known to mediate leukocyte function and homeostasis. Severe burn injury can lead to an immunosuppressive state that is characterized by decreased leukocyte function and numbers as well as increased susceptibility to infection. Based upon the intersection of these facts, we hypothesized that amitriptyline-treated, scald-injured mice would have an altered immune response to injury as compared with untreated scald mice. Prior to burn, mice were pretreated with amitriptyline. Drug- or saline-treated mice were subjected full thickness dorsal scald- or sham-injury. Immune cells from spleen, thymus, and bone marrow were subsequently harvested and characterized. We first observed that amitriptyline prior to burn injury increased body mass loss and spleen contraction. Both amitriptylinetreatment and burn injury resulted in a 40% decrease of leukocyte Asm activity. Following scald injury, we demonstrate increased reduction of lymphocyte precursors in the bone marrow and thymus, as well as mature leukocytes in the spleen in mice that were treated with amitriptyline. We also demonstrate that amitriptyline treatment prior to injury reduced neutrophil accumulation following peptidoglycan stimulus in scald-injured mice. These data show that Asm alterations can play a significant role in mediating alterations to the immune system after injury. The data further suggest that those taking antidepressants may be at a higher risk for complications following burn injury.

  19. Uptake and retention of amitriptyline by kaolinite.

    PubMed

    Lv, Guocheng; Stockwell, Christie; Niles, Jacqueline; Minegar, Skylar; Li, Zhaohui; Jiang, Wei-Teh

    2013-12-01

    As the most commonly prescribed tricyclic antidepressant, amitriptyline (AT) is frequently detected in wastewater, surface runoff, and effluents from sewage treatment plants, and could potentially reach agriculture land through the application of municipal biosolids or reclaimed water. Kaolinite is one of the most important soil components under warm and humid climate conditions. In this study, the uptake and retention of AT by kaolinite from aqueous solution were investigated by batch tests, XRD, and FTIR analyses. The uptake of AT on kaolinite was instantaneous, attributed to surface adsorption as confirmed by XRD analyses. Quantitative correlation between desorption of exchangeable cations and AT adsorption confirmed experimentally that cation exchange was the dominant mechanism of AT uptake on kaolinite. The values for free energy of adsorption also suggested physi-sorption such as cation exchange. Solution pH had minimal influence at pH 5-11 even though the pKa value of AT was 9.4 and the surface charge of kaolinite was pH-dependent.

  20. Trial of Amitriptyline, Topiramate, and Placebo for Pediatric Migraine

    PubMed Central

    Powers, Scott W.; Coffey, Christopher S.; Chamberlin, Leigh A.; Ecklund, Dixie J.; Klingner, Elizabeth A.; Yankey, Jon W.; Korbee, Leslie L.; Porter, Linda L.; Hershey, Andrew D.

    2016-01-01

    BACKGROUND Which, medication, if any, to use to prevent the headache of pediatric migraine has not been established. METHODS We conducted a randomized, double-blind, placebo-controlled trial of amitriptyline (1 mg per kilogram of body weight per day), topiramate (2 mg per kilogram per day), and placebo in children and adolescents 8 to 17 years of age with migraine. Patients were randomly assigned in a 2:2:1 ratio to receive one of the medications or placebo. The primary outcome was a relative reduction of 50% or more in the number of headache days in the comparison of the 28-day baseline period with the last 28 days of a 24-week trial. Secondary outcomes were headache-related disability, headache days, number of trial completers, and serious adverse events that emerged during treatment. RESULTS A total of 361 patients underwent randomization, and 328 were included in the primary efficacy analysis (132 in the amitriptyline group, 130 in the topiramate group, and 66 in the placebo group). The trial was concluded early for futility after a planned interim analysis. There were no significant between-group differences in the primary outcome, which occurred in 52% of the patients in the amitriptyline group, 55% of those in the topiramate group, and 61% of those in the placebo group (amitriptyline vs. placebo, P = 0.26; topiramate vs. placebo, P = 0.48; amitriptyline vs. topiramate, P = 0.49). There were also no significant between-group differences in headache-related disability, headache days, or the percentage of patients who completed the 24-week treatment period. Patients who received amitriptyline or topiramate had higher rates of several adverse events than those receiving placebo, including fatigue (30% vs. 14%) and dry mouth (25% vs. 12%) in the amitriptyline group and paresthesia (31% vs. 8%) and weight loss (8% vs. 0%) in the topiramate group. Three patients in the amitriptyline group had serious adverse events of altered mood, and one patient in the topiramate

  1. Trial of Amitriptyline, Topiramate, and Placebo for Pediatric Migraine.

    PubMed

    Powers, Scott W; Coffey, Christopher S; Chamberlin, Leigh A; Ecklund, Dixie J; Klingner, Elizabeth A; Yankey, Jon W; Korbee, Leslie L; Porter, Linda L; Hershey, Andrew D

    2017-01-12

    Which medication, if any, to use to prevent the headache of pediatric migraine has not been established. We conducted a randomized, double-blind, placebo-controlled trial of amitriptyline (1 mg per kilogram of body weight per day), topiramate (2 mg per kilogram per day), and placebo in children and adolescents 8 to 17 years of age with migraine. Patients were randomly assigned in a 2:2:1 ratio to receive one of the medications or placebo. The primary outcome was a relative reduction of 50% or more in the number of headache days in the comparison of the 28-day baseline period with the last 28 days of a 24-week trial. Secondary outcomes were headache-related disability, headache days, number of trial completers, and serious adverse events that emerged during treatment. A total of 361 patients underwent randomization, and 328 were included in the primary efficacy analysis (132 in the amitriptyline group, 130 in the topiramate group, and 66 in the placebo group). The trial was concluded early for futility after a planned interim analysis. There were no significant between-group differences in the primary outcome, which occurred in 52% of the patients in the amitriptyline group, 55% of those in the topiramate group, and 61% of those in the placebo group (amitriptyline vs. placebo, P=0.26; topiramate vs. placebo, P=0.48; amitriptyline vs. topiramate, P=0.49). There were also no significant between-group differences in headache-related disability, headache days, or the percentage of patients who completed the 24-week treatment period. Patients who received amitriptyline or topiramate had higher rates of several adverse events than those receiving placebo, including fatigue (30% vs. 14%) and dry mouth (25% vs. 12%) in the amitriptyline group and paresthesia (31% vs. 8%) and weight loss (8% vs. 0%) in the topiramate group. Three patients in the amitriptyline group had serious adverse events of altered mood, and one patient in the topiramate group had a suicide attempt

  2. Coenzyme Q{sub 10} and alpha-tocopherol protect against amitriptyline toxicity

    SciTech Connect

    Cordero, Mario D.; Moreno-Fernandez, Ana Maria; Gomez-Skarmeta, Jose Luis; Miguel, Manuel de; Garrido-Maraver, Juan; Oropesa-Avila, Manuel; Rodriguez-Hernandez, Angeles; Navas, Placido; Sanchez-Alcazar, Jose Antonio

    2009-03-15

    Since amitriptyline is a very frequently prescribed antidepressant drug, it is not surprising that amitriptyline toxicity is relatively common. Amitriptyline toxic systemic effects include cardiovascular, autonomous nervous, and central nervous systems. To understand the mechanisms of amitriptyline toxicity we studied the cytotoxic effects of amitriptyline treatment on cultured primary human fibroblasts and zebrafish embryos, and the protective role of coenzyme Q{sub 10} and alpha-tocopherol, two membrane antioxidants. We found that amitriptyline treatment induced oxidative stress and mitochondrial dysfunction in primary human fibroblasts. Mitochondrial dysfunction in amitriptyline treatment was characterized by reduced expression levels of mitochondrial proteins and coenzyme Q{sub 10}, decreased NADH:cytochrome c reductase activity, and a drop in mitochondrial membrane potential. Moreover, and as a consequence of these toxic effects, amitriptyline treatment induced a significant increase in apoptotic cell death activating mitochondrial permeability transition. Coenzyme Q{sub 10} and alpha-tocopherol supplementation attenuated ROS production, lipid peroxidation, mitochondrial dysfunction, and cell death, suggesting that oxidative stress affecting cell membrane components is involved in amitriptyline cytotoxicity. Furthermore, amitriptyline-dependent toxicity and antioxidant protection were also evaluated in zebrafish embryos, a well established vertebrate model to study developmental toxicity. Amitriptyline significantly increased embryonic cell death and apoptosis rate, and both antioxidants provided a significant protection against amitriptyline embryotoxicity.

  3. Severe childhood amitriptyline intoxication and plasmapheresis: a case report.

    PubMed

    Karacı, Mehmet; Özçetin, Mustafa; Dilsiz, Günter; Güçlü-Songür, Yaşar Gözde

    2013-01-01

    Tricyclic antidepressant intoxication is one of the most frequently encountered and life-threatening causes of intoxication among referrals to emergency departments due to drug intoxication. There is no known antidote against any of the tricyclic antidepressants. The American Society for Apheresis (ASFA) recommends plasmapheresis to support primary treatment in this type of drug poisoning, which does not respond to certain and traditional treatments. We present a 15-year-old girl who ingested amitriptyline with suicidal intent. On admission, she was in a comatose state (Glasgow Coma Scale score: 5), with no spontaneous respiration and presence of pathological reflexes. Due to the intake history of lethal doses and the severe clinical picture, plasmapheresis was performed. She was discharged on her fifth day of hospitalization.Due to the high plasma protein binding property of amitriptyline, plasma exchange therapy should be considered in cases of severe amitriptyline intoxication as a life-saving therapeutic modality.

  4. Antimalarial properties of imipramine and amitriptyline

    SciTech Connect

    Dutta, P.; Siegel, L.; Pinto, J.; Meshnick, S.

    1986-03-01

    This laboratory has previously demonstrated that imipramine (IM) and amitriptyline (AM), inhibit the conversion of riboflavin to its coenzymic derivatives. Several other laboratories have shown that dietary riboflavin deficiency is protective against malarial infection. In the present investigation, the authors determined whether IM and AM exert antimalarial effects similar to that of riboflavin deficiency, as they have hypothesized. In addition, they evaluated whether these drugs, like other antimalarial agents, increase the hemolytic response to ferriprotoporphyrin IX (FP). The growth of P. falciparum (FCR3) in the absence or presence of these drugs (80 ..mu..M) was measured by incubating parasitized erythrocytes for 48 h in RPMI 1640 medium. Parasitemia was determined by counting erythrocyte smears and monitoring (/sup 3/H)hypoxanthine uptake. With no drug, parasitemia was 20.3 +/- 5.3%, whereas in the presence of IM and AM, parasitemia was reduced to 7.3 +/- 0.8% and 13.6 +/- 2.8%, respectively. The uptake of (/sup 3/H)hypoxanthine was reduced to 47 +/- 3.6% and 54 +/- 2.9% of control by IM and AM, respectively. Assays of hemolysis were conducted by incubating 0.5% RBC suspension in NaCl-Tris buffer for 3 h at 37/sup 0/C with variable concentrations of drugs and/or FP (1-7 ..mu..M). Both drugs at 10 to 100 ..mu..M significantly enhanced hemolysis induced by FP. No hemolysis by these drugs was detected in the absence of FP. It is concluded that the tricyclic antidepressants, IM and AM, possess substantial antimalarial properties, thereby supporting the hypothesis that drugs which interfere with riboflavin metabolism should also provide protection against malaria.

  5. Hemodiafiltration: A Novel Approach for Treating Severe Amitriptyline Intoxication

    PubMed Central

    Ozayar, Esra; Degerli, Semih; Gulec, Handan

    2012-01-01

    Tricyclic antidepressant overdose is one of the most common cause of serious drug poisonings. Sometimes amitriptyline intoxication can be difficult to treat with standard treatments. At that case hemodiafiltration (HD) can be an eligible choice. We report a successful treatment of severe case using hemodiafiltration in addition to the supportive measures. Management with gastric lavage, activated charcoal, alkalinization and supportive care is the common approach and not enough for patients in deep coma. We satisfied that HD may have a beneficial role in lethal doses of amitriptyline as an additional therapy. PMID:23293473

  6. Meta-analysis of randomized, double-blind, placebo-controlled, efficacy and safety studies of mirtazapine versus amitriptyline in major depression.

    PubMed

    Stahl, S; Zivkov, M; Reimitz, P E; Panagides, J; Hoff, W

    1997-01-01

    A meta-analysis was performed on efficacy and safety data from 4 randomized, double-blind, 6-week, single-center studies comparing mirtazapine (n = 194; 5-35 mg/day) with amitriptyline (n = 193, 40-280 mg/day) and placebo (n = 193) in outpatients with a DSM-III diagnosis of major depressive episode. On all the main efficacy variables both active drugs consistently produced significantly greater improvements and significantly greater percentages of responders or remitters than placebo. The meta-analysis of adverse events shows that mirtazapine was better tolerated than amitriptyline, particularly with respect to anticholinergic and cardiac adverse events. There were no differences between mirtazapine and placebo regarding the incidence of serotonergic adverse events. In conclusion, the results of this meta-analysis demonstrate that mirtazapine is as effective as amitriptyline but has a better tolerability profile.

  7. Effects of chronic doxepin and amitriptyline administration in naïve mice and in neuropathic pain mice model.

    PubMed

    Mika, J; Jurga, A M; Starnowska, J; Wasylewski, M; Rojewska, E; Makuch, W; Kwiatkowski, K; Malek, N; Przewlocka, B

    2015-05-21

    Neuropathic pain is a severe clinical problem, often appearing as a co-symptom of many diseases or manifesting as a result of damage to the nervous system. Many drugs and agents are currently used for the treatment of neuropathic pain, such as tricyclic antidepressants (TCAs). The aims of this paper were to test the effects of two classic TCAs, doxepin and amitriptyline, in naïve animals and in a model of neuropathic pain and to determine the role of cytokine activation in the effects of these drugs. All experiments were carried out with Albino-Swiss mice using behavioral tests (von Frey test and the cold plate test) and biochemical analyses (qRT-PCR and Western blot). In the mice subjected to chronic constriction injury (CCI), doxepin and amitriptyline attenuated the symptoms of neuropathic pain and diminished the CCI-induced increase in the levels of spinal interleukin (IL)-6 and -1β mRNA, but not the protein levels of these cytokines, measured on day 12. Unexpectedly, chronic administration of doxepin or amitriptyline for 12 days produced allodynia and hyperalgesia in naïve mice. The treatment with these drugs did not influence the spinal levels of IL-1β and IL-6 mRNA, however, the protein levels of these pronociceptive factors were increased. The administration of ondansetron (5-HT3 receptor antagonist) significantly weakened the allodynia and hyperalgesia induced by both antidepressants in naïve mice; in contrast, yohimbine (α2-adrenergic receptors antagonist) did not influence these effects. Allodynia and hyperalgesia induced in naïve animals by amitriptyline and doxepin may be associated with an increase in the levels of pronociceptive cytokines resulting from 5-HT3-induced hypersensitivity. Our results provide new and important information about the possible side effects of antidepressants. Further investigation of these mechanisms may help to guide decisions about the use of classic TCAs for therapy.

  8. The dexamethasone suppression test (DST) in predicting response to desipramine and amitriptyline in depressed outpatients.

    PubMed

    Peselow, E D; Goldring, N; Stanley, M; Barouche, F; Fieve, R R

    1986-01-01

    The predictive value of the dexamethasone suppression test (DST) was evaluated in two consecutive clinical trials involving 99 individuals treated with amitriptyline or desipramine. Following one week observation, and following one week on low-dose desipramine or amitriptyline (50 mg), all patients who remained depressed (Hamilton score 16 or greater) were given a full clinical trial of either desipramine or amitriptyline (150-300 mg/day) over a minimum 3-5 week period. In all, 68 patients required this trial, 31 receiving amitriptyline and 37 receiving desipramine. For these patients there was no relationship between DST suppression/non-suppression vs clinical response to either desipramine or amitriptyline. There was a non-significant trend for suppressors (negative DST) to respond either spontaneously or to low-dose desipramine or amitriptyline as opposed to non-suppressors (positive DST).

  9. Treatment of amitriptyline intoxications by extended high cut-off dialysis.

    PubMed

    Schmidt, Julius J; Bertram, Anna; Kühn-Velten, W Nikolaus; Suhling, Hendrik; Wiesner, Olaf; Schneider, Andrea; Kielstein, Jan T

    2015-12-01

    Antidepressants, especially amitriptyline, are among the most frequent drug classes involved in intoxications. Despite its small molecular weight, amitriptyline is not considered to be eliminated by extracorporeal treatment methods due to its high protein binding and large volume of distribution. New high cut-off dialysers have so far not been used for removal of amitriptyline. We report two cases of amitriptyline poisoning in which we measured the amitriptyline elimination using extended high cut-off (HCO) dialysis. Despite dialyser clearances of 33 and 58 mL/min, resulting in the reduction of initial serum concentrations by ∼30%, only 211 and 920 µg of amitryptilin, respectively, (<3% of the ingested amount) could be recovered in the total collected dialysate. Hence, due to the high volume of distribution of amitriptyline, even HCO dialysis does not contribute substantially to the extracorporeal removal of amitryptilin.

  10. Treatment of amitriptyline intoxications by extended high cut-off dialysis

    PubMed Central

    Schmidt, Julius J.; Bertram, Anna; Kühn-Velten, W. Nikolaus; Suhling, Hendrik; Wiesner, Olaf; Schneider, Andrea; Kielstein, Jan T.

    2015-01-01

    Antidepressants, especially amitriptyline, are among the most frequent drug classes involved in intoxications. Despite its small molecular weight, amitriptyline is not considered to be eliminated by extracorporeal treatment methods due to its high protein binding and large volume of distribution. New high cut-off dialysers have so far not been used for removal of amitriptyline. We report two cases of amitriptyline poisoning in which we measured the amitriptyline elimination using extended high cut-off (HCO) dialysis. Despite dialyser clearances of 33 and 58 mL/min, resulting in the reduction of initial serum concentrations by ∼30%, only 211 and 920 µg of amitryptilin, respectively, (<3% of the ingested amount) could be recovered in the total collected dialysate. Hence, due to the high volume of distribution of amitriptyline, even HCO dialysis does not contribute substantially to the extracorporeal removal of amitryptilin. PMID:26613042

  11. Safety evaluation of topically applied amitriptyline in porcine full-thickness wounds.

    PubMed

    Pomahac, Bohdan; Zuhaili, Bara; Kudsi, Yusef; Bleiziffer, Oliver; Velander, Patrik; Eriksson, Elof; Gerner, Peter

    2007-01-01

    The tricyclic antidepressant amitriptyline is frequently used in pain clinics for management of pain. It has also been suggested that topical application of amitriptyline could be useful for the treatment of neuropathic pain. In this report we investigated the effect of amitriptyline on porcine full thickness wounds resembling excised burn wounds. We assessed if daily topical application of amitriptyline into the wound chambers for 10 days impedes wound healing as measured by (1) wound contraction and (2) histopathological findings. Full-thickness wounds measuring 1.5 cm square were created on the dorsum of Yorkshire pigs and were enclosed in polyurethane wound chambers. Amitriptyline was applied daily at various concentrations. Bupivacaine (0.5%) or normal saline were used as controls. Daily wound serum levels were obtained and the level of amitriptyline and nortriptyline obtained. Pictures were taken daily and the wound surface analyzed for contraction. Cross-sectional, full-thickness skin biopsies were obtained at days 2, 8 and 10 and evaluated microscopically for re-epithelialization, inflammation, and necrosis. The high serum level of amitriptyline and nortriptyline did not affect wound healing; re-epithelialization, wound contraction, and inflammation were not significantly different between amitriptyline and control groups. Amitriptyline at the concentrations of 0.0625% and 0.125% applied daily via chambers covering wounds in a full-thickness pig excision model has no overt toxic effect on wound healing as measured by wound contraction and histological assessment.

  12. A proposed mechanism for amitriptyline neurotoxicity based on its detergent nature

    SciTech Connect

    Kitagawa, Norihito . E-mail: kitagawa@mail.anes.saga-med.ac.jp; Oda, Mayuko; Nobutaka, I.; Satoh, Hidetoshi; Totoki, Tadahide; Morimoto, Masatoshi

    2006-11-15

    Although amitriptyline has gained attention as a potent local anesthetic, recent animal studies showed that it can cause irreversible neural impairment. We hypothesized that nerve membrane disruption caused by solubilization, a common detergent property, accounted for amitriptyline neurotoxicity. We used a two-phase approach to test our hypothesis. Firstly, we determined (1) the molecular aggregation concentration of amitriptyline (2) the concentration of amitriptyline that disrupts artificial lipid membranes and (3) the concentration of amitriptyline that causes hemolysis. Secondly, we compared these levels with neurotoxic concentrations determined from assessment in a rat model of spinal anesthesia using changes in cutaneous stimulus threshold (CST). Amitriptyline concentrations that caused molecular aggregation, model membrane disruption and hemolysis were 0.46%, 0.35% and 0.3%, respectively. Animal study showed a significant increase in CST at {>=} 0.3% of amitriptyline, indicating neurological impairment. Since amitriptyline caused model membrane disruption and hemolysis at the molecular aggregation concentration, solubilization plays a role in the destruction of artificial membranes and erythrocytes. Furthermore, these concentrations are also in good agreement with the minimum concentration causing neurological injury. Therefore, while additional studies, including histopathology, are necessary to clarify this observation, amitriptyline neurotoxicity appears to be associated with its detergent nature.

  13. Effect of psychotropic drugs on gastric ulcers induced by immobilization: Increased protective effect of amitriptyline caused by chlordiazepoxide

    NASA Technical Reports Server (NTRS)

    Blum, J. E.; Huerlimann, A.

    1980-01-01

    Amitriptyline, but not chlordiazepoxide, protects rats from the occurrence of gastric erosions and ulcers following immobilization. When, however, chlordiazepoxide is given together with amitriptyline the protective effect of the latter is markedly increased.

  14. Dramatic resuscitation with Intralipid in an epinephrine unresponsive cardiac arrest following overdose of amitriptyline and propranolol.

    PubMed

    Le Fevre, Philippe; Gosling, Mark; Acharya, Keyur; Georgiou, Andrew

    2017-03-02

    Amitriptyline and propranolol are life threatening in overdose. The efficacy of intravenous lipid emulsion (ILE) in tricyclic antidepressant and propranolol overdose is unclear. We report a dramatic response to ILE following pulseless electrical activity arrest due to mixed amitriptyline and propranolol overdose.

  15. Aromatic-aromatic interaction of amitriptyline: implication of overdosed drug detoxification.

    PubMed

    Lee, Dong-Won; Flint, Jason; Morey, Timothy; Dennis, Donn; Partch, Richard; Baney, Ronald

    2005-02-01

    The objectives of this work are to explore the pi-pi complexation of amitriptyline with pi electron-deficient aromatic rings and demonstrate the feasibility of pi-pi complexation for overdosed drug detoxification. Water-soluble oligochitosan was chemically modified with dinitrobenzenesulfonyl groups to induce selective binding toward amitriptyline through pi-pi complexation. NMR studies showed that benzenesulfonyl and dinitrobenzenesulfonyl protons were upfield shifted by the addition of amitriptyline, indicating the formation of pi-pi complexes. The pi-pi complexation of amitriptyline is driven primarily by a desolvation driving force, whereas the magnitude of interaction is dictated by the complementrary electrostatic interaction. Isolated rat heart tests revealed that dinitrobenzenesulfonyl oligochitosan prevented the amitriptyline-induced cardiotoxicity and was itself not cardiotoxic.

  16. A double-blind comparative trial with mianserin and amitriptyline in outpatients with major depressive disorders

    PubMed Central

    Feighner, John P.; Jacobs, Robert S.; Jackson, Ronald E.; Hendrickson, Gordon; Merideth, Charles H.; O'Meara, Patrick D.

    1983-01-01

    1 A double-blind trial with parallel treatment groups was conducted to compare the safety and efficacy of mianserin with amitriptyline. 2 This was a six week trial with weekly visits. Measurements at each visit included: 21 item Hamilton Depression (HAMD) Scale, Clinical Global Impression (CGI) Scale and Treatment Emergent Symptom Scale (TESS). 3 Mianserin and amitriptyline were comparable with respect to efficacy. 4 More adverse experiences were reported by amitriptyline patients. The predominant amitriptyline adverse experiences were of the anticholinergic type; the predominant mianserin adverse experience was drowsiness/fatigue. 5 The Efficacy Index (EI), a scale combining efficacy and adverse experiences, clearly demonstrated the superiority of mianserin over amitriptyline. PMID:6337610

  17. Massive intoxication involving unusual high concentration of amitriptyline.

    PubMed

    Margalho, Cláudia; Barroso, Mário; Gallardo, Eugenia; Monsanto, Paula; Vieira, Duarte Nuno

    2007-08-01

    Amitriptyline is a tricyclic antidepressant widely used in the treatment of depression. Antidepressant drugs are among the most commonly encountered causes of self-poisoning, as illustrated by several published cases in the literature. This investigation reports a case of massive amitriptyline intoxication, involving a 44-year old female found dead in bed. The presence of this tricyclic antidepressant was revealed by a routine screening procedure. The concentration was calculated by gas chromatography/ electron ionization-mass spectrometry in the selected ion monitoring mode after solid-phase extraction using proadifen as internal standard and was in the post-mortem whole blood sample 85.9 mug/mL. This value was much higher than the reported toxic values ever found in the literature, and may therefore have caused the victim's death. Nortriptyline was also detected in the toxic concentration range, as well as therapeutic levels of diazepam and nor-diazepam. Taking into account both the available circumstantial information and toxicological results, it is very likely that death was caused by self-poisoning. Human & Experimental Toxicology (2007) 26, 667-670.

  18. Pretreatment with intrathecal amitriptyline potentiates anti-hyperalgesic effects of post-injury intra-peritoneal amitriptyline following spinal nerve ligation

    PubMed Central

    2012-01-01

    Background Amitriptyline, a tricyclic antidepressant and potent use-dependent blocker of sodium channels, has been shown to attenuate acute and chronic pain in several preclinical modes. The purpose of this study was to investigate whether intrathecal pretreatment with amitriptyline combined with post-injury intra-peritoneal amitriptyline is more effective than post-injury treatment alone on L5 spinal nerve ligation (SNL)-induced neuropathic pain. Methods 96 adult male Sprague–Dawley rats were allocated into 4 groups: group S, Sham; group L, L5 spinal nerve Ligation with vehicle treatment; group A, SNL and post-injury intra-peritoneal (Abdominal) amitriptyline twice daily × 3 days; group P, intrathecal Pretreatment with amitriptyline, SNL and intra-peritoneal amitriptyline twice daily × 3 days. Responses to thermal and mechanical stimuli, as well as sodium channel expression in injured dorsal root ganglion (DRG) and activated glial cells in spinal dorsal horn (SDH) were measured pre-operatively and on post-operative day (POD) 4, 7, 14, 21 and 28. Results SNL-evoked hyper-sensitivity responses to thermal and mechanical stimuli, up-regulated Nav1.3 and down-regulated Nav1.8 expression in DRG, and activated microglia and astrocytes in SDH. In group A, intra-peritoneal amitriptyline alone alleviated thermal hypersensitivity on POD7, reversed Nav1.8 and reduced activated microglia on POD14. In group P, intrathecal pretreatment with amitriptyline not only potentiated the effect of intra-peritoneal amitriptyline on thermal hypersensitivity and Nav1.8, but attenuated mechanical hypersensitivity on POD7 and reduced up-regulated Nav1.3 on POD14. Furthermore, this treatment regimen reduced astrocyte activation on POD14. Conclusions Concomitant intrathecal pretreatment and post-injury intra-peritoneal amitriptyline was more effective than post-injury treatment alone on attenuation of behavioral hypersensitivity, decrease of activated microglia and astrocytes

  19. Amitriptyline induces mitophagy that precedes apoptosis in human HepG2 cells.

    PubMed

    Villanueva-Paz, Marina; Cordero, Mario D; Pavón, Ana Delgado; Vega, Beatriz Castejón; Cotán, David; De la Mata, Mario; Oropesa-Ávila, Manuel; Alcocer-Gomez, Elizabet; de Lavera, Isabel; Garrido-Maraver, Juan; Carrascosa, José; Zaderenko, Ana Paula; Muntané, Jordi; de Miguel, Manuel; Sánchez-Alcázar, José Antonio

    2016-07-01

    Systemic treatments for hepatocellular carcinoma (HCC) have been largely unsuccessful. This study investigated the antitumoral activity of Amitriptyline, a tricyclic antidepressant, in hepatoma cells. Amitriptyline-induced toxicity involved early mitophagy activation that subsequently switched to apoptosis. Amitriptyline induced mitochondria dysfunction and oxidative stress in HepG2 cells. Amitriptyline specifically inhibited mitochondrial complex III activity that is associated with decreased mitochondrial membrane potential (∆Ψm) and increased reactive oxygen species (ROS) production. Transmission electron microscopy (TEM) studies revealed structurally abnormal mitochondria that were engulfed by double-membrane structures resembling autophagosomes. Consistent with mitophagy activation, fluorescence microscopy analysis showed mitochondrial Parkin recruitment and colocalization of mitochondria with autophagosome protein markers. Pharmacological or genetic inhibition of autophagy exacerbated the deleterious effects of Amitriptyline on hepatoma cells and led to increased apoptosis. These results suggest that mitophagy acts as an initial adaptive mechanism of cell survival. However persistent mitochondrial damage induced extensive and lethal mitophagy, autophagy stress and autophagolysome permeabilization leading eventually to cell death by apoptosis. Amitriptyline also induced cell death in hepatoma cells lines with mutated p53 and non-sense p53 mutation. Our results support the hypothesis that Amitriptyline-induced mitochondrial dysfunction can be a useful therapeutic strategy for HCC treatment, especially in tumors showing p53 mutations and/or resistant to genotoxic treatments.

  20. Amitriptyline induces mitophagy that precedes apoptosis in human HepG2 cells

    PubMed Central

    Villanueva-Paz, Marina; Cordero, Mario D.; Pavón, Ana Delgado; Vega, Beatriz Castejón; Cotán, David; De la Mata, Mario; Oropesa-Ávila, Manuel; Alcocer-Gomez, Elizabet; de Lavera, Isabel; Garrido-Maraver, Juan; Carrascosa, José; Zaderenko, Ana Paula; Muntané, Jordi; de Miguel, Manuel; Sánchez-Alcázar, José Antonio

    2016-01-01

    Systemic treatments for hepatocellular carcinoma (HCC) have been largely unsuccessful. This study investigated the antitumoral activity of Amitriptyline, a tricyclic antidepressant, in hepatoma cells. Amitriptyline-induced toxicity involved early mitophagy activation that subsequently switched to apoptosis. Amitriptyline induced mitochondria dysfunction and oxidative stress in HepG2 cells. Amitriptyline specifically inhibited mitochondrial complex III activity that is associated with decreased mitochondrial membrane potential (∆Ψm) and increased reactive oxygen species (ROS) production. Transmission electron microscopy (TEM) studies revealed structurally abnormal mitochondria that were engulfed by double-membrane structures resembling autophagosomes. Consistent with mitophagy activation, fluorescence microscopy analysis showed mitochondrial Parkin recruitment and colocalization of mitochondria with autophagosome protein markers. Pharmacological or genetic inhibition of autophagy exacerbated the deleterious effects of Amitriptyline on hepatoma cells and led to increased apoptosis. These results suggest that mitophagy acts as an initial adaptive mechanism of cell survival. However persistent mitochondrial damage induced extensive and lethal mitophagy, autophagy stress and autophagolysome permeabilization leading eventually to cell death by apoptosis. Amitriptyline also induced cell death in hepatoma cells lines with mutated p53 and non-sense p53 mutation. Our results support the hypothesis that Amitriptyline-induced mitochondrial dysfunction can be a useful therapeutic strategy for HCC treatment, especially in tumors showing p53 mutations and/or resistant to genotoxic treatments. PMID:27738496

  1. A placebo controlled double-blind evaluation of the pharmacodynamics of fengabine vs amitriptyline following single and multiple doses in elderly volunteers.

    PubMed Central

    Fairweather, D B; Kerr, J S; Hilton, S; Hindmarch, I

    1993-01-01

    1. The effects of fengabine were compared with those of amitriptyline in healthy elderly volunteers. Doses were administered double-blind and assessments were made before and after ingestion. 2. Psychomotor performance and cognitive ability were measured using tests of choice reaction time, tracking, critical flicker fusion threshold, memory scanning and word recognition. Subjective feelings were assessed using the Leeds sleep evaluation questionnaire (LSEQ) and line analogue rating scales (LARS). 3. Pharmacokinetic data suggest that fengabine may induce its own metabolism following repeated dosing. 4. The findings of this study show that fengabine 200 mg and 400 mg does not produce any noticeable behavioural toxicity in elderly volunteers, in contrast to amitriptyline which had a disruptive effect throughout. PMID:8471403

  2. Pharmacokinetics of Amitriptyline HCl and Its Metabolites in Healthy African Grey Parrots ( Psittacus erithacus ) and Cockatoos (Cacatua Species).

    PubMed

    Visser, Marike; Ragsdale, Michelle M; Boothe, Dawn M

    2015-12-01

    Amitriptyline, a tricyclic antidepressant, is used clinically to treat feather-destructive behavior in psittacine birds at a recommended dosage of 1-5 mg/kg PO q12-24h, which has been extrapolated from human medicine and based on anecdotal reports. The purpose of this pilot study was to describe the individual and population pharmacokinetic parameters of amitriptyline after a single oral dose at 1.5 mg/kg, 4.5 mg/kg, and 9 mg/kg in healthy African grey parrots ( Psittacus erithacus , n = 3) and cockatoos (Cacatua species, n = 3). Three birds received an initial 1.5 mg/kg oral dose, and blood samples were collected for 24 hours at fixed time intervals. Serum concentrations of amitriptyline and its metabolites were determined by polarized immunofluorescence. After determining the initial parameters and a 14-day washout period, 2 African grey parrots and 1 cockatoo received a single oral dose at 4.5 mg/kg, and 3 cockatoos and 1 African grey parrot received a single oral dose at 9 mg/kg. Concentrations reached the minimum therapeutic range reported in people (60 ng/mL) in 4 of 10 birds (4.5 and 9.0 mg/kg). Concentrations were within the toxic range in 1 African grey parrot (9 mg/kg), with regurgitation, ataxia, and dullness noted. Serum concentrations were nondetectable in 3 birds (1.5 and 4.5 mg/kg) and detectable but below the human therapeutic range in 3 birds (1.5 mg/kg and 9 mg/kg). Drug concentrations were continuing to increase at the end of the study (24 hours) in 1 bird. Elimination half-life varied from 1.6 to 91.2 hours. Population pharmacokinetics indicated significantly varied absorption, and elimination constants varied between species. Although amitriptyline appeared to be tolerated in most birds, disposition varies markedly among and within species, between the 2 genera, and within individual birds. The current recommended dosage of 1-5 mg/kg q12h in psittacine birds appears insufficient to achieve serum concentrations within the human therapeutic range

  3. [Effects of amitriptyline, fluoxetine, and tianeptine on the content of monoamines and their metabolites in Wistar rat brain structures].

    PubMed

    Kudrin, V S; Mosin, V M; Klodt, P M; Narkevich, V B; Molodavkin, G M; Voronina, T A

    2010-03-01

    The effects of antidepressant drugs belonging to different pharmacological groups--amitriptyline, fluoxetine (prozac), and tianeptine (coaxyl)--on the content of monoamines and their metabolites in Wistar rat brain structures (frontal cortex, hypothalamus, nucleus accumbens, striatum, and hippocamp) has been studied using HPLC with electrochemical detection. Tricyclic antidepressant amitriptyline (10 mg/kg) was found to produce a moderate increase in the DOPAC/dopamine turnover index in nucleus accumbens, but did not influence the levels of serotonin (5-HT), dopamine, and its metabolites (5-HIAA, DOPAC, and HVA) in other brain structures studied (frontal cortex, hypothalamus, striatum, hippocamp). Fluoxetine (Prozac) (20 mg/kg) decreased both the 5-HIAA content and the 5-HIAA/5-HT (5-HT turnover index) in all brain structures of Wistar rats. In contrast, the effects of Prozac on the level of catecholamines and their metabolites in various brain regions was more complex. Tianeptine (Coaxyl) was demonstrated to increase both the 5-HIAA content and the 5-HIAA/5-HT ratio in all the structures studied (except for nucleus accumbens), in good agreement with the hypothesis concerning a two-phase mode of tianeptine action with enhanced 5-HT secretion in the synaptic gap in the first stage of pharmacological response.

  4. Topical amitriptyline and ketamine for post-herpetic neuralgia and other forms of neuropathic pain.

    PubMed

    Sawynok, Jana; Zinger, Celia

    2016-01-01

    Neuropathic pain (NP) has several therapeutic options but efficacy is limited and adverse effects occur, such that additional treatment options are needed. A topical formulation containing amitriptyline 4% and ketamine 2% (AmiKet) may provide such an option. This report summarizes both published and unpublished results of clinical trials with AmiKet. In post-herpetic neuralgia (PHN), AmiKet produces a significant analgesia which is comparable to that produced by oral gabapentin. In diabetic painful neuropathy, AmiKet showed a strong trend towards pain reduction. In mixed neuropathic pain, case series reports suggest a favourable response rate, but are limited by trial characteristics. AmiKet is absorbed minimally following topical administration. Over 700 patients have now received topical AmiKet in clinical regimens, and it is well-tolerated with the adverse effects mainly being application site reactions. Both agents are polymodal, and several mechanisms may contribute to the peripheral efficacy of AmiKet. Topical AmiKet has the potential to be a first-line treatment option for PHN, and to be useful in other NP conditions. Furthermore, AmiKet has the potential to be an adjunct to systemic therapies, with the targeting of a peripheral compartment in addition to central sites of action representing a rational drug combination.

  5. Randomised clinical trial comparing melatonin 3 mg, amitriptyline 25 mg and placebo for migraine prevention

    PubMed Central

    Gonçalves, Andre Leite; Martini Ferreira, Adriana; Ribeiro, Reinaldo Teixeira; Zukerman, Eliova; Cipolla-Neto, José; Peres, Mario Fernando Prieto

    2016-01-01

    Introduction Melatonin has been studied in headache disorders. Amitriptyline is efficacious for migraine prevention, but its unfavourable side effect profile limits its use. Methods A randomised, double-blind, placebo-controlled study was carried out. Men and women, aged 18–65 years, with migraine with or without aura, experiencing 2–8 attacks per month, were enrolled. After a 4-week baseline phase, 196 participants were randomised to placebo, amitriptyline 25 mg or melatonin 3 mg, and 178 took a study medication and were followed for 3 months (12 weeks). The primary outcome was the number of migraine headache days per month at baseline versus last month. Secondary end points were responder rate, migraine intensity, duration and analgesic use. Tolerability was also compared between groups. Results Mean headache frequency reduction was 2.7 migraine headache days in the melatonin group, 2.2 for amitriptyline and 1.1 for placebo. Melatonin significantly reduced headache frequency compared with placebo (p=0.009), but not to amitriptyline (p=0.19). Melatonin was superior to amitriptyline in the percentage of patients with a greater than 50% reduction in migraine frequency. Melatonin was better tolerated than amitriptyline. Weight loss was found in the melatonin group, a slight weight gain in placebo and significantly for amitriptyline users. Conclusions Melatonin 3 mg is better than placebo for migraine prevention, more tolerable than amitriptyline and as effective as amitriptyline 25 mg. PMID:27165014

  6. The signaling of amitriptyline-induced inhibitory effect on electrical field stimulation response in colon smooth muscle.

    PubMed

    Zaw, Tin Sandar; Khin, Phyu Phyu; Sohn, Uy Dong

    2016-09-01

    Amitriptyline, a well-known antidepressant, exerts inhibitory effect on electrically stimulated rat colon smooth muscle contraction. In this study, we investigated the signaling pathway of amitriptyline-induced inhibitory effect. Changes in isometric force of colon muscle were recorded on polygraph, and data were analyzed by measuring the inhibitory extent induced by amitriptyline. Firstly, muscles were contracted by stimulation with electric field stimulation (EFS), and then, amitriptyline was added cumulatively to determine its influence effect on EFS. Amitriptyline significantly inhibited EFS-induced contraction dose dependently. Then, the mechanism of inhibitory effect of amitriptyline was evaluated by pretreating with various antagonists such as L-NAME, methylene blue, atropine, 5-HT receptors blockers, guanethidine, prazosin, guanabenz, isoprenaline, Y27632 (Rho-kinase inhibitor), ML9 (myosin light chain kinase (MLCK) inhibitor), U73122 (PLC inhibitor), and chelerythrine (PKC inhibitor). Then, Ca(2+) channel blocker (nifedipine) and K(+)channel blockers, tetraethylammonium (TEA), 4-aminopyridine (4-AP), and glybenclamide, were used to determine the involvement of ion channels. L-NAME, guanabenz, 5HT4 receptor blocker, ML9, and Y27632 enhanced the effect of amitriptyline. Meanwhile, methylene blue, atropine, guanethidine, prazosin, methylsergide, ondansetron, U73122, and chelerythrine blocked its effect. It was also shown that nifedipine enhanced but TEA and glybenclamide blocked amitriptyline-induced inhibitory effect on EFS. Our results indicated that amitriptyline may exert inhibitory effect in response to EFS by inhibiting muscarinic receptors and then PLC-mediated PKC pathway leading to opening of ATP-sensitive potassium channel.

  7. Amitriptyline vs divalproate in migraine prophylaxis: a randomized controlled trial.

    PubMed

    Kalita, J; Bhoi, S K; Misra, U K

    2013-07-01

    This study compares efficacy and safety of divalproate extended release (DVA-ER) and amitriptyline (AMT) in migraine. Three hundred migraineurs having >4 attacks monthly were randomized into DVA-ER or AMT. The primary end points were >50% reduction in frequency, ≥1 grade improvement in the severity, and >50% improvement in a visual analogue scale (VAS). Secondary end points were functional disability, rescue medication, and adverse events. The median age was 32 years, and 241 were women. 150 patients each received DVA-ER and AMT. At 3 months, 74.7% in DVA-ER and 62% patients in AMT group improved in headache frequency (P = 0.02) and at 6 months, 65.3% and 54%, respectively (P = 0.90). At 3 months, the VAS score improved by >50% in 80.7% in DVA-ER and 64% in AMT (P = 0.005). At 6 months, there was no significant difference between the two groups in VAS score (69.3% vs 56%; P = 0.47) and other outcome parameters. The composite side effects were also not different between the two groups (68% vs 81%); however, hair fall, menstrual irregularity, polycystic ovary, and weight gain were commoner in DVA-ER group. Divalproate extended release is more effective at 3 months than AMT; however, at 6 months, both are equally effective in migraine prophylaxis. © 2013 John Wiley & Sons A/S.

  8. Bioconcentration and Biotransformation of Amitriptyline in Gilt-Head Bream.

    PubMed

    Ziarrusta, Haizea; Mijangos, Leire; Izagirre, Urtzi; Plassmann, Merle M; Benskin, Jonathan P; Anakabe, Eneritz; Olivares, Maitane; Zuloaga, Olatz

    2017-02-21

    Extensive global use of the serotonin-norepinephrine reuptake inhibitor Amitriptyline (AMI) for treatment of mental health problems has led to its common occurrence in the aquatic environment. To assess AMI bioconcentration factors, tissue distribution, and metabolite formation in fish, we exposed gilt-head bream (Sparus aurata) to AMI in seawater for 7 days at two concentrations (0.2 μg/L and 10 μg/L). Day 7 proportional bioconcentration factors (BCFs) ranged from 6 (10 μg/L dose, muscle) to 127 (0.2 μg/L dose, brain) and were consistently larger at the low dose level. The relative tissue distribution of AMI was consistent at both doses, with concentrations decreasing in the order brain ≈ gill > liver > plasma > bile ≫ muscle. Using a suspect screening workflow based on liquid chromatography-high resolution (Orbitrap) mass spectrometry we identified 33 AMI metabolites (both Phase I and Phase II), occurring mostly in bile, liver and plasma. Ten structures are reported for the first time. Remarkably, all 33 metabolites retained the tricyclic ring structure common to tricyclic antidepressants, which may be toxicologically relevant. Collectively these data indicate that, in addition to AMI, a broad suite of metabolites should be included in biomonitoring campaigns in order to fully characterize exposure in aquatic wildlife.

  9. Mechanism of amitriptyline adsorption on Ca-montmorillonite (SAz-2).

    PubMed

    Chang, Po-Hsiang; Jiang, Wei-Teh; Li, Zhaohui; Kuo, Chung-Yih; Jean, Jiin-Shuh; Chen, Wan-Ru; Lv, Guocheng

    2014-07-30

    The uptake of amitriptyline (AMI) from aqueous environment by Ca-montmorillonite (SAz-2) was studied in a batch system under different physicochemical conditions. The adsorbent was characterized by X-ray diffraction and Fourier transform infrared (FTIR) analyses. The AMI adsorption on SAz-2 obeyed the Langmuir isotherm with a capacity of 330mg/g (1.05mmol/g) at pH 6-7. The adsorption kinetics was fast, almost reaching equilibrium in 2h, and followed a pseudo-second-order kinetic model. Desorption of exchangeable cations correlated with the AMI adsorption well, indicating that cation exchange was the major mechanism. X-ray diffraction patterns showing significant expansions of the d001 spacing and characteristic FTIR band shifts toward higher frequencies after AMI adsorption onto SAz-2 indicated that the adsorbed AMI molecules were intercalated into the interlayers of the mineral. Thermodynamic parameters based on partitioning coefficients suggested that the AMI adsorption was an endothermic physisorption at high adsorption levels. At low and higher AMI adsorption levels, the intercalated AMI molecules take a horizontal monolayer and bilayer conformation, respectively. The higher adsorption capacity suggested that SAz-2 could be a good candidate to remove AMI from wastewater and would be an important environmental sink for the fate and transport of AMI in soils and groundwater.

  10. Amitriptyline down-regulates coenzyme Q10 biosynthesis in lung cancer cells.

    PubMed

    Ortiz, Tamara; Villanueva-Paz, Marina; Díaz-Parrado, Eduardo; Illanes, Matilde; Fernández-Rodríguez, Ana; Sánchez-Alcázar, José A; de Miguel, Manuel

    2017-02-15

    Amitriptyline, a tricyclic antidepressant, has been proposed as an antitumoral drug in oxidative therapy. Its pro-apoptotic effects, mediated by high reactive oxygen species generation, have been already described. In this study we analysed the effect of amitriptyline on the biosynthesis of coenzyme Q10 (CoQ), an essential component for electron transport and a potent membrane antioxidant involved in redox signaling. We treated H460 cells, a non-small-cell lung cancer cell line, with amitriptyline and we analysed CoQ levels by HPLC and CoQ biosynthesis rate, as well as the enzymes involved in CoQ biosynthesis by real-time PCR and Western blot. Amitriptyline treatment induced a dose-dependent decrease in CoQ levels in tumor cells. CoQ decreased levels were associated with down-regulation of the expression of COQ4 gene, as well as decreased Coq4 and Coq6 protein levels. Our findings suggest that the effect of amitriptyline on CoQ biosynthesis highlights the potential of this drug for antitumoral oxidative therapy.

  11. Open comparative randomised study of moclobemide versus amitriptyline in major depressive illness (DSM IIIR) in Nigeria.

    PubMed

    Ononye, F; Sijuola, O A; Chukwuani, C M; Mume, O C; Makanjuola, R O

    2000-01-01

    In a multi-centre study, 60 patients (20 males and 40 females aged 43 +/- 15 and 37 +/- 15 years respectively) with a DSM-IIIR diagnosis of major depressive disorders were randomly assigned to treatment with either Moclobemide (maximum dose 600 mg per day) or Amitriptyline (maximum dose 150 mg per day) for eight weeks. Patients were evaluated pretreatment and over the 8 weeks treatment period using Hamilton Depression Rating Scale (HDRS) and the clinical global impressions (CGI). The Adverse Drug Effects Schedule, clinical, haematological and biochemical status were also evaluated pre, during and post treatment. Of the 60 patients enrolled for the study 54 were found evaluable for efficacy whilst all 60 were evaluated for safety (Adverse Event). On the HDRS and CGI scale there was no significant difference in the therapeutic outcome between the two treatment groups. In the overall clinical assessment rating at the end of treatment 94.1% of patients in the Moclobemide group were rated 'very good to good' and 94.4% with Amitriptyline. Moclobemide appeared to have a slightly better safety profile, the incidence of adverse event was 9.0% compared to 19.0% with Amitriptyline. The drop out rate was 16.7% and 26.7% for moclobemide and amitriptyline respectively. These differences were however not statistically significant. It was therefore concluded that moclobemide is an effective and safe alternative to amitriptyline, with attractive potential for out patients management of depressive illness.

  12. Potentiation of Amitriptyline Anti-Hyperalgesic-Like Action By Astroglial Connexin 43 Inhibition in Neuropathic Rats

    PubMed Central

    Jeanson, Tiffany; Duchêne, Adeline; Richard, Damien; Bourgoin, Sylvie; Picoli, Christèle; Ezan, Pascal; Mouthon, Franck; Giaume, Christian; Hamon, Michel; Charvériat, Mathieu

    2016-01-01

    Antidepressants, prescribed as first line treatment of neuropathic pain, have a limited efficacy and poorly tolerated side effects. Because recent studies pointed out the implication of astroglial connexins (Cx) in both neuropathic pain and antidepressive treatment, we investigated whether their blockade by mefloquine could modulate the action of the tricyclic antidepressant amitriptyline. Using primary cultures, we found that both mefloquine and amitriptyline inhibited Cx43-containing gap junctions, and that the drug combination acted synergically. We then investigated whether mefloquine could enhance amitriptyline efficacy in a preclinical model of neuropathic pain. Sprague-Dawley rats that underwent chronic unilateral constriction injury (CCI) to the sciatic nerve (SN) were treated with either amitriptyline, mefloquine or the combination of both drugs. Whereas acute treatments were ineffective, chronic administration of amitriptyline reduced CCI-SN-induced hyperalgesia-like behavior, and this effect was markedly enhanced by co-administration of mefloquine, which was inactive on its own. No pharmacokinetic interactions between both drugs were observed and CCI-SN-induced neuroinflammatory and glial activation markers remained unaffected by these treatments in dorsal root ganglia and spinal cord. Mechanisms downstream of CCI-SN-induced neuroinflammation and glial activation might therefore be targeted. Connexin inhibition in astroglia could represent a promising approach towards improving neuropathic pain therapy by antidepressants. PMID:27941941

  13. Mirtazapine vs. amitriptyline vs. placebo in the treatment of major depressive disorder.

    PubMed

    Smith, W T; Glaudin, V; Panagides, J; Gilvary, E

    1990-01-01

    Patients (n = 150) were randomized to a 6-week, double-blind study to evaluate the relative efficacy and safety of mirtazapine, amitriptyline, and placebo in the treatment of major depressive disorder symptoms. Average daily modal doses were mirtazapine, 18 mg; amitriptyline, 111 mg; and placebo, 4.6 capsules. Mirtazapine- and amitriptyline-treated patients had statistically significantly greater mean Hamilton Rating Scale for Depression (HAM-D) score reductions (weekly visits 1, 2, 4, and endpoint) compared to placebo. These findings were supported by the Montgomery-Asberg Depression Rating Scale (MADRS); the Zung Self-rating Depression Scale (SDS); and the Clinical Global Impressions (CGI) scales. Somnolence and weight gain were the only adverse clinical experiences (ACEs) reported substantially more often by mirtazapine-treated patients than by those in the placebo group. However, more amitriptyline-treated patients reported decreased visual accommodation, dry mouth, dyspepsia, constipation, tachycardia, hypertension, hypotension, discoordination, dizziness, and tremor than mirtazapine- or placebo-treated patients. Results of this study indicate that mirtazapine is more effective than placebo in the treatment of these patients, and superior to amitriptyline in respect to anticholinergic and cardiovascular effects.

  14. Biowaiver monographs for immediate release solid oral dosage forms: amitriptyline hydrochloride.

    PubMed

    Manzo, R H; Olivera, M E; Amidon, G L; Shah, V P; Dressman, J B; Barends, D M

    2006-05-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing amitriptyline hydrochloride are reviewed. Its therapeutic uses, its pharmacokinetic properties, the possibility of excipient interactions and reported BE/bioavailability (BA) problems are also taken into consideration. Literature data indicates that amitriptyline hydrochloride is a highly permeable active pharmaceutical ingredient (API). Data on the solubility according to the current Biopharmaceutics Classification System (BCS) were not fully available and consequently amitriptyline hydrochloride could not be definitively assigned to either BCS Class I or BCS Class II. But all evidence taken together, a biowaiver can currently be recommended provided that IR tablets are formulated with excipients used in existing approved products and that the dissolution meets the criteria defined in the Guidances.

  15. Amitriptyline- and mianserin-induced changes in acquisition of paired-association learning-task.

    PubMed

    Liljequist, R; Seppälä, T; Mattila, M J

    1978-02-01

    1 The double-blind study on twenty healthy students was an attempt at assessing the effects of 2-week's treatment with amitriptyline (25 mg three times a day) and mianserin (10 mg three times a day), each alone or separatively inbibed with alcohol (0.5 g/kg) on the immediate memory and on the acquisition of a paired-association learning-task. 2 Amitriptyline impaired both the short-term memory-span and acquisition, and alcohol potentiated these effects. The action of mianserin did not deviate significantly from that of the placebo, and it also failed to interact with alcohol. 3 It is concluded that the decrement in learning capacity, that occurs after the 2-week's treatment with therapeutic doses of amitriptyline, reflects changes in both the intrinsic and the regulatory mechanisms of learning.

  16. Effects of amitriptyline and mianserin on psychomotor skills and memory in man

    PubMed Central

    Mattila, M. J.; Liljequist, R.; Seppälä, T.

    1978-01-01

    1 Twenty volunteers were treated with amitriptyline 25 mg, mianserin 10 mg, and placebo, three times daily for 2 weeks each, in a double-blind cross-over study. Tests of psychomotor function and of learning and memory, were carried out after consumption of alcohol or a placebo drink at intervals during each treatment period. 2 Coordinative and reactive skills were affected by mianserin on the first day only, but by amitriptyline up to day 7 in most of the tests. Both drugs seemed to interact additively with alcohol. 3 Amitriptyline impaired short-term memory span and acquisition, and alcohol enhanced these effects. Mianserin did not affect learning and memory, and did not interact with alcohol in this respect. 4 The differing effects of amitripyline and mianserin are considered in relation to anticholinergic properties. PMID:341944

  17. Disputed case of homicide by smothering due to severe amitriptyline intoxication of the victim.

    PubMed

    Stiakakis, Ioannis; Belivanis, Stamatis D; Tzatzarakis, Manolis N; Fragoulis, Manolis; Tsatsakis, Aristidis M

    2009-07-01

    We report a fatal case of a female for whom the forensic autopsy revealed injuries to the external respiratory orifices indicating smothering. Subsequent postmortem toxicological analysis confirmed heavy amitriptyline acute intoxication. The victim had serious psychological problems, was under long-term treatment with antidepressants and was a systematic alcohol abuser. Forensic autopsy determined damage to the external airways, along with multiple formal petechial hemorrhages (Tardieu) in various parts of the body. The presence of amitriptyline, nortriptyline and 10-hydroxynortriptyline was confirmed by GC-MS and quantified by HPLC in blood (7.0 microg/ml amitriptyline and 7.4 microg/ml nortriptyline). The cause of death was disputed between severe intoxication (poisoning or suicide attempt) and smothering due to controversial evidence.

  18. Comparative study of clinical efficacy of amitriptyline and pregabalin in postherpetic neuralgia.

    PubMed

    Achar, Arun; Chakraborty, Partha Pratim; Bisai, Samiran; Biswas, Asish; Guharay, Tapobrata

    2012-01-01

    The most common complication of herpes zoster in immunocompetent patients is postherpetic neuralgia, which is very difficult to treat. Significant beneficial effects have been found for amitriptyline, gabapentin, pregabalin, carbamazepine, sodium valproate, oxycodone, corticosteroid, topical capsaicin, tramadol, etc. The aim of this open randomized comparative study was to demonstrate clinical efficacy of amitriptyline and pregabalin. The study included 50 patients, 32 (64%) male and 18 (36%) female, randomized to receive either amitriptyline or pregabalin (n=25 each). Amitriptyline was administered in a dose of 25 mg once daily and pregabalin in a dose of 75 mg twice daily. Inclusion criteria were as follows: postherpetic neuralgia of more than 1 month duration; pain of at least moderate severity; and patient age 40 years or older and no pregnancy. Patients with a history of any serious diseases (renal, cardiac, hepatic or seizure) were excluded. Total treatment period spanned 8 weeks, with patient follow up visits at 2, 4 and 8 weeks to assess the degree of improvement in pain perception and any adverse reaction. Patients with four herpes zoster types were included in this study, of which thoracic type predominated (54%). Other types were cervical in 12 (24%), trigeminal in 8 (16%) and lumbosacral in 3 (6%) patients. Prodromal symptoms before herpes zoster were reported by 66% of study patients. Satisfactory improvements of pain perception at the end of 8 weeks (>75%) were noticed in pregabalin group, which was statistically significant (χ(2)2=10.08; P<0.05). Dry mouth was the commonest complication in amitriptyline group and dizziness in pregabalin group. More importantly, none of the patients stopped treatment due to adverse reaction. In conclusion, therapy with pregabalin is better compared to amitriptyline in postherpetic neuralgia patients. However, a similar study in a larger sample is required to validate the present findings.

  19. Amitriptyline Dose and Treatment Outcomes in Specialty Headache Practice: A Retrospective Cohort Study.

    PubMed

    Doyle Strauss, Lauren; Weizenbaum, Emma; Loder, Elizabeth W; Rizzoli, Paul B

    2016-11-01

    To characterize treatment patterns and real world outcomes in headache patients treated with amitriptyline in an academic headache center. A retrospective chart review identified 178 patients in our center who were given a new prescription for amitriptyline in treatment of headache, and who were seen in follow-up within one year. Charts were reviewed to identify dosing patterns (initial and maximum dose) and persistence, patient-reported headache benefit, and reported side effects. Variables assessed in relation to medication use were comorbid psychiatric disease, headache characteristics, and prior use of a preventive medication. We followed patients for an average of 6.5 months. Initial and maximum prescribed amitriptyline doses were characterized as: "very low" (≤10 mg daily), "low" (11-25 mg daily), and "traditional" (≥25 mg daily). The initial dose of amitriptyline ranged from 2.5 to 50 mg daily, though most patients were started on a dose of 10 mg daily (112/178, 63%). Approximately 3/4 of the patients were found to have improvement (134/178) and 85% (129/151) were still taking amitriptyline at the last follow-up appointment. Maximum dosing ranged from 2.5 to 100 mg daily with most patients taking 10-25 mg (86/146, 58%). The most commonly reported adverse effect was daytime fatigue (17/151, 11%). There did not appear to be any effect from gender, ethnicity, race, diagnosis of sleep apnea, chronicity of migraine, presence of aura on our outcome measures. Our study supports the common clinical practice of using low doses of amitriptyline to treat chronic headache disorders and suggests that it was effective and well tolerated at doses lower than those used in many clinical trials. Use of low dosage amitriptyline may also improve medication persistence, an important clinical consideration in the management of this common and chronic condition. A subgroup of patients may experience a dramatic benefit from amitriptyline and this could warrant further

  20. Pharmacological Evaluation of Antidepressant-Like Effect of Genistein and Its Combination with Amitriptyline: An Acute and Chronic Study

    PubMed Central

    Gupta, Gaurav; Jia Jia, Tay; Yee Woon, Lim; Kumar Chellappan, Dinesh; Candasamy, Mayuren; Dua, Kamal

    2015-01-01

    The present study was designed to evaluate the acute and chronic antidepressant effect of genistein in combination with amitriptyline in mice. Animals were divided into six groups (n = 6) for treatment with water, genistein, or amitriptyline, either alone or in combination for ten days. Animals were subjected to locomotor activity testing; tail suspension test (TST); and forced swim test (FST) and immobility time was recorded on day one and day ten. Acute treatment of all treatment groups did not significantly reduce the immobility time (p > 0.05). Chronic treatment of combination of genistein (10 mg/kg) and amitriptyline (5 mg/kg and 10 mg/kg) significantly reduced the immobility time as compared to control group (p < 0.001) and was comparable to amitriptyline alone (10 mg/kg). However, no changes in anti-immobility activity in combination of subeffective doses of genistein (5 mg/kg) and amitriptyline (5 mg/kg) were observed. Genistein at its standard dose (10 mg/kg) rendered synergistic effects in combination with subeffective dose of amitriptyline (5 mg/kg) and additive effects in combination with therapeutic dose of amitriptyline (10 mg/kg). PMID:26681936

  1. Quantitative HPLC Analysis of a Psychotherapeutic Medication: Simultaneous Determination of Amitriptyline Hydrochloride and Perphenazine

    NASA Astrophysics Data System (ADS)

    Ferguson, Glenda K.

    1998-12-01

    A quantitative high-performance liquid chromatography (HPLC) laboratory experiment which entails the isocratic separation and simultaneous determination of the two active components of a commercial antipsychotic tablet has been developed. The prescription formulation used in this experiment contains amitriptyline hydrochloride (a tricyclic antidepressant) and perphenazine (a tranquilizer). Our experiment makes use of a straightforward HPLC separation on a cyanopropyl-packed column with an acetonitrile:methanol:aqueous monopotassium phosphate mobile phase pumped at a flow rate of 2.0 mL/min. Analytes are detected by UV absorbance at 215 nm. These conditions yield highly symmetrical and well-resolved peaks in less than 5 min after the injection of a mixture. In the experiment, students are given amitriptyline hydrochloride-perphenazine tablets without the manufacturer's labeled composition claim and a stock solution mixture with known concentrations of amitriptyline hydrochloride and perphenazine. They prepare four standards and a pharmaceutical sample of unknown concentration, assay each solution in quadruplicate, and plot average peak areas of the concentrations of the known solutions in the construction of a standard curve. From the mathematical relationships that result, the average masses of amitriptyline hydrochloride and perphenazine in the prescription tablet are determined. Finally, the standard deviations of the mean masses are calculated. The entire laboratory procedure and statistical data analysis can be completed in a single 3-hour period.

  2. A Comparison of Pharmacological (Amitriptyline HCL) and Nonpharmacological (Cognitive-Behavioral) Therapies for Chronic Tension Headaches.

    ERIC Educational Resources Information Center

    Holroyd, Kenneth A.; And Others

    1991-01-01

    Randomly assigned 41 recurrent tension headache sufferers to either cognitive-behavioral therapy or to amitriptyline therapy. Both therapies yielded clinically significant improvements in headache activity. In instances where differences in treatment effectiveness were observed, cognitive-behavioral therapy yielded somewhat more positive outcomes…

  3. A Comparison of Pharmacological (Amitriptyline HCL) and Nonpharmacological (Cognitive-Behavioral) Therapies for Chronic Tension Headaches.

    ERIC Educational Resources Information Center

    Holroyd, Kenneth A.; And Others

    1991-01-01

    Randomly assigned 41 recurrent tension headache sufferers to either cognitive-behavioral therapy or to amitriptyline therapy. Both therapies yielded clinically significant improvements in headache activity. In instances where differences in treatment effectiveness were observed, cognitive-behavioral therapy yielded somewhat more positive outcomes…

  4. An alternative antidote therapy in amitriptyline-induced rat toxicity model: theophylline.

    PubMed

    Oransay, Kubilay; Kalkan, Sule; Hocaoglu, Nil; Arici, Aylin; Tuncok, Yesim

    2011-01-01

    We planned this study in order to investigate the effects of theophylline on cardiovascular parameters in an anaesthetized rat model of amitriptyline toxicity. In the preliminary study, we tested theophylline as 1 mg/kg of bolus, followed by a 0.5-mg/kg infusion. Toxicity was induced by the infusion of 0.94 mg/kg/min of amitriptyline up to the point of a 40-45% inhibition of mean arterial pressure (MAP). The rats were randomized to two groups: a group of 5% dextrose bolus followed by 5% dextrose infusion, and another group with theophylline bolus followed by infusion. Amitriptyline caused a significant decrease in MAP and prolongation in QRS; however, it did not alter heart rate (HR). When compared to the dextrose group, theophylline administration increased MAP, shortened prolonged QRS duration, and increased HR (P < 0.05, respectively). There was no statistically significant difference in the results of arterial blood-gas analyses among the groups (P > 0.05). Bolus doses followed by a continuous infusion of theophylline were found to be effective in reversing the hypotension and QRS prolongation seen in amitriptyline toxicity. One of the possible explanations of this beneficial effect is nonselective adenosine antagonism of theophylline. Further studies are needed to reveal the exact mechanism of the observed effect.

  5. Amitriptyline modifies the visceral hypersensitivity response to acute stress in the irritable bowel syndrome.

    PubMed

    Thoua, N M; Murray, C D R; Winchester, W J; Roy, A J; Pitcher, M C L; Kamm, M A; Emmanuel, A V

    2009-03-01

    Acute physical stress causes alteration in gut autonomic function and visceral hypersensitivity in patients with irritable bowel syndrome (IBS). We have developed a model to measure this stress response. To assess whether treatment with a drug effective in treating IBS (amitriptyline) alters the response to acute stress in IBS patients. Nineteen patients with IBS were given amitriptyline 25-50 mg. Patients underwent physical stress (cold pressor) test at baseline and after 3 months of treatment. Physiological parameters measured were: stress perception; systemic autonomic tone [heart rate (HR) and blood pressure (BP)]; gut specific autonomic innervation [rectal mucosal blood flow (RMBF)] and visceral sensitivity (rectal electrosensitivity). Fourteen of 19 (74%) patients improved symptomatically after 3 months of amitriptyline. Acute stress induced increased perception of stress and systemic autonomic tone and reduced RMBF in symptomatic responders and nonresponders (P > 0.05 for all). All nonresponders but only 3 of 14 responders continued to exhibit stress-induced reduced pain threshold at 3 months (change from baseline -31% vs. +2%, P < 0.03 respectively). In this open study, amitriptyline appears to decrease stress-induced electrical hypersensitivity; this effect is independent of autonomic tone. The gut response to acute stress deserves further study as a model to study drug efficacy in IBS.

  6. Comparison of the effects of binodaline and amitriptyline on peripheral autonomic functions in healthy volunteers.

    PubMed Central

    Longmore, J; Szabadi, E; Bradshaw, C M

    1985-01-01

    Twelve healthy male volunteers participated in five experimental sessions separated by weekly intervals. At the beginning of each session the subjects received one single oral dose of the following drugs, according to a double-blind, balanced cross-over design: binodaline hydrochloride (50 mg or 100 mg); amitriptyline hydrochloride (50 mg or 100 mg); lactose placebo. Salivation and resting pupil diameter were assessed before and 2 h after the ingestion of the drugs; baseline sweating, carbachol- or phenylephrine-evoked sweating were measured 2 h following drug taking. Binodaline, like placebo, had little effect on salivary output, whereas amitriptyline caused a dose-dependent decrease in salivation. None of the drugs caused any significant change in resting pupil diameter or in baseline sweating. Carbachol-evoked sweating did not differ significantly following the ingestion of binodaline or placebo; on the other hand responses to carbachol were significantly reduced following amitriptyline. Phenylephrine-evoked sweating was reduced by both binodaline and amitriptyline. The lack of effect of binodaline on salivation, resting pupil diameter, baseline and carbachol-evoked sweating is in agreement with the results of animal experiments indicating the lack of an interaction of this drug with cholinergic mechanisms. The reduction in phenylephrine-evoked sweating would be indicative of an alpha-adrenoceptor blocking property of this drug. PMID:3986084

  7. Effect of amitriptyline treatment on neurofilament-H protein in an experimental model of depression.

    PubMed

    Sanna, Maria Domenica; Ghelardini, Carla; Galeotti, Nicoletta

    2017-01-01

    It has been proposed that depression is associated with dysfunction of hippocampal plasticity. Novel hypotheses suggest that antidepressants induce neuronal structural plasticity, although the underlying mechanisms still remain unclear. Therefore, the aim of this study was to investigate the effects of amitriptyline on levels of phosphorylated heavy neurofilament subunit (NF-H) in the hippocampus of mice exposed to acute and chronic behavioral despair paradigms. Immunoblotting experiments showed that animals exposed to the tail suspension test (TST) displayed diminished levels of pNF-H 24h after testing. Repeated administration of amitriptyline (10mg/kg i.p.) prevented this decreased hippocampal phosphorylation of NF-H. Conversely, administration of citalopram (10mg/kg i.p.) left unchanged pNF-H levels. The expression of pNF-H was also analyzed by immunofluorescence in mice exposed to the unpredictable chronic mild stress paradigm (UCMS), an experimental model of depression. Mice that developed a depressive-like behavior showed a decreased pNF-H immunostaining selectively in the hippocampal CA3 region. Chronic administration of amitriptyline reversed the despaired behavior induced by exposure to UCMS paradigm and, fully recovered pNF-H labeling to control values. Our results indicate that the cytoskeletal remodeling induced by amitriptyline in the hippocampal CA3 region might underpin its behavioral efficacy. Hippocampal alterations of the NF appeared associated with the mechanism of this antidepressant drug and may contribute to its psychotherapeutic actions. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. A Retrospective Study of Amitriptyline in Youth with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Bhatti, Irfan; Thome, Andrew; Smith, Patricia Oxler; Cook-Wiens, Galen; Yeh, Hung Wen; Gaffney, Gary R.; Hellings, Jessica A.

    2013-01-01

    We performed a retrospective chart review of 50 youths with Autism Spectrum Disorder (ASD), prescribed amitriptyline (AMI) for hyperactivity and impulsivity. Data was systematically extracted from 50 outpatient clinic charts, including AMI treatment duration, dose, trough levels and adverse events. Mean age was 9.4 years (4.6-17.9); 40 were males…

  9. A Retrospective Study of Amitriptyline in Youth with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Bhatti, Irfan; Thome, Andrew; Smith, Patricia Oxler; Cook-Wiens, Galen; Yeh, Hung Wen; Gaffney, Gary R.; Hellings, Jessica A.

    2013-01-01

    We performed a retrospective chart review of 50 youths with Autism Spectrum Disorder (ASD), prescribed amitriptyline (AMI) for hyperactivity and impulsivity. Data was systematically extracted from 50 outpatient clinic charts, including AMI treatment duration, dose, trough levels and adverse events. Mean age was 9.4 years (4.6-17.9); 40 were males…

  10. An evaluation of possible interactions between ethanol and trazodone or amitriptyline.

    PubMed Central

    Warrington, S J; Ankier, S I; Turner, P

    1984-01-01

    The pharmacodynamic effects of single doses of trazodone (100 mg), amitriptyline (50 mg) or placebo either alone or with ethanol (0.5 ml/kg) were investigated in six healthy volunteers in a double-blind crossover study. Plasma concentrations of the drugs and ethanol were also measured. Pharmacodynamic tests were critical flicker fusion frequency threshold (CFF), choice reaction time (CRT), manual dexterity, a digit span test and visual analogue scales. Blood ethanol concentrations were not influenced by the co-administration of either antidepressant. tmax for trazodone was prolonged by ethanol but the other pharmacokinetic parameters for trazodone and amitriptyline were not influenced by ethanol. Trazodone and amitriptyline caused the expected profound depressant effects on CFF, CRT, manual dexterity and on the rating scales for drowsiness, 'clear-headedness', aggression and disinhibition. Ethanol alone impaired manual dexterity, increased drowsiness, reduced 'clear headedness' and also tended to reduce feelings of aggression. In combination with either trazodone or amitriptyline, ethanol caused little additional effect except in the case of manual dexterity which was further impaired. This result may reflect the profound effects of the antidepressants alone and does not suggest that it is safe for patients receiving antidepressant medication to take ethanolic drinks. PMID:6487494

  11. Tricyclic analogs cyclobenzaprine, amitriptyline and cyproheptadine inhibit the spinal reflex transmission through 5-HT(2) receptors.

    PubMed

    Honda, Motoko; Nishida, Takashi; Ono, Hideki

    2003-01-01

    The centrally acting muscle relaxant cyclobenzaprine decreases the amplitude of monosynaptic reflex potentials by inhibiting the facilitatory descending serotonergic influences in the spinal cord. Interestingly, the structure of cyclobenzaprine is much similar to those of amitriptyline and cyproheptadine. In the present study, we attempted to elucidate the relationship between 5-HT(2) receptor antagonistic and inhibitory effects of cyclobenzaprine, amitriptyline, cyproheptadine and ketanserin on the spinal reflexes. Cyclobenzaprine, amitriptyline, cyproheptadine, and ketanserin significantly inhibited facilitatory effects of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) on flexor reflexes and mono- and polysynaptic spinal reflex potentials in spinalized rats. In intact rats, these drugs significantly reduced the mono- and polysynaptic reflex potentials. 5-HT depletion significantly prevented the depression of the spinal reflex potentials induced by these drugs. These results suggest that the inhibitory effects of cyclobenzaprine, amitriptyline, and cyproheptadine on mono- and polysynaptic reflex potentials are due to the inhibition of descending serotonergic systems through 5-HT(2) receptors in the spinal cord.

  12. Acute herpes zoster and postherpetic neuralgia: effects of acyclovir and outcome of treatment with amitriptyline.

    PubMed Central

    Bowsher, D

    1992-01-01

    This retrospective study was designed to assess the effects of acyclovir treatment of acute herpes zoster on subsequent postherpetic neuralgia, and to examine the effects of amitriptyline in the treatment of postherpetic neuralgia. Eighty seven patients with postherpetic neuralgia of three or more months' duration were studied: 24 of them had had their herpes zoster treated with oral acyclovir. At first presentation, only 25% of the 24 patients who had had their herpes zoster treated with acyclovir selected the word group containing burning on the McGill pain questionnaire compared with 76% of the 63 patients who had not received acyclovir. A higher proportion of patients who had had acyclovir than had not selected the word group which contains the word aching (63% versus 49%). Acyclovir thus appears to change the nature of postherpetic neuralgia. Postherpetic neuralgia was treated with amitriptyline, alone or in combination with distigmine and/or sodium valproate. There was a strong correlation between pain relief and the interval between the occurrence of herpes zoster and the initiation of treatment with amitriptyline--early treatment is almost twice as likely to be successful as late. Since conventional analgesics and sympatholytic drugs are of no benefit in the treatment of established postherpetic neuralgia, the sequelae of herpes zoster must, therefore, be recognized and treated with amitriptyline as soon as possible. PMID:1419247

  13. Evaluation of the pharmacokinetics of oral amitriptyline and its active metabolite nortriptyline in fed and fasted Greyhound dogs.

    PubMed

    Norkus, C; Rankin, D; KuKanich, B

    2015-12-01

    This study reports the pharmacokinetics of oral amitriptyline and its active metabolite nortriptyline in Greyhound dogs. Five healthy Greyhound dogs were enrolled in a randomized crossover design. A single oral dose of amitriptyline hydrochloride (actual mean dose 8.1 per kg) was administered to fasted or fed dogs. Blood samples were collected at predetermined times from 0 to 24 h after administration, and plasma drug concentrations were measured by liquid chromatography with mass spectrometry. Noncompartmental pharmacokinetic analyses were performed. Two dogs in the fasted group vomited following amitriptyline administration and were excluded from analysis. The range of amitriptyline CMAX for the remaining fasted dogs (n = 3) was 22.8-64.5 ng/mL compared to 30.6-127 ng/mL for the fed dogs (n = 5). The range of the amitriptyline AUCINF for the three fasted dogs was 167-720 h·ng/mL compared to 287-1146 h·ng/mL for fed dogs. The relative bioavailability of amitriptyline in fasted dogs compared to fed dogs was 69-91% (n = 3). The exposure of the active metabolite nortriptyline was correlated to amitriptyline exposure (R(2)  = 0.84). Due to pharmacokinetic variability and the small number of dogs completing this study, further studies are needed assessing the impact of feeding on oral amitriptyline pharmacokinetics. Amitriptyline may be more likely to cause vomiting in fasted dogs. © 2015 John Wiley & Sons Ltd.

  14. Attenuation of morphine-induced dependence and tolerance by ceftriaxone and amitriptyline in mice.

    PubMed

    Habibi-Asl, Bohlul; Vaez, Haleh; Najafi, Moslem; Bidaghi, Ali; Ghanbarzadeh, Saeed

    2014-12-01

    Tolerance to and dependence on the analgesic effect of opioids is a pharmacological phenomenon that occurs after their prolonged administration. The aim of this study was to evaluate the protective effects of ceftriaxone and amitriptyline on the development of morphine-induced tolerance and dependence. In this study, 18 groups (9 groups each for tolerance and dependency tests) of mice (n = 8) received saline [10 mL/kg, intraperitoneally (i.p.)], morphine (50 mg/kg, i.p.), ceftriaxone (50 mg/kg, i.p., 100 mg/kg, i.p., and 200 mg/kg, i.p.), amitriptyline (5 mg/kg, i.p., 10 mg/kg, i.p., and 15 mg/kg, i.p.), or a combination of ceftriaxone (50 mg/kg, i.p.) and amitriptyline (5 mg/kg, i.p.) once per day for 4 days for investigation and comparison of the effects of ceftriaxone and amitriptyline on the prevention of dependency and tolerance to morphine. Tolerance was assessed with administration of morphine (9 mg/kg, i.p.) and using the hot plate test on the 5(th) day. In dependency tests, withdrawal symptoms were assessed on the 4(th) day for each animal 30 minutes after the administration of naloxone (4 mg/kg, i.p.; 2 hours after the last dose of morphine). It was found that treatment with ceftriaxone or amitriptyline attenuated the development of tolerance to the antinociceptive effect of morphine and also reduced naloxone-precipitated withdrawal jumping and standing on feet. Furthermore, coadministration of ceftriaxone and amitriptyline at low doses (50 mg/kg, i.p. and 5 mg/kg, i.p., respectively) prior to morphine injection also decreased both morphine-induced tolerance and dependence. Results indicate that the treatment with ceftriaxone and amitriptyline, alone or in combination, could attenuate the development of morphine-induced tolerance and dependence. Copyright © 2014. Published by Elsevier B.V.

  15. Cognitive Behavioral Therapy plus Amitriptyline for Children and Adolescents with Chronic Migraine Reduces Headache Days to ≤4 Per Month.

    PubMed

    Kroner, John W; Hershey, Andrew D; Kashikar-Zuck, Susmita M; LeCates, Susan L; Allen, Janelle R; Slater, Shalonda K; Zafar, Marium; Kabbouche, Marielle A; O'Brien, Hope L; Shenk, Chad E; Rausch, Joseph R; Kroon Van Diest, Ashley M; Powers, Scott W

    2016-04-01

    The objective of this secondary analysis of results from a previously published trial (Clinical Trials Registration Number: NCT00389038) in chronic migraine in children and adolescents was to examine if participants who received cognitive behavioral therapy and amitriptyline reached a greater level of reduction in headache frequency that no longer indicated a recommendation for preventive treatment as compared to those who received headache education and amitriptyline. Chronic migraine negatively affects children's home, school, and social activities. Preventive medication therapy is suggested for 5 or more headaches per month. Reduction to one headache day per week or less may suggest that preventive treatment is no longer indicated and provide a clinically relevant outcome for treatment efficacy and patient care. Randomized study participants (N = 135) kept a daily record of their headache frequency during 20 weeks of treatment and during a 1 year follow-up period. Baseline headache frequency was determined at the end of a 28 day screening period. Post treatment frequency was determined at 20 weeks (N = 128 completed) and post treatment follow-up was measured 12 months later (N = 124 completed). A chi-square test of independence was conducted by treatment group and by time point to determine group differences in the proportion of headache days experienced. At 20 weeks (post treatment), 47% of the cognitive behavioral therapy plus amitriptyline group had ≤4 headache days per month compared to 20% of the headache education plus amitriptyline group, (P = .0011), and 32% of the cognitive behavioral therapy plus amitriptyline group had ≤3 headache days per month at 20 weeks compared to 16% of the headache education plus amitriptyline group, (P = .0304). At the month 12 follow-up, 72% of the cognitive behavioral therapy plus amitriptyline group had ≤4 headache days per month compared to 52% of the headache education plus amitriptyline group

  16. Influence of amitriptyline on eryptosis, parasitemia and survival of Plasmodium berghei-infected mice.

    PubMed

    Brand, Verena; Koka, Saisudha; Lang, Camelia; Jendrossek, Verena; Huber, Stephan M; Gulbins, Erich; Lang, Florian

    2008-01-01

    Plasmodia express a sphingomyelinase, which is apparently required for their development. On the other hand, the sphingomyelinase product ceramide has previously been shown to delay parasite development. Moreover, ceramide triggers suicidal erythrocyte death or eryptosis, characterized by exposure of phosphatidylserine at the erythrocyte surface and cell shrinkage. Accelerated eryptosis of infected erythrocytes is considered to clear infected erythrocytes from circulating blood and, thus, to favourably influence the clinical course of malaria. The present experiments explored whether the sphingomyelinase inhibitor amitriptyline or genetic knockout of host acid sphingomyelinase influence in vitro parasite growth, eryptosis of Plasmodium falciparum-infected human erythrocytes, in vivo parasitemia and survival of P. berghei-infected mice. Phosphatidylserine exposure was determined by annexin V-binding and cell volume by forward scatter in FACS analysis. In vitro infection of human erythrocytes increased annexin- binding, an effect blunted in the presence of amitriptyline (>or=50 microM). Amitriptyline did not significantly alter intraerythrocytic parasite development but significantly (>or= 1 microM) delayed the increase in parasitemia in vitro. Most importantly, amitriptyline treatment (1 mM in drinking water) resulted in a significant delay of parasitemia and death of infected mice. However, upon infection, ceramide formation was stimulated in both, acid sphingomyelinase knockout mice (Smpd1(-/-)) and their wild type littermates (Smpd1(+/+)). Parasitemia following P. berghei infection was significantly lower in Smpd1(-/-) than in Smpd1(+/+) mice but did not significantly extend the life span of infected animals. In conclusion, mammalian and parasite sphingomyelinase contribute to ceramide formation during malaria, whereby the parasite sphingomyelinase ultimately determines the course of the infection. Amitriptyline presumably blocks both sphingomyelinases and, thus

  17. Amitriptyline and phenytoin prevents memory deficit in sciatic nerve ligation model of neuropathic pain.

    PubMed

    Abdulmajeed, Wahab Imam; Ibrahim, Ridwan Babatunde; Ishola, Azeez Olakunle; Balogun, Wasiu Gbolahan; Cobham, Ansa Emmanuel; Amin, Abdulbasit

    2016-03-01

    Phenytoin and amitriptyline are often reported to attenuate pain in chronic conditions. Information on their ability to ameliorate cognitive impairment associated with neuropathic pain remains unclear due to mixed results from studies. This study investigated the effects of phenytoin and amitriptyline on memory deficit associated with neuropathic pain. Twenty-eight adult male Wistar rats were randomly divided into four groups: A, B, C, and D (n=7). Groups A, B, C, and D served as sham control, sciatic nerve ligated untreated, sciatic nerve ligated receiving amitriptyline (5 mg/kg), and sciatic nerve ligated receiving phenytoin (10 mg/kg) respectively. Treatments lasted for 14 days, after which both 'Y' maze and novel object recognition test (NOR) were performed. On the last day of treatment, the animals were anesthetized and their brain excised, and the prefrontal cortices and sciatic nerve were processed histologically using hematoxylin and eosin. There was memory impairment in the sciatic nerve ligated untreated group which was statistically significant (p<0.05) when compared to the phenytoin-treated, amitriptyline-treated, and sham control groups using the 'Y' maze and NOR tests. Histological quantification showed that the prefrontal cortices of the ligated animals showed increased neural population in comparison to normal control. These increases were significantly marked in the untreated ligated group. Sciatic nerve of untreated ligated group showed high demyelination and axonal degeneration which was ameliorated in the treated animals. The administration of amitriptyline and phenytoin can ameliorate neuronal injury, demyelination, and memory impairment associated with neuropathic pain in Wistar rats.

  18. Cognitive behavioral therapy plus amitriptyline for chronic migraine in children and adolescents: a randomized clinical trial.

    PubMed

    Powers, Scott W; Kashikar-Zuck, Susmita M; Allen, Janelle R; LeCates, Susan L; Slater, Shalonda K; Zafar, Marium; Kabbouche, Marielle A; O'Brien, Hope L; Shenk, Chad E; Rausch, Joseph R; Hershey, Andrew D

    2013-12-25

    Early, safe, effective, and durable evidence-based interventions for children and adolescents with chronic migraine do not exist. To determine the benefits of cognitive behavioral therapy (CBT) when combined with amitriptyline vs headache education plus amitriptyline. A randomized clinical trial of 135 youth (79% female) aged 10 to 17 years diagnosed with chronic migraine (≥15 days with headache/month) and a Pediatric Migraine Disability Assessment Score (PedMIDAS) greater than 20 points were assigned to the CBT plus amitriptyline group (n = 64) or the headache education plus amitriptyline group (n = 71). The study was conducted in the Headache Center at Cincinnati Children's Hospital between October 2006 and September 2012; 129 completed 20-week follow-up and 124 completed 12-month follow-up. Ten CBT vs 10 headache education sessions involving equivalent time and therapist attention. Each group received 1 mg/kg/d of amitriptyline and a 20-week end point visit. In addition, follow-up visits were conducted at 3, 6, 9, and 12 months. The primary end point was days with headache and the secondary end point was PedMIDAS (disability score range: 0-240 points; 0-10 for little to none, 11-30 for mild, 31-50 for moderate, >50 for severe); both end points were determined at 20 weeks. Durability was examined over the 12-month follow-up period. Clinical significance was measured by a 50% or greater reduction in days with headache and a disability score in the mild to none range (<20 points). At baseline, there were a mean (SD) of 21 (5) days with headache per 28 days and the mean (SD) PedMIDAS was 68 (32) points. At the 20-week end point, days with headache were reduced by 11.5 for the CBT plus amitriptyline group vs 6.8 for the headache education plus amitriptyline group (difference, 4.7 [95% CI, 1.7-7.7] days; P = .002). The PedMIDAS decreased by 52.7 points for the CBT group vs 38.6 points for the headache education group (difference, 14.1 [95% CI, 3

  19. Cognitive Behavioral Therapy Plus Amitriptyline for Chronic Migraine in Children and Adolescents

    PubMed Central

    Powers, Scott W.; Kashikar-Zuck, Susmita M.; Allen, Janelle R.; LeCates, Susan L.; Slater, Shalonda K.; Zafar, Marium; Kabbouche, Marielle A.; O’Brien, Hope L.; Shenk, Chad E.; Rausch, Joseph R.; Hershey, Andrew D.

    2016-01-01

    IMPORTANCE Early, safe, effective, and durable evidence-based interventions for children and adolescents with chronic migraine do not exist. OBJECTIVE To determine the benefits of cognitive behavioral therapy (CBT) when combined with amitriptyline vs headache education plus amitriptyline. DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial of 135 youth (79% female) aged 10 to 17 years diagnosed with chronic migraine (≥15 days with headache/month) and a Pediatric Migraine Disability Assessment Score (PedMIDAS) greater than 20 points were assigned to the CBT plus amitriptyline group (n = 64) or the headache education plus amitriptyline group (n = 71). The study was conducted in the Headache Center at Cincinnati Children’s Hospital between October 2006 and September 2012; 129 completed 20-week follow-up and 124 completed 12-month follow-up. INTERVENTIONS Ten CBT vs 10 headache education sessions involving equivalent time and therapist attention. Each group received 1 mg/kg/d of amitriptyline and a 20-week end point visit. In addition, follow-up visits were conducted at 3, 6, 9, and 12 months. MAIN OUTCOMES AND MEASURES The primary end point was days with headache and the secondary end point was PedMIDAS (disability score range: 0–240 points; 0–10 for little to none, 11–30 for mild, 31–50 for moderate, >50 for severe); both end points were determined at 20 weeks. Durability was examined over the 12-month follow-up period. Clinical significance was measured by a 50% or greater reduction in days with headache and a disability score in the mild to none range (<20 points). RESULTS At baseline, there were a mean (SD) of 21 (5) days with headache per 28 days and the mean (SD) PedMIDAS was 68 (32) points. At the 20-week end point, days with headache were reduced by 11.5 for the CBT plus amitriptyline group vs 6.8 for the headache education plus amitriptyline group (difference, 4.7 [95% CI, 1.7–7.7] days; P = .002). The PedMIDAS decreased by 52.7 points

  20. [Exploratory study of amitriptyline resistance in depressed patients: results of WHO French collaborating center on depressions resistant to treatments].

    PubMed

    Loas, G; Rose, D; Nowaczkowski, P; Lernout, P; Duron, B

    1996-06-01

    A multicountry, multicentre double-blind study in a group of depressives, coordinated by the Mental Health Division of the World Health Association (WHO) has been done. The goal of the study is to determine whether the therapeutic effects of amitriptyline can be enhanced and potentiated by combining it with an antioxydant (gingko biloba). An exploratory study has preceded the main study which had the objective to estimate the proportion of non-response patient to amitriptyline. We report the results concerning the French center. 23 inpatients meet the ICD-10 criteria for depression (F32 and F33) and were treated during 6 weeks by amitriptyline with the initial daily dose of 50 mg until the maximum dose of 200 mg. The proportion of non-responsive patient to amitriptyline was 34.78 (95% confidence interval : 15.32 to 54.24%), all clinically deteriorated.

  1. Growth inhibition and coordinated physiological regulation of zebrafish (Danio rerio) embryos upon sublethal exposure to antidepressant amitriptyline.

    PubMed

    Yang, Ming; Qiu, Wenhui; Chen, Jingsi; Zhan, Jing; Pan, Chenyuan; Lei, Xiangjie; Wu, Minghong

    2014-06-01

    Amitriptyline is a tricyclic antidepressant used for decades. It is present at low detectable concentrations in the aquatic environment, but relative few studies have focused on its ecotoxicological effects on non-target aquatic animals. The present study conducted an acute toxicity test of waterborne amitriptyline exposure using zebrafish (Danio rerio) embryos 4 to 124 h-post-fertilization. Time-dependent lethal concentrations were firstly determined and at mg/L levels. Effects of amitriptyline on zebrafish embryos were then evaluated under amitriptyline exposure at sublethal concentrations of 1, 10, 100 ng/L, 1, 10, 100 μg/L and 1mg/L. Our results showed that amitriptyline significantly reduced the hatching time and body length of embryos after exposure in a concentration-dependent manner. Our study also revealed that the exposure evoked a coordinated modulation of physiological and biochemical parameters in exposed zebrafish embryos, including alterations of adrenocorticotropic hormone (ACTH) level, oxidative stress and antioxidant parameters, as well as nitric oxide (NO) production and total nitric oxide synthase (TNOS) activity. A U-shaped concentration-dependent response curve was observed in ACTH level in response to amitriptyline exposure. However, both U-shaped and inversed U-shaped curves were indicated in the responses of antioxidant parameters, including total antioxidant capacity, antioxidant enzyme activities (catalase, superoxide dismutase and peroxidase), glutathione content and glutathione reductase activity. Correspondingly, hydroxyl radical formation and lipid peroxidation indices changed in similar U-shaped concentration-dependent patterns, which together the results of antioxidant parameters suggested induction of oxidative stress in embryos exposed to amitriptyline at high concentrations. Moreover, NO production and TNOS activity were both significantly affected by amitriptyline exposure. Notably, significant correlations between these

  2. Mirtazapine versus amitriptyline in the long-term treatment of depression: a double-blind placebo-controlled study.

    PubMed

    Montgomery, S A; Reimitz, P E; Zivkov, M

    1998-03-01

    Of 580 patients randomly assigned to short-term, double-blind treatment with either mirtazapine, amitriptyline or placebo, a total of 217 patients clinically judged to be responders subsequently continued on the same medication for up to 2 years in the long-term treatment study (mirtazapine, n = 74; amitriptyline, n = 86 and placebo, n = 57). The efficacy of mirtazapine in relapse prevention was seen in an analysis of the first 20 weeks data. Significantly fewer patients relapsed during treatment with mirtazapine compared with placebo (p < 0.05), and a significantly longer time to relapse was shown on the survival analysis. There was a significant advantage for amitriptyline compared with placebo in the first 20 weeks, with fewer patients relapsing. There was a significant advantage for mirtazapine compared with amitriptyline at 20 weeks seen on the survival analysis (p < 0.05). The significant advantage for mirtazapine compared with placebo was also seen in the prophylactic phase of treatment after 20 weeks. At the endpoint there were significantly more patients in the placebo group with a return of symptoms and significantly fewer showing sustained response. Amitriptyline was better than placebo with fewer patients suffering a recurrence of symptoms, but there was no difference from placebo in the proportion of patients with sustained response. Mirtazapine was well tolerated with a side-effect profile similar to that of placebo. The only adverse event reported significantly more frequently on mirtazapine than on placebo was weight gain. Objectively measured weight gain was more frequent with amitriptyline (22% of patients) compared with mirtazapine (13% of patients). Amitriptyline was associated with significantly more adverse events than either mirtazapine or placebo, in particular sedative and anticholinergic side effects. The efficacy of mirtazapine in reducing the risk of relapse and the recurrence of depression, which on some measures showed an advantage

  3. Amitriptyline induces brain-derived neurotrophic factor (BDNF) mRNA expression through ERK-dependent modulation of multiple BDNF mRNA variants in primary cultured rat cortical astrocytes and microglia.

    PubMed

    Hisaoka-Nakashima, Kazue; Kajitani, Naoto; Kaneko, Masahiro; Shigetou, Takahiro; Kasai, Miho; Matsumoto, Chie; Yokoe, Toshiki; Azuma, Honami; Takebayashi, Minoru; Morioka, Norimitsu; Nakata, Yoshihiro

    2016-03-01

    A significant role of brain-derived neurotrophic factor (BDNF) has been previously implicated in the therapeutic effect of antidepressants. To ascertain the contribution of specific cell types in the brain that produce BDNF following antidepressant treatment, the effects of the tricyclic antidepressant amitriptyline on rat primary neuronal, astrocytic and microglial cortical cultures were examined. Amitriptyline increased the expression of BDNF mRNA in astrocytic and microglial cultures but not neuronal cultures. Antidepressants with distinct mechanisms of action, such as clomipramine, duloxetine and fluvoxamine, also increased BDNF mRNA expression in astrocytic and microglial cultures. There are multiple BDNF mRNA variants (exon I, IIA, IV and VI) expressed in astrocytes and microglia and the variant induced by antidepressants has yet to be elaborated. Treatment with antidepressants increased the expression of exon I, IV and VI in astrocyte and microglia. Clomipramine alone significantly upregulated expression of exon IIA. The amitriptyline-induced expression of both total and individual BDNF mRNA variants (exon I, IV and VI) were blocked by MEK inhibitor U0126, indicating MEK/ERK signaling is required in the expression of BDNF. These findings indicate that non-neural cells are a significant target of antidepressants and further support the contention that glial production of BDNF is crucial role in the therapeutic effect of antidepressants. The current data suggest that targeting of glial function could lead to the development of antidepressants with a truly novel mechanism of action.

  4. Anti-inflammatory Effect of Amitriptyline on Ulcerative Colitis in Normal and Reserpine-Induced Depressed Rats

    PubMed Central

    Fattahian, Ehsan; Hajhashemi, Valiollah; Rabbani, Mohammad; Minaiyan, Mohsen; Mahzouni, Parvin

    2016-01-01

    Depressive disorders are more common among persons with chronic diseases such as inflammatory bowel disease and anti-inflammatory effect of some antidepressants such as amitriptyline has been reported. Acetic acid colitis was induced in both reserpinised (depressed) and non-reserpinised (normal) rats. Reserpinised groups received reserpine (6 mg/kg, i.p.) one hour prior to colitis induction. Then Amitriptyline (5, 10, 20 mg/kg, i.p.) was administered to separate groups of male Wistar rats. All treatments were carried out two hours after colitis induction and continued daily for four days. Dexamethasone (1 mg/kg) and normal saline (1 mL/kg) were used in reference and control groups, respectively. At day five, animals were euthanized and colonic tissue injuries were assessed macroscopically and pathologically. Myeloperoxidase activity as a marker of neutrophil infiltration was also measured in colonic tissues. Results showed that reserpine (6 mg/kg, i.p.) intensified colitic condition. Compared to control, amitriptyline (10, 20 mg/kg) and dexamethasone significantly decreased weight of colon and ulcer index in normal and reserpine-induced depressed rats. Myeloperoxidase activity and pathological assessments also proved anti-inflammatory effect of amitriptyline. Our results suggest that amitriptyline, a tricyclic antidepressant, could reduce inflammatory and ulcerative injuries of colon both in normal and depressed rats. So among the wide spread anti-depressant drugs, amitriptyline is a good choice to treat depression comorbidities in patients with IBD. PMID:28228811

  5. TRANSITORY CONSECUTIVE ESOTROPIA AFTER AMITRIPTYLINE TREATMENT FOR NOCTURNAL ENURESIS -CASE REPORT.

    PubMed

    Cioplean, E Daniela; Camburu, L Raluca

    2015-01-01

    We report the case of a 9-year-old child operated for intermittent exotropia and V-pattern with a good result 2 months after bilateral Lateral Rectus Muscle Recession. The binocular vision was restored in primary position and down-gaze with excellent stereopsis at near and distance and a deviation of +4 PD in primary position. Three months later, the patient developed a consecutive esotropia of + 18 PD in primary position with diplopia in all gazes triggered by Amitriptyline treatment prescribed one month earlier for nocturnal enuresis. Diplopia was solved in time after anticholinergic medication cessation. During the recovery period, Fresnell prisms have been used in order to eliminate diplopia. Three months after diplopia onset, the binocular vision was restored showing a transitory and reversible effect of the Amitriptyline treatment. Fusion vulnerability can be a possible risk factor in developing diplopia and esotropia in patients treated with anticholinergic drugs.

  6. Conditioning of amitriptyline-induced REM sleep suppression in healthy participants: A randomized controlled trial.

    PubMed

    Winkler, Alexander; Rheker, Julia; Doering, Bettina K; Rief, Winfried

    2016-10-01

    Clinical trials in sleep disorders report substantial improvement in symptoms in their placebo groups. Behavioral conditioning is one of the underlying mechanisms of the placebo response. However, we do not know whether, and if so, the extent to which sleep architecture is influenced by behavioral conditioning, similarly to other physiological responses (i.e., those in the immune system). We therefore applied a conditioning paradigm to 39 healthy adults pairing a novel-tasting drink (conditioned stimulus, CS) with the REM sleep suppressing tricyclic antidepressant amitriptyline as unconditioned stimulus during the acquisition phase. Subsequent sole presentation of the CS (together with a placebo pill) in an evocation night led to significantly more REM sleep in the amitriptyline group. Instead of the expected REM sleep suppression in the evocation night, we observed more REM sleep, indicating a rebound that interferes with the conditioned response. © 2016 Society for Psychophysiological Research.

  7. Treatment of cyclic vomiting syndrome with co-enzyme Q10 and amitriptyline, a retrospective study

    PubMed Central

    2010-01-01

    Background Cyclic vomiting syndrome (CVS), which is defined by recurrent stereotypical episodes of nausea and vomiting, is a relatively-common disabling condition that is associated with migraine headache and mitochondrial dysfunction. Co-enzyme Q10 (Co-Q) is a nutritional supplement that has demonstrated efficacy in pediatric and adult migraine. It is increasingly used in CVS despite the complete lack of studies to demonstrate its value in treatment Methods Using an Internet-based survey filled out by subjects with CVS or their parents, the efficacy, tolerability and subject satisfaction in CVS prophylaxis were queried. Subjects taking Co-Q (22 subjects) were compared against those taking amitriptyline (162 subjects), which is the general standard-of-care. Results Subjects/parents reported similar levels of efficacy for a variety of episode parameters (frequency, duration, number of emesis, nausea severity). There was a 50% reduction in at least one of those four parameters in 72% of subjects treated with amitriptyline and 68% of subjects treated Co-Q. However, while no side effects were reported on Co-Q, 50% of subjects on amitriptyline reported side effects (P = 5 × 10-7), resulting in 21% discontinuing treatment (P = 0.007). Subjects/parents considered the benefits to outweigh the risks of treatment in 47% of cases on amitriptyline and 77% of cases on Co-Q (P = 0.008). Conclusion Our data suggest that the natural food supplement Co-Q is potentially efficacious and tolerable in the treatment of CVS, and should be considered as an option in CVS prophylaxis. Our data would likely be helpful in the design of a double-blind clinical trial. PMID:20109231

  8. Prolonged analgesic effect of amitriptyline base on thermal hyperalgesia in an animal model of neuropathic pain.

    PubMed

    Huang, Kuo-Lun; Shieh, Ja-Ping; Chu, Chin-Chen; Cheng, Kuang-I; Wang, Jhi-Joung; Lin, Mao-Tsun; Yeh, Mou-Yung

    2013-02-28

    The best analgesic drugs for neuropathic pain have a long duration of action, can be given via multiple routes, and can be used preemptively. We evaluated the antinociceptive effects and duration of action of subcutaneously injected amitriptyline base (AMT-Base) (in oil). A plantar test in a spinal nerve ligation (SNL) model of neuropathic pain in rats showed that typical amitriptyline HCl (AMT-HCl) (in saline) and AMT-Base had a significant dose-dependent antinociceptive effect: the antinociceptive duration of a single 100 μmol/kg injection of AMT-HCl was 5 h and of AMT-Base was 24 h when given 7 days after a SNL, and of a single 200 μmol/kg injection of AMT-Base was 39 days when given 1 h before and 4 days when given 7 days after a SNL. The post-ligation antinociceptive duration of AMT-Base was 4.8 times that of AMT-HCl, but the duration of preemptive (pre-ligation) AMT-Base treatment was 9.7 times that of AMT-Base. We can conclude that preemptive amitriptyline base provides long-lasting antinociception for neuropathic pain experimentally.

  9. Amitriptyline aggravates the fibrosis process in a rat model of infravesical obstruction

    PubMed Central

    de Almeida Prado, Patrícia S; Soares, Maria Fernanda; Lima, Flávio O; Schor, Nestor; Teixeira, Vicente PC

    2012-01-01

    Summary Infravesical obstruction (IVO) secondary to benign prostatic hypertrophy can affect up to 50% of men over 50 years old and may cause serious and irreversible alterations throughout the urinary tract, especially in the bladder. Therapeutic approaches are currently limited. Amitriptyline has recently been described as an analgesic, anti-inflammatory and myorelaxant in some experimental models. The objective of this study was to investigate the effects of amitriptyline hydrochloride on the process of fibrosis in a bladder outlet obstruction model in rats. Male Wistar rats were subjected to IVO and studied at intervals of 1 and 14 days postprocedure. The rats were randomly divided into five groups: sham, IVO1-T, IVO1-NT, IVO14-T and IVO14-NT. Bladder tissue was processed for histopathology, immunohistochemistry and RT-PCR. The IVO14 groups presented bladder fibrosis, smooth muscle cell hypertrophy and bladder wall thickening. The IVO14-T group demonstrated a higher intensity of fibrosis, higher macrophage infiltration rate and higher gene expression of Transforming growth factor (TGF) Tgf-β1. Thus this data shows that in this experimental mode amitriptyline had an amplifying effect on the process of fibrosis as a whole. PMID:22563623

  10. Long-term effects of maternal separation on chronic stress response suppressed by amitriptyline treatment.

    PubMed

    Cotella, E M; Mestres Lascano, I; Franchioni, L; Levin, G M; Suárez, M M

    2013-07-01

    Abstract The early-life environment has many long-term effects on mammals. Maternal interaction and early stressful events may affect regulation of the HPA axis during adulthood, leading to differential glucocorticoid secretion in response to stressful situations. These adverse experiences during postnatal development may even sensitize specific neurocircuits to subsequent stressors. Later in life, the overreaction of the HPA axis to stress can constitute a risk factor for metabolic and mental diseases. As tricyclic antidepressants are known to correct glucocorticoid hypersecretion during depression, we treated maternally separated animals with amitriptyline, at a lower dose than habitually used in depression models, to prevent the response to chronic stress during adulthood. Male Wistar rats were separated from the mother for 4.5 h every day for the first 3 weeks of life. From postnatal day 50, animals were subjected to chronic variable stress during 24 d (five types of stressors at different times of day). During the stress, protocol rats were orally administered amitriptyline (5 mg/kg) daily. We observed that maternal separation caused a reduction in plasma ACTH levels (p < 0.05), but evoked hypersecretion of corticosterone (p < 0.05) when it was combined with stress in adulthood. This rise was completely prevented by antidepressant treatment with amitriptyline.

  11. Clinical evaluation of amitriptyline for the control of chronic pain caused by temporomandibular joint disorders.

    PubMed

    Rizzatti-Barbosa, Célia M; Nogueira, Mariana T P; de Andrade, Eduardo D; Ambrosano, Gláucia M B; de Barbosa, José R Albergaria

    2003-07-01

    Temporomandibular disorder (TMD) is characterized by a combination of symptoms affecting the temporomandibular joint and/or chewing muscles. The two most common clinical TMD symptoms are pain and dysfunction. Pain is usually caused by dysfunction, and emergency therapy has focused on controlling it. Recent investigations into TMD have led to the recommendation of antidepressants as a supporting treatment against constant neuralgic pain. The aim of this double-blind study was to verify the efficiency of antidepressants (amitriptyline) as a support in the treatment of chronic TMD pain. Twelve female volunteers presenting chronic TMD pain were divided into two groups and treated for 14 days: Group 1 with 25 mg/day of amitriptyline and Group 2 with a placebo. The intensity of pain and discomfort was evaluated daily, using a visual analog scale (VAS), over a period of seven days preceding the treatment (baseline), during the 14-day treatment, and for seven days after the treatment. The results revealed a significant reduction of pain and discomfort in Group 1 (75%) compared to Group 2 (28%) during the three weeks beginning at baseline (p < 0.01). Amitriptyline proved to be an efficient alternative treatment for chronic pain in TMD patients.

  12. Amitriptyline is efficacious in ameliorating muscle inflammation and depressive symptoms in the mdx mouse model of Duchenne muscular dystrophy.

    PubMed

    Manning, Jennifer; Kulbida, Rebecca; Rai, Prerana; Jensen, Lindsay; Bouma, Judith; Singh, Sanjay P; O'Malley, Dervla; Yilmazer-Hanke, Deniz

    2014-10-01

    Mutations in the structural protein dystrophin underlie muscular dystrophies characterized by progressive deterioration of muscle function. Dystrophin-deficient mdx mice are considered a model for Duchenne muscular dystrophy (DMD). Individuals with DMD are also susceptible to mood disorders, such as depression and anxiety. Therefore, the study objectives were to investigate the effects of the tricyclic antidepressant amitriptyline on mood, learning, central cytokine expression and skeletal muscle inflammation in mdx mice. Amitriptyline-induced effects (10 mg kg(-1) daily s.c. injections, 25 days) on the behaviour of mdx mice were investigated using the open field arena and tail suspension tests. The effects of chronic amitriptyline treatment on inflammatory markers were studied in the muscle and plasma of mdx mice, and mood-associated monoamine and cytokine concentrations were measured in the amygdala, hippocampus, prefrontal cortex, striatum, hypothalamus and midbrain. The mdx mice exhibited increased levels of anxiety and depressive-like behaviour compared with wild-type mice. Amitriptyline treatment had anxiolytic and antidepressant effects in mdx mice associated with elevations in serotonin levels in the amygdala and hippocampus. Inflammation in mdx skeletal muscle tissue was also reduced following amitriptyline treatment as indicated by decreased immune cell infiltration of muscle and lower levels of the pro-inflammatory cytokines tumour necrosis factor-α and interleukin-6 in the forelimb flexors. Interleukin-6 mRNA expression was remarkably reduced in the amygdala of mdx mice by chronic amitriptyline treatment. Positive effects of amitriptyline on mood, in addition to its anti-inflammatory effects in skeletal muscle, may make it an attractive therapeutic option for individuals with DMD. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

  13. Effect of Amitriptyline and Escitalopram on Functional Dyspepsia: a Multi-Center, Randomized, Controlled Study

    PubMed Central

    Talley, Nicholas J.; Locke, G. Richard; Saito, Yuri A.; Almazar, Ann E.; Bouras, Ernest P.; Howden, Colin W.; Lacy, Brian E.; DiBaise, John K.; Prather, Charlene M.; Abraham, Bincy P.; El-Serag, Hashem B.; Moayyedi, Paul; Herrick, Linda M.; Szarka, Lawrence A.; Camilleri, Michael; Hamilton, Frank A.; Schleck, Cathy D.; Tilkes, Katherine E.; Zinsmeister, Alan R.

    2015-01-01

    Background & Aims Anti-depressants are frequently prescribed to treat functional dyspepsia (FD), a common disorder characterized by upper abdominal symptoms, including discomfort or post-prandial fullness. However, there is little evidence for the efficacy of these drugs in patients with FD. We performed a randomized, double-blind, placebo-controlled trial to evaluate the effects of anti-depressant therapy effects on symptoms, gastric emptying (GE), and mealinduced satiety in patients with FD. Methods We performed a study at 8 North American sites of patients who met the Rome II criteria for FD and did not have depression or use anti-depressants. Subjects (n=292; 44±15 y old, 75% female, 70% with dysmotility-like FD, and 30% with ulcer-like FD) were randomly assigned to groups given placebo, 50 mg amitriptyline, or 10 mg escitalopram for 10 weeks. The primary endpoint was adequate relief of FD symptoms for ≥5 weeks of the last 10 weeks (out of 12). Secondary endpoints included GE time, maximum tolerated volume in a nutrient drink test, and FD-related quality of life. Results An adequate relief response was reported by 39 subjects given placebo (40%), 51 given amitriptyline (53%), and 37 given escitalopram (38%) (P=.05, following treatment, adjusted for baseline balancing factors including all subjects). Subjects with ulcer-like FD given amitriptyline were more than 3-fold more likely to report adequate relief than those given placebo (odds ratio=3.1; 95% confidence interval, 1.1–9.0). Neither amitriptyline nor escitalopram appeared to affect GE or meal-induced satiety after the 10 week period in any group. Subjects with delayed GE were less likely to report adequate relief than subjects with normal GE (odds ratio=0.4; 95% confidence interval, 0.2–0.8). Both anti-depressants improved overall quality-of-life. Conclusions Amitriptyline, but not escitalopram, appears to benefit some patients with FD— particularly those with ulcer-like (painful) FD. Patients

  14. Perisurgical management of patients with neuromuscular disorders.

    PubMed

    Bertorini, Tulio E

    2004-05-01

    Patients with neuromuscular disorders who undergo surgical procedures are particularly predisposed to complications during the perioperative period. Such complications may arise from respiratory failure, arrhythmias,or infections, and particularly MH. It is recommended that these patients be monitored for respiratory and cardiovascular complications and receive proper respiratory toilet, physio-therapy, and incentive respirometry. Proper electrolyte balance is mandatory. They should be monitored in the ICU when necessary. Excessive sedation of these patients, and drugs that could aggravate weakness or cause MH, should be avoided. Those at risk of MH should not receive drugs that may precipitate an attack.

  15. Can empirical hypertonic saline or sodium bicarbonate treatment prevent the development of cardiotoxicity during serious amitriptyline poisoning? Experimental research.

    PubMed

    Paksu, Muhammet Sukru; Zengin, Halit; Ilkaya, Fatih; Paksu, Sule; Guzel, Hasan; Ucar, Durmus; Uzun, Adem; Alacam, Hasan; Duran, Latif; Murat, Naci; Guzel, Ahmet

    2015-01-01

    The aim of this experimental study was to investigate whether hypertonic saline or sodium bicarbonate administration prevented the development of cardiotoxicity in rats that received toxic doses of amitriptyline. Thirty-six Sprague Dawley rats were used in the study. The animals were divided into six groups. Group 1 received toxic doses of i.p. amitriptyline. Groups 2 and 3 toxic doses of i.p. amitriptyline, plus i.v. sodium bicarbonate and i.v. hypertonic saline, respectively. Group 4 received only i.v. sodium bicarbonate, group 5 received only i.v. hypertonic saline, and group 6 was the control. Electrocardiography was recorded in all rats for a maximum of 60 minutes. Blood samples were obtained to measure the serum levels of sodium and ionised calcium. The survival time was shorter in group 1. In this group, the animals' heart rates also decreased over time, and their QRS and QTc intervals were significantly prolonged. Groups 2 and 3 showed less severe changes in their ECGs and the rats survived for a longer period. The effects of sodium bicarbonate or hypertonic saline treatments on reducing the development of cardiotoxicity were similar. The serum sodium levels decreased in all the amitriptyline-applied groups. Reduction of serum sodium level was most pronounced in group 1. Empirical treatment with sodium bicarbonate or hypertonic saline can reduce the development of cardiotoxicity during amitriptyline intoxication. As hypertonic saline has no adverse effects on drug elimination, it should be considered as an alternative to sodium bicarbonate therapy.

  16. Activated Charcoal Haemoperfusion in the Treatment of Experimental Amitriptyline Poisoning in Pigs - The Effect on Amitriptyline Plasma Concentration and Haemodynamic Parameters.

    PubMed

    Jansen, Tejs; Petersen, Henrik; Malskaer, Cecilie M; Gabel-Jensen, Charlotte; Dalhoff, Kim; Eriksen, Thomas; Belhage, Bo; Hoegberg, Lotte C G

    2017-05-01

    Coated activated charcoal haemoperfusion (CAC-HP) is a well-known treatment modality. Case reports have revealed conflicting results about the efficacy of CAC-HP in the treatment of amitriptyline (AT) poisoning, and no randomized clinical trials have been identified in the literature. This study aimed at quantifying the efficacy of modern CAC-HP as an adjunctive treatment of AT intoxication compared with standard care alone. Fourteen female Danish landrace pigs were randomized to either standard care or standard care plus 4 hr of CAC-HP. The pigs were anaesthetized, and vital parameters were continuously recorded. Amitriptyline infusion (7.5 mg/kg) was completed in 20 min. Thirty minutes after AT infusion, activated charcoal was instilled orally in both groups. In the intervention group, CAC-HP was initiated 60 min. after AT infusion. Blood and urine samples were collected as were vital parameters at specific time intervals. The protocol was approved by the Danish Experimental Animal Expectorate and complied with the NIH guide for care and use of laboratory animals. Data were managed according to the ARRIVE guidelines. No statistical significant differences between intervention and control groups were found when analysing for differences in AT levels in plasma at any time-point. Furthermore, significant differences between the control and intervention groups in regard to vital parameters could not be found either. In our animal model, the addition of CAC-HP did not improve the clearance of AT compared with standard treatment alone. We suggest that the effect of modern CAC-HP as a treatment modality in AT-poisoned human patients may be inadequate. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  17. Spectrophotometric and Chromatographic Simultaneous Estimation of Amitriptyline Hydrochloride and Chlordiazepoxide in Tablet Dosage Forms

    PubMed Central

    Patel, Sejal; Patel, N. J.

    2009-01-01

    A binary mixture of amitriptyline HCl and chlordiazepoxide was determined by three different methods. The first method involved determination of amitriptyline HCl and chlordiazepoxide using the first derivative spectrophotometric technique at 219 and 230 nm over the concentration ranges of 1-20 and 2-24 μg/ml with mean accuracies 100.9±0.87 and 99.2±1.0%, respectively. The second method was reversed-phase high performance liquid chromatography using methanol: acetonitrile: 0.065 M ammonium acetate buffer (50:20:30, v/v/v), final pH adjust to 5.5 ± 0.02 with ortho phosphoric acid as the mobile phase and was pumped at a flow rate of 1.0 ml/min. Quantification was achieved with ultraviolet detection at 240 nm over concentration ranges of 0.25-4 and 0.1-1.6 μg/ml; mean accuracies were 100.55±0.62 and 100.71±0.81%, respectively. The third method utilized high performance thin layer chromatography method in tablet dosage form. The method was based on separation of the two drugs followed by densitometric measurements of their spots at 240 nm. The separation was carried out on Merck thin layer chromatographic aluminium sheets of silica gel 60 F254 using carbon tetrachloride: acetone: triethylamine (6:3:0.2, v/v/v) as mobile phase. The linearity was found to be in the range of 50-600 and 20-240 ng/spot for amitriptyline hydrochloride and chlordiazepoxide, respectively. The methods were successively applied to pharmaceutical formulation because no chromatographic interferences from the tablet excipients were found. The suitability of these methods for the quantitative determination of the compounds was proved by validation. PMID:20502562

  18. Effect of Amitriptyline on Symptoms in Treatment Naïve Patients with Interstitial Cystitis/Painful Bladder Syndrome

    PubMed Central

    Foster, Harris E.; Hanno, Philip M.; Nickel, J. Curtis; Payne, Christopher K.; Mayer, Robert D.; Burks, David A.; Yang, Claire C.; Chai, Toby C.; Kreder, Karl J.; Peters, Kenneth M.; Lukacz, Emily S.; FitzGerald, Mary P.; Cen, Liyi; Landis, J. Richard; Propert, Kathleen J.; Yang, Wei; Kusek, John W.; Nyberg, Leroy M.

    2010-01-01

    Background Amitriptyline is frequently used to treat patients with IC/PBS. The evidence to support this practice is derived mainly from a small single site clinical trial and case reports. Methods We conducted a multi-center, randomized, double blind, placebo controlled clinical trial of amitriptyline in subjects with IC/PBS who were naive to therapy. Study participants in both treatment arms received a standardized education and behavioral modification program (EBMP). The drug dose was increased over a six-week period from 10 mg up to 75 mg once daily. The primary outcome was a patient-reported global response assessment (GRA) of symptom improvement evaluated after 12 weeks of treatment. Results A total of 271 subjects were randomized and 231 (85%) provided a GRA at 12 weeks of follow-up. Study participants were primarily women (83%), Caucasian (74%) with a median age of 38 years. In an intention-to-treat analysis (n=271), the rate of response of subjects reporting either moderately or markedly improved from baseline in the amitriptyline and placebo groups was 55% and 45% respectively (p=0.12). Among the subgroup of subjects (n=207) who achieved a drug dose of at least 50 mg, a significantly higher response rate was observed in the amitriptyline group (66%) compared to placebo (47%) (p=0.01). Conclusion When all randomized subjects were considered, amitriptyline in combination with an EBMP did not significantly improve symptoms in patients with IC/PBS who are treatment naïve. Amitriptyline, however, may be beneficial in persons who can achieve a daily dose of 50 mg or greater, although this subgroup comparison was not specified in advance. PMID:20303115

  19. The tricyclic antidepressants amitriptyline, nortriptyline and imipramine are weak antagonists of human and rat alpha1B-adrenoceptors.

    PubMed

    Nojimoto, F D; Mueller, A; Hebeler-Barbosa, F; Akinaga, J; Lima, V; Kiguti, L R de A; Pupo, A S

    2010-01-01

    Although it is long known that the tricyclic antidepressants amitriptyline, nortriptyline and imipramine inhibit the noradrenaline transporter and alpha(1)-adrenoceptors with similar affinities, which may lead to self-cancelling actions, the selectivity of these drugs for alpha(1)-adrenoceptor subtypes is unknown. The present study investigates the selectivity of amitriptyline, nortriptyline and imipramine for human recombinant and rat native alpha(1)-adrenoceptor subtypes. The selectivity of amitriptyline, nortriptyline and imipramine was investigated in HEK-293 cells expressing each of the human alpha(1)-subtypes and in rat native receptors from the vas deferens (alpha(1A)), spleen (alpha(1B)) and aorta (alpha(1D)) through [(3)H]prazosin binding, and noradrenaline-induced intracellular Ca(2+) increases and contraction assays. Amitriptyline, nortriptyline and imipramine showed considerably higher affinities for alpha(1A)- (approximately 25- to 80-fold) and alpha(1D)-adrenoceptors (approximately 10- to 25-fold) than for alpha(1B)-adrenoceptors in both contraction and [(3)H]prazosin binding assays with rat native and human receptors, respectively. In addition, amitriptyline, nortriptyline and imipramine were substantially more potent in the inhibition of noradrenaline-induced intracellular Ca(2+) increases in HEK-293 cells expressing alpha(1A)- or a truncated version of alpha(1D)-adrenoceptors which traffics more efficiently towards the cell membrane than in cells expressing alpha(1B)-adrenoceptors. Amitriptyline, nortriptyline and imipramine are much weaker antagonists of rat and human alpha(1B)-adrenoceptors than of alpha(1A)- and alpha(1D)-adrenoceptors. The differential affinities for these receptors indicate that the alpha(1)-adrenoceptor subtype which activation is most increased by the augmented noradrenaline availability resultant from the blockade of neuronal reuptake is the alpha(1B)-adrenoceptor. This may be important for the behavioural effects of these

  20. Amitriptyline/Ketamine as therapy for neuropathic pruritus and pain secondary to herpes zoster.

    PubMed

    Griffin, John R; Davis, Mark D P

    2015-02-01

    Frequent causes of morbidity secondary to herpes zoster include acute pain, secondary infection, and postherpetic neuralgia. A less documented complication is pruritus, which can be either acute or postinfectious when it persists more than 3 months after the rash has healed. We discuss a case of severe, acute neuropathic pruritus and pain secondary to active herpes zoster that was unresponsive to standard medical therapy, including oral antihistamines, topical lidocaine, oral gabapentin, and local wound care. Modest control of the pruritus and pain was achieved with continued multimodal therapy and the addition of topical 2% amitriptyline/0.5% ketamine gel.

  1. A placebo controlled comparison of the effects of pirenzepine and amitriptyline on the tyramine pressor test in healthy volunteers.

    PubMed Central

    Wilkins, M R; Wynne, R D; Kendall, M J

    1985-01-01

    The possibility of an interaction between pirenzepine, an antimuscarinic drug structurally similar to the tricyclic antidepressants, and sympathomimetic agents was investigated in a group of healthy volunteers. The effect of pirenzepine on response to intravenous tyramine was compared with that of placebo and amitriptyline. The mean dose of tyramine required to elevate systolic blood pressure by 30 mm Hg was 5.0 mg (+/- s.d. 0.8) after placebo, 5.1 mg (+/- 1.0) after pirenzepine and 11.3 mg (+/- 1.8) after amitriptyline. These results suggest that pirenzepine will not potentiate the effects of concurrently administered sympathomimetic drugs. PMID:3839679

  2. Differential effectiveness of tianeptine, clonidine and amitriptyline in blocking traumatic memory expression, anxiety and hypertension in an animal model of PTSD.

    PubMed

    Zoladz, Phillip R; Fleshner, Monika; Diamond, David M

    2013-07-01

    Individuals exposed to life-threatening trauma are at risk for developing post-traumatic stress disorder (PTSD), a debilitating condition that involves persistent anxiety, intrusive memories and several physiological disturbances. Current pharmacotherapies for PTSD manage only a subset of these symptoms and typically have adverse side effects which limit their overall effectiveness. We evaluated the effectiveness of three different pharmacological agents to ameliorate a broad range of PTSD-like symptoms in our established predator-based animal model of PTSD. Adult male Sprague-Dawley rats were given 1-h cat exposures on two occasions that were separated by 10 days, in conjunction with chronic social instability. Beginning 24 h after the first cat exposure, rats received daily injections of amitriptyline, clonidine, tianeptine or vehicle. Three weeks after the second cat exposure, all rats underwent a battery of behavioral and physiological tests. The vehicle-treated, psychosocially stressed rats demonstrated a robust fear memory for the two cat exposures, as well as increased anxiety expressed on the elevated plus maze, an exaggerated startle response, elevated heart rate and blood pressure, reduced growth rate and increased adrenal gland weight, relative to the vehicle-treated, non-stressed (control) rats. Neither amitriptyline nor clonidine was effective at blocking the entire cluster of stress-induced sequelae, and each agent produced adverse side effects in control subjects. Only the antidepressant tianeptine completely blocked the effects of psychosocial stress on all of the physiological and behavioral measures that were examined. These findings illustrate the differential effectiveness of these three treatments to block components of PTSD-like symptoms in rats, and in particular, reveal the profile of tianeptine as the most effective of all three agents.

  3. Comparison of Tolerance of Venlafaxine, Paroxetine and Amitriptyline in Depression Therapy

    PubMed Central

    Miskovic, Mirjana

    2015-01-01

    Introduction: There are no controlled studies dedicated to research of side effects of antidepressants. It is a well known fact that antidepressants reciprocally differ according to their type, intensity and frequency of appearance of certain side effects. For example, cardiovascular and anticholinergic effects are essential feature of the tricyclics whereas gastrointestinal and sexual side effects are registered during the use of selective serotonin reuptake inhibitors. Interruptions of therapy or irregular use of drugs because of the appearance of side effects are not rare. Serious side effects of drugs are the fourth cause of death in the USA. Aim: The aim of this study is the evaluation of appearance of side effects comparing three different groups of antidepressants: venlafaxine, amitriptyline and paroxetine. Material and methods: The study included 90 in-patients as well as outpatients of both sexes aged 18-65 who were treated for major depressive disorder at Psychiatric Clinic in Banjaluka. 30 patients were treated with amitriptyline 75-250 mg, 30 patients were treated with paroxetine 20-40 mg and 30 patients were treated with venlafaxine 75-300 mg. The selection of patients was done on the basis of diagnosis of major depressive disorder. Results: Most patients did not have serious side effects. The study confirmed high efficiency of the mentioned drugs as well as the fact that paroxetine causes a bit more side effects in comparison with two other antidepressants. PMID:26005260

  4. Tricyclic Antidepressant Amitriptyline-induced Glial Cell Line-derived Neurotrophic Factor Production Involves Pertussis Toxin-sensitive Gαi/o Activation in Astroglial Cells*

    PubMed Central

    Hisaoka-Nakashima, Kazue; Miyano, Kanako; Matsumoto, Chie; Kajitani, Naoto; Abe, Hiromi; Okada-Tsuchioka, Mami; Yokoyama, Akinobu; Uezono, Yasuhito; Morioka, Norimitsu; Nakata, Yoshihiro; Takebayashi, Minoru

    2015-01-01

    Further elaborating the mechanism of antidepressants, beyond modulation of monoaminergic neurotransmission, this study sought to elucidate the mechanism of amitriptyline-induced production of glial cell line-derived neurotrophic factor (GDNF) in astroglial cells. Previous studies demonstrated that an amitriptyline-evoked matrix metalloproteinase (MMP)/FGF receptor (FGFR)/FGFR substrate 2α (FRS2α)/ERK cascade is crucial for GDNF production, but how amitriptyline triggers this cascade remains unknown. MMP is activated by intracellular mediators such as G proteins, and this study sought to clarify the involvement of G protein signaling in amitriptyline-evoked GDNF production in rat C6 astroglial cells (C6 cells), primary cultured rat astrocytes, and normal human astrocytes. Amitriptyline-evoked GDNF mRNA expression and release were inhibited by pertussis toxin (PTX), a Gαi/o inhibitor, but not by NF449, a Gαs inhibitor, or YM-254890, a Gαq inhibitor. The activation of the GDNF production cascade (FGFR/FRS2α/ERK) was also inhibited by PTX. Deletion of Gαο1 and Gαi3 by RNAi demonstrated that these G proteins play important roles in amitriptyline signaling. G protein activation was directly analyzed by electrical impedance-based biosensors (CellKeyTM assay), using a label-free (without use of fluorescent proteins/probes or radioisotopes) and real time approach. Amitriptyline increased impedance, indicating Gαi/o activation that was suppressed by PTX treatment. The impedance evoked by amitriptyline was not affected by inhibitors of the GDNF production cascade. Furthermore, FGF2 treatment did not elicit any effect on impedance, indicating that amitriptyline targets PTX-sensitive Gαi/o upstream of the MMP/FGFR/FRS2α/ERK cascade. These results suggest novel targeting for the development of antidepressants. PMID:25869129

  5. Tricyclic Antidepressant Amitriptyline-induced Glial Cell Line-derived Neurotrophic Factor Production Involves Pertussis Toxin-sensitive Gαi/o Activation in Astroglial Cells.

    PubMed

    Hisaoka-Nakashima, Kazue; Miyano, Kanako; Matsumoto, Chie; Kajitani, Naoto; Abe, Hiromi; Okada-Tsuchioka, Mami; Yokoyama, Akinobu; Uezono, Yasuhito; Morioka, Norimitsu; Nakata, Yoshihiro; Takebayashi, Minoru

    2015-05-29

    Further elaborating the mechanism of antidepressants, beyond modulation of monoaminergic neurotransmission, this study sought to elucidate the mechanism of amitriptyline-induced production of glial cell line-derived neurotrophic factor (GDNF) in astroglial cells. Previous studies demonstrated that an amitriptyline-evoked matrix metalloproteinase (MMP)/FGF receptor (FGFR)/FGFR substrate 2α (FRS2α)/ERK cascade is crucial for GDNF production, but how amitriptyline triggers this cascade remains unknown. MMP is activated by intracellular mediators such as G proteins, and this study sought to clarify the involvement of G protein signaling in amitriptyline-evoked GDNF production in rat C6 astroglial cells (C6 cells), primary cultured rat astrocytes, and normal human astrocytes. Amitriptyline-evoked GDNF mRNA expression and release were inhibited by pertussis toxin (PTX), a Gα(i/o) inhibitor, but not by NF449, a Gα(s) inhibitor, or YM-254890, a Gαq inhibitor. The activation of the GDNF production cascade (FGFR/FRS2α/ERK) was also inhibited by PTX. Deletion of Gα(ο1) and Gα(i3) by RNAi demonstrated that these G proteins play important roles in amitriptyline signaling. G protein activation was directly analyzed by electrical impedance-based biosensors (CellKey(TM) assay), using a label-free (without use of fluorescent proteins/probes or radioisotopes) and real time approach. Amitriptyline increased impedance, indicating Gα(i/o) activation that was suppressed by PTX treatment. The impedance evoked by amitriptyline was not affected by inhibitors of the GDNF production cascade. Furthermore, FGF2 treatment did not elicit any effect on impedance, indicating that amitriptyline targets PTX-sensitive Gα(i/o) upstream of the MMP/FGFR/FRS2α/ERK cascade. These results suggest novel targeting for the development of antidepressants.

  6. Randomized, Double-Blind, Crossover Trial of Amitriptyline for Analgesia in Painful HIV-Associated Sensory Neuropathy.

    PubMed

    Dinat, Natalya; Marinda, Edmore; Moch, Shirra; Rice, Andrew S C; Kamerman, Peter R

    2015-01-01

    We conducted a randomized, double-blind, placebo-controlled, crossover study at a single center in South Africa, to ascertain whether amitriptyline is an effective analgesic for painful HIV-associated sensory neuropathy of moderate to severe intensity in: i) antiretroviral drug naive individuals, and ii) antiretroviral drug users. 124 HIV-infected participants (antiretroviral drug naive = 62, antiretroviral drug users = 62) who met the study criteria for painful HIV-associated sensory neuropathy were randomized to once-daily oral amitriptyline (titrated to a median: interquartile range of 50: 25-50 mg) or placebo for six weeks, followed by a three-week washout period and subsequent treatment crossover. The primary outcome measure was change from baseline in worst pain intensity of the feet (measured by participant self-report using an 11-point numerical pain rating scale) after six weeks of treatment. 122 of 124 participants completed all study visits and were included in the analysis of the primary outcome. In the antiretroviral drug-naive group (n = 61) there was no significant difference in the mean change in pain score from baseline after six weeks of treatment with placebo or amitriptyline [amitriptyline: 2.8 (SD 3.3) vs. placebo: 2.8 (3.4)]. Similarly, there was no significant difference in the change in pain score after six weeks of treatment with placebo or amitriptyline in the antiretroviral drug-user group (n = 61) [amitriptyline: 2.7 (3.3) vs. placebo: 2.1 (2.8)]. Controlling for period effects and treatment order effects did not alter the outcome of the analyses. Nor did analyzing the intention-to-treat cohort (missing data interpolated using baseline observation carried forward) alter the outcome of the analyses. In summary, amitriptyline, at the doses used here, was no more effective than an inactive placebo at reducing pain intensity in individuals with painful HIV-associated sensory neuropathy of moderate to severe intensity, irrespective of whether

  7. Effects of 2-Hydroxypropyl-Beta-Cyclodextrin on Cardiovascular Signs of Amitriptyline Poisoning in a Rat Model.

    PubMed

    Aydin, Burc; Hocaoglu, Nil; Micili, Serap Cilaker; Ergur, Bekir Ugur; Kalkan, Sule

    2016-10-01

    The aim of this study was to investigate the efficacy of 2-hydroxypropyl-beta-cyclodextrin (HPBCD) as an antidotal treatment for the in vivo cardiovascular effects of amitriptyline poisoning. Experiments were carried out on 33 Wistar rats. To evaluate cardiovascular effects of HPBCD, rats were infused with dextrose or HPBCD. In the poisoning model, amitriptyline (0.94 mg/kg/min) was infused until the mean arterial blood pressure (MAP) dropped to 50 % of the baseline. Following amitriptyline infusion, dextrose, low-dose HPBCD (4.19 mg/kg/min), or high-dose HPBCD (16.76 mg/kg/min) was infused, and MAP, heart rate (HR), and electrocardiogram were recorded for 60 min. Hearts were examined for tissue damage and apoptosis. HPBCD infusion alone did not yield significant difference for MAP, HR, QRS duration, QT interval, and cardiac tissue damage when compared to dextrose (p > 0.05). In the poisoning model, MAP and HR decreased, while QRS duration and QT interval prolonged significantly following amitriptyline infusion (p < 0.0167). Dextrose, low-dose HPBCD, and high-dose HPBCD infusion similarly corrected MAP, HR, QRS duration, and QT interval values at the end-experiment time point (p > 0.05). Histological scores for tissue damage and apoptosis showed no significant difference between the groups (p > 0.05). Based on our results, HPBCD did not show cardiovascular toxicity, while it was not more effective than dextrose for the treatment of amitriptyline poisoning. Further antidotal studies of cyclodextrins with higher doses and/or binding affinities are needed for poisonings.

  8. Long-term Stability of Zonisamide, Amitriptyline, and Glycopyrrolate in Extemporaneously Prepared Liquid-dosage Forms at Two Temperatures.

    PubMed

    Nahata, Milap C

    2016-01-01

    The lack of commercially available liquid dosage forms for pediatric patients prompted this study. The objectives of our study were to determine the stability of zonisamide, amitriptyline, and glycopyrrolate in extemporaneously prepared oral suspensions in plastic prescription bottles. One group of suspensions was prepared in OraPlus:OraSweet (1:1) for each drug and stored either under refrigeration (4°C) or at room temperature (25°C). A second group of suspensions were compounded in 1% methylcellulose:simple syrup at a 1:10 proportion for zonisamide, amitriptyline, and glycopyrrolate; these suspensions were stored at either under refrigeration (4°C) or at room temperature (25°C). The drug concentrations were measured by the stability-indicating high-performance liquid chromatographic methods. The mean concentration of zonisamide (10 mg/mL) remained above 95% of the original concentration for 91 days in each group of suspensions at both 4°C and 25°C. The mean concentration of amitriptyline (20 mg/mL) was above 95% for 91 days in the suspensions containing OraPlus/ OraSweet at both 4°C and 25°C. However, in the suspensions containing methylcellulose:simple syrup, the mean concentration of amitriptyline was about 95% for 42 days at 4°C and 28 days at 25°C. The mean concentration of glycopyrrolate (0.2 mg/mL) was above 95% in each group of suspensions during the 14-day study period. These data indicate that zonisamide, amitriptyline, and glycopyrrolate can be prepared extemporaneously as suspensions and stored in plastic prescription bottles for varying periods at 4°C and 25°C for use in pediatric patients.

  9. Treatment of the painful shoulder syndrome with amitriptyline and lithium carbonate

    PubMed Central

    Tyber, M. A.

    1974-01-01

    Thirty-four patients with painful shoulder syndrome (PSS) were psychologically assessed and the results compared with those from a control group presenting other musculoskeletal disorders. A significantly greater prevalence of depression was found in the former group. Fifty-six patients with PSS were treated with only lithium and amitriptyline for four months; 44 patients showed marked clinical improvement and radiologic clearing of dystrophic calcification. Lithiumamitriptyline therapy, when compared with physiotherapy in another series of 11 patients, was found to be far superior. Some possible biochemical links between depression and PSS are outlined, and the theory that PSS may be a clinical entity of psychogenic origin is discussed. ImagesFIG. 5FIG. 6 PMID:4841835

  10. Amitriptyline and bromazepam in the treatment of vibratory angioedema: which role for neuroinflammation?

    PubMed

    Guarneri, Fabrizio; Guarneri, Claudio; Marini, Herbert Ryan

    2014-01-01

    Vibratory angioedema is a rare form of physical urticaria, hereditary or acquired, which occurs at body sites exposed to vibrations. Pathogenic mechanisms of disease are not completely clear and, consequently, current pharmacological treatment is sometimes unsatisfactory. We report the case of a horn player affected by acquired vibratory angioedema, relapsing after prolonged use of the instrument and resistant to systemic antihistamines and corticosteroids, which successfully responded to therapy with low doses of amitriptyline and bromazepam. A neuroinflammatory mechanism can be likely implicated in the pathogenesis of vibratory angioedema, in line with many different cutaneous/mucosal diseases involving a complex interplay of homeostatic/allostatic systems. Furthermore, in mucosal diseases, such as vibratory angioedema, physical/psychological stressors have a relevant role. In such cases, because of the complex interplay between nervous and immune system, the pharmacological activity of benzodiazepines and typical antidepressants may downregulate neuroinflammation. © 2014 Wiley Periodicals, Inc.

  11. Hydrogen bonding-assisted interaction between amitriptyline hydrochloride and hemoglobin: spectroscopic and molecular dynamics studies.

    PubMed

    Maurya, Neha; Maurya, Jitendra Kumar; Kumari, Meena; Khan, Abbul Bashar; Dohare, Ravins; Patel, Rajan

    2017-05-01

    Herein, we have explored the interaction between amitriptyline hydrochloride (AMT) and hemoglobin (Hb), using steady-state and time-resolved fluorescence spectroscopy, UV-visible spectroscopy, and circular dichroism spectroscopy, in combination with molecular docking and molecular dynamic (MD) simulation methods. The steady-state fluorescence reveals the static quenching mechanism in the interaction system, which was further confirmed by UV-visible and time-resolved fluorescence spectroscopy. The binding constant, number of binding sites, and thermodynamic parameters viz. ΔG, ΔH, ΔS are also considered; result confirms that the binding of the AMT with Hb is a spontaneous process, involving hydrogen bonding and van der Waals interactions with a single binding site, as also confirmed by molecular docking study. Synchronous fluorescence, CD data, and MD simulation results contribute toward understanding the effect of AMT on Hb to interpret the conformational change in Hb upon binding in aqueous solution.

  12. Spinal serotonin 5-HT7 and adenosine A1 receptors, as well as peripheral adenosine A1 receptors, are involved in antinociception by systemically administered amitriptyline.

    PubMed

    Liu, Jean; Reid, Allison R; Sawynok, Jana

    2013-01-05

    The present study explored a link between spinal 5-HT(7) and adenosine A(1) receptors in antinociception by systemic amitriptyline in normal and adenosine A(1) receptor knock-out mice using the 2% formalin test. In normal mice, antinociception by systemic amitriptyline 3mg/kg was blocked by intrathecal administration of the selective adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) 10 nmol. Blockade was also seen in adenosine A(1) receptor +/+ mice, but not in -/- mice lacking these receptors. In both normal and adenosine A(1) receptor +/+ mice, the selective 5-HT(7) receptor antagonist (2R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine hydrochloride (SB269970) 3 μg blocked antinociception by systemic amitriptyline, but it did not prevent antinociception in adenosine A(1) receptor -/- mice. In normal mice, flinching was unaltered when the selective 5-HT(7) receptor agonist (2S)-(+)-5-(1,3,5-trimethylpyrazol-4-yl)-2-(dimethylamino)tetralin (AS-19) 20 μg was administered alone, but increased when co-administered intrathecally with DPCPX 10 nmol or SB269970 3 μg. Intrathecal AS-19 decreased flinching in adenosine A(1) receptor +/+ mice compared to -/- mice. Systemic amitriptyline appears to reduce nociception by activating spinal adenosine A(1) receptors secondarily to 5-HT(7) receptors. Spinal actions constitute only one aspect of antinociception by amitriptyline, as intraplantar DPCPX 10 nmol blocked antinociception by systemic amitriptyline in normal and adenosine A(1) receptor +/+, but not -/- mice. Adenosine A(1) receptor interactions are worthy of attention, as chronic oral caffeine (0.1, 0.3g/L, doses considered relevant to human intake levels) blocked antinociception by systemic amitriptyline in normal mice. In conclusion, adenosine A(1) receptors contribute to antinociception by systemic amitriptyline in both spinal and peripheral compartments.

  13. Amitriptyline in neuropathic cancer pain in patients on morphine therapy: a randomized placebo-controlled, double-blind crossover study.

    PubMed

    Mercadante, Sebastiano; Arcuri, Edoardo; Tirelli, Walter; Villari, Patrizia; Casuccio, Alessandra

    2002-01-01

    Amitriptyline is the most common analgesic adjuvant used in cancer patients with neuropathic pain, even though no specific studies have demonstrated a benefit. A randomized placebo-controlled, double-blind crossover study was designed to evidence the effects of amitriptyline in patients with neuropathic cancer pain. Sixteen advanced cancer patients with neuropathic pain on systemic morphine therapy, no longer receiving oncologic treatment, presenting moderate pain (about 4 or more, but less than 7, on a numerical scale of 0-10) in the last week, and given a stable morphine dose in the last 2 days were admitted to the study. During the first week of study, patients were administered 25 mg of amitriptyline or equivalent drops of placebo at night for 3 days and 50 mg for the following 4 days. Doses for patients aged more than 65 years were 15 mg (first 3 days) and 30 mg (3 days after). After a week, a crossover took place for the second week, with the other treatment at an inverse sequence. Opioid consumption, pain intensity, symptoms and adverse effects, mood, sleep, patient's preference, quality of life before starting the study, the first week after and the second week after were recorded. No significant benefits in analgesia were found in the global pain intensity of the previous week of treatment, the least pain intensity or the pain evaluated just after a week of treatment, at the moment of the visit, when amitriptyline was compared with placebo. A significant difference was evidenced for the worst pain (P < 0.035). No differences in opioid doses during the period of study were found. Drowsiness, confusion and dry mouth were significantly more intense with amitriptyline than with placebo (P < 0.036, 0.003, and 0.034, respectively). There were no substantial differences between the two treatments in Spitzer's quality of life score and for each item. No differences in patients' preference for the two treatment periods were found. The analgesic effects of

  14. Amitriptyline-mediated cognitive enhancement in aged 3×Tg Alzheimer's disease mice is associated with neurogenesis and neurotrophic activity.

    PubMed

    Chadwick, Wayne; Mitchell, Nick; Caroll, Jenna; Zhou, Yu; Park, Sung-Soo; Wang, Liyun; Becker, Kevin G; Zhang, Yongqing; Lehrmann, Elin; Wood, William H; Martin, Bronwen; Maudsley, Stuart

    2011-01-01

    Approximately 35 million people worldwide suffer from Alzheimer's disease (AD). Existing therapeutics, while moderately effective, are currently unable to stem the widespread rise in AD prevalence. AD is associated with an increase in amyloid beta (Aβ) oligomers and hyperphosphorylated tau, along with cognitive impairment and neurodegeneration. Several antidepressants have shown promise in improving cognition and alleviating oxidative stress in AD but have failed as long-term therapeutics. In this study, amitriptyline, an FDA-approved tricyclic antidepressant, was administered orally to aged and cognitively impaired transgenic AD mice (3×TgAD). After amitriptyline treatment, cognitive behavior testing demonstrated that there was a significant improvement in both long- and short-term memory retention. Amitriptyline treatment also caused a significant potentiation of non-toxic Aβ monomer with a concomitant decrease in cytotoxic dimer Aβ load, compared to vehicle-treated 3×TgAD controls. In addition, amitriptyline administration caused a significant increase in dentate gyrus neurogenesis as well as increases in expression of neurosynaptic marker proteins. Amitriptyline treatment resulted in increases in hippocampal brain-derived neurotrophic factor protein as well as increased tyrosine phosphorylation of its cognate receptor (TrkB). These results indicate that amitriptyline has significant beneficial actions in aged and damaged AD brains and that it shows promise as a tolerable novel therapeutic for the treatment of AD.

  15. Impact of CYP2D6 genotype on amitriptyline efficacy for the treatment of diabetic peripheral neuropathy: a pilot study.

    PubMed

    Chaudhry, Mamoonah; Alessandrini, Marco; Rademan, Jacobus; Dodgen, Tyren M; Steffens, Francois E; van Zyl, Danie G; Gaedigk, Andrea; Pepper, Michael S

    2017-04-01

    Therapy with low-dose amitriptyline is commonly used to treat painful diabetic peripheral neuropathy. There is a knowledge gap, however, regarding the role of variable CYP2D6-mediated drug metabolism and side effects (SEs). We aimed to generate pilot data to demonstrate that SEs are more frequent in patients with variant CYP2D6 alleles. To that end, 31 randomly recruited participants were treated with low-dose amitriptyline for painful diabetic peripheral neuropathy and their CYP2D6 gene sequenced. Patients with predicted normal or ultra-rapid metabolizer phenotypes presented with less SEs compared with individuals with decreased CYP2D6 activity. Hence, CYP2D6 genotype contributes to treatment outcome and may be useful for guiding drug therapy. Future investigations in a larger patient population are planned to support these preliminary findings.

  16. Evaluation of milnacipran, in comparison with amitriptyline, on cold and mechanical allodynia in a rat model of neuropathic pain.

    PubMed

    Berrocoso, Esther; Mico, Juan-Antonio; Vitton, Olivier; Ladure, Philippe; Newman-Tancredi, Adrian; Depoortère, Ronan; Bardin, Laurent

    2011-03-25

    Milnacipran, a serotonin/norepinephrine reuptake inhibitor (SNRI), has shown efficacy against several chronic pain conditions, including fibromyalgia. Here, we evaluated, in rats, its anti-allodynic effects following acute or sub-chronic treatment in a model of neuropathic pain (chronic constriction injury, CCI, of the sciatic nerve). Amitriptyline, a tricyclic antidepressant active pre-clinically and clinically against neuropathic pains, was added as a comparison compound. Upon acute i.p. administration, milnacipran was potently efficacious in the CCI model. It significantly reduced thermal allodynia in the cold (4°C) plate test (MED=2.5mg/kg), and attenuated mechanical allodynia in the von Frey filaments test (MED=10mg/kg). Given sub-chronically (7day, b.i.d.), milnacipran was effective at 10mg/kgi.p. in both tests. Acute amitriptyline (10mg/kgi.p.) was efficacious against mechanical, but less so against cold allodynia; under sub-chronic conditions, it was only active against mechanical allodynia. These data show that milnacipran is as efficacious as the reference compound amitriptyline in a pre-clinical model of injury-induced neuropathy, and demonstrate for the first time that it is active acutely and sub-chronically against cold allodynia. They also suggest that milnacipran has the potential to alleviate allodynia associated with nerve compression-induced neuropathic pain in the clinic (for example following discal hernia, avulsion or cancer-induced tissue damage).

  17. Topical amitriptyline combined with ketamine for the treatment of erythromelalgia: a retrospective study of 36 patients at Mayo Clinic.

    PubMed

    Poterucha, Timothy J; Weiss, William T; Warndahl, Roger A; Rho, Richard H; Sandroni, Paola; Davis, Mark D P; Murphy, Sinead L

    2013-03-01

    Erythromelalgia is an uncommon neurovascular disorder characterized by redness, increased skin temperature, and pain that usually occurs in the extremities. Treatment remains challenging because of its varying response to medical therapy. The objective of this study was to assess the response of erythromelalgia to compounded topical amitriptyline-ketamine. We retrospectively evaluated 36 patients with erythromelalgia who were treated with compounded topical amitriptyline-ketamine from January 1, 2004, through January 31, 2011. Thirty-two patients (89%) were female. Mean (standard deviation) age was 44.7 (15.8) years (range, 5-74 years). Patients applied the medication 1 to 6 times per day (median, 5 times). One patient (3%) had complete relief from symptoms, 14 (39%) had substantial relief, 12 (33%) had some relief, 7 (19%) had no relief, and 2 (6%) had local worsening of symptoms. No patients had systemic adverse effects. A majority of patients with erythromelalgia (75%) reported improvement in pain with topical application of a compounded amitriptyline-ketamine formulation. The medication was well tolerated.

  18. Amitriptyline may have a supportive role in cancer treatment by inhibiting glutathione S-transferase pi (GST-π) and alpha (GST-α).

    PubMed

    Kulaksiz-Erkmen, Gulnihal; Dalmizrak, Ozlem; Dincsoy-Tuna, Gamze; Dogan, Arın; Ogus, I Hamdi; Ozer, Nazmi

    2013-02-01

    A tricyclic anti-depressant, amitriptyline, is a highly prescribed drug for cancer patients for mood elevation but there are limited studies about the interaction of amitriptyline with glutathione S-transferases pi (GST-π) and glutathione S-transferases alpha (GST-α). GST isozymes have been implicated in chemotherapeutic drug resistance. We demonstrated that the concentration dependent inhibition of GST-π and GST-α by amitriptyline followed inverse hyperbolic inhibition curves with IC(50) values of 5.54 and 8.32 mM, respectively. When the varied substrate was GSH, amitriptyline inhibited both isozymes competitively and similar K(i) values were found for GST-π (K(i) = 1.61 ± 0.17 mM) and GST-α (K(i) = 1.45 ± 0.20 mM). On the other hand, when the varied substrate was CDNB, the inhibition types were non-competitive for GST-π (K(i) = 1.98 ± 0.31 mM) and competitive for GST-α (K(i) = 1.57 ± 0.16 mM). Amitriptyline, in addition to its antidepressant effect, might also have a minor supportive role on the effectiveness of the anticancer drugs by decreasing their elimination through inhibiting GST-π and GST-α.

  19. Imipramine and amitriptyline ameliorate the rotenone model of Parkinson's disease in rats.

    PubMed

    Kandil, Esraa A; Abdelkader, Noha F; El-Sayeh, Bahia M; Saleh, Samira

    2016-09-22

    Amitriptyline (AMI), a commonly prescribed tricyclic antidepressant (TCA) to parkinsonian patients, specifically showed a significant delay in dopaminergic therapy initiation and improvement in motor disability in parkinsonian patients. Moreover, it was recently shown that AMI has neuroprotective properties; however, the mechanisms underlying this effect in Parkinson's disease (PD) are not fully understood. The current study aimed to investigate the possible neuroprotective mechanisms afforded by AMI in the rotenone model of PD and to assess whether another TCA member, imipramine (IMI), shows a corresponding effect. Rats were allocated into seven groups. Four groups were given either saline, dimethyl sulfoxide, AMI or IMI. Three rotenone groups were either untreated or treated with AMI or IMI. Rats receiving rotenone exhibited motor impairment in open field and rotarod tests. Additionally, immunohistochemical examination revealed dopaminergic neuronal damage in substantia nigra. Besides, striatal monoamines and brain derived neurotrophic factor levels were declined. Furthermore, oxidative stress, microglial activation and inflammation were evident in the striata. Pretreatment of rotenone groups with AMI or IMI prevented rotenone-induced neuronal degeneration and increased striatal dopamine level with motor recovery. These effects were accompanied by restoring striatal monoamines and brain-derived neurotrophic factor levels, as well as reducing oxidative damage, microglial activation and expression of proinflammatory cytokines and inducible nitric oxide synthase. The present results suggest that modulation of noradrenaline and serotonin levels, up-regulation of neurotrophin, inhibition of glial activation, anti-oxidant and anti-inflammatory activities could serve as important mechanisms underlying the neuroprotective effects of the used drugs in the rotenone model of PD. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. Interaction of valproic acid and amitriptyline: analysis of therapeutic drug monitoring data under naturalistic conditions.

    PubMed

    Unterecker, Stefan; Burger, Rainer; Hohage, Amelie; Deckert, Jürgen; Pfuhlmann, Bruno

    2013-08-01

    Amitriptyline (AMI) and valproic acid (VPA) are common psychotropic drugs which are frequently used in psychiatry and also administered in neurology or anesthesia in the absence of a psychiatric indication. On the basis of the case of a 73-year-old man with therapy-resistant major depressive episode who experienced anticholinergic delirium after adding VPA to AMI, we retrospectively analyzed therapeutic drug monitoring data of the years 2008 to 2010. We assessed cases receiving a combination of AMI and VPA, and obtained a control sample of AMI patients without VPA which were matched for sex, age, daily dose, and comedication. Both samples were compared regarding the serum levels of AMI and nortriptyline (NOR) as well as the ratio of NOR and AMI with the Mann-Whitney U test. The combination of AMI and VPA led to a remarkable increase of AMI and NOR serum levels. When comparing 33 patients who received comedication with VPA versus 33 matched controls, the total concentration by combining mean AMI and NOR serum levels (237.1 [119.9] vs 126.4 [52.8] ng/mL) and NOR/AMI ratio (1.300 [0.905] vs 0.865 [0.455]) was significantly higher. Both AMI and VPA are widely prescribed drugs. A combination of both is common for psychiatric or neurologic patients. A cautious dosing of AMI with VPA comedication is advisable, and therapeutic drug monitoring should be performed because this combination may lead to a remarkable increase of AMI and NOR serum levels.

  1. Autonomic actions and interactions of mianserin hydrochloride (Org. GB 94) and amitriptyline in patients with depressive illness.

    PubMed

    Ghose, K; Coppen, A; Turner, P

    1976-09-17

    The clinical pharmacology of mianserin hydrochloride was studied in patients suffering from a primary depressive illness after steady-state plasma concentration of the drug had been achieved. The results were compared with those found with amitriptyline in both open and double-blind studies. The two drugs are equally effective in their antidepressive effect. Mianserin hydrochloride appears to be free of anticholinergic effects as assessed by the measurement of salivary volume, pupil diameter and the interactions with guanethidine and thymoxamine on the pupil. No peripheral adrenergic interaction as studied by the tyramine dose-pressor-response test were observed in patients treated with mianserin hydrochloride (20 mg three times daily).

  2. Comparison of triple quadrupole, hybrid linear ion trap triple quadrupole, time-of-flight and LTQ-Orbitrap mass spectrometers in drug discovery phase metabolite screening and identification in vitro--amitriptyline and verapamil as model compounds.

    PubMed

    Rousu, Timo; Herttuainen, Jukka; Tolonen, Ari

    2010-04-15

    Liquid chromatography in combination with mass spectrometry (LC/MS) is a superior analytical technique for metabolite profiling and identification studies performed in drug discovery and development laboratories. In the early phase of drug discovery the analytical approach should be both time- and cost-effective, thus providing as much data as possible with only one visit to the laboratory, without the need for further experiments. Recent developments in mass spectrometers have created a situation where many different mass spectrometers are available for the task, each with their specific strengths and drawbacks. We compared the metabolite screening properties of four main types of mass spectrometers used in analytical laboratories, considering both the ability to detect the metabolites and provide structural information, as well as the issues related to time consumption in laboratory and thereafter in data processing. Human liver microsomal incubations with amitriptyline and verapamil were used as test samples, and early-phase 'one lab visit only' approaches were used with all instruments. In total, 28 amitriptyline and 69 verapamil metabolites were found and tentatively identified. Time-of-flight mass spectrometry (TOFMS) was the only approach detecting all of them, shown to be the most suitable instrument for elucidating as comprehensive metabolite profile as possible leading also to lowest overall time consumption together with the LTQ-Orbitrap approach. The latter however suffered from lower detection sensitivity and false negatives, and due to slow data acquisition rate required slower chromatography. Approaches with triple quadrupole mass spectrometry (QqQ) and hybrid linear ion trap triple quadrupole mass spectrometry (Q-Trap) provided the highest amount of fragment ion data for structural elucidation, but, in addition to being unable to produce very high-important accurate mass data, they suffered from many false negatives, and especially with the Qq

  3. Assessing free and total morphine following heroin overdose when complicated by the presence of toxic amitriptyline levels.

    PubMed

    Avella, Joseph; Katz, Michael; Lehrer, Michael

    2007-10-01

    A 43-year-old female was reported to inject heroin, which led to her rapid death. Because of the potential for criminal charges, laboratory results that could verify "hotshot" heroin overdose were valuable. Initial toxicological analysis detected morphine (0.78 mg/L), amitriptyline (2.91 mg/L), and nortriptyline (2.80 mg/L) in femoral blood. Because these tricyclic antidepressant levels alone might normally be associated with a fatal outcome, the ratio of free versus total morphine (88.6%) and presence of 6-monoacetylmorphine in vitreous fluid were used support a history of rapid death following intravenous (IV) administration. The distribution of amitriptyline and nortriptyline was consistent with accumulation of drug after chronic dosing. Our other results suggest that the low morphine level in vitreous humor fluid (0.16 mg/L) relative to free morphine in femoral blood (0.78 mg/L) may also be an indicator of limited survival time following exposure to morphine. Based upon comprehensive toxicologic analysis, we determined overdose due to IV abuse of heroin was likely to have precipitated the fatal outcome. This case underscores the need for complete toxicologic workup and to consider individual variation in the dose response during toxicologic interpretation of postmortem results.

  4. The stability of amitriptyline N-oxide and clozapine N-oxide on treated and untreated dry blood spot cards.

    PubMed

    Temesi, David; Swales, John; Keene, Warren; Dick, Samuel

    2013-03-25

    Procedures for drug monitoring based on Dried Blood Spot (DBS) sampling are gaining acceptance for an increasing number of clinical and preclinical applications, where ease of use, small sample requirement, and improved sample stability have been shown to offer advantages over blood tube sampling. However, to-date, the vast majority of this work has described the analysis of well characterized drugs. Using amitriptyline, clozapine, and their potentially labile N-oxide metabolites as model compounds, we consider the merits of using DBS for discovery pharmacokinetic (PK) studies where the metabolic fate of test compounds are often unknown. Both N-oxide metabolites reverted to parent compound under standard drying (2hr) and extraction conditions. Card type significantly affected the outcome, with 14% and 22% degradation occurring for clozapine-N-oxide and amitriptyline-N-oxide on a brand of untreated DBS cards, compared to 59 and 88% on a brand of treated DBS cards. Enrichment of the parent compound ex vivo leads to overestimation of circulating blood concentration and inaccurate determination of the PK profile.

  5. Sitagliptin, sitagliptin and metformin, or sitagliptin and amitriptyline attenuate streptozotocin-nicotinamide induced diabetic neuropathy in rats

    PubMed Central

    Sharma, Ashish Kumar; Sharma, Akash; Kumari, Rita; Kishore, Kunal; Sharma, Divya; Srinivasan, Bharthu Parthsarthi; Sharma, Ashok; Singh, Santosh Kumar; Gaur, Samir; Jatav, Vijay Singh; Sharma, Prashant; Srivastava, Varnika; Joshi, Sneha; Joshi, Megha; Dhakad, Prashant Kumar; Kanawat, Davender Singh; Mishra, Akanksha; Sharma, Anil; Singh, Dharmendra; Singh, Ravinder Pal; Chawda, Himmat Singh; Singh, Rambir; Raikwar, Sachin Kumar; Kurmi, Muneem Kumar; Khatri, Pankaj; Agarwal, Ashutosh; Munajjam, Arshee

    2012-01-01

    Diabetic neuropathies are a family of nerve disorders caused by diabetes. Symptoms of the disease include nerve palsy, mononeuropathy, mononeuropathy multiplex, diabetic amyotrophy, painful polyneuropathy, autonomic neuropathy, and thoracoabdominal neuropathy. In this study, type 2 diabetes in rats was induced with nicotinamide-streptozotocin. Drug treatment was initiated on the d 15, with the combination regimen of metformin, pioglitazone and glimipiride or metformin and sitagliptin or sitagliptin, amitriptyline and sitagliptin and led to significantly improved glycemic control, increased grip strength and paw jumping response on d 21, 28 and 35 (P < 0.001). Significant increases in blood protein levels and decreases in urinary protein levels were observed in the animals treated with the different regimens on d 21, 28 and 35 (P < 0.001). Combined treatment of streptozotocin and nicotinamide caused marked degeneration of nerve cells, while administration of metformin and sitagliptin showed tissue regeneration and no body weight gain. In conclusion, treatment with sitagliptin and sitagliptin combined with metformin or amitriptyline results in no body weight gain, but causes an increase in grip strength and pain sensitivity, exhibits neural protection, and reverses the alteration of biochemical parameters in rats with streptozotocin-nicotinamide induced type 2 diabetes. PMID:23554750

  6. Ultrasensitive label-free immunoassay for optical determination of amitriptyline and related tricyclic antidepressants in human serum.

    PubMed

    Krieg, Anne Katrin; Gauglitz, Günter

    2015-09-01

    The present work focuses on the development of a label-free and ultrasensitive immunoassay for the detection of the drug amitriptyline in human serum. Reflectometric interference spectroscopy is used as the detection method, providing a simple, but highly sensitive optical setup. Amitriptyline is a common antidepressant; however, it has a small therapeutic window and can cause severe side effects in case of wrong dosage. Therefore, it is highly recommended for therapeutic drug monitoring to control the drug level. The limit of detection for this optical immunosensor was determined in buffer (0.3 μg/L) and in human serum (0.5 μg/L). It has become evident that this assay can compete with HPLC measurements. For drug concentrations at a normal level or above, the sample can be diluted up to 1:100. Especially for limited sample volumes, this is a great advantage. The sensor surface shows very high stability, and together with the regeneration solution 80 measurement cycles can be performed on each transducer chip. Cross-reactivity experiments indicate that a sum determination of several tricyclic antidepressants is possible.

  7. Hypnotic relaxation vs amitriptyline for tension-type headache: let the patient choose.

    PubMed

    Ezra, Yacov; Gotkine, Marc; Goldman, Sylvie; Adahan, Haim Moshe; Ben-Hur, Tamir

    2012-05-01

    Although both pharmacological and behavioral interventions may relieve tension-type headache, data are lacking regarding treatment preference, long-term patient compliance, and feasibility of behavioral intervention in a standard neurological outpatient clinic setting. To describe patient choice, long-term compliance, and clinical outcome in a neurological clinic setting where patients are given the choice of the approach they wish to pursue. Patients presenting to the headache clinic with a diagnosis of tension-type headache that justified prophylactic therapy (frequent episodic tension-type headache or chronic tension-type headache) were given the choice of amitriptyline (AMT) treatment or hypnotic relaxation (HR), and were treated accordingly. Patients were given the option to cross-over to the other treatment group at each visit. HR was performed during standard length neurology clinic appointments by a neurologist trained to perform hypnosis (Y.E.). Follow-up interviews were performed between 6 and 12 months following treatment initiation to evaluate patient compliance, changes in headache frequency or severity, and quality-of-life parameters. Ninety-eight patients were enrolled, 92 agreed to receive prophylactic therapy of some kind. Fifty-three (57.6%) patients chose HR of which 36 (67.9%) actually initiated this treatment, while 39 (42.4%) chose pharmacological therapy with AMT of which 25 (64.1%) patients actually initiated therapy. Patients with greater analgesic use were more likely to opt for AMT (P= .0002). Eleven of the patients initially choosing AMT and 2 of the patients initially choosing HR crossed over to the other group. Seventy-four percent of the patients in the HR group and 58% of patients in the AMT group had a 50% reduction in the frequency of headaches (P= .16). Long-term adherence to treatment with HR exceeded that of AMT. At the end of the study period, 26 of 47 patients who tried HR compared with 10 of 27 who tried AMT continued

  8. Successful use of therapeutic hypothermia after cardiac arrest due to amitriptyline and venlafaxine intoxication.

    PubMed

    Kontio, Terhi; Salo, Ari; Kantola, Teemu; Toivonen, Lauri; Skrifvars, Markus B

    2015-06-01

    The prognosis of out-of-hospital cardiac arrest (OHCA) due to intoxication is dismal. Tricyclic antidepressants (TCAs) are widely used in the treatment of depression, but possess significant cardiotoxicity, and are one of the most common medications used in suicide attempts worldwide. TCA poisoning can cause hypotension, seizures, and cardiac conduction disturbances, which can lead to life-threatening arrhythmia. Current guidelines recommend mild therapeutic hypothermia (TH) for unconscious survivors of OHCA, but hypothermia treatment itself can cause disturbances in cardiac conduction, which could aggravate the effect of TCAs on cardiac conduction. We report the successful use of TH in a 19-year-old woman who was resuscitated from ventricular tachycardia after intentional ingestion of amitriptyline and venlafaxine, a serotonin-norepinephrine reuptake inhibitor. The cardiac arrest was witnessed, but no bystander cardiopulmonary resuscitation (CPR) was performed. The initial rhythm was ventricular tachycardia with no detectable pulse. Three defibrillations, magnesium sulfate, and sodium bicarbonate were given and her trachea was intubated, after which return of spontaneous circulation (ROSC) was achieved in 26 minutes. After ROSC, she had seizures and was sedated with propofol. Out-of-hospital TH was initiated with 1500 mL of cold Ringer's acetate. An infusion of norepinephrine was initiated for low blood pressure. On arrival at the university hospital, she was unconscious and had dilated pupils. She was tachycardic with a body temperature of 33.5°C. She was transferred to the intensive care unit and TH was maintained with invasive cooling. During the TH treatment, she did not experience any serious cardiac arrhythmia, transthoracic echocardiogram was normal, and the electrocardiogram (ECG) returned to normal. The patient was extubated 45 hours after the cardiac arrest. After the extubation, she was alert and cooperative, but slightly delusional. She was

  9. Amitriptyline poisoning of a baby: how informative can hair analysis be?

    PubMed

    Allibe, Nathalie; Eysseric-Guerin, Hélène; Kintz, Pascal; Bartoli, Mireille; Bost-Bru, Cécile; Grenier, Florian; Scolan, Virginie; Stanke-Labesque, Françoise

    2015-04-01

    We reported a case of a 6-month-old baby girl who was hospitalized in the pediatric emergency for central nervous system disorders then coma. Toxicology analysis showed the presence of amitriptyline (AMI) and its metabolite nortriptyline (NOR) in blood and urine of the baby. Additional investigations suggested a shaken baby syndrome. Given the family context, a judge ordered hair tests for both the child and his parents to document drug exposure. A liquid chromatography tandem mass spectrometric (LC-MS/MS) method was then developed to quantify AMI and NOR in hair. After decontamination and segmentation, 20 mg of hair was incubated overnight at 55 °C in methanol (MeOH). The LC-MS/MS method used an online solid phase extraction and the analysis was performed using two transitions per compound. The LOQ and LOD for the two compounds were estimated at 0.0075 ng/mg and 0.005 ng/mg respectively. All hair segments tested for both parents were negative. For the baby two strands of hair were collected one day after the acute intoxication for the first and 5 weeks later for the second. The first strand was not decontaminated before analysis to avoid losing specimen. The high and relatively homogenous concentrations of AMI (with a range of value from 6.65 to 9.69 ng/mg) and NOR (with a range of value from 7.12 to 8.96 ng/mg) measured suggested that contamination could have occurred. The analysis of the second strand after decontamination allowed to detect AMI and NOR in all hair segments. The obtained values varied between 0.54 and 1.41 ng/mg for AMI and between 1.26 and 4.00 ng/mg for NOR. These results supported the hypothesis of a chronic exposure during several months before hair collection with regular increase. However a single overdose could not be totally excluded. The interpretation of results must take into account the pharmacological and physiological parameters of hair of the children.

  10. The effects of St. John's wort extract and amitriptyline on autonomic responses of blood vessels and sweat glands in healthy volunteers.

    PubMed

    Siepmann, Martin; Kirch, Wilhelm; Krause, Stephanie; Joraschky, Peter; Mueck-Weymann, Michael

    2004-02-01

    St. John's wort extract is widely used and advertised as a "natural antidepressant" lacking autonomic side effects. This randomized, double-blind, placebo-controlled study compared the effects of St. John's wort extract on autonomic responses of blood vessels and sweat glands with those of amitriptyline and placebo. A randomized, double-blind, crossover study was performed in healthy male volunteers aged 22 to 31 years (25 +/- 3 years; mean +/- SD) years. Subjects orally received capsules with 255 to 285 mg St. John's wort extract (900 microg hypericin content), 25 mg amitriptyline, and placebo 3 times daily for periods of 14 days each with at least 14 days between. Vasoconstrictory response of cutaneous blood flow (VR) and skin conductance response (SR) following a single deep inspiration were employed as parameters of autonomic function. St. John's wort extract had no effect on VR and SR. In contrast, SR was diminished and the dilation phase of VR was prolonged following multiple dosing with amitriptyline (P < 0.05). Decreased electrodermal reactivity observed with amitriptyline reflects inhibition of acetylcholine at peripheral m3-cholinoreceptors, whereas prolongation of VR induced by the tricyclic drug may be due to sustained activation of central and/or peripheral sympathetic neurons.

  11. Effects of amitriptyline and intra-oral device appliance on clinical and laser-evoked potentials features in chronic tension-type headache.

    PubMed

    de Tommaso, M; Shevel, E; Libro, G; Guido, M; Di Venere, D; Genco, S; Monetti, C; Serpino, C; Barile, G; Lamberti, P; Livrea, P

    2005-05-01

    In the present study, we examined clinical and laser-evoked potentials (LEP) features in two groups of chronic tension-type headache (CTTH) patients treated with two different approaches: intra-oral appliance of prosthesis, aiming to reduce muscular tenderness, and 10 mg daily amitriptyline. Eighteen patients suffering from CTTH (IHS, 2004) participated in the study. We performed a basal evaluation of clinical features and LEPs in all patients (T0) vs. 12 age- and sex-matched controls; successively, patients were randomly assigned to a two-month treatment by amitriptyline or intra-oral device appliance. The later LEPs, especially the P2 component, were significantly increased in amplitude in the CTTH group. Both the intra-oral prosthesis and amitriptyline significantly reduced headache frequency. Total Tenderness Score was significantly reduced in the group treated by the prosthesis. The amplitude of P2 response elicited by stimulation of pericranial zones showed a reduction after amitriptyline treatment. The results of this study may confirm that pericranial tenderness is primarily a phenomenon initiating a self-perpetuating circuit, favoured by central sensitisation at the level of the cortical nociceptive areas devoted to the attentive and emotive compounds of pain. Both the interventions at the peripheral and central levels may interrupt this reverberating circuit, improving the outcome of headache.

  12. Amitriptyline 2% cream vs. capsaicin 0.75% cream in the treatment of painful diabetic neuropathy (Double blind, randomized clinical trial of efficacy and safety).

    PubMed

    Kiani, Javad; Ahmad Nasrollahi, Saman; Esna-Ashari, Farzaneh; Fallah, Puyan; Sajedi, Firuzeh

    2015-01-01

    Because of less systemic side effects of topical medications in pain relief of the painful form of diabetic peripheral neuropathy, this study aimed to compare the effect of amitriptyline and capsaicin cream in relieving pain in this condition. In this randomized, double-blind and non -inferiority trial, 102 patients received amitriptyline 2% and capsaicin 0.75% creams 3 times a day for 12 weeks on the feet. Pain relief was measured by the visual analog scale (0-10). Treatment responding was considered as cure rate greater than 50% from baseline. Evaluations of the pain severity, compliance and drugs adverse effects were performed at each of the 4-week follow -up visits. Both drugs significantly relieved pain in 12 weeks compared with baseline values (P < 0.001 for both). Treatment responders were similar in both groups (P = 0.545). Intention-To-Treat analysis showed no significant difference in the efficacy between the two treatments (P = 0.703). Adverse events were more common in capsaicin group (P = 0.001). Dermatologic complications were the most common: itching, blister formation and erythema in the capsaicin group and skin dryness and itching in the amitriptyline group. This study demonstrates the similar efficacy of amitriptyline cream with capsaicin cream in managing diabetic neuropathic pain with fewer side effects.

  13. A novel strategy for spectrophotometric simultaneous determination of amitriptyline and nortriptyline based on derivation with a quinonoid compound in serum samples

    NASA Astrophysics Data System (ADS)

    Farnoudian-Habibi, Amir; Massoumi, Bakhshali; Jaymand, Mehdi

    2016-11-01

    A novel and efficient strategy for the simultaneous determination of two tricyclic antidepressant (TCA) drugs [amitriptyline (AT), and its main metabolite (nortriptyline; NT)] via a combination of magnetic solid phase extraction (MSPE), and spectrophotometric techniques in serum is suggested. For this purpose, the imidazolium ionic liquid (Imz)-modified Fe3O4@SiO2 nanoparticles (Fe3O4@SiO2-Imz) was employed as an adsorbent for the MSPE. Preconcentration (loading-desorption) studies were performed under optimized conditions including pH, adsorbent amount, contact time, eluent volume, and desorption time. Afterward, determination of each drug was carried out by specific strategy. Acetaldehyde (AC), and 2,3,5,6-tetrachloro-1,4-benzoquinone (chloranil; CL) were used as chemical reagents for reaction with NT, while AT did not react with these reagents. This method is based on the condensation reaction between secondary amine group of NT and AC to afford an enamine, and subsequently reaction with CL to produce a chlorinated quinone-substituted enamine. The final product exhibited maximum absorption at 556 nm, while the AT was determined at 240 nm. The limits of detections (LODs) for NT and AT in serum sample were obtained as 0.19 and 0.90 ng mL- 1, respectively. The limits of quantifications (LOQs) were obtained to be 0.63 and 2.93 ng mL- 1 for NT and AT, respectively. A linear range was obtained to be 1 to 5 ng mL- 1. Results indicated that the suggested method is applicable for simultaneous determination of NT and AT in serum samples.

  14. Sildenafil, a phosphodiesterase type 5 inhibitor, enhances the antidepressant activity of amitriptyline but not desipramine, in the forced swim test in mice.

    PubMed

    Socała, Katarzyna; Nieoczym, Dorota; Wyska, Elżbieta; Poleszak, Ewa; Wlaź, Piotr

    2012-06-01

    The cholinergic theory of depression highlights the involvement of muscarinic acetylcholine receptors in the neurobiology of mood disorders. The present study was designed to investigate the effect of sildenafil, a phosphodiesterase type 5 inhibitor which exhibits cholinomimetic properties, alone and in combination with scopolamine in the forced swim test in mice. Moreover, we assessed the ability of sildenafil to modify the antidepressant activity of two tricyclic antidepressants with distinct cholinolytic activity, amitriptyline and desipramine. Swim sessions were conducted by placing mice in glass cylinders filled with water for 6 min and the duration of behavioral immobility during the last 4 min of the test was evaluated. Locomotor activity was measured with photoresistor actimeters. To evaluate the potential pharmacokinetic interaction between amitriptyline and sildenafil, brain and serum concentrations of amitriptyline were determined by HPLC. Sildenafil (1.25-20 mg/kg) as well as scopolamine (0.5 mg/kg) and its combination with sildenafil (1.25 mg/kg) did not affect the total immobility time duration. However, joint administration of scopolamine with sildenafil at doses of 2.5 and 5 mg/kg significantly reduced immobility time as compared to control group. Moreover, co-administration of scopolamine with sildenafil at the highest dose (5 mg/kg) significantly decreased immobility time as compared to scopolamine-treated group. Sildenafil (1.25, 2.5 and 5 mg/kg) significantly enhanced the antidepressant activity of amitriptyline (5 mg/kg). No changes in anti-immobility action of desipramine (20 mg/kg) in combination with sildenafil (5, 10 and 20 mg/kg) were observed. Sildenafil did not affect amitriptyline level in both brain and serum. In conclusion, the present study suggests that sildenafil may enhance the activity of antidepressant drugs which exhibit cholinolytic activity.

  15. Tricyclic antidepressant amitriptyline activates fibroblast growth factor receptor signaling in glial cells: involvement in glial cell line-derived neurotrophic factor production.

    PubMed

    Hisaoka, Kazue; Tsuchioka, Mami; Yano, Ryoya; Maeda, Natsuko; Kajitani, Naoto; Morioka, Norimitsu; Nakata, Yoshihiro; Takebayashi, Minoru

    2011-06-17

    Recently, both clinical and animal studies demonstrated neuronal and glial plasticity to be important for the therapeutic action of antidepressants. Antidepressants increase glial cell line-derived neurotrophic factor (GDNF) production through monoamine-independent protein-tyrosine kinase, extracellular signal-regulated kinase (ERK), and cAMP responsive element-binding protein (CREB) activation in glial cells (Hisaoka, K., Takebayashi, M., Tsuchioka, M., Maeda, N., Nakata, Y., and Yamawaki, S. (2007) J. Pharmacol. Exp. Ther. 321, 148-157; Hisaoka, K., Maeda, N., Tsuchioka, M., and Takebayashi, M. (2008) Brain Res. 1196, 53-58). This study clarifies the type of tyrosine kinase and mechanism of antidepressant-induced GDNF production in C6 glioma cells and normal human astrocytes. The amitriptyline (a tricyclic antidepressant)-induced ERK activation was specifically and completely inhibited by fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitors and siRNA for FGFR1 and -2. Treatment with amitriptyline or several different classes of antidepressants, but not non-antidepressants, acutely increased the phosphorylation of FGFRs and FGFR substrate 2α (FRS2α). Amitriptyline-induced CREB phosphorylation and GDNF production were blocked by FGFR-tyrosine kinase inhibitors. Therefore, antidepressants activate the FGFR/FRS2α/ERK/CREB signaling cascade, thus resulting in GDNF production. Furthermore, we attempted to elucidate how antidepressants activate FGFR signaling. The effect of amitriptyline was inhibited by heparin, non-permeant FGF-2 neutralizing antibodies, and matrix metalloproteinase (MMP) inhibitors. Serotonin (5-HT) also increased GDNF production through FGFR2 (Tsuchioka, M., Takebayashi, M., Hisaoka, K., Maeda, N., and Nakata, Y. (2008) J. Neurochem. 106, 244-257); however, the effect of 5-HT was not inhibited by heparin and MMP inhibitors. These results suggest that amitriptyline-induced FGFR activation might occur through an extracellular pathway

  16. Detection of amitriptyline, nortriptyline and bromazepam in liver, CSF and hair in the homicidal poisoning of a one-month-old girl autopsied 8 months after death.

    PubMed

    Gaillard, Yvan; Breuil, Rémi; Doche, Christophe; Romeuf, Ludovic; Lemeur, Catherine; Prevosto, Jean Michel; Fanton, Laurent

    2011-04-15

    We reported on the death by poisoning of a one-month-old baby that had followed the death of one of her sister (due to cyamemazine overdose). Exhumation of the corpse was done 8 months after burial and revealed the presence of amitriptyline. Parent drug and its metabolite were analysed by HPLC-MS/MS in positive ionisation mode on a C(18) analytical column using a gradient of acetonitrile and 2mM formate buffer at pH=3. Quantification is based on the main ion m/z=233, the common product ion of nortriptyline (MH(+), m/z 264), amitriptyline (MH(+), m/z 278) and nortriptyline D3 used as internal standard (MH(+), m/z 267). Amitriptyline and nortriptyline in the liver were measured at a concentration of 29.8 and 3.6 μg/g, respectively. Hair analyses revealed the presence of amitriptyline and nortriptyline at concentrations of 1811 and 43 pg/mg, respectively, while complementary analyses showed the presence of bromazepam in the hair at a concentration of 740 pg/mg, thus documenting previous administrations. The mother confessed later having used the drinkable form of the pharmaceutical LAROXYL(®) by pouring the content of a 20 ml bottle (at 40 mg/ml) into the feeding-bottle of her child. The milk was sweet but still bitter and following the testimony of a close relative, the whole family helped to feed the crying baby. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  17. A double-hit model of stress dysregulation in rats: implications for limbic corticosteroid receptors and anxious behavior under amitriptyline treatment.

    PubMed

    Cotella, Evelin M; Durando, Patricia E; Suárez, Marta M

    2014-05-01

    Adversity during early life can lead to diverging endocrine and behavioral responses to stress in adulthood. In our laboratory, we evaluated the long-term effects of early life adversity and its interaction with chronic stress during adulthood. We propose this as a model of vulnerability to dysregulation of the stress response. We hypothesized that rats subjected to both protocols would show differential expression of corticosteroid receptors measured as number of neurons immunoreactive for glucocorticoid receptors (GR) or mineralocorticoid receptors (MR), in limbic areas related to the control of anxiety-like behavior. We also evaluated the effect of amitriptyline expecting to prevent the outcomes of the model. Male Wistar rats were separated from the mother (MS) for 4.5 h every day for the first 3 weeks of life. From postnatal day 50, rats were subjected to chronic variable stress (CVS) during 24 d (five types of stressor at different times of day). During the stress protocol, the rats were administered amitriptyline (10 mg/kg i.p.) daily. MS evoked lower MR expression in the central amygdaloid nucleus and this was reversed by amitriptyline. Furthermore, CVS increased MR immunoreactivity in the hippocampal area CA2 and increased anxious behavior; both effects were prevented by the antidepressant. When MS was combined with CVS during adulthood, there was a reduction of locomotor activity, with no corrective effect of amitriptyline. The differential effects among groups could mean that MS would promote an alternative phenotype that is expressed when facing CVS (a double hit) later in life.

  18. Antinociceptive effects of AS1069562, the (+)-isomer of indeloxazine, on spinal hypersensitivity induced by intrathecal injection of prostaglandin in mice: comparison with duloxetine and amitriptyline.

    PubMed

    Murai, Nobuhito; Tsukamoto, Mina; Tamura, Seiji; Aoki, Toshiaki; Matsuoka, Nobuya

    2014-06-15

    The (+)-isomer of indeloxazine AS1069562 exerts multiple pharmacological actions including the inhibition of serotonin (5-HT) and norepinephrine reuptake and analgesia in experimental animal pain models. Here, we evaluated the antinociceptive effects of AS1069562 and the antidepressants duloxetine and amitriptyline in mouse models of prostaglandin-induced spinal hypersensitivity. Prostaglandin E2 (PGE2) and F2α (PGF2α) were intrathecally administered to induce spinal hypersensitivity, causing tactile allodynia in mice. Allodynia induced by PGF2α but not by PGE2 was suppressed by desensitization of C-fibers with systemic pretreatment with resiniferatoxin. C-fiber hyperexcitability might therefore play a role in allodynia induced by PGF2α but not PGE2. In the PGE2-induced allodynia model, AS1069562 and duloxetine significantly suppressed allodynia, whereas amitriptyline did not. In the PGF2α-induced allodynia model, AS1069562 and amitriptyline significantly ameliorated allodynia, whereas duloxetine did not. To demonstrate the broad effects of AS1069562 compared to duloxetine, additional studies were conducted to elucidate other target mechanisms of AS1069562 beyond 5-HT and norepinephrine reuptake inhibition. AS1069562 exhibited affinity for both 5-HT1A and 5-HT3 receptors, and the analgesic effect of AS1069562 on PGF2α-induced allodynia was significantly blocked by the 5-HT1A receptor antagonist (S)-WAY100135 and the 5-HT3 receptor agonist SR57227. Taken together, these results indicate that AS1069562 inhibits both C-fiber- and non-C-fiber-dependent prostaglandin-induced allodynia, while duloxetine inhibits only non-C-fiber-triggered allodynia, and amitriptyline inhibits only C-fiber-triggered allodynia. These broad antinociceptive effects of AS1069562 may be due not only to 5-HT and norepinephrine reuptake inhibition but also to its effects on 5-HT receptors such as 5-HT1A and 5-HT3 receptors.

  19. Leptin plasma concentrations increase during antidepressant treatment with amitriptyline and mirtazapine, but not paroxetine and venlafaxine: leptin resistance mediated by antihistaminergic activity?

    PubMed

    Schilling, Claudia; Gilles, Maria; Blum, Werner F; Daseking, Emmerich; Colla, Michael; Weber-Hamann, Bettina; Lederbogen, Florian; Krumm, Bertram; Heuser, Isabella; Wudy, Stefan A; Kopf, Daniel; Deuschle, Michael

    2013-02-01

    Treatment with several psychopharmacological agents has been associated with increased leptin plasma concentrations. We measured leptin plasma concentrations in 76 adult depressed patients after a 6-day washout phase and again after 35 days of treatment with amitriptyline or paroxetine, as well as in 73 depressed patients after 28 days of treatment with either mirtazapine or venlafaxine. Leptin plasma concentrations increased during treatment with amitriptyline and mirtazapine, even after controlling for increased body mass index and irrespective of response to treatment [14.5 (13.8) vs 20.3 (18.7) ng/mL, and 12.2 (15.8) vs 14.4 (16.5) ng/mL in the 2 cohorts, respectively]. In contrast, paroxetine and venlafaxine treatment was not associated with changes in leptin plasma concentrations [14.8 (12.0) vs 13.6 (10.6); 15.9 (17.3) vs 13.5 (14.6) ng/mL] nor with weight gain. We conclude that treatment with amitriptyline or mirtazapine is associated with an increase in leptin secretion beyond change in weight. Thus, high leptin levels apparently are ineffective in the control of weight gain, indicating leptin resistance. Leptin resistance may be mediated by an antihistaminergic effect on hypothalamic nuclei integrating signals relevant for energy balance.

  20. The influence of microglia activation on the efficacy of amitriptyline, doxepin, milnacipran, venlafaxine and fluoxetine in a rat model of neuropathic pain.

    PubMed

    Zychowska, Magdalena; Rojewska, Ewelina; Makuch, Wioletta; Przewlocka, Barbara; Mika, Joanna

    2015-02-15

    The analgesic properties of antidepressants are often used in the treatment of neuropathy; however their influence on glial cells in maintaining neuropathic pain is unknown. Our studies examined the neuropathic pain-relieving properties after intraperitoneal injection of amitriptyline, doxepin, milnacipran, venlafaxine and fluoxetine 7 days after sciatic nerve injury (CCI) in rats and its influence on microglia/macrophages (IBA-1) and astroglia (GFAP) activation in the spinal cord and dorsal root ganglia (DRG) using Western blot. All tested antidepressants significantly reduced CCI-induced allodynia but hyperalgesia was only antagonised by fluoxetine, doxepine and venlafaxine. The strongest analgesia was observed after fluoxetine administration. Western blot analysis showed the upregulation of the IBA-1 in the lumbar spinal cord and DRG after amitriptyline or milnacipran administration in CCI-exposed rats, whereas after fluoxetine the downregulation was observed. The administration of doxepin did not change the IBA-1 protein level in both studied structures; however venlafaxine decreased the IBA-1 only in the DRG. No changes in the GFAP level in both structures were observed after any of listed above antidepressants administration. Chronic minocycline treatment enhanced amitriptyline and milnacipran, but did not fluoxetine analgesia under neuropathic pain in rats. Our results suggest that nerve injury-induced pain is related with the activation of microglia, which is diminished by fluoxetine treatment in the neuropathic pain model.

  1. Spectrophotometric determination of trazodone, amineptine and amitriptyline hydrochlorides through ion-pair formation with molybdenum and thiocyanate.

    PubMed

    Mohamed, Gehad G; Nour El-Dien, F A; Khalil, S M; Mohamed, Nehad A

    2006-12-01

    Extraction spectrophotometric method has been developed for the determination of tricyclic drugs such as trazodone (TZH), amineptine (APH) and amitriptyline (ATPH) hydrochlorides in pure form and in the dosage forms coming from different Egyptian markets. The method based on the formation of ion-pairs between these drugs under investigation and inorganic complex of Mo(V)-thiocyanate followed by its extraction with methylene chloride. The optimum conditions for the ion-pairs formation are established. The method permits the determination of TZH, APH and ATPH over the concentration range of 2-28, 2-32 and 1-30 microg ml(-1), respectively. The Sandell sensitivity (S) is found to be 0.105, 0.138 and 0.118 g cm(-2) for TZH, APH and ATPH, respectively. The SD is found to be 0.16-0.377, 0.12-0.259 and 0.091-0.286 and the R.S.D. are 0.14-0.55, 0.12-0.399 and 0.095-0.485 for TZH, APH and ATPH, respectively. The method is applicable for the assay of the investigated drugs in different dosage forms and the results are in good agreement with those obtained by the official method.

  2. Development of new phosphated cellulose for application as an efficient biomaterial for the incorporation/release of amitriptyline.

    PubMed

    Bezerra, Roosevelt D S; Morais, Alan I S; Osajima, Josy A; Nunes, Livio C C; Silva Filho, Edson C

    2016-05-01

    In the last years has increased the study about the using of natural biopolymers and theirs derivatives in the removal (adsorption/incorporation) of contaminats of medium aqueous, and theirs utilization in the desorption (release) de drugs. However, there not in the literature studies about the utilization of the cellulose and cellulose phosphate in the adsorption (incorporation)/desorption (release) of the drug amitriptyline (AMI). Therefore, in this study was accomplished the synthesized of the phosphated cellulose (PC) through the reaction of pure cellulose (C) with sodium trimetaphosphate (P) under-reflux, for 4h and at 393K. The efficiency of the reaction was observed by XRD, TG/DTG, (31)P NMR and EDS. The adsorption study for the AMI in aqueous medium was carried out by varying the time, pH, concentration, temperature and ionic strength. The results showed that the PC showed a greater adsorption capacity of AMI than pure cellulose, presenting an increase of about 102.72% in the adsorption capacity of the drug by cellulose after the phosphating reaction. In desorption of drug from the surface of biomaterials was performed by varying the pH and time, where it was observed that PC showed a maximum release of 40.98% ± 0.31% at pH 7.

  3. Spectrophotometric determination of trazodone, amineptine and amitriptyline hydrochlorides through ion-pair formation with molybdenum and thiocyanate

    NASA Astrophysics Data System (ADS)

    Mohamed, Gehad G.; Nour El-Dien, F. A.; Khalil, S. M.; Mohamed, Nehad A.

    2006-12-01

    Extraction spectrophotometric method has been developed for the determination of tricyclic drugs such as trazodone (TZH), amineptine (APH) and amitriptyline (ATPH) hydrochlorides in pure form and in the dosage forms coming from different Egyptian markets. The method based on the formation of ion-pairs between these drugs under investigation and inorganic complex of Mo(V)-thiocyanate followed by its extraction with methylene chloride. The optimum conditions for the ion-pairs formation are established. The method permits the determination of TZH, APH and ATPH over the concentration range of 2-28, 2-32 and 1-30 μg ml -1, respectively. The Sandell sensitivity ( S) is found to be 0.105, 0.138 and 0.118 g cm -2 for TZH, APH and ATPH, respectively. The SD is found to be 0.16-0.377, 0.12-0.259 and 0.091-0.286 and the R.S.D. are 0.14-0.55, 0.12-0.399 and 0.095-0.485 for TZH, APH and ATPH, respectively. The method is applicable for the assay of the investigated drugs in different dosage forms and the results are in good agreement with those obtained by the official method.

  4. Spectrophotometric determination of trazodone, amineptine and amitriptyline hydrochlorides through ion-pair formation using methyl orange and bromocresol green reagents

    NASA Astrophysics Data System (ADS)

    Nour El-Dien, Faten A. F.; Mohamed, Gehad G.; Mohamed, Nehad A.

    2006-09-01

    A simple and rapid extraction spectrophotometric procedure has been developed for the determination of tricyclic anti-depressant drugs such as trazodone (TZH), amineptine (APH) and amitriptyline (ATPH) hydrochlorides in pure form and in different dosage forms. The method involves the formation of intense yellow ion-pairs between these drugs under investigation and methyl orange (MO) and bromocresol green (BCG) reagents followed by their extraction with 1,2-dichloroethane and quantitative microdetermination at 420 and 410 nm using MO or BCG, respectively. The optimum experimental conditions for the ion-pairs formation are established. The method permits the determination of TZH, APH and ATPH over a concentration range of 2-50, 2-50 and 1-25 μg ml -1 for TZH, APH and ATPH, using MO and 1-25 μg ml -1 for TZH, APH and ATPH, using BCG, respectively. The Sandell sensitivity ( S) is found to be 0.106, 0.1071 and 0.0907 g cm -2 for TZH, APH and ATPH, respectively, using MO reagent and 0.0788, 0.0661 and 0.0494 g cm -2 for TZH, APH and ATPH, respectively, using BCG. The method is applicable for the assay of the investigated drugs in different dosage forms and the results are in good agreement with those obtained by the official method.

  5. NCAM-deficient mice show prominent abnormalities in serotonergic and BDNF systems in brain - Restoration by chronic amitriptyline.

    PubMed

    Aonurm-Helm, Anu; Anier, Kaili; Zharkovsky, Tamara; Castrén, Eero; Rantamäki, Tomi; Stepanov, Vladimir; Järv, Jaak; Zharkovsky, Alexander

    2015-12-01

    Mood disorders are associated with alterations in serotonergic system, deficient BDNF (brain-derived neurotrophic factor) signaling and abnormal synaptic plasticity. Increased degradation and reduced functions of NCAM (neural cell adhesion molecule) have recently been associated with depression and NCAM deficient mice show depression-related behavior and impaired learning. The aim of the present study was to investigate potential changes in serotonergic and BDNF systems in NCAM knock-out mice. Serotonergic nerve fiber density and SERT (serotonin transporter) protein levels were robustly reduced in the hippocampus, prefrontal cortex and basolateral amygdala of adult NCAM(-)(/-) mice. This SERT reduction was already evident during early postnatal development. [(3)H]MADAM binding experiments further demonstrated reduced availability of SERT in cell membranes of NCAM(-)(/-) mice. Moreover, the levels of serotonin and its major metabolite 5-HIAA were down regulated in the brains of NCAM(-)(/-) mice. NCAM(-)(/-) mice also showed a dramatic reduction in the BDNF protein levels in the hippocampus and prefrontal cortex. This BDNF deficiency was associated with reduced phosphorylation of its receptor TrkB. Importantly, chronic administration of antidepressant amitriptyline partially or completely restored these changes in serotonergic and BDNF systems, respectively. In conclusion, NCAM deficiency lead to prominent and persistent abnormalities in brain serotonergic and BDNF systems, which likely contributes to the behavioral and neurobiological phenotype of NCAM(-/-) mice.

  6. Administration of amitriptyline attenuates noise-induced hearing loss via glial cell line-derived neurotrophic factor (GDNF) induction.

    PubMed

    Shibata, Seiji Bruce; Osumi, Yasunori; Yagi, Masao; Kanda, Seiji; Kawamoto, Kohei; Kuriyama, Hiromichi; Nishiyama, Toshimasa; Yamashita, Toshio

    2007-05-04

    Antidepressant treatments have been described to induce neurotrophic factors (NTFs) and reverse the cell loss observed in rodent stress models. Amitriptyline (AT), a tricyclic antidepressant agent, has been reported in recent studies to induce glial cell line-derived neurotrophic factor (GDNF) synthesis and release in rat C6 glioblastoma cells. GDNF has shown protection against acoustic trauma in previous studies. Therefore, we investigated whether AT could induce GDNF synthesis in the cochlea and attenuate cochlea damage against acoustic trauma. We used Hartley guinea pigs and injected AT (30 mg/kg) or saline into the peritoneum. Subjects were exposed to 117 dB SPL octave band noise centered at 4 kHz for 24 h. Noise-induced hearing loss (NIHL) was assessed with auditory brain stem response (ABR) at 4, 8 and 16 kHz measured prior to the injection, 3 days and 7 days after noise exposure. For histological assessment, we observed the sensory epithelium using a surface preparation technique and assessed the quantitative hair cell (HC) damage. We evaluated GDNF synthesis with or without intense noise exposure at 3, 12 and 24 h after the administration of AT in the cochlea using Western blot analysis. GDNF expression was shown 3 h and 12 h after the injection without noise, whereas with noise the GDNF expression lasted for 24 h. The AT-administrated group showed significantly reduced ABR threshold shift and less HC damage than the saline-administrated group. These findings suggest that the administration of AT-induced GDNF levels in the cochlea and attenuated cochlea damage from NIHL.

  7. Hair analysis to demonstrate administration of amitriptyline, temazepam, tramadol and dihydrocodeine to a child in a case of kidnap and false imprisonment.

    PubMed

    Chatterton, Craig; Kintz, Pascal

    2014-03-01

    Amitriptyline, temazepam, tramadol and dihydrocodeine are prescription-only-medications that are rarely prescribed to children. Each of these drugs has a sedative effect on the central nervous system; their combined use could cause an exacerbation of the sedative effects. Amitriptyline (a tricyclic antidepressant) can be prescribed to treat nocturnal enuresis; temazepam (a hypnotic) can be used as a premedicant in inpatient and day-case surgery; tramadol (a synthetic opioid analgesic) is used to treat moderate or severe pain, though it is not recommended for children under the age of 12 years and dihydrocodeine (opioid analgesic), which is available in combination with acetaminophen (Co-dydramol), is not recommended for children under the age of 4 years; in children over 4 years, a reduced dose is necessary. The North West Forensic Science Service Laboratory, Euxton, Lancashire, was asked by a British police force to analyze three separate hair samples, which had been collected from a young child following their discovery as a result of a large scale kidnap and false imprisonment investigation. After decontamination and segmentation (20 x 1-cm section), two of the three hair specimens were analyzed by liquid chromatography coupled with tandem mass spectrometry after alkaline (pH 9.5) extraction using methylene chloride/isopropanol/n-heptane (25:10:65, v/v/v). The entire length of each hair specimen tested positive for amitriptyline and nortriptyline (7-314 pg/mg amitriptyline; 7-318 pg/mg nortriptyline), temazepam (2-29 pg/mg), tramadol (60-2000 pg/mg) and dihydrocodeine (10-90 pg/mg) demonstrating that the child had ingested these drugs on more than one occasion prior to the kidnap. In this case, the child's mother and the mothers' partner were found guilty of kidnap, false imprisonment and perverting the course of justice. There are very few studies citing the concentrations of these drugs in children - especially children's hair samples. This case demonstrates

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

    PubMed

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

    2002-01-01

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

  9. A Randomized Controlled Trial on the Effectiveness of Court-Type Traditional Thai Massage versus Amitriptyline in Patients with Chronic Tension-Type Headache

    PubMed Central

    Damapong, Peerada; Kanchanakhan, Naowarat; Eungpinichpong, Wichai; Putthapitak, Prasobsook; Damapong, Pongmada

    2015-01-01

    This study aimed to evaluate the effectiveness of the court-type traditional Thai massage (CTTM) to treat patients with chronic tension-type headaches (CTTHs) comparing with amitriptyline taking. A randomized controlled trial was conducted. Sixty patients diagnosed with CTTH were equally divided into a treatment and a control group. The treatment group received a 45-minute course of CTTM twice per week lasting 4 weeks while the control group was prescribed 25 mg of amitriptyline once a day before bedtime lasting 4 weeks. Outcome measures were evaluated in week 2, week 4 and followed up in week 6 consisting of visual analog scale (VAS), tissue hardness, pressure pain threshold (PPT), and heart rate variability (HRV). The results demonstrated a significant decrease in VAS pain intensity for the CTTM group at different assessment time points while a significant difference occurred in within-group and between-group comparison (P < 0.05) for each evaluated measure. Moreover, the tissue hardness of the CTTM group was significantly lower than the control group at week 4 (P < 0.05). The PPT and HRV of the CTTM group were significantly increased (P < 0.05). CTTM could be an alternative therapy for treatment of patients with CTTHs. PMID:26472986

  10. A Randomized Controlled Trial on the Effectiveness of Court-Type Traditional Thai Massage versus Amitriptyline in Patients with Chronic Tension-Type Headache.

    PubMed

    Damapong, Peerada; Kanchanakhan, Naowarat; Eungpinichpong, Wichai; Putthapitak, Prasobsook; Damapong, Pongmada

    2015-01-01

    This study aimed to evaluate the effectiveness of the court-type traditional Thai massage (CTTM) to treat patients with chronic tension-type headaches (CTTHs) comparing with amitriptyline taking. A randomized controlled trial was conducted. Sixty patients diagnosed with CTTH were equally divided into a treatment and a control group. The treatment group received a 45-minute course of CTTM twice per week lasting 4 weeks while the control group was prescribed 25 mg of amitriptyline once a day before bedtime lasting 4 weeks. Outcome measures were evaluated in week 2, week 4 and followed up in week 6 consisting of visual analog scale (VAS), tissue hardness, pressure pain threshold (PPT), and heart rate variability (HRV). The results demonstrated a significant decrease in VAS pain intensity for the CTTM group at different assessment time points while a significant difference occurred in within-group and between-group comparison (P < 0.05) for each evaluated measure. Moreover, the tissue hardness of the CTTM group was significantly lower than the control group at week 4 (P < 0.05). The PPT and HRV of the CTTM group were significantly increased (P < 0.05). CTTM could be an alternative therapy for treatment of patients with CTTHs.

  11. Global transcriptomic analysis of zebrafish in response to embryonic exposure to three antidepressants, amitriptyline, fluoxetine and mianserin.

    PubMed

    Wu, Minghong; Liu, Shuai; Hu, Lei; Qu, Haidong; Pan, Chenyuan; Lei, Penghui; Shen, Yingjia; Yang, Ming

    2017-09-28

    Antidepressants are among the most commonly detected pharmaceuticals in aqueous systems, and, as emerging organic pollutants, may exert negative effects on non-target aquatic organisms. Previously, it has been revealed that antidepressant exposure significantly inhibits the growth and development of fish during their early developmental stages. Thus, in the present study, we aimed to identify and compare the underlying mechanisms of action of different antidepressants at the transcriptional level using zebrafish (Danio rerio) embryos. Through high-throughput RNA sequencing (RNA-Seq) data analysis, 32, 34, and 130 differentially expressed genes (DEGs) were obtained from zebrafish larvae after 120h of embryonic exposure to sublethal concentrations of amitriptyline, fluoxetine, and mianserin, respectively. The expression profiles of the identified DEGs showed similar trends in response to the three antidepressant treatments, suggesting consistent toxic effects of low concentrations of these three drugs on the regulation of gene expression in fish. Several metabolic and signaling pathways, including glycolysis/gluconeogenesis and the insulin pathway, were affected in the exposed fish larvae. The expression profiles of selected DEGs were then verified by the qRT-PCR method, which indicated significant positive correlations with the RNA-Seq results. Next, we determined the concentration-dependent expression patterns of 6 selected DEGs in fish larvae exposed to three antidepressants at a series of environmentally relevant concentrations. The results revealed a significant concentration-dependent reduction in the levels of dual-specificity phosphatase 5 (dusp5) mRNA, as well as a non-concentration-dependent gene expression inhibition of prostaglandin D2 synthase b (ptgdsb); the circadian rhythm-related genes, i.e. those encoding nuclear receptor subfamily 1, group D, member 1 (nr1d1) and period 2 (per2); and genes encoding early growth response factors (egr1 and egr4), in

  12. Amitriptyline hydrochloride overdose

    MedlinePlus

    ... a prescription medicine. It is sold under these brand names: Adepril Amitid Amitril Elavil Emitrip Endep Enovil ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

  13. Amitriptyline and perphenazine overdose

    MedlinePlus

    ... Fever Lack of alertness Lower than normal body temperature Restlessness Seizures Uncoordinated movement Tremor Weakness REPRODUCTIVE SYSTEM Change in menstrual patterns SKIN Itchy skin Rash STOMACH AND INTESTINES Constipation Loss of appetite Nausea and ...

  14. Quality by Design approach in the development of a solvent-modified micellar electrokinetic chromatography method: finding the design space for the determination of amitriptyline and its impurities.

    PubMed

    Furlanetto, S; Orlandini, S; Pasquini, B; Del Bubba, M; Pinzauti, S

    2013-11-13

    A solvent-modified micellar electrokinetic chromatography method was set up for the simultaneous determination of the tricyclic antidepressant amitriptyline (AMI) and its main impurities. The method was developed following Quality by Design (QbD) principles according to ICH Guideline Q8(R2). QbD approach made it possible to find the design space (DS), where quality was assured. After a scouting phase, aimed at selecting a suitable capillary electrophoresis pseudostationary phase, risk assessment tools were employed to define the critical process parameters (CPPs) to be considered in a screening phase (applied voltage, concentration and pH of the background electrolyte, concentration of the surfactant sodium dodecyl sulphate, of the cosurfactant n-butanol and of the organic modifiers acetonitrile and urea). The effects of the seven selected CPPs on critical quality attributes (CQAs), namely resolution values between critical peak pairs and analysis time, were investigated throughout the knowledge space by means of a symmetric screening matrix. Response surface study was then carried out on four selected CPPs by applying a Doehlert Design. Monte-Carlo simulations were performed in order to estimate the probability of meeting the desired specifications on CQAs, and thus to define the DS by means of a risk of failure map. Additional points at the edges of the DS were tested in order to verify the requirements for CQAs to be fulfilled. A control strategy was implemented by defining system suitability tests. The developed method was validated following ICH Guideline Q2(R1), including robustness assessment by Plackett-Burman design, and was applied to the analysis of real samples of amitriptyline coated tablets.

  15. Gabapentin and pregabalin, but not morphine and amitriptyline, block both static and dynamic components of mechanical allodynia induced by streptozocin in the rat.

    PubMed

    Field, M J; McCleary, S; Hughes, J; Singh, L

    1999-03-01

    A single injection of streptozocin (50 mg/kg, i.p.) led to the development of static and dynamic allodynia in the rat. The two responses were detected, respectively, by application of pressure using von Frey hairs or lightly stroking the hind paw with a cotton bud. Static allodynia was present in the majority of the animals within 10 days following streptozocin. In contrast, dynamic allodynia took almost twice as long to develop and was only present in approximately 60% of rats. Morphine (1-3 mg/kg, s.c.) and amitriptyline (0.25-2.0 mg/kg, p.o.) dose-dependently blocked static allodynia. However, neither of the compounds was effective against dynamic allodynia. In contrast, gabapentin (10-100 mg/kg, p.o.) and the related compound pregabalin (3-30 mg/kg, p.o.) dose-dependently blocked both types of allodynia. However, the corresponding R-enantiomer (10-100 mg/kg, p.o.) of pregabalin, was found to be inactive. The intrathecal administration of gabapentin dose-dependently (1-100 microg/animal) blocked both static and dynamic allodynia. In contrast, administration of similar doses of gabapentin into the hind paw failed to block these responses. It is suggested that in this model of neuropathic pain dynamic allodynia is mediated by A beta-fibres and the static type involves small diameter nociceptive fibres. These data suggest that gabapentin and pregabalin possess a superior antiallodynic profile than morphine and amitriptyline, and may represent a novel class of therapeutic agents for the treatment of neuropathic pain.

  16. Amitriptyline plays important roles in modifying the ovarian morphology and improving its functions in rats with estradiol valerate-induced polycystic ovary.

    PubMed

    Li, Xinqiang; Wang, Shufen; Zhang, Li; Zhang, Lei; Liu, Jiali; Luo, Haoshu; Gou, Kemian; Cui, Sheng

    2017-09-08

    Previous studies demonstrated that depression is more prevalent in women with polycystic ovary syndrome (PCOS). In this study, we aimed to determine whether amitriptyline (AMT), an antidepressant drug, plays a role in preventing PCOS. The results showed that AMT modified ovarian morphology improved the ovarian functions and estrus cycle in estradiol valerate (EV)-induced polycystic ovary (PCO). AMT restored the levels of estradiol (E2), testosterone (T) and progesterone (P4) to normal, and elevated the level of luteinizing hormone (LH) in EV-induced PCO. No significant changes in follicle stimulating hormone (FSH) levels were observed in rats with EV or AMT treatment. The restoration of norepinephrine (NE) level was detected in rats with EV-induced PCO. AMT also altered the expression levels of steroidogenesis genes and beta2-adrenoceptor (beta2-AR) in EV-induced PCO. Our data revealed that AMT improves the ovarian morphology and modifies ovarian expression of beta2-AR and steroidogenesis genes in rats with EV-induced rat PCO. Our data provide support for the hypothesis that AMT is considered as a candidate drug for preventing and treating PCOS along with depression.

  17. A highly improved method for sensitive determination of amitriptyline in pharmaceutical formulations using an unmodified carbon nanotube electrode in the presence of sulfuric acid.

    PubMed

    Duarte, Eduardo Henrique; dos Santos, William Pereira; Hudari, Felipe Fantinato; Bott Neto, José Luiz; Sartori, Elen Romão; Dall'Antonia, Luiz Henrique; Pereira, Arnaldo César; Tarley, César Ricardo Teixeira

    2014-09-01

    The present paper describes a novel, simple and reliable differential pulse voltammetric method for determining amitriptyline (AMT) in pharmaceutical formulations. It has been described for many authors that this antidepressant is electrochemically inactive at carbon electrodes. However, the procedure proposed herein consisted in electrochemically oxidizing AMT at an unmodified carbon nanotube paste electrode in the presence of 0.1 mol L(-1) sulfuric acid used as electrolyte. At such concentration, the acid facilitated the AMT electroxidation through one-electron transfer at 1.33 V vs. Ag/AgCl, as observed by the augmentation of peak current. Concerning optimized conditions (modulation time 5 ms, scan rate 90 mV s(-1), and pulse amplitude 120 mV) a linear calibration curve was constructed in the range of 0.0-30.0 μmol L(-1), with a correlation coefficient of 0.9991 and a limit of detection of 1.61 μmol L(-1). The procedure was successfully validated for intra- and inter-day precision and accuracy. Moreover, its feasibility was assessed through analysis of commercial pharmaceutical formulations and it has been compared to the UV-vis spectrophotometric method used as standard analytical technique recommended by the Brazilian Pharmacopoeia. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Amitriptyline improves motor function via enhanced neurotrophin signaling and mitochondrial functions in the murine N171-82Q Huntington disease model.

    PubMed

    Cong, Wei-Na; Chadwick, Wayne; Wang, Rui; Daimon, Caitlin M; Cai, Huan; Amma, Jennifer; Wood, William H; Becker, Kevin G; Martin, Bronwen; Maudsley, Stuart

    2015-01-30

    Huntington disease (HD) is a neurodegenerative disorder characterized by progressive motor impairment and cognitive alterations. Hereditary HD is primarily caused by the expansion of a CAG trinucleotide repeat in the huntingtin (Htt) gene, which results in the production of mutant huntingtin protein (mHTT) with an expanded amino-terminal polyglutamine (poly(Q)) stretch. Besides pathological mHTT aggregation, reduced brain-derived neurotrophic factor (BDNF) levels, impaired neurotrophin signaling, and compromised mitochondrial functions also contribute to the deleterious progressive etiology of HD. As a well tolerated Food and Drug Administration-approved antidepressant, amitriptyline (AMI) has shown efficacy in treating neurodegenerative murine models via potentiation of BDNF levels and amelioration of alterations in neurotrophin signaling pathways. In this study, we observed profound improvements in the motor coordination of AMI-treated N171-82Q HD model mice. The beneficial effects of AMI treatment were associated with its ability to reduce mHTT aggregation, potentiation of the BDNF-TrkB signaling system, and support of mitochondrial integrity and functionality. Our study not only provides preclinical evidence for the therapeutic potency of AMI in treating HD, but it also represents an important example of the usefulness of additional pharmacogenomic profiling of pre-existing drugs for novel therapeutic effects with often intractable pathological scenarios.

  19. Amitriptyline Improves Motor Function via Enhanced Neurotrophin Signaling and Mitochondrial Functions in the Murine N171-82Q Huntington Disease Model*

    PubMed Central

    Cong, Wei-Na; Chadwick, Wayne; Wang, Rui; Daimon, Caitlin M.; Cai, Huan; Amma, Jennifer; Wood, William H.; Becker, Kevin G.; Martin, Bronwen; Maudsley, Stuart

    2015-01-01

    Huntington disease (HD) is a neurodegenerative disorder characterized by progressive motor impairment and cognitive alterations. Hereditary HD is primarily caused by the expansion of a CAG trinucleotide repeat in the huntingtin (Htt) gene, which results in the production of mutant huntingtin protein (mHTT) with an expanded amino-terminal polyglutamine (poly(Q)) stretch. Besides pathological mHTT aggregation, reduced brain-derived neurotrophic factor (BDNF) levels, impaired neurotrophin signaling, and compromised mitochondrial functions also contribute to the deleterious progressive etiology of HD. As a well tolerated Food and Drug Administration-approved antidepressant, amitriptyline (AMI) has shown efficacy in treating neurodegenerative murine models via potentiation of BDNF levels and amelioration of alterations in neurotrophin signaling pathways. In this study, we observed profound improvements in the motor coordination of AMI-treated N171-82Q HD model mice. The beneficial effects of AMI treatment were associated with its ability to reduce mHTT aggregation, potentiation of the BDNF-TrkB signaling system, and support of mitochondrial integrity and functionality. Our study not only provides preclinical evidence for the therapeutic potency of AMI in treating HD, but it also represents an important example of the usefulness of additional pharmacogenomic profiling of pre-existing drugs for novel therapeutic effects with often intractable pathological scenarios. PMID:25505248

  20. Assessment of the UV/Cl2 advanced oxidation process for the degradation of the emerging contaminants amitriptyline hydrochloride, methyl salicylate and 2-phenoxyethanol in water systems.

    PubMed

    Javier Benitez, F; Real, Francisco J; Acero, Juan L; Casas, Francisco

    2017-10-01

    Three emerging contaminants (amitriptyline hydrochloride (AH), methyl salicylate (MS) and 2-phenoxyethanol (PE)) frequently found in wastewaters were selected to be individually degraded in ultra-pure water by the advanced oxidation process (AOP) constituted by the combination of UV radiation and chlorine. The influence of pH, initial chlorine concentration and nature of the contaminants was firstly explored. The trend for the reactivity of the selected compounds was deduced: AH > MS > PE. A later kinetic study was carried out focused on the evaluation of the first-order rate constants and the determination of the partial contribution to the global reaction of the direct photochemical pathway and the radical pathway. In a second stage, the simultaneous oxidation of mixtures of the selected contaminants in several types of water was also performed by the same combination UV/Cl2. The efficiency of this combined system UV/Cl2 was compared to other oxidants such as the UV/[Formula: see text] and UV/H2O2 AOPs, and the influence of the operating variables was discussed. Results confirmed that the UV/Cl2 system provides higher elimination efficiencies among the AOPs tested. The presence of dissolved organic matter and bicarbonate ions in the water matrix caused a decrease in the treatment efficiency.

  1. Comparison of activated charcoal and sodium polystyrene sulfonate resin efficiency on reduction of amitriptyline oral absorption in rat as treatments for overdose and toxicities

    PubMed Central

    Yousefi, Gholamhossein; Bizhani, Mohammad; Jamshidzadeh, Akram; Gholamzadeh, Saeid

    2017-01-01

    Objective(s): Comparative in vivo studies were carried out to determine the adsorption characteristics of amitriptyline (AMT) on activated charcoal (AC) and sodium polystyrene sulfonate (SPS). AC has been long used as gastric decontamination agent for tricyclic antidepressants and SPS has showed to be highly effective on in-vitro drugs adsorption. Materials and Methods: Sprague-Dawley male rats were divided into six groups. Group I: control, group II: AMT 200 mg/kg as single dose orally, group III and IV: AC 1g/kg as single dose orally 5 and 30 min after AMT administration respectively, and group 5 and 6: SPS 1 g/kg as single dose orally 5 and 30 min after AMT administration, respectively. 60 min after oral administration of AMT (Tmax of AMT determined in rats), Cmax plasma levels were determined by a validated GC-Mass method. Results: The Cmax values for groups II to IV were determined as 1.1, 0.5, 0.6, 0.1 and 0.3 µg/ml, respectively. Conclusion: AC and SPS could significantly reduce Cmax of AMT when administrated either 5 or 30 min after AMT overdose (P<0.05). However, SPS showed to be more effective than AC in reducing Cmax when was administrated immediately (5 min) after AMT overdose. The results suggest a more efficient alternative to AC for AMT and probably other TCA overdoses. PMID:28133524

  2. [The effects of antidepressants on sleep in depressed patients with particular reference to trazodone in comparison to agomelatine, amitriptyline, doxepin, mianserine and mirtazapine].

    PubMed

    Wichniak, Adam; Wierzbicka, Aleksandra

    2011-07-01

    Disturbed sleep is a core symptom of depression and is among diagnostic criteria for depressive episode. Effects of an antidepressant drug on sleep are important for its clinical profile. Rapid improvement of sleep quality is particularly indicated in depressed patients with insomnia, anxiety, agitation and suicidal thoughts. The aim of the study was to evaluate the effects of trazodone on sleep in depressed patients in comparison to other sleep promoting antidepressants: agomelatine, amitriptyline, doxepin, mianserine and mirtazapine according to analysis of scientific publications. Sedative antidepressants including trazodone are regarded as treatment of choice in depression with agitation, anxiety or insomnia. They are also frequently used in low dose to promote sleep, as an alternative to hypnotics. Such approach to treatment of insomnia in depressed patients protects them against dependence on hypnotic drugs. Additionally, the antagonistic action of antidepressants on serotonergic 5-HT2 receptors improves not only the sleep continuity, but promotes also slow wave sleep. Trazodone and mirtazapine in comparison to many other antidepressants do not suppress REM sleep. Antidepressants have different effects on sleep. In treatment of depression sedative antidepressants should be administered in the full, recommended dose. However, if they are administered as concomitant treatment only to promote sleep, low doses are indicated. Too late administration time and too high dose are the most common factors related to failure of insomnia treatment with these drugs.

  3. Valproate and Amitriptyline Exert Common and Divergent Influences on Global and Gene Promoter-Specific Chromatin Modifications in Rat Primary Astrocytes

    PubMed Central

    Perisic, Tatjana; Zimmermann, Nicole; Kirmeier, Thomas; Asmus, Maria; Tuorto, Francesca; Uhr, Manfred; Holsboer, Florian; Rein, Theo; Zschocke, Jürgen

    2010-01-01

    Aberrant biochemical processes in the brain frequently go along with subtle shifts of the cellular epigenetic profile that might support the pathogenic progression of psychiatric disorders. Although recent reports have implied the ability of certain antidepressants and mood stabilizers to modulate epigenetic parameters, studies comparing the actions of these compounds under the same conditions are lacking. In this study, we screened amitriptyline (AMI), venlafaxine, citalopram, as well as valproic acid (VPA), carbamazepine, and lamotrigine for their potential actions on global and local epigenetic modifications in rat primary astrocytes. Among all drugs, VPA exposure evoked the strongest global chromatin modifications, including histone H3/H4 hyperacetylation, 2MeH3K9 hypomethylation, and DNA demethylation, as determined by western blot and luminometric methylation analysis, respectively. CpG demethylation occurred independently of DNA methyltransferase (DNMT) suppression. Strikingly, AMI also induced slight cytosine demethylation, paralleled by the reduction in DNMT enzymatic activity, without affecting the global histone acetylation status. Locally, VPA-induced chromatin modifications were reflected at the glutamate transporter (GLT-1) promoter as shown by bisulfite sequencing and acetylated histone H4 chromatin immunoprecipitation analysis. Distinct CpG sites in the distal part of the GLT-1 promoter were demethylated and enriched in acetylated histone H4 in response to VPA. For the first time, we could show that these changes were associated with an enhanced transcription of this astrocyte-specific gene. In contrast, AMI failed to stimulate GLT-1 transcription and to alter promoter methylation levels. In conclusion, VPA and AMI globally exerted chromatin-modulating activities using different mechanisms that divergently precipitated at an astroglial gene locus. PMID:19924110

  4. Utility of 7,7,8,8-tetracyanoquinodimethane charge transfer reagent for the spectrophotometric determination of trazodone, amineptine and amitriptyline hydrochlorides

    NASA Astrophysics Data System (ADS)

    Mohamed, Gehad G.; El-Dien, Faten A. F. Nour; Mohamed, Nehad A.

    2007-12-01

    A simple and rapid spectrophotometric method has been developed for the determination of tricyclic anti-depressant drugs such as trazodone (TZH), amineptine (APH) and amitriptyline (ATPH) hydrochlorides in pure form and in different pharmaceutical preparations. The charge transfer (CT) reaction between TZH, APH and ATPH as electron donors and TCNQ as electron acceptor was utilized for their spectrophotometric determination. The optimum experimental conditions, like time, temperature, stoichiometry, solvents, for the CT complex formation are established. The method permits the determination of TZH, APH and ATPH over a concentration range of 10-400, 10-440 and 10-300 μg ml -1, respectively. The sensitivity ( S) is found to be 0.09, 0.087 and 0.069 g cm -2 for TZH, APH and ATPH, respectively. The SD values are found to be 0.146-0.293, 0.154-0.285 and 0.091-0.212 and RSD values are 0.142-1.92, 0.297-1.92 and 0.212-0.915 for TZH, APH and ATPH, respectively. The low values of the relative standard deviation indicate the high accuracy and precision of the method. The mean recovery values obtained together with a high correlation coefficient values, amount in the range 98-101.5, 98.7-102.9 and 93-101.9 for TZH, APH and ATPH, respectively. The method is applicable for the assay of the investigated drugs in different dosage forms and the results are in good agreement with those obtained by the official method.

  5. A simple dried blood spot method for therapeutic drug monitoring of the tricyclic antidepressants amitriptyline, nortriptyline, imipramine, clomipramine, and their active metabolites using LC-MS/MS.

    PubMed

    Berm, E J J; Paardekooper, J; Brummel-Mulder, E; Hak, E; Wilffert, B; Maring, J G

    2015-03-01

    Therapeutic drug monitoring (TDM) of tricyclic antidepressants (TCAs) is considered useful in patients with major depressive disorder, since these drugs display large individual differences in clearance, and the therapeutic windows of these drugs are relatively small. We developed an assay for determination of amitriptyline (ATP), nortriptyline (NTP), imipramine (IMP), desipramine (DSP) clomipramine (CMP) and desmethyl-clomipramine (DCMP) in dried blood spots (DBS). A fast and robust LC-MS/MS method was developed and analytically validated for simultaneous determination of ATP, NTP, IMP, DSP, CMP, and DCMP in DBS. Six mm circles were punched out from DBS collected on Whatman DMPK-C paper and mixed with acetonitrile: methanol 1:3 containing the internal standard. The extract was analyzed by LC-MS/MS. Total LC-MS/MS runtime was 4.8 min. The assay was linear in the range 20-500 µg/L for all compounds. Overall-assay accuracy and precision were<20% for the lower limit of quantification (LLOQ), except for CMP (CV=22.3%), and <15% at other concentrations. The initial LLOQ was 20 µg/L however for CMP and DMCP it was increased to 40 µg/L. The blood volume per spot did not influence the results, but a low hematocrit (≤ 30%) was associated with a >15% negative bias for all compounds. Punching at the perimeter of the blood spot instead of the center was associated with a positive bias. A good correlation was found between patients plasma and DBS samples of ATP, NTP and DMCP, but not for CMP. In addition, proportional differences were found. This LC-MS/MS method was analytically validated for determination of TCAs in DBS. Future validation will focus on the clinical application of the method.

  6. Childhood and Adolescent Migraine Prevention (CHAMP) Study: A Double-blinded, Placebo-controlled, Comparative Effectiveness Study of Amitriptyline, Topiramate and Placebo in the Prevention of Childhood and Adolescent Migraine

    PubMed Central

    Hershey, Andrew D.; Powers, Scott W.; Coffey, Christopher S.; Eklund, Dixie D.; Chamberlin, Leigh Ann; Korbee, Leslie L.

    2013-01-01

    Background Migraine is one of the most common health problems for children and adolescents. If not successfully treated, it can impact patients and families with significant disability due to loss of school, work and social function. When headaches become frequent, it is essential to try to prevent the headaches. For children and adolescents this is guided by extrapolation from adult studies, a limited number of small studies in children and adolescents and practitioner preference. The aim of the Childhood and Adolescent Migraine Prevention (CHAMP) study is to determine the most effective preventive agent to use in children and adolescents. Methods CHAMP is a double-blinded, placebo-controlled, multi-center, comparative-effectiveness study of amitriptyline and topiramate for the prevention of episodic and chronic migraine, designed to mirror real-world practice, sponsored by the US National Institute of Neurological Disorders and Stroke/National Institutes of Health (U01NS076788). The study will recruit 675 subjects between the ages of 8 and 17 years old, inclusive, who have migraine with or without aura or chronic migraine as defined by the International Classification of Headache Disorders, 2nd Edition, with at least 4 headaches in the 28 days prior to randomization. The subjects will be randomized in a 2:2:1 (amitriptyline: topiramate: placebo) ratio. Doses are weight based and will be slowly titrated over an 8 week period to a target dose of 1 mg/kg of amitriptyline and 2 mg/kg of topiramate. The primary outcome will be a 50% reduction in headache frequency between the 28 day baseline and the final 28 days of treatment (weeks 20–24). Conclusions The goal of the CHAMP study is to obtain level 1 evidence for the effectiveness of amitriptyline and topiramate in the prevention of migraine in children and adolescents. If this study proves to be positive, it will provide information to the practicing physician as how to best prevent migraine in children and

  7. Comparative assessment of selected intraoral microorganisms – potential factors for peri-surgical management complications

    PubMed

    Zawadzki, Paweł J.; Starościak, Bohdan; Perkowski, Konrad; Baltaza, Wanda; Padzik, Marcin; Pionkowski, Krzysztof; Chomicz, Lidia

    2016-10-01

    In this research, a comparative analysis of results of investigations involving different human populations, in terms of a relation between the oral cavity health and the species composition of mouth microbiota is reported. The purpose of this analysis was to identify and assess microorganisms that could cause health complications in patients with neoplasm requiring dental problem-related surgical management. The patients with the oral cancer surgically treated and those without neoplasm were assessed for their oral health: status of teeth, gingiva, periodontium, and occurrence of inflammatory processes. From each patient, microorganisms isolated of periodontium, dental plaque, and dental pocket swabs were identified in wet and stained microscopic preparations; standard microbiology in vitro techniques were also applied to determine the fungal and bacterial strains. The comparative analysis of results of direct microscopic examinations and in vitro cultures assessment indicated significant differences in prevalences of fungi, parasitic oral protozoans and bacteriae in particular patient’s groups. Yeast-like fungi belonging to Candida genus, mostly of C. albicans group, were identified in 93.75% patients with the oral cancer, while in 25% of individuals assessed without neoplasm. E. gingivalis amoebae were only found in 12.5% patients with the serious disease; no trichomonads were detected in all patients analyzed. Among bacteria species, potentially pathogenic Enterobacteriaceae were found in the patients with oral cancer. The pronounced shift in the microbiota species composition in the patients who needed prolonged treatment due to oral cavity cancer, compared to other generally healthy persons has been showed in this analysis.

  8. [Use of a portable ultrasound system in the perisurgical assessment of head and neck patients].

    PubMed

    Angerer, F; Zenk, J; Iro, H; Bozzato, A

    2013-10-01

    The use of high resolution ultrasound is an established diagnostic method. A disadvantage of current high end systems is that transporting the device into the operating theatre or an intensive care unit requires time and logistic effort. We report results of an evaluation of a portable ultrasound system in the diagnosis and treatment of the head and neck area. Indications and value of a portable device in the clinical setting of an operation theatre and intensive care unit were assessed. Within a period of 5 months, 48 patients were included in this prospectively designed study using a portable ultrasound system with B-scan/color Doppler mode (SonoSite TITAN, Firma SonoSite® Germany) and an 7.5 MHz broadband linear array transducer. Two experienced physicians recorded the location and examination conditions, imaging mode, time expenditure, indication and diagnosis. The examiner also commented about whether the use of a portable laptop system considerably improved the therapy decision. The analysis included descriptive statistics for interpretation of the results. The most frequent use of the ultrasound system was the pre- or intrasurgical "pinpointing" of tumours in the soft tissues of the neck or in salivary glands. The average time for the examination was 6 min. In 79 % of the cases, the examiner stated a definite improvement of the therapy decision through the use of the portable ultrasound. We could demonstrate that a portable ultrasound system is a time-saving, economic and ubiquitously applicable method of imaging. Diagnosis and surgical planning are optimized. Thus, in larger hospitals and clinics, a portable ultrasound device is a logical complement to a stationary unit.

  9. Enzyme kinetic modelling as a tool to analyse the behaviour of cytochrome P450 catalysed reactions: application to amitriptyline N-demethylation

    PubMed Central

    SCHMIDER, JÜRGEN; GREENBLATT, DAVID J.; HARMATZ, JEROLD S.; SHADER, RICHARD I.

    1996-01-01

    1To determine kinetic parameters (Vmax, Km) for cytochrome P450 (CYP) mediated metabolic pathways, nonlinear least squares regression is commonly used to fit a model equation (e.g., Michaelis Menten [MM]) to sets of data points (reaction velocity vs substrate concentration). This method can also be utilized to determine the parameters for more complex mechanisms involving allosteric or multi-enzyme systems. Akaike's Information Criterion (AIC), or an estimation of improvement of fit as successive parameters are introduced in the model ( F-test), can be used to determine whether application of more complex models is helpful. To evaluate these approaches, we have examined the complex enzyme kinetics of amitriptyline (AMI) N-demethylation in vitro by human liver microsomes. 2For a 15-point nortriptyline (NT) formation rate vs substrate (AMI) concentration curve, a two enzyme model, consisting of one enzyme with MM kinetics (Vmax=1.2 nmol min−1 mg−1, Km=24 μm) together with a sigmoidal component (described by an equation equivalent to the Hill equation for cooperative substrate binding; Vmax=2.1 nmol min−1 mg−1, K′=70 μm; Hill exponent n=2.34), was favoured according to AIC and the F-test. 3Data generated by incubating AMI under the same conditions but in the presence of 10 μm ketoconazole (KET), a CYP3A3/4 inhibitor, were consistent with a single enzyme model with substrate inhibition (Vmax=0.74 nmol min−1 mg−1, Km=186 μm, K1=0.0028 μm−1). 4Sulphaphenazole (SPA), a CYP2C9 inhibitor, decreased the rate of NT formation in a concentration dependent manner, whereas a polyclonal rat liver CYP2C11 antibody, inhibitory for S-mephenytoin 4′-hydroxylation in humans, had no important effect on this reaction. 5Incubation of AMI with 50 μm SPA resulted in a curve consistent with a two enzyme model, one with MM kinetics (Vmax=0.72 nmol min−1 mg−1, Km=54 μm) the other with ‘Hill-kinetics’ (Vmax=2.1

  10. Project Produce

    ERIC Educational Resources Information Center

    Wolfinger, Donna M.

    2005-01-01

    The grocery store produce section used to be a familiar but rather dull place. There were bananas next to the oranges next to the limes. Broccoli was next to corn and lettuce. Apples and pears, radishes and onions, eggplants and zucchinis all lay in their appropriate bins. Those days are over. Now, broccoli may be next to bok choy, potatoes beside…

  11. Project Produce

    ERIC Educational Resources Information Center

    Wolfinger, Donna M.

    2005-01-01

    The grocery store produce section used to be a familiar but rather dull place. There were bananas next to the oranges next to the limes. Broccoli was next to corn and lettuce. Apples and pears, radishes and onions, eggplants and zucchinis all lay in their appropriate bins. Those days are over. Now, broccoli may be next to bok choy, potatoes beside…

  12. Effect of intravenous lidocaine combined with amitriptyline on pain intensity, clinical manifestations and the concentrations of IL-1, IL-6 and IL-8 in patients with fibromyalgia: A randomized double-blind study.

    PubMed

    Albertoni Giraldes, Ana Laura; Salomão, Reinaldo; Leal, Plinio da Cunha; Brunialti, Milena Karina Coló; Sakata, Rioko Kimiko

    2016-10-01

    Regarding the use of intravenous lidocaine in fibromyalgia, there are no well-controlled studies. This study aimed to evaluate the effect of intravenous lidocaine on pain intensity, clinical manifestations and plasma levels of interleukin (IL)-1, IL-6, and IL-8 in fibromyalgia patients. In a randomized double-blind study, group 1 patients received 240 mg of lidocaine in 125 mL of saline solution, while group 2 patients received 125 mL of saline, both once a week for 4 weeks (T1, T2, T3 and T4). All patients received amitriptyline. The following were assessed: pain intensity before treatment (T0) and at 1, 2, 3, 4 and 8 weeks after treatment; clinical manifestations; the fibromyalgia impact questionnaire (FIQ) before and at 4 and 8 weeks after; the levels of IL 1, 6 and 8 before and at 4 and 8 weeks after treatment. Lower pain intensity was observed in the lidocaine group at T2, with no difference at the other time points. There was a reduction in pain intensity in both groups. The use of paracetamol and tramadol and plasma levels of IL-1, IL-6 and IL-8 did not differ between the groups. Clinical manifestations and side effects did not differ between groups. The combination of 240 mg of intravenous lidocaine (once a week for 4 weeks) with 25 mg of amitriptyline for 8 weeks had no meaningful impact in fibromyalgia patients. © 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

  13. Design for Producibility. A Design Producibility Algorithm

    DTIC Science & Technology

    1990-03-01

    year. NOFORN, REL, ITAR ). Block 3. Tve of Report and Dates Covered. State whether report is interim, fihal, etc. If DOD See DoDD 5230.24, "Distribution...3.0 PRODUCIBILITY TOOLS 2 4.0 SCHEDULES/PHASES 3 4.1 PRIOR TO SRR 3 4.2 AT THE SRR 3 4.3 THE FLOW FROM SRR TO SDR 4 4.4 AT THE SDR 16 4.5 THE FLOW FROM... SDR TO CDR 16 4.6 AT THE PDR 23 4.7 BETWEEN PDR AND CDR 23 4.8 AT THE CDR 24 4.9 THE FLOW BEYOND CDR 24 5.0 PRODUCIBILITY SUCCESS MEASUREMENT 25 6.0

  14. Method of producing hydrogen

    DOEpatents

    Bingham, Dennis N.; Klingler, Kerry M.; Wilding, Bruce M.; Zollinger, William T.

    2006-12-26

    A method of producing hydrogen is disclosed and which includes providing a first composition; providing a second composition; reacting the first and second compositions together to produce a chemical hydride; providing a liquid and reacting the chemical hydride with the liquid in a manner to produce a high pressure hydrogen gas and a byproduct which includes the first composition; and reusing the first composition formed as a byproduct in a subsequent chemical reaction to form additional chemical hydride.

  15. Fungi producing significant mycotoxins.

    PubMed

    2012-01-01

    Mycotoxins are secondary metabolites of microfungi that are known to cause sickness or death in humans or animals. Although many such toxic metabolites are known, it is generally agreed that only a few are significant in causing disease: aflatoxins, fumonisins, ochratoxin A, deoxynivalenol, zearalenone, and ergot alkaloids. These toxins are produced by just a few species from the common genera Aspergillus, Penicillium, Fusarium, and Claviceps. All Aspergillus and Penicillium species either are commensals, growing in crops without obvious signs of pathogenicity, or invade crops after harvest and produce toxins during drying and storage. In contrast, the important Fusarium and Claviceps species infect crops before harvest. The most important Aspergillus species, occurring in warmer climates, are A. flavus and A. parasiticus, which produce aflatoxins in maize, groundnuts, tree nuts, and, less frequently, other commodities. The main ochratoxin A producers, A. ochraceus and A. carbonarius, commonly occur in grapes, dried vine fruits, wine, and coffee. Penicillium verrucosum also produces ochratoxin A but occurs only in cool temperate climates, where it infects small grains. F. verticillioides is ubiquitous in maize, with an endophytic nature, and produces fumonisins, which are generally more prevalent when crops are under drought stress or suffer excessive insect damage. It has recently been shown that Aspergillus niger also produces fumonisins, and several commodities may be affected. F. graminearum, which is the major producer of deoxynivalenol and zearalenone, is pathogenic on maize, wheat, and barley and produces these toxins whenever it infects these grains before harvest. Also included is a short section on Claviceps purpurea, which produces sclerotia among the seeds in grasses, including wheat, barley, and triticale. The main thrust of the chapter contains information on the identification of these fungi and their morphological characteristics, as well as factors

  16. METHOD OF PRODUCING NEUTRONS

    DOEpatents

    Imhoff, D.H.; Harker, W.H.

    1964-01-14

    This patent relates to a method of producing neutrons in which there is produced a heated plasma containing heavy hydrogen isotope ions wherein heated ions are injected and confined in an elongated axially symmetric magnetic field having at least one magnetic field gradient region. In accordance with the method herein, the amplitude of the field and gradients are varied at an oscillatory periodic frequency to effect confinement by providing proper ratios of rotational to axial velocity components in the motion of said particles. The energetic neutrons may then be used as in a blanket zone containing a moderator and a source fissionable material to produce heat and thermal neutron fissionable materials. (AEC)

  17. Vehicle gas producers

    NASA Astrophysics Data System (ADS)

    Donath, E. E.

    1980-05-01

    The present petroleum supply situation with the possibility of unscheduled interruptions and the definite expectation of continued price increases calls for an investigation of the use of solid fuels for the propulsion of vehicles. The paper reviews the use of solid fuel gas producers with high thermal efficiency on motor vehicles, especially trucks and buses. Some economic comparisons are presented for pre-World War II conditions. Suggestions are made for possible future development of vehicle gas producers. The types of producers are described, along with their performance, special problems, and the importance of fuel properties.

  18. Coal markets squeeze producers

    SciTech Connect

    Ryan, M.

    2005-12-01

    Supply/demand fundamentals seem poised to keep prices of competing fossil fuels high, which could cushion coal prices, but increased mining and transportation costs may squeeze producer profits. Are markets ready for more volatility?

  19. Design Producibility Assessment System

    DTIC Science & Technology

    1989-06-30

    68 7.11 Part Detail ............... 69 7.11 Continued.. .Part Detail ... .......... 70 iv TABLES Page TABLE 1. Producibility Rating Factors...design type. Instead, an empirical approach has been selected to calculate the MI. An examination of a large number of metal components suggest that...normally cause the 80% of the producibility problems. Table 1 shows a sample list of those factors. It is important to recognize however, that the list of

  20. Produce Sanitation System Evaluation

    DTIC Science & Technology

    2011-05-01

    SAFETY NAVAL VESSELS WASHERS(CLEANERS) FRUITS CLEANING WORKLOAD MONITORING LABOR SAVINGS NATURAL RESOURCES WATER ... fruits and vegetables (FF&V) aboard Navy vessels, The sink saves labor associated with the washing of produce in food service operations by...Systems  Equipment and Engineering Team (SEET). This system, produced by SteelKor, was designed to  clean and sanitize fresh  fruits  and vegetables

  1. Manufacturing and producibility technology

    NASA Technical Reports Server (NTRS)

    Hankins, J. D.; Dreshfield, R. L.

    1985-01-01

    Activities of the manufacturing/producibility working group within the Advanced High-Pressure O2/H2 Technology Program are summarized. The objectives of the M/P working group are: to develop and evaluate process and manufacturing techniques for advanced propulsion hardware design and selected materials; and to optimize the producibility of (SSME) components and assemblies by improved performance, increased life, greater reliability, and/or reduced cost. The technologies being developed include: plasma arc, laser, and inertia welding; combustion chamber and turbine blade coatings; coating processes; high performance alloy electroforming; and process control technology.

  2. Producing CD-ROMs.

    ERIC Educational Resources Information Center

    Hyams, Peter, Ed.

    1992-01-01

    This issue presents 11 articles that address issues relating to the production of CD-ROMs. Highlights include current uses of CD-ROM; standards; steps involved in producing CD-ROMs, including data capture, conversion, and tagging, product design, and indexing; authoring; selecting indexing and retrieval software; costs; multimedia CD-ROMs; and…

  3. Carbapenemase-Producing Enterobacteriaceae

    PubMed Central

    Doi, Yohei; Paterson, David L.

    2015-01-01

    Carbapenemase-producing Enterobacteriaceae (CPE) were almost nonexistent up to the 1990s, but are today encountered routinely in hospitals and other healthcare facilities in many countries including the United States. KPC-producing Klebsiella pneumoniae was the first to emerge and spread globally and is endemic in the United States, Israel, Greece, and Italy. Recently, NDM-producing Enterobacteriaceae and OXA-48-producing K. pneumoniae appear to be disseminating from South Asia and Northern Africa, respectively. They are almost always resistant to all β-lactams including carbapenems and many other classes. Mortality from invasive CPE infections reaches up to 40%. To obtain the maximal benefit from the limited options available, dosing of antimicrobial agents should be optimized based on pharmacokinetic data, especially for colistin and carbapenems. In addition, multiple observational studies have associated combination antimicrobial therapy with lower mortality compared with monotherapy for these infections. The outcomes appear to be especially favorable when patients are treated with a carbapenem and a second agent such as colistin, tigecycline, and gentamicin, but the best approach is yet to be defined. PMID:25643272

  4. PRODUCING HIGH CORN YIELDS.

    ERIC Educational Resources Information Center

    Illinois Univ., Urbana. Coll. of Agriculture.

    RESOURCE MATERIAL ON CORN PRODUCTION FOR HIGH SCHOOL VOCATIONAL AGRICULTURE AND ADULT FARMER CLASSES WAS DESIGNED BY A STATE LEVEL GROUP OF SUBJECT MATTER SPECIALISTS, TEACHER EDUCATORS, SUPERVISORS, AND TEACHERS TO HELP SOLVE PROBLEMS THAT CONFRONT CORN PRODUCERS AT PLANTING TIME. THE SUBJECT MATTER CONCERNS PLANTING TIME, DEPTH, ROW WIDTH,…

  5. Producing superhydrophobic roof tiles.

    PubMed

    Carrascosa, Luis A M; Facio, Dario S; Mosquera, Maria J

    2016-03-04

    Superhydrophobic materials can find promising applications in the field of building. However, their application has been very limited because the synthesis routes involve tedious processes, preventing large-scale application. A second drawback is related to their short-term life under outdoor conditions. A simple and low-cost synthesis route for producing superhydrophobic surfaces on building materials is developed and their effectiveness and their durability on clay roof tiles are evaluated. Specifically, an organic-inorganic hybrid gel containing silica nanoparticles is produced. The nanoparticles create a densely packed coating on the roof tile surface in which air is trapped. This roughness produces a Cassie-Baxter regime, promoting superhydrophobicity. A surfactant, n-octylamine, was also added to the starting sol to catalyze the sol-gel process and to coarsen the pore structure of the gel network, preventing cracking. The application of ultrasound obviates the need to use volatile organic compounds in the synthesis, thereby making a 'green' product. It was also demonstrated that a co-condensation process effective between the organic and inorganic species is crucial to obtain durable and effective coatings. After an aging test, high hydrophobicity was maintained and water absorption was completely prevented for the roof tile samples under study. However, a transition from a Cassie-Baxter to a Wenzel state regime was observed as a consequence of the increase in the distance between the roughness pitches produced by the aging of the coating.

  6. Producer/Consumer Image

    ERIC Educational Resources Information Center

    Englander, Meryl E.; Marsh, John

    1977-01-01

    The work ethic and the success of a system based increasingly upon consumerism has created an image of man in which the quality of life is measured in terms of quantity and ownership of goods; in ethics and attitude, our system of education is creating an ideally receptive population for the producer-consumer society. (JD)

  7. Interventions for fresh produce

    USDA-ARS?s Scientific Manuscript database

    Environmental matrices such as soil, water, and dust harbor microorganisms. Many of the microorganisms found in the environment are essential for biogeochemical cycles and are essential for plant growth. The microbiome of the produce production environment might also contain foodborne pathogens and ...

  8. Computer Produced Media Guides.

    ERIC Educational Resources Information Center

    Jeffcott, Janet B.

    To increase access to the media collection at the Madison Area Technical College (Wisconsin) a computer-produced key work index was created using an International Business Machine (IBM) 360 model 40 computer and a duplicating facility with offset capability. A standard 80 column IBM card was used reserving columns 1-9 for the media item number,…

  9. Producing superhydrophobic roof tiles

    NASA Astrophysics Data System (ADS)

    Carrascosa, Luis A. M.; Facio, Dario S.; Mosquera, Maria J.

    2016-03-01

    Superhydrophobic materials can find promising applications in the field of building. However, their application has been very limited because the synthesis routes involve tedious processes, preventing large-scale application. A second drawback is related to their short-term life under outdoor conditions. A simple and low-cost synthesis route for producing superhydrophobic surfaces on building materials is developed and their effectiveness and their durability on clay roof tiles are evaluated. Specifically, an organic-inorganic hybrid gel containing silica nanoparticles is produced. The nanoparticles create a densely packed coating on the roof tile surface in which air is trapped. This roughness produces a Cassie-Baxter regime, promoting superhydrophobicity. A surfactant, n-octylamine, was also added to the starting sol to catalyze the sol-gel process and to coarsen the pore structure of the gel network, preventing cracking. The application of ultrasound obviates the need to use volatile organic compounds in the synthesis, thereby making a ‘green’ product. It was also demonstrated that a co-condensation process effective between the organic and inorganic species is crucial to obtain durable and effective coatings. After an aging test, high hydrophobicity was maintained and water absorption was completely prevented for the roof tile samples under study. However, a transition from a Cassie-Baxter to a Wenzel state regime was observed as a consequence of the increase in the distance between the roughness pitches produced by the aging of the coating.

  10. Directionally Solidified Ceramics Produced

    NASA Technical Reports Server (NTRS)

    Farmer, Serene C.; Sayir, Ali

    2000-01-01

    Produced Multiphase, interpenetrating structures are an alternative route to obtaining structural ceramic materials with adequate strength, toughness, and stability for high-temperature aerospace applications. The eutectic architecture, a continuous-reinforcing phase within a higher volume phase or matrix, can be described as a naturally occurring, in situ composite. The phases of a eutectic are thermodynamically compatible at high homologous temperatures. Strong and stable materials have been produced. Toughness, however, remains a technical obstacle. The potential for producing materials with enhanced toughness along with adequate strength and stability was demonstrated using the laser-heated float zone (LHFZ) growth method at the NASA Glenn Research Center at Lewis Field. LHFZ growth at Glenn provides a means to efficiently produce and record the underlying growth phenomena associated with two-phase structures. To initiate directional solidification, a seed of single-crystal sapphire (<0001> direction) was lowered onto the molten liquid until wetting occurred and then withdrawn at a constant rate. Neither the crystal nor the source rod was rotated. The materials produced were tested mechanically in tension, and the resulting microstructure was examined with a scanning electron microscope. Both the inherent properties of the constituent phases and the properties of the interface between them affect the mechanical behavior and the fracture surfaces. The following scanning electron micrographs show the microstructures of two different materials that were tested to failure in tension. In the left micrograph, the flat fracture surface is typical of a material that is strong but has low toughness. In the right micrograph, the crack is effectively deflected at the interface between the two phases, achieving higher toughness at moderately lower strength levels. Conducting mechanical tests to determine the high temperature properties of these materials is the next step

  11. METHOD OF PRODUCING NEUTRONS

    DOEpatents

    Imhoff, D.H.; Harker, W.H.

    1964-02-01

    A method for producing neutrons is described in which there is employed a confinement zone defined between longitudinally spaced localized gradient regions of an elongated magnetic field. Changed particles and neutralizing electrons, more specifically deuterons and tritons and neutralizng electrons, are injected into the confinement field from ion sources located outside the field. The rotational energy of the parrticles is increased at the gradients by imposing an oscillating transverse electrical field thereacross. The imposition of such oscillating transverse electrical fields improves the reflection capability of such gradient fielda so that the reactive particles are retained more effectively within the zone. With the attainment of appropriate densities of plasma particles and provided that such particles are at a sufficiently high temperature, neutron-producing reactions ensue and large quantities of neutrons emerge from the containment zone. (AEC)

  12. Process for producing silicon

    DOEpatents

    Olson, Jerry M.; Carleton, Karen L.

    1984-01-01

    A process for producing silicon includes forming an alloy of copper and silicon and positioning the alloy in a dried, molten salt electrolyte to form a solid anode structure therein. An electrically conductive cathode is placed in the electrolyte for plating silicon thereon. The electrolyte is then purified to remove dissolved oxides. Finally, an electrical potential is applied between the anode and cathode in an amount sufficient to form substantially pure silicon on the cathode in the form of substantially dense, coherent deposits.

  13. Method of producing imines

    DOEpatents

    Sithambaram, Shanthakumar [Storrs, CT; Son, Young-Chan [Storrs, CT; Suib, Steven L [Storrs, CT

    2008-04-08

    A method for forming an imine comprises reacting a first reactant comprising a hydroxyl functionality, a carbonyl functionality, or both a hydroxyl functionality and a carbonyl functionality with a second reactant having an amine functionality in the presence of ordered porous manganese-based octahedral molecular sieves and an oxygen containing gas at a temperature and for a time sufficient for the imine to be produced.

  14. Method of producing imines

    DOEpatents

    Sithambaram, Shanthakumar; Son, Young-Chan; Suib, Steven L.

    2008-04-08

    A method for forming an imine comprises reacting a first reactant comprising a hydroxyl functionality, a carbonyl functionality, or both a hydroxyl functionality and a carbonyl functionality with a second reactant having an amine functionality in the presence of ordered porous manganese-based octahedral molecular sieves and an oxygen containing gas at a temperature and for a time sufficient for the imine to be produced.

  15. 7 CFR 1250.305 - Egg producer or producer.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Egg producer or producer. 1250.305 Section 1250.305... AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE EGG RESEARCH AND PROMOTION Egg Research and Promotion Order Definitions § 1250.305 Egg producer or producer. Egg producer or...

  16. 7 CFR 1250.305 - Egg producer or producer.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false Egg producer or producer. 1250.305 Section 1250.305... AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE EGG RESEARCH AND PROMOTION Egg Research and Promotion Order Definitions § 1250.305 Egg producer or producer. Egg producer or...

  17. 7 CFR 1250.305 - Egg producer or producer.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Egg producer or producer. 1250.305 Section 1250.305... AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE EGG RESEARCH AND PROMOTION Egg Research and Promotion Order Definitions § 1250.305 Egg producer or producer. Egg producer or...

  18. 7 CFR 1250.305 - Egg producer or producer.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Egg producer or producer. 1250.305 Section 1250.305... AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE EGG RESEARCH AND PROMOTION Egg Research and Promotion Order Definitions § 1250.305 Egg producer or producer. Egg producer or...

  19. 7 CFR 1250.305 - Egg producer or producer.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Egg producer or producer. 1250.305 Section 1250.305... AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE EGG RESEARCH AND PROMOTION Egg Research and Promotion Order Definitions § 1250.305 Egg producer or producer. Egg producer or...

  20. ION PRODUCING MECHANISM

    DOEpatents

    Backus, J.G.

    1958-09-01

    This patent relates to improvements in calutron devices and particularly describes a novel ion source. The unique feature of this source lies in the shaping of the ionizing electron stream to conform to the arc plasma boundary at the exit slit of the ionization chamber, thereby increasing the ion density produced at the plasma boundary. The particular structure consists of an electron source disposed at onc end of an elongated ionization chambcr and a coilimating electrode positioned to trim the electron stream to a crescent shape before entering the ionization chamber.

  1. ION PRODUCING MECHANISM

    DOEpatents

    Lawrence, E.O.

    1958-09-16

    Improvements are presented in calutron devices and, more specifically, dealswith an improved mounting arrangement fer the ion source of the calutron. An important feature of the invention resides in a pluraiity of insulators so mounted as to be accessible from the exterior of the calutron tank and supporting at their inner ends the ion source. These insutators are arranged in mutually parallel relation and also parallel to the flux of the nmgnetic field, whereby the strain of the supporting elements is reduced to a minimum. In addition the support assembly is secured to a removable wall portion of the task to facilitate withdrawal and examination of the ion producing mechanism.

  2. Producing Hydrogen With Sunlight

    NASA Technical Reports Server (NTRS)

    Biddle, J. R.; Peterson, D. B.; Fujita, T.

    1987-01-01

    Costs high but reduced by further research. Producing hydrogen fuel on large scale from water by solar energy practical if plant costs reduced, according to study. Sunlight attractive energy source because it is free and because photon energy converts directly to chemical energy when it breaks water molecules into diatomic hydrogen and oxygen. Conversion process low in efficiency and photochemical reactor must be spread over large area, requiring large investment in plant. Economic analysis pertains to generic photochemical processes. Does not delve into details of photochemical reactor design because detailed reactor designs do not exist at this early stage of development.

  3. Producing Hydrogen With Sunlight

    NASA Technical Reports Server (NTRS)

    Biddle, J. R.; Peterson, D. B.; Fujita, T.

    1987-01-01

    Costs high but reduced by further research. Producing hydrogen fuel on large scale from water by solar energy practical if plant costs reduced, according to study. Sunlight attractive energy source because it is free and because photon energy converts directly to chemical energy when it breaks water molecules into diatomic hydrogen and oxygen. Conversion process low in efficiency and photochemical reactor must be spread over large area, requiring large investment in plant. Economic analysis pertains to generic photochemical processes. Does not delve into details of photochemical reactor design because detailed reactor designs do not exist at this early stage of development.

  4. Drugs producing vitamin deficiencies.

    PubMed

    Montenero, A S

    1980-01-01

    Many drugs produce vitamin deficiencies. They belong to the most important and common therapeutical classes: analgesics, antianemics, antibacterial and antiblastic agents, antibiotics, antidiabetics, antimalarials, antiphlogistics, antipyretics, diuretics, laxatives and purgatives, tranquilizers and anticonvulsives, radiomimetics, hormones and vitamins themselves. The vitamin deprivation processes may be produced by a variety of mechanisms and may involve all vitamins. Recent experiments indicate that there is a competition for binding sites on proteins between vitamin C and salicylate and between dicoumarol and vitamin K. Usually a drug exerts a "devitaminizing" action with respect to only one vitamin. However there are examples of multiple vitamin deficiencies induced by a single drug, like salicylate which deprives the organism of vitamins C, K and pantothenate. These deficiencies may develop either all at the same time or successively. A direct and concomitant vitamin depriving action occurs when an antibiotic blocks the production of vitamins by the enteric flora. A different mode of action occurs in the drug induced folic acid deficiency, which in turn induces a deficiency of vitamin B12. It has been reported that a vitamin deficiency may result from intake of high pharmacological doses of other vitamins. These data need confirmation in patients treated with high doses of nicotinic acid. The drug induced vitamin deficiencies are studied with the same methodology employed for avitaminoses in general; hence they can be diagnosed using the same criteria.

  5. Process for producing ethanol

    SciTech Connect

    Lantero, O.J.; Fish, J.J.

    1993-07-27

    A process is described for producing ethanol from raw materials containing a high dry solid mash level having fermentable sugars or constituents which can be converted into sugars, comprising the steps of: (a) liquefaction of the raw materials in the presence of an alpha amylase to obtain liquefied mash; (b) saccharification of the liquefied mash in the presence of a glucoamylase to obtain hydrolysed starch and sugars; (c) fermentation of the hydrolysed starch and sugars by yeast to obtain ethanol; and (d) recovering the obtained ethanol, wherein an acid fungal protease is introduced to the liquefied mash during the saccharification and/or to the hydrolysed starch and sugars during the fermentation, thereby increasing the rate of production of ethanol as compared to a substantially similar process conducted without the introduction of the protease.

  6. APPARATUS FOR PRODUCING SHADOWGRAPHS

    DOEpatents

    Wilson, R.R.

    1959-08-11

    An apparatus is presented for obtaining shadowgraphs or radiographs of an object exposed to x rays or the like. The device includes the combination of a cloud chamber having the interior illuminated and a portion thereof transparent to light rays and x'rays, a controlled source of x rays spaced therefrom, photographic recording disposed laterally of the linear path intermediate the source and the chamber portion in oblique angularity in aspect to the path. The object to be studied is disposed intermediate the x-ray source and chamber in the linear path to provide an x-ray transmission barrier therebetween. The shadowgraph is produced in the cloud chamber in response to initiation of the x- ray source and recorded photographically.

  7. ION PRODUCING MECHANISMS

    DOEpatents

    Brobeck, W.M.

    1959-02-10

    Ion generating means and means for producing ions of material for isotopic separation are discussed. One feature of the invention resides in providing a heater means located in the source block approximately equidistant from a charge reservoir and an arc chamber, whereby the heat distribution in the block is such as to avoid overheating and to maintain the temperature of the various critical localities of the unit at their optimum values. Another feature consists of a pair of plates disposed on either side of the arc chamber exit opening to define a narrow slit for the egression of the ion beam. When the adjacent edges of the plates have become worn, the plates may be detached and reversed to use the opposite edges thereof to define the exit opening.

  8. Fermentation method producing ethanol

    SciTech Connect

    Wang, D.I.C.; Dalal, R.

    1986-02-04

    This patent describes a process for preparing and isolating a mutant strain of Clostridium thermosaccharolyticum. The mutant strain is able to ferment hexose and pentose carbohydrates to produce ethanol and acetic acid in gram ratios of at least about 8:1. The process includes the steps of: 1.) exposing Clostridium thermosaccharolyticum cells to a mutagenic agent sufficient to effect mutation of the cells; 2.) culturing the mutated cells in a growth medium containing minimal carbon sources and pyruvate for a predetermined time period; 3.) enriching the growth medium with at least one antibiotic, the antibiotic killing the actively growing cells in the medium without substantially affecting the non-actively growing cells; and 4.) isolating a mutant Clostridium thermosaccharolyticium strain from the non-actively growing cells via the inability to utilize pyruvate as a carbon source.

  9. Process for thermochemically producing hydrogen

    DOEpatents

    Bamberger, Carlos E.; Richardson, Donald M.

    1976-01-01

    Hydrogen is produced by the reaction of water with chromium sesquioxide and strontium oxide. The hydrogen producing reaction is combined with other reactions to produce a closed chemical cycle for the thermal decomposition of water.

  10. Producing VOT contrasts

    NASA Astrophysics Data System (ADS)

    Lofqvist, Anders

    2001-05-01

    The development of voice onset time (VOT) as an acoustic index for studying and classifying stop consonants also prompted a large number of studies examining laryngeal activity and interarticulator timing related to VOT. A collaboration between the Research Institute of Logopedics and Phoniatrics at the University of Tokyo and Haskins Laboratories resulted in a long line of studies using electromyographic and other techniques that provided much of the empirical foundations for what we know about laryngeal function in speech, in particular the production of voiced and voiceless consonants. This presentation will review the articulatory control of VOT differences. To make a consonant voiceless, a speaker uses a combination of glottal abduction and vocal fold tensing. The distinction between voiceless stops with long and short VOT is basically due to a difference in the timing between the glottal abduction gesture and the oral closing and opening gestures. Variations in the size of the glottal gesture also occur. More generally, variations in interarticulator timing between glottal and oral movements are used to produce the different stop categories that occur in the languages of the world. [Work supported by NIH.

  11. Method for producing capsular polysaccharides

    NASA Technical Reports Server (NTRS)

    Kern, Roger G. (Inventor); Petersen, Gene R. (Inventor); Richards, Gil F. (Inventor)

    1994-01-01

    Structurally altered capsular polysaccharides are produced by mutant bacteria. These polysaccharides are isolated by selecting a wild type bacterial strain and a phage producing degradative enzymes that have substrate specificity for the capsular polysaccharides produced by the wild type bacteria. Phage-resistant mutants producing capsular polysaccharides are selected and the structurally altered capsular polysaccharide is isolated therefrom.

  12. Methods for producing complex films, and films produced thereby

    DOEpatents

    Duty, Chad E.; Bennett, Charlee J. C.; Moon, Ji -Won; Phelps, Tommy J.; Blue, Craig A.; Dai, Quanqin; Hu, Michael Z.; Ivanov, Ilia N.; Jellison, Jr., Gerald E.; Love, Lonnie J.; Ott, Ronald D.; Parish, Chad M.; Walker, Steven

    2015-11-24

    A method for producing a film, the method comprising melting a layer of precursor particles on a substrate until at least a portion of the melted particles are planarized and merged to produce the film. The invention is also directed to a method for producing a photovoltaic film, the method comprising depositing particles having a photovoltaic or other property onto a substrate, and affixing the particles to the substrate, wherein the particles may or may not be subsequently melted. Also described herein are films produced by these methods, methods for producing a patterned film on a substrate, and methods for producing a multilayer structure.

  13. Producing Runaway Stars

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-07-01

    How are the hypervelocity stars weve observed in our galaxy produced? A recent study suggests that these escapees could be accelerated by a massive black hole in the center of the Large Magellanic Cloud.A Black Hole SlingshotSince their discovery in 2005, weve observed dozens of candidate hypervelocity stars stars whose velocity in the rest frame of our galaxy exceeds the local escape velocity of the Milky Way. These stars present a huge puzzle: how did they attain these enormous velocities?One potential explanation is known as the Hills mechanism. In this process, a stellar binary is disrupted by a close encounter with a massive black hole (like those thought to reside at the center of every galaxy). One member of the binary is flung out of the system as a result of the close encounter, potentially reaching very large velocities.A star-forming region known as LHA 120-N 11, located within the LMC. Some binary star systems within the LMC might experience close encounters with a possible massive black hole at the LMCs center. [ESA/NASA/Hubble]Blame the LMC?Usually, discussions of the Hills mechanism assume that Sagittarius A*, the supermassive black hole at the center of the Milky Way, is the object guilty of accelerating the hypervelocity stars weve observed. But what if the culprit isnt Sgr A*, but a massive black hole at the center of the Large Magellanic Cloud (LMC), one of the Milky Ways satellite galaxies?Though we dont yet have evidence of a massive black hole at the center of the LMC, the dwarf galaxy is large enough to potentially host one as large as 100,000 solar masses. Assuming that it does, two scientists at the University of Cambridge, Douglas Boubert and Wyn Evans, have now modeled how this black hole might tear apart binary star systems and fling hypervelocity stars around the Milky Way.Models for AccelerationBoubert and Evans determined that the LMCs hypothetical black hole could easily eject stars at ~100 km/s, which is the escape velocity of the

  14. Method of producing submicron size particles and product produced thereby

    DOEpatents

    Bourne, R.S.; Eichman, C.C.; Welbon, W.W.

    1988-05-11

    Submicron size particles are produced by using a sputtering process to deposit particles into a liquid. The liquid is processed to recover the particles therefrom, and the particles have sizes in the range of twenty to two hundred Angstroms. Either metallic or non-metallic particles can be produced, and the metallic particles can be used in ''metallic inks.'' 4 figs.

  15. Bacteriocins produced by Leuconostoc species.

    PubMed

    Stiles, M E

    1994-09-01

    Leuconostoc spp. are lactic acid bacteria that are commonly associated with foods and that are used as starter bacteria in some dairy fermentations. Lactic acid bacteria are inhibitory to other bacteria because of pH, organic acids, hydrogen peroxide, and other chemicals produced during their growth, including bacteriocins. Bacteriocin production by Leuconostoc spp. was first observed in the 1950s, but only since 1984, when antagonistic activity of Leuconostoc spp. was reported, have more extensive studies of bacteriocins produced by Leuconostoc spp. been conducted, including mesentericin Y105, produced by Leuconostoc mesenteroides spp. mesenteroides; leucocin A-UAL 187, produced by Leuconostoc gelidum; carnosin 44A, produced by Leuconostoc carnosum; and leuconocin S, produced by Leuconostoc paramesenteroides. Bacteriocins produced by leuconostocs may or may not be active against other lactic acid bacteria, but all include Listeria in their activity spectra. Mesentericin Y105 is reported to be exclusively active against Listeria spp. The amino acid sequences for leucocin A and mesentericin Y105 have been determined. Despite considerable differences in antibacterial spectra, only two amino acids differ between these bacteriocins. The prevalence of leuconostocs in many adventitious fermentations of food and the use of leuconostocs as starter bacteria in controlled fermentations make the bacteriocins produced by these bacteria of interest as possible food preservatives by addition of the bacteriocin or its producer organism to foods.

  16. Method for producing a borohydride

    DOEpatents

    Kong, Peter C.

    2010-06-22

    A method for producing a borohydride is described that includes the steps of providing a source of borate; providing a material that chemically reduces the source of the borate to produce a borohydride; and reacting the source of the borate and the material by supplying heat at a temperature that substantially effects the production of the borohydride.

  17. Guide to Producing Print Materials.

    ERIC Educational Resources Information Center

    Far West Lab. for Educational Research and Development, San Francisco, CA.

    This is a simple how-to-do it manual intended to help projects that wish to produce print materials. It highlights the stages involved in producing print materials, giving an overview of the steps required and offering hints on different approaches to the various processes. The manual begins with the comprehensive layout (dummy) stage and proceeds…

  18. Method of producing molybdenum-99

    SciTech Connect

    Pitcher, Eric John

    2013-05-28

    Method of producing molybdenum-99, comprising accelerating ions by means of an accelerator; directing the ions onto a metal target so as to generate neutrons having an energy of greater than 10 MeV; directing the neutrons through a converter material comprising techentium-99 to produce a mixture comprising molybdenum-99; and, chemically extracting the molybdenum-99 from the mixture.

  19. Method for producing a borohydride

    DOEpatents

    Kong, Peter C.

    2008-09-02

    A method for producing a borohydride is described and which includes the steps of providing a source of borate; providing a material which chemically reduces the source of the borate to produce a borohydride; and reacting the source of borate and the material by supplying heat at a temperature which substantially effects the production of the borohydride.

  20. Microorganisms for producing organic acids

    DOEpatents

    Pfleger, Brian Frederick; Begemann, Matthew Brett

    2014-09-30

    Organic acid-producing microorganisms and methods of using same. The organic acid-producing microorganisms comprise modifications that reduce or ablate AcsA activity or AcsA homolog activity. The modifications increase tolerance of the microorganisms to such organic acids as 3-hydroxypropionic acid, acrylic acid, propionic acid, lactic acid, and others. Further modifications to the microorganisms increase production of such organic acids as 3-hydroxypropionic acid, lactate, and others. Methods of producing such organic acids as 3-hydroxypropionic acid, lactate, and others with the modified microorganisms are provided. Methods of using acsA or homologs thereof as counter-selectable markers are also provided.

  1. Methods of producing cesium-131

    DOEpatents

    Meikrantz, David H; Snyder, John R

    2012-09-18

    Methods of producing cesium-131. The method comprises dissolving at least one non-irradiated barium source in water or a nitric acid solution to produce a barium target solution. The barium target solution is irradiated with neutron radiation to produce cesium-131, which is removed from the barium target solution. The cesium-131 is complexed with a calixarene compound to separate the cesium-131 from the barium target solution. A liquid:liquid extraction device or extraction column is used to separate the cesium-131 from the barium target solution.

  2. Microorganisms for producing organic acids

    SciTech Connect

    Pfleger, Brian Frederick; Begemann, Matthew Brett

    2014-09-30

    Organic acid-producing microorganisms and methods of using same. The organic acid-producing microorganisms comprise modifications that reduce or ablate AcsA activity or AcsA homolog activity. The modifications increase tolerance of the microorganisms to such organic acids as 3-hydroxypropionic acid, acrylic acid, propionic acid, lactic acid, and others. Further modifications to the microorganisms increase production of such organic acids as 3-hydroxypropionic acid, lactate, and others. Methods of producing such organic acids as 3-hydroxypropionic acid, lactate, and others with the modified microorganisms are provided. Methods of using acsA or homologs thereof as counter-selectable markers are also provided.

  3. Cellulase producing microorganism ATCC 55702

    DOEpatents

    Dees, H.C.

    1997-12-30

    Bacteria which produce large amounts of cellulase--containing cell-free fermentate have been identified. The original bacterium (ATCC 55703) was genetically altered using nitrosoguanidine (MNNG) treatment to produce the enhanced cellulase producing bacterium (ATCC 55702), which was identified through replicate plating. ATCC 55702 has improved characteristics and qualifies for the degradation of cellulosic waste materials for fuel production, food processing, textile processing, and other industrial applications. ATCC 55702 is an improved bacterial host for genetic manipulations using recombinant DNA techniques, and is less likely to destroy genetic manipulations using standard mutagenesis techniques. 5 figs.

  4. Cellulase producing microorganism ATCC 55702

    DOEpatents

    Dees, H. Craig

    1997-01-01

    Bacteria which produce large amounts of cellulase--containing cell-free fermentate have been identified. The original bacterium (ATCC 55703) was genetically altered using nitrosoguanidine (MNNG) treatment to produce the enhanced cellulase producing bacterium (ATCC 55702), which was identified through replicate plating. ATCC 55702 has improved characteristics and qualifies for the degradation of cellulosic waste materials for fuel production, food processing, textile processing, and other industrial applications. ATCC 55702 is an improved bacterial host for genetic manipulations using recombinant DNA techniques, and is less likely to destroy genetic manipulations using standard mutagenesis techniques.

  5. Jet Shockwaves Produce Gamma Rays

    NASA Image and Video Library

    Theorists believe that GRB jets produce gamma rays by two processes involving shock waves. Shells of material within the jet move at different speeds and collide, generating internal shock waves th...

  6. Process for producing mesophase pitch

    SciTech Connect

    Shibatani, H.; Kameda, T.; Takahashi, K.

    1985-07-09

    Mesophase pitch containing quinoline soluble mesophase is produced from a pitch having a specific aromatic hydrogen content with a short heat treatment time without conducting any special treatment such as extraction.

  7. Methods of producing transportation fuel

    DOEpatents

    Nair, Vijay [Katy, TX; Roes, Augustinus Wilhelmus Maria [Houston, TX; Cherrillo, Ralph Anthony [Houston, TX; Bauldreay, Joanna M [Chester, GB

    2011-12-27

    Systems, methods, and heaters for treating a subsurface formation are described herein. At least one method for producing transportation fuel is described herein. The method for producing transportation fuel may include providing formation fluid having a boiling range distribution between -5.degree. C. and 350.degree. C. from a subsurface in situ heat treatment process to a subsurface treatment facility. A liquid stream may be separated from the formation fluid. The separated liquid stream may be hydrotreated and then distilled to produce a distilled stream having a boiling range distribution between 150.degree. C. and 350.degree. C. The distilled liquid stream may be combined with one or more additives to produce transportation fuel.

  8. Human body may produce bacteria.

    PubMed

    Salerian, Alen J

    2017-06-01

    "Human body may produce bacteria" proposes that human body may produce bacteria and represent an independent source of infections contrary to the current paradigm of infectious disorders proposed by Louis Pasteur in 1880. The following observations are consistent with this hypothesis: A. Bidirectional transformations of both living and nonliving things have been commonly observed in nature. B. Complex multicellular organisms harbor the necessary properties to produce bacteria (water, nitrogen and oxygen). C. Physical laws suggest any previously observed phenomenon or action will occur again (life began on earth; a non living thing). D. Animal muscle cells may generate energy (fermentation). E. Sterilized food products (i.e. boiled eggs), may produce bacteria and fungus under special conditions and without any exposure to foreign living cells. "Human body may produce bacteria" may challenge the current medical paradigm that views human infectious disorders as the exclusive causative byproducts of invading foreign cells. It may also introduce new avenues to treat infectious disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Postharvest treatments of fresh produce

    PubMed Central

    Mahajan, P. V.; Caleb, O. J.; Singh, Z.; Watkins, C. B.; Geyer, M.

    2014-01-01

    Postharvest technologies have allowed horticultural industries to meet the global demands of local and large-scale production and intercontinental distribution of fresh produce that have high nutritional and sensory quality. Harvested products are metabolically active, undergoing ripening and senescence processes that must be controlled to prolong postharvest quality. Inadequate management of these processes can result in major losses in nutritional and quality attributes, outbreaks of foodborne pathogens and financial loss for all players along the supply chain, from growers to consumers. Optimal postharvest treatments for fresh produce seek to slow down physiological processes of senescence and maturation, reduce/inhibit development of physiological disorders and minimize the risk of microbial growth and contamination. In addition to basic postharvest technologies of temperature management, an array of others have been developed including various physical (heat, irradiation and edible coatings), chemical (antimicrobials, antioxidants and anti-browning) and gaseous treatments. This article examines the current status on postharvest treatments of fresh produce and emerging technologies, such as plasma and ozone, that can be used to maintain quality, reduce losses and waste of fresh produce. It also highlights further research needed to increase our understanding of the dynamic response of fresh produce to various postharvest treatments. PMID:24797137

  10. Producing liquid fuels from biomass

    NASA Astrophysics Data System (ADS)

    Solantausta, Yrjo; Gust, Steven

    The aim of this survey was to compare, on techno-economic criteria, alternatives of producing liquid fuels from indigenous raw materials in Finland. Another aim was to compare methods under development and prepare a proposal for steering research related to this field. Process concepts were prepared for a number of alternatives, as well as analogous balances and production and investment cost assessments for these balances. Carbon dioxide emissions of the alternatives and the price of CO2 reduction were also studied. All the alternatives for producing liquid fuels from indigenous raw materials are utmost unprofitable. There are great differences between the alternatives. While the production cost of ethanol is 6 to 9 times higher than the market value of the product, the equivalent ratio for substitute fuel oil produced from peat by pyrolysis is 3 to 4. However, it should be borne in mind that the technical uncertainties related to the alternatives are of different magnitude. Production of ethanol from barley is of commercial technology, while biomass pyrolysis is still under development. If the aim is to reach smaller carbon dioxide emissions by using liquid biofuels, the most favorable alternative is pyrolysis oil produced from wood. Fuels produced from cultivated biomass are more expensive ways of reducing CO2 emissions. Their potential of reducing CO2 emissions in Finland is insignificant. Integration of liquid fuel production to some other production line is more profitable.

  11. Postharvest treatments of fresh produce.

    PubMed

    Mahajan, P V; Caleb, O J; Singh, Z; Watkins, C B; Geyer, M

    2014-06-13

    Postharvest technologies have allowed horticultural industries to meet the global demands of local and large-scale production and intercontinental distribution of fresh produce that have high nutritional and sensory quality. Harvested products are metabolically active, undergoing ripening and senescence processes that must be controlled to prolong postharvest quality. Inadequate management of these processes can result in major losses in nutritional and quality attributes, outbreaks of foodborne pathogens and financial loss for all players along the supply chain, from growers to consumers. Optimal postharvest treatments for fresh produce seek to slow down physiological processes of senescence and maturation, reduce/inhibit development of physiological disorders and minimize the risk of microbial growth and contamination. In addition to basic postharvest technologies of temperature management, an array of others have been developed including various physical (heat, irradiation and edible coatings), chemical (antimicrobials, antioxidants and anti-browning) and gaseous treatments. This article examines the current status on postharvest treatments of fresh produce and emerging technologies, such as plasma and ozone, that can be used to maintain quality, reduce losses and waste of fresh produce. It also highlights further research needed to increase our understanding of the dynamic response of fresh produce to various postharvest treatments.

  12. Natural gas supply - a producer`s perspective

    SciTech Connect

    Papa, M.G.

    1994-12-31

    The supply of natural gas from the producers standpoint is discussed. The following factors in the marketing demand for natural gas are considered to be important: gas demand is growing, U.S. gas resource base is large, chronic gas bubble has shrunk, and North American supply is more resilient than expected.

  13. [Bronchopulmonary ACTH-producing tumors].

    PubMed

    Pikunov, M Iu; Kuznetsov, N S; Latkina, N V; Dobreva, E A; Remizov, O V

    2014-01-01

    Neuroendocrine tumors have the ability to produce the hormones and vasoactive peptides. Excess of these hormones leads to different symptoms and syndromes because of organs' injuries. Detection of ACTH origin by using of modern diagnostic methods is not always possible. Lungs and bronchi are one of the most frequent localization of ACTH-producing tumors. It is considered that carcinoids with bronchopulmonary localization like a benign tumors in the clinical course. But at the same time carcinoid tends to metastasize, so timely diagnostics and treatment improve quality of life significant and increase the life expectancy of patients. The modern state of diagnostics and surgical treatment problem of ACTH-producing tumors with bronchopulmonary localization is presented in the article. It was described the brief historical background, clinical symptoms, instrumental and biochemical methods of diagnosis. The principles of surgical treatment are presented in the article.

  14. Method for producing mesophase pitch

    SciTech Connect

    Watarabe, M.

    1985-07-16

    A method for producing a 100% mesophase pitch composed only of Q.I. and Q.S. components is provided. This method comprises subjecting petroleum-origin pitch to heat treatment with stirring under a stream of a hydrocarbon gas of small carbon atom numbers at atmospheric or superatmospheric pressure, holding said heat-treated pitch in quiescent state to melt and coalesce only the mesophase therein and dividing and separating non-mesophase and mesophase layers. Resulting 100% mesophase enables us to produce high strength, high modulus carbon fibers.

  15. Process for producing mesophase pitch

    SciTech Connect

    Izumi, T.; Igarashi, S.; Naito, T.

    1985-08-06

    A substantially uniform mesophase pitch is prepared by treating a mesophase forming pitch material at elevated temperatures above about 380/sup 0/ C. to produce a mixture of mesophase and non-mesophase pitch containing about 20% to about 80% mesophase. The mixture is then maintained at a temperature below about 400/sup 0/ C. for a time sufficient to allow the mesophase to coalesce and settle as a lower separable layer. A mesophase pitch so produced may contain from 90 to 100% mesophase with a softening point of less than 320/sup 0/ C.

  16. Producing undistorted acoustic sine waves.

    PubMed

    Boutin, Henri; Smith, John; Wolfe, Joe

    2014-04-01

    A simple digital method is described that can produce an undistorted acoustic sine wave using an amplifier and loudspeaker having considerable intrinsic distortion, a common situation at low frequencies and high power. The method involves, first, using a pure sine wave as the input and measuring the distortion products. An iterative procedure then progressively adds harmonics with appropriate amplitude and phase to cancel any distortion products. The method is illustrated by producing a pure 52 Hz sine wave at 107 dB sound pressure level with harmonic distortion reduced over the audible range to >65 dB below the fundamental.

  17. Apparatus for producing laser targets

    DOEpatents

    Jarboe, T.R.; Baker, W.R.

    1975-09-23

    This patent relates to an apparatus and method for producing deuterium targets or pellets of 25u to 75u diameter. The pellets are sliced from a continuously spun solid deuterium thread at a rate of up to 10 pellets/second. The pellets after being sliced from the continuous thread of deuterium are collimated and directed to a point of use, such as a laser activated combustion or explosion chamber wherein the pellets are imploded by laser energy or laser produced target plasmas for neutral beam injection. (auth)

  18. Method for producing laser targets

    DOEpatents

    Jarboe, Thomas R.; Baker, William R.

    1977-01-01

    An apparatus and method for producing deuterium targets or pellets of 25.mu. to 75.mu. diameter. The pellets are sliced from a continuously spun solid deuterium thread at a rate of up to 10 pellets/second. The pellets after being sliced from the continuous thread of deuterium are collimated and directed to a point of use, such as a laser activated combustion or explosion chamber wherein the pellets are imploded by laser energy or laser produced target plasmas for neutral beam injection.

  19. Method for producing redox shuttles

    SciTech Connect

    Pupek, Krzysztof Z.; Dzwiniel, Trevor L.; Krumdick, Gregory K.

    2015-03-03

    A single step method for producing a redox shuttle having the formula 2,5-di-tert-butyl-1,4-phenylene tetraethyl bis(phosphate) is provided, the method comprising phosphorylating tert butyl hydroquinone with a phosphate-containing reagent. Also provided is method for producing 2,5-di-tert-butyl-1,4-phenylene tetraethyl bis(phosphate), the method comprising solubilizing tert-butyl hydroquinone and tetrabutylammonium bromide with methyltetrahydrofuran to create a mixture; heating the mixture while adding base to the mixture in an amount to turn the mixture orange; and adding diethyl chlorophosphate to the orange mixture in an amount to phosphorylate the hydroquinone.

  20. Student Produced Advanced Mathematical Software.

    ERIC Educational Resources Information Center

    Hogben, Leslie

    The intent of this project was to develop a course for mathematics graduate students at Iowa State University. They would design and write computer programs for use by undergraduate mathematics students, and then offer the course and actually produce the software. Phase plane graphics for ordinary differential equations was selected as the topic.…

  1. The Top STEM Degree Producers

    ERIC Educational Resources Information Center

    Diverse: Issues in Higher Education, 2012

    2012-01-01

    This article presents a list of the top Science, Technology, Engineering, and Mathematics (STEM) degree producers in the U.S. This list is broken down into seven categories: (1) Total Minority Research/Scholarship and Other Doctoral: Mathematics and Statistics; (2) Total Minority Bachelors: Biological and Biomedical Sciences; (3) Total Minority…

  2. Marketing Hardwoods to Furniture Producers

    Treesearch

    Steven A. Sinclair; Robert J. Bush; Philip A. Araman

    1989-01-01

    This paper discusses some of the many problems in developing marketing programs for small wood products manufacturers. It examines the problems of using price as a dominant means for getting and attracting customers. The marketing of hardwood lumber to furniture producers is then used as an example. Data from 36 furniture lumber buyers is presented to illustrate...

  3. Institutional Producers of Physics Research.

    ERIC Educational Resources Information Center

    Cooper, Marianne; Watterson, Hermine M.

    In order to identify producers of physics research and to determine their relative productivity, institutional affiliations of authors as given in nine physics journals were studied. Organizations were classified and analyzed by type and geographical location, and productivity established. Findings indicate that organizations differ in their rate…

  4. Resonating feathers produce courtship song.

    PubMed

    Bostwick, Kimberly S; Elias, Damian O; Mason, Andrew; Montealegre-Z, Fernando

    2010-03-22

    Male Club-winged Manakins, Machaeropterus deliciosus (Aves: Pipridae), produce a sustained tonal sound with specialized wing feathers. The fundamental frequency of the sound produced in nature is approximately 1500 Hz and is hypothesized to result from excitation of resonance in the feathers' hypertrophied shafts. We used laser Doppler vibrometry to determine the resonant properties of male Club-winged Manakin's wing feathers, as well as those of two unspecialized manakin species. The modified wing feathers exhibit a response peak near 1500 Hz, and unusually high Q-values (a measure of resonant tuning) for biological objects (Q up to 27). The unmodified wing feathers of the Club-winged Manakin do not exhibit strong resonant properties when measured in isolation. However, when measured still attached to the modified feathers (nine feathers held adjacent by an intact ligament), they resonate together as a unit near 1500 Hz, and the wing produces a second harmonic of similar or greater amplitude than the fundamental. The feathers of the control species also exhibit resonant peaks around 1500 Hz, but these are significantly weaker, the wing does not resonate as a unit and no harmonics are produced. These results lend critical support to the resonant stridulation hypothesis of sound production in M. deliciosus.

  5. The Top STEM Degree Producers

    ERIC Educational Resources Information Center

    Diverse: Issues in Higher Education, 2012

    2012-01-01

    This article presents a list of the top Science, Technology, Engineering, and Mathematics (STEM) degree producers in the U.S. This list is broken down into seven categories: (1) Total Minority Research/Scholarship and Other Doctoral: Mathematics and Statistics; (2) Total Minority Bachelors: Biological and Biomedical Sciences; (3) Total Minority…

  6. Methods of Producing Thin Films,

    DTIC Science & Technology

    The report describes various methods of producing thin films , especially for microelectronics. In addition to the classical methods of forming thin ... films by vacuum vapor deposition, it also describes processes of diode sputtering and modern methods of cathode sputtering by means of a third

  7. The Top Theological Degree Producers

    ERIC Educational Resources Information Center

    Diverse: Issues in Higher Education, 2012

    2012-01-01

    Each year, "Diverse: Issues in Higher Education" publishes a list of the Top 100 producers of associate, bachelor's and graduate degrees awarded to minority students based on research conducted by Dr. Victor M. H. Borden, professor of educational leadership and policy studies at Indiana University Bloomington. This year, for the first…

  8. Secretaries as Producers of Texts.

    ERIC Educational Resources Information Center

    Smith, Ronald E.

    1992-01-01

    Researches secretarial writing in a medium-sized manufacturing company. Finds that secretaries' duties include correcting grammar and usage, providing proper format for letters and memoranda, and generating texts. Supports further research into the role of secretaries as producers of texts. (MM)

  9. METHOD FOR PRODUCING DIBORON TETRACHLORIDE

    DOEpatents

    Frazer, J.W.; Holzmann, R.T.

    1961-08-01

    A method of producing diboron tetrachloride from boron trichloride is described. Gaseous boron trichloride is passed through a cavity resonating at a microwave frequency whereby a portion of the boron trichloride is converted into diboron tetrachloride. The diboron tetrachloride may then be separated from the boron trichloride by conventional means. (AEC)

  10. Producing Exciting and Motivating Dittos.

    ERIC Educational Resources Information Center

    Tuttle, Harry Grover

    This guide presents techniques to enable teachers to produce dittos that generate student interest. One major technique for creating different dittos is variation of format or layout; another way to create appealing dittos is to use color to emphasize a new spelling, grammar, or vocabulary point. Crossword puzzles, word searches, and anagrams (not…

  11. Process for producing chalcogenide semiconductors

    DOEpatents

    Noufi, R.; Chen, Y.W.

    1985-04-30

    A process for producing chalcogenide semiconductor material is disclosed. The process includes forming a base metal layer and then contacting this layer with a solution having a low pH and containing ions from at least one chalcogen to chalcogenize the layer and form the chalcogenide semiconductor material.

  12. Process for producing chalcogenide semiconductors

    DOEpatents

    Noufi, Rommel; Chen, Yih-Wen

    1987-01-01

    A process for producing chalcogenide semiconductor material is disclosed. The process includes forming a base metal layer and then contacting this layer with a solution having a low pH and containing ions from at least one chalcogen to chalcogenize the layer and form the chalcogenide semiconductor material.

  13. Process for producing advanced ceramics

    DOEpatents

    Kwong, Kyei-Sing

    1996-01-01

    A process for the synthesis of homogeneous advanced ceramics such as SiC+AlN, SiAlON, SiC+Al.sub.2 O.sub.3, and Si.sub.3 N.sub.4 +AlN from natural clays such as kaolin, halloysite and montmorillonite by an intercalation and heat treatment method. Included are the steps of refining clays, intercalating organic compounds into the layered structure of clays, drying the intercalated mixture, firing the treated atmospheres and grinding the loosely agglomerated structure. Advanced ceramics produced by this procedure have the advantages of homogeneity, cost effectiveness, simplicity of manufacture, ease of grind and a short process time. Advanced ceramics produced by this process can be used for refractory, wear part and structure ceramics.

  14. PROCESS FOR PRODUCING URANIUM TETRAFLUORIDE

    DOEpatents

    Harvey, B.G.

    1954-09-14

    >This patent relates to improvements in the method for producing uranium tetrafluoride by treating an aqueous solutlon of a uranyl salt at an elevated temperature with a reducing agent effective in acld solutlon in the presence of hydrofluoric acid. Uranium tetrafluoride produced this way frequentiy contains impurities in the raw material serving as the source of uranium. Uranium tetrafluoride much less contaminated with impurities than when prepared by the above method can be prepared from materials containing such impurities by first adding a small proportion of reducing agent so as to cause a small fraction, for example 1 to 5% of the uranium tetrafluoride to be precipitated, rejecting such precipitate, and then precipitating and recovering the remainder of the uranium tetrafluoride.

  15. PROCESS FOR PRODUCING URANIUM HALIDES

    DOEpatents

    Murphree, E.V.

    1957-10-29

    A process amd associated apparatus for producing UF/sub 4/ from U/sub 3/ O/sub 8/ by a fluidized'' technique are reported. The U/sub 3/O/sub 8/ is first reduced to UO/sub 2/ by reaction with hydrogen, and the lower oxide of uranium is then reacted with gaseous HF to produce UF/sub 4/. In each case the reactant gas is used, alone or in combination with inert gases, to fluidize'' the finely divided reactant solid. The complete setup of the plant equipment including bins, reactor and the associated piping and valving, is described. An auxiliary fluorination reactor allows for the direct production of UF/sub 6/ from UF/sub 4/ and fluorine gas, or if desired, UF/sub 4/ may be collected as the product.

  16. Method for producing carbon nanotubes

    DOEpatents

    Phillips, Jonathan; Perry, William L.; Chen, Chun-Ku

    2006-02-14

    Method for producing carbon nanotubes. Carbon nanotubes were prepared using a low power, atmospheric pressure, microwave-generated plasma torch system. After generating carbon monoxide microwave plasma, a flow of carbon monoxide was directed first through a bed of metal particles/glass beads and then along the outer surface of a ceramic tube located in the plasma. As a flow of argon was introduced into the plasma through the ceramic tube, ropes of entangled carbon nanotubes, attached to the surface of the tube, were produced. Of these, longer ropes formed on the surface portion of the tube located in the center of the plasma. Transmission electron micrographs of individual nanotubes revealed that many were single-walled.

  17. Method for producing mesophase continuously

    SciTech Connect

    Watanabe, M.

    1985-04-23

    A method for producing continuously 100% mesophase composed only of Q.I. component and Q.S. component in which a raw material of petroleum origin pitch is subjected continuously to a heat-treatment step in an amount necessary to produce a 100% mesophase taken out from a mesophase-growing and coalescing step, transferring the heat-formed pitch formed in the heat treatment step to a mesophase growing and coalescing step, taking out a definite amount of a non-mesophase pitch from the mesophase growing and coalescing step after stirring and heating treatment to return it to the heat-treatment step to repeat the stirring and heating treatment, and at the same time to take out 100% mesophase having constant properties from the mesophase growing and coalescing step.

  18. PROCESS OF PRODUCING SHAPED PLUTONIUM

    DOEpatents

    Anicetti, R.J.

    1959-08-11

    A process is presented for producing and casting high purity plutonium metal in one step from plutonium tetrafluoride. The process comprises heating a mixture of the plutonium tetrafluoride with calcium while the mixture is in contact with and defined as to shape by a material obtained by firing a mixture consisting of calcium oxide and from 2 to 10% by its weight of calcium fluoride at from 1260 to 1370 deg C.

  19. Method for producing metallic nanoparticles

    DOEpatents

    Phillips, Jonathan; Perry, William L.; Kroenke, William J.

    2004-02-10

    Method for producing metallic nanoparticles. The method includes generating an aerosol of solid metallic microparticles, generating non-oxidizing plasma with a plasma hot zone at a temperature sufficiently high to vaporize the microparticles into metal vapor, and directing the aerosol into the hot zone of the plasma. The microparticles vaporize in the hot zone to metal vapor. The metal vapor is directed away from the hot zone and to the plasma afterglow where it cools and condenses to form solid metallic nanoparticles.

  20. Method for producing metallic microparticles

    DOEpatents

    Phillips, Jonathan; Perry, William L.; Kroenke, William J.

    2004-06-29

    Method for producing metallic particles. The method converts metallic nanoparticles into larger, spherical metallic particles. An aerosol of solid metallic nanoparticles and a non-oxidizing plasma having a portion sufficiently hot to melt the nanoparticles are generated. The aerosol is directed into the plasma where the metallic nanoparticles melt, collide, join, and spheroidize. The molten spherical metallic particles are directed away from the plasma and enter the afterglow where they cool and solidify.

  1. ACTH-producing pituitary tumors.

    PubMed

    Grua, J R; Nelson, D H

    1991-06-01

    Adrenocorticotropin (ACTH)-producing tumors of the pituitary gland usually, though not in all cases, initially show evidence of excess cortisol. The pathogenesis of these tumors--monoclonal versus polyclonal and intermediate lobe versus anterior lobe--continues to prompt debate. Important advances in the diagnostic methods (such as petrosal sinus sampling for ACTH and other hormones) are described. While the mainstay of therapy is still selective adenomectomy via the transsphenoidal approach, total hypophysectomy may occasionally be indicated.

  2. Method for producing monodisperse aerosols

    DOEpatents

    Ortiz, Lawrence W.; Soderholm, Sidney C.

    1990-01-01

    An aerosol generator is described which is capable of producing a monodisperse aerosol within narrow limits utilizing an aqueous solution capable of providing a high population of seed nuclei and an organic solution having a low vapor pressure. The two solutions are cold nebulized, mixed, vaporized, and cooled. During cooling, particles of the organic vapor condense onto the excess seed nuclei, and grow to a uniform particle size.

  3. Method for producing hydrophobic aerogels

    DOEpatents

    Hrubesh, Lawrence W.; Poco, John F.; Coronado, Paul R.

    1999-01-01

    A method for treating a dried monolithic aerogel containing non-dispersed particles, with an organometallic surface modifying agent to produce hydrophobic aerogels. The dried, porous hydrophobic aerogels contain a protective layer of alkyl groups, such as methyl groups, on the modified surfaces of the pores of the aerogel. The alkyl groups at the aerogel surface typically contain at least one carbon-metal bond per group.

  4. Fullerenes produced by harnessing sunlight

    SciTech Connect

    Not Available

    1993-08-01

    Two independent groups of researchers have demonstrated that fullerenes can be produced by harnessing focused sunlight to vaporize carbon. Adapted to a large scale, generation of the carbon-cage molecules in solar furnaces might overcome yield-limiting problems associated with other fullerene production techniques, the researchers suggest. At Rice University, Houston, chemistry professor Richard E. Smalley and graduate students L.P. Felipe Chibante, Andreas Thess, J. Michael Alford, and Michael D. Diener used a parabolic mirror to focus sunlight on a graphite target to produce what appears to be a high yield of fullerenes. At the National Renewable Energy Laboratory (NREL), Golden, Colo., Roland R. Pitts, Mary Jane Hale, Carl Bingham, Allan Lewandowski, and David E.King, working in collaboration with Clark L. Fields, a chemistry professor at the University of Northern Colorado, Greeley, used NREL's high-flux solar furnace to produce soot that contains C[sub 60] and C[sub 70]. Papers describing the Rice and NREL results appeared together in last week's Journal of Physical Chemistry (97, 8696 and 8701 (1993)).

  5. Wall force produced during disruptions

    NASA Astrophysics Data System (ADS)

    Strauss, H.; Paccagnella, R.; Breslau, J.

    2009-11-01

    The study of disruptions is of great importance for ITER. Previous work on disruptions [1] is extended to compute toroidally asymmetric wall force in ITER, using the M3D code. The disruptions are produced by n = 1 resistive wall modes or external kink modes. A thin wall resistive boundary model is used to calculate the wall forces. The symmetric wall force, produced by a VDE, and the asymmetric wall force, produced by n = 1 modes, are comparable in magnitude. It is found that the asymmetric and axisymmetric forces scale with the growth rate of the instability multiplied by the square of the current divided by magnetic field. A similar scaling was reported for VDEs in JET [2]. Numerically, the study of disruptions is very challenging. In the M3D extended MHD code, dealiasing was applied in the toroidal direction. Advection terms were treated with a numerical upwind method. These techniques provided sufficient numerical stability to simulate entire disruption events. [4pt] [1] R. Paccagnella, H. R. Strauss, and J. Breslau, Nucl. Fusion (2009) 49 035003. [2] V. Riccardo, T. C. Hender, P. J. Lomas, et al., Plasma Phys. Control. Fusion (2004)

  6. Method for producing a tube

    DOEpatents

    Peterson, Kenneth A.; Rohde, Steven B.; Pfeifer, Kent B.; Turner, Timothy S.

    2007-01-02

    A method is described for producing tubular substrates having parallel spaced concentric rings of electrical conductors that can be used as the drift tube of an Ion Mobility Spectrometer (IMS). The invention comprises providing electrodes on the inside of a tube that are electrically connected to the outside of the tube through conductors that extend between adjacent plies of substrate that are combined to form the tube. Tubular substrates are formed from flexible polymeric printed wiring board materials, ceramic materials and material compositions of glass and ceramic, commonly known as Low Temperature Co-Fired Ceramic (LTCC). The adjacent plies are sealed together around the electrode.

  7. Producing biofuels using polyketide synthases

    DOEpatents

    Katz, Leonard; Fortman, Jeffrey L; Keasling, Jay D

    2013-04-16

    The present invention provides for a non-naturally occurring polyketide synthase (PKS) capable of synthesizing a carboxylic acid or a lactone, and a composition such that a carboxylic acid or lactone is included. The carboxylic acid or lactone, or derivative thereof, is useful as a biofuel. The present invention also provides for a recombinant nucleic acid or vector that encodes such a PKS, and host cells which also have such a recombinant nucleic acid or vector. The present invention also provides for a method of producing such carboxylic acids or lactones using such a PKS.

  8. Method for producing viscous hydrocarbons

    DOEpatents

    Poston, Robert S.

    1982-01-01

    A method for recovering viscous hydrocarbons and synthetic fuels from a subterranean formation by drilling a well bore through the formation and completing the well by cementing a casing means in the upper part of the pay zone. The well is completed as an open hole completion and a superheated thermal vapor stream comprised of steam and combustion gases is injected into the lower part of the pay zone. The combustion gases migrate to the top of the pay zone and form a gas cap which provides formation pressure to produce the viscous hydrocarbons and synthetic fuels.

  9. Method for producing mesophase pitch

    SciTech Connect

    Watanale, M.

    1985-07-16

    A method for producing a 100% mesophase composed only of Q.I. component and Q.S. component is provived. This method comprises forming mesophase by the heat treatment of petroleum-origin pitch, subjecting the heat-formed pitch to a condition of heating under quiescent state to cause only the mesophase in the heat-formed pitch to grow and coalesce, separating only the non-mesophase of the upper layer and repeating the operation of the heat treatment and maintenance of heating under a quiescent state by the separated non-mesophase, as a raw material.

  10. Method of continuously producing coke

    SciTech Connect

    Pietzka, G.; Romey, I.; Tillmanns, H.

    1980-08-26

    Continuous production of coke by pyrolysis of a hydrocarbon mixture containing petroleum tar, coal tar pitch or pyrolysis tars in which the hyrocarbon mixture and recycled condensate is heated in a preheater at a rate to increase the mesophase content of the mixture up to 30 to 60%; the preheated mixture is then heated in a coking zone at a rate to form a raw coke having a mesophase content of 70 to 100%; continuously removing the raw coke from the coking zone and heating it in a calciner. The coke produced is more uniform and the process more efficient.

  11. Fatty acid-producing hosts

    DOEpatents

    Pfleger, Brian F; Lennen, Rebecca M

    2013-12-31

    Described are hosts for overproducing a fatty acid product such as a fatty acid. The hosts include an exogenous nucleic acid encoding a thioesterase and, optionally, an exogenous nucleic acid encoding an acetyl-CoA carboxylase, wherein an acyl-CoA synthetase in the hosts are functionally delected. The hosts prefereably include the nucleic acid encoding the thioesterase at an intermediate copy number. The hosts are preferably recominantly stable and growth-competent at 37.degree. C. Methods of producing a fatty acid product comprising culturing such hosts at 37.degree. C. are also described.

  12. METHOD FOR PRODUCING THORIUM TETRACHLORIDE

    DOEpatents

    Mason, E.A.; Cobb, C.M.

    1960-03-15

    A process for producing thorium tetrachloride from thorium concentrate comprises reacting thorium concentrates with a carbonaceous reducing agent in excess of 0.05 part by weight per part of thoriferous concentrate at a temperature in excess of 1300 deg C, cooling and comminuting the mass, chlorinating the resulting comminuting mass by suspending in a gaseous chlorinating agent in a fluidized reactor at a temperatare maintained between about l85 deg C and 770 deg C, and removing the resulting solid ThCl/sub 4/ from the reaction zone.

  13. Sideways Force Produced During Disruptions

    NASA Astrophysics Data System (ADS)

    Strauss, H. R.; Paccagnella, R.; Breslau, J.; Jardin, S.; Sugiyama, L.

    2012-10-01

    We extend previous studies [1] of vertical displacement events (VDE) which can produce disruptions. The emphasis is on the non axisymmetric ``sideways'' wall force Fx. Simulations are performed using the M3D [2] code. A VDE expels magnetic flux through the resistive wall until the last closed flux surface has q < 3. At this point the plasma is unstable to an (m,n) = (2,1) mode. A theory of sideways force produced by this mode in the presence of a VDE is presented. The wall force depends strongly on γτw, where γ is the mode growth rate and τw is the wall resistive penetration time. The force Fx is largest when γτw is a constant of order unity, which depends on the initial conditions. For large values of γτw, the wall force asymptotes to a relatively smaller value, well below the critical value ITER is designed to withstand. The principle of disruption mitigation by massive gas injection is to cause a disruption with large γτw. [4pt] [1] H. R. Strauss, R. Paccagnella, and J. Breslau,Phys. Plasmas 17, 082505 (2010) [2] W. Park, E.V. Belova, G.Y. Fu, X. Tang, H.R. Strauss, L.E. Sugiyama, Phys. Plasmas 6, 1796 (1999).

  14. Thermal efficient steam producing systems

    SciTech Connect

    Fox, R.L.

    1982-01-01

    Enhanced Energy Systems Inc. manufactures compact, high-pressure combustion direct-contact steam generation systems for thermal stimulation of oil-bearing formations. The products were designed to leverage off the field experience and test information obtained under the U.S. Department of Energy Project Deep Steam. The thermal- efficient line of steam stimulation systems is the result of extensive design and testing activities aimed at modifying the technology demonstrated in the Deep Steam Project for reliable and cost effective commercial recovery operations. Specific products are produced for steam and inert gas stimulation in a wide range of reservoir conditions using either wellhead or downhole positioning of the steam generator. The steam systems utilize full electronic monitoring on all products and electronic control for downhole systems.

  15. ANTIPROTONS PRODUCED IN SUPERNOVA REMNANTS

    SciTech Connect

    Berezhko, E. G.; Ksenofontov, L. T.

    2014-08-20

    We present the energy spectrum of an antiproton cosmic ray (CR) component calculated on the basis of the nonlinear kinetic model of CR production in supernova remnants (SNRs). The model includes the reacceleration of antiprotons already existing in the interstellar medium as well as the creation of antiprotons in nuclear collisions of accelerated protons with gas nuclei and their subsequent acceleration by SNR shocks. It is shown that the production of antiprotons in SNRs produces a considerable effect in their resultant energy spectrum, making it essentially flatter above 10 GeV so that the spectrum at TeV energies increases by a factor of 5. The calculated antiproton spectrum is consistent with the PAMELA data, which correspond to energies below 100 GeV. As a consistency check, we have also calculated within the same model the energy spectra of secondary nuclei and show that the measured boron-to-carbon ratio is consistent with the significant SNR contribution.

  16. Reactor-Produced Medical Radionuclides

    SciTech Connect

    Mirzadeh, Saed; Mausner, Leonard; Garland, Marc A

    2011-01-01

    The therapeutic use of radionuclides in nuclear medicine, oncology and cardiology is the most rapidly growing use of medical radionuclides. Since most therapeutic radionuclides are neutron rich and decay by beta emission, they are reactor-produced. This chapter deals mainly with production approaches with neutrons. Neutron interactions with matter, neutron transmission and activation rates, and neutron spectra of nuclear reactors are discussed in some detail. Further, a short discussion of the neutron-energy dependence of cross sections, reaction rates in thermal reactors, cross section measurements and flux monitoring, and general equations governing the reactor production of radionuclides are presented. Finally, the chapter is concluded by providing a number of examples encompassing the various possible reaction routes for production of a number of medical radionuclides in a reactor.

  17. Laser-produced annular plasmas

    SciTech Connect

    Veloso, F.; Chuaqui, H.; Aliaga-Rossel, R.; Favre, M.; Mitchell, I. H.; Wyndham, E.

    2006-06-15

    A new technique is presented for the formation of annular plasmas on a metal surface with a high-power laser using a combination of axicon and converging lenses. The annular plasma formed on a titanium target in a chamber of hydrogen gas was investigated using schlieren imaging and Mach Zehnder interferometry. Expansion of the plasma was shown to be anisotropic with velocities of {approx}10{sup 3}-10{sup 4} m/s. Electron densities of 10{sup 18} cm{sup -3} were measured with radial profiles that confirm the presence of a hollow structure. The interferometric observations also show the presence of an inward shock wave traveling to the center of the annular plasma, which compresses the background neutrals, reaching a density around 18 times initial gas density, at 95 ns after the initial annular plasma is produced.

  18. Methods for producing secreted polypeptides

    SciTech Connect

    Maiyuran, Suchindra; Fidantsef, Ana; Brody, Howard

    2008-07-01

    The present invention relates to methods for producing a polypeptide, comprising: (a) cultivating a fungal host cell in a medium conducive for the production of the polypeptide, wherein the fungal host cell comprises a nucleic acid construct comprising a first nucleotide sequence encoding a signal peptide operably linked to a second nucleotide sequence encoding the polypeptide, wherein the first nucleotide sequence is foreign to the second nucleotide sequence and the 3' end of the first nucleotide sequence is immediately upstream of the initiator codon of the second nucleotide sequence. The present invention also relates to the isolated signal peptide sequences and to constructs, vectors, and fungal host cells comprising the signal peptide sequences operably linked to nucleotide sequences encoding polypeptides.

  19. Methods for producing secreted polypeptides

    SciTech Connect

    Maiyuran, Suchindra; Fidantsef, Ana; Brody, Howard

    2013-07-30

    The present invention relates to methods for producing a polypeptide, comprising: (a) cultivating a fungal host cell in a medium conducive for the production of the polypeptide, wherein the fungal host cell comprises a nucleic acid construct comprising a first nucleotide sequence encoding a signal peptide operably linked to a second nucleotide sequence encoding the polypeptide, wherein the first nucleotide sequence is foreign to the second nucleotide sequence and the 3' end of the first nucleotide sequence is immediately upstream of the initiator codon of the second nucleotide sequence. The present invention also relates to the isolated signal peptide sequences and to constructs, vectors, and fungal host cells comprising the signal peptide sequences operably linked to nucleotide sequences encoding polypeptides.

  20. HFIR-produced medical radioisotopes

    SciTech Connect

    Mirzadeh, S.; Knapp, F.F. Jr.; Beets, A.L.; Alexander, C.W.

    1997-12-01

    We have experimentally determined the yields of a number of medical radioisotopes produced in the Oak Ridge National Laboratory High Flux Isotope Reactor (HFIR) Hydraulic Tube (HT) facility. The HT facility is located in the very high flux region in the flux trap of the reactor, providing on-line access capability while the reactor is operating. The HT facility consists of nine vertically stacked capsules centered just adjacent to the core horizontal midplane. HFIR operates at a nominal power level of 85 MW. The capabilities of the HFIR-HT facilities offer increased efficiency, greater availability, and optimization of radioisotope production, and, as a result, the conservation of rare or expensive target isotopes.

  1. Method of producing metallic materials

    DOEpatents

    Branagan, Daniel J.

    2004-02-10

    The invention includes a method of producing a hard metallic material by forming a mixture containing at least 55% iron and at least one of B, C, Si and P. The mixture is formed into an alloy and cooled to form a metallic material having a hardness greater than about 9.2 GPa. The invention includes a method of forming a wire by combining a metal strip and a powder. The strip and the powder are rolled to form a wire containing at least 55% iron and from 2-7 additional elements including at least one of C, Si and B. The invention also includes a method of forming a hardened surface on a substrate by processing a solid mass to form a powder, applying the powder to a surface to form a layer containing metallic glass, and converting the glass to a crystalline material having a nanocrystalline grain size.

  2. R-body-producing bacteria.

    PubMed Central

    Pond, F R; Gibson, I; Lalucat, J; Quackenbush, R L

    1989-01-01

    Until 10 years ago, R bodies were known only as diagnostic features by which endosymbionts of paramecia were identified as kappa particles. They were thought to be limited to the cytoplasm of two species in the Paramecium aurelia species complex. Now, R bodies have been found in free-living bacteria and other Paramecium species. The organisms now known to form R bodies include the cytoplasmic kappa endosymbionts of P. biaurelia and P. tetraurelia, the macronuclear kappa endosymbionts of P. caudatum, Pseudomonas avenae (a free-living plant pathogen), Pseudomonas taeniospiralis (a hydrogen-oxidizing soil microorganism), Rhodospirillum centenum (a photosynthetic bacterium), and a soil bacterium, EPS-5028, which is probably a pseudomonad. R bodies themselves fall into five distinct groups, distinguished by size, the morphology of the R-body ribbons, and the unrolling behavior of wound R bodies. In recent years, the inherent difficulties in studying the organization and assembly of R bodies by the obligate endosymbiont kappa, have been alleviated by cloning and expressing genetic determinants for these R bodies (type 51) in Escherichia coli. Type 51 R-body synthesis requires three low-molecular-mass polypeptides. One of these is modified posttranslationally, giving rise to 12 polypeptide species, which are the major structural subunits of the R body. R bodies are encoded in kappa species by extrachromosomal elements. Type 51 R bodies, produced in Caedibacter taeniospiralis, are encoded by a plasmid, whereas bacteriophage genomes probably control R-body synthesis in other kappa species. However, there is no evidence that either bacteriophages or plasmids are present in P. avenae or P. taeniospiralis. No sequence homology was detected between type 51 R-body-encoding DNA and DNA from any R-body-producing species, except C. varicaedens 1038. The evolutionary relatedness of different types of R bodies remains unknown. Images PMID:2651865

  3. 7 CFR 1280.117 - Producer information.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE LAMB PROMOTION, RESEARCH, AND INFORMATION ORDER Lamb Promotion, Research, and Information Order Definitions § 1280.117 Producer information. Producer information means activities designed to provide producers, feeders, and first handlers with...

  4. 7 CFR 1280.116 - Producer.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE LAMB PROMOTION, RESEARCH, AND INFORMATION ORDER Lamb Promotion, Research, and Information Order Definitions § 1280.116 Producer. Producer means any person who owns and produces lambs in the United States for sale. ...

  5. Screening For Alcohol-Producing Microbes

    NASA Technical Reports Server (NTRS)

    Schubert, Wayne W.

    1988-01-01

    Dye reaction rapidly identifies alcohol-producing microbial colonies. Method visually detects alcohol-producing micro-organisms, and distinguishes them from other microbial colonies that do not produce alcohol. Method useful for screening mixed microbial populations in environmental samples.

  6. 7 CFR 926.7 - Producer.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... REQUIREMENTS APPLICABLE TO CRANBERRIES NOT SUBJECT TO THE CRANBERRY MARKETING ORDER § 926.7 Producer. Producer is synonymous with grower and means any person who produces cranberries for market and has a...

  7. 7 CFR 926.7 - Producer.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... REQUIREMENTS APPLICABLE TO CRANBERRIES NOT SUBJECT TO THE CRANBERRY MARKETING ORDER § 926.7 Producer. Producer is synonymous with grower and means any person who produces cranberries for market and has a...

  8. 7 CFR 926.7 - Producer.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... REQUIREMENTS APPLICABLE TO CRANBERRIES NOT SUBJECT TO THE CRANBERRY MARKETING ORDER § 926.7 Producer. Producer is synonymous with grower and means any person who produces cranberries for market and has a...

  9. 7 CFR 926.7 - Producer.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... REQUIREMENTS APPLICABLE TO CRANBERRIES NOT SUBJECT TO THE CRANBERRY MARKETING ORDER § 926.7 Producer. Producer is synonymous with grower and means any person who produces cranberries for market and has a...

  10. 7 CFR 926.7 - Producer.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... REQUIREMENTS APPLICABLE TO CRANBERRIES NOT SUBJECT TO THE CRANBERRY MARKETING ORDER § 926.7 Producer. Producer is synonymous with grower and means any person who produces cranberries for market and has a...

  11. 7 CFR 1230.615 - Producer.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PORK PROMOTION, RESEARCH, AND... Producer means a person who produces porcine animals in the United States for sale in commerce. ...

  12. 7 CFR 1230.615 - Producer.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PORK PROMOTION, RESEARCH, AND... Producer means a person who produces porcine animals in the United States for sale in commerce. ...

  13. 7 CFR 1230.615 - Producer.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PORK PROMOTION, RESEARCH, AND... Producer means a person who produces porcine animals in the United States for sale in commerce. ...

  14. 7 CFR 65.225 - Produced.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., PEANUTS, AND GINSENG General Provisions Definitions § 65.225 Produced. Produced in the case of a perishable agricultural commodity, peanuts, ginseng, pecans, and macadamia nuts means harvested....

  15. 7 CFR 65.225 - Produced.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., PEANUTS, AND GINSENG General Provisions Definitions § 65.225 Produced. Produced in the case of a perishable agricultural commodity, peanuts, ginseng, pecans, and macadamia nuts means harvested....

  16. 7 CFR 65.225 - Produced.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., PEANUTS, AND GINSENG General Provisions Definitions § 65.225 Produced. Produced in the case of a perishable agricultural commodity, peanuts, ginseng, pecans, and macadamia nuts means harvested....

  17. 7 CFR 65.225 - Produced.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., PEANUTS, AND GINSENG General Provisions Definitions § 65.225 Produced. Produced in the case of a perishable agricultural commodity, peanuts, ginseng, pecans, and macadamia nuts means harvested....

  18. 7 CFR 65.225 - Produced.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., PEANUTS, AND GINSENG General Provisions Definitions § 65.225 Produced. Produced in the case of a perishable agricultural commodity, peanuts, ginseng, pecans, and macadamia nuts means harvested....

  19. AUTOPHAGIC VACUOLES PRODUCED IN VITRO

    PubMed Central

    Fedorko, Martha E.; Hirsch, James G.; Cohn, Zanvil A.

    1968-01-01

    Continuous phase-contrast observations have been made on macrophages following exposure to chloroquine. The initial abnormality is the appearance in the Golgi region of small vacuoles with an intermediate density between that of pinosomes and granules. Over the course of 1–2 hr these vacuoles grow larger and accumulate amorphous material or lipid. Pinosomes or granules frequently fuse with the toxic vacuoles. Chloroquine derivatives can be seen by fluorescence microscopy; the drug is rapidly taken up by macrophages and localized in small foci in the Golgi region. Chloroquine continues to produce vacuoles when pinocytosis is suppressed. Electron microscopic studies of chloroquine effects on macrophages preincubated with colloidal gold to label predominately pinosomes or granules suggest that toxic vacuoles can arise from unlabeled organelles. Later vacuoles regularly acquire gold label, apparently by fusion, from both granules and pinosomes. L cells also develop autophagic vacuoles after exposure to chloroquine. Smooth endoplasmic reticulum apparently is involved early in the autophagic process in these cells. Information now available suggests an initial action of chloroquine on Golgi or smooth endoplasmic reticulum vesicles, and on granules, with alterations in their membranes leading to fusion with one another and with pinosomes. PMID:4874492

  20. Engineering microbes to produce biofuels

    SciTech Connect

    Wackett, LP

    2011-06-01

    The current biofuels landscape is chaotic. It is controlled by the rules imposed by economic forces and driven by the necessity of finding new sources of energy, particularly motor fuels. The need is bringing forth great creativity in uncovering new candidate fuel molecules that can be made via metabolic engineering. These next generation fuels include long-chain alcohols, terpenoid hydrocarbons, and diesel-length alkanes. Renewable fuels contain carbon derived from carbon dioxide. The carbon dioxide is derived directly by a photosynthetic fuel-producing organism(s) or via intermediary biomass polymers that were previously derived from carbon dioxide. To use the latter economically, biomass depolymerization processes must improve and this is a very active area of research. There are competitive approaches with some groups using enzyme based methods and others using chemical catalysts. With the former, feedstock and end-product toxicity loom as major problems. Advances chiefly rest on the ability to manipulate biological systems. Computational and modular construction approaches are key. For example, novel metabolic networks have been constructed to make long-chain alcohols and hydrocarbons that have superior fuel properties over ethanol. A particularly exciting approach is to implement a direct utilization of solar energy to make a usable fuel. A number of approaches use the components of current biological systems, but re-engineer them for more direct, efficient production of fuels.

  1. Ion produced cometary organic crust

    NASA Technical Reports Server (NTRS)

    Baratta, G. Antonio; Strazzulla, G.

    1992-01-01

    For several years many experimental results have been obtained on the chemical and physical changes induced by ion and electron irradiation of materials with a view to their Astrophysical relevance. Among the studied effects, one of particular interest is the formation of an organic refractory residue left over after ion irradiation and warming-up at room temperature. We call this residue IPHAC (ion produced hydrogenated amorphous carbon). Although 'in situ' infrared spectroscopy points out the formation of new molecular species during bombardment at low temperature, it is not clear if IPHAC is already formed or if its formation is triggered by temperature increase during warming-up of the irradiated target. Since Raman Spectroscopy is a technique particularly suitable for the analysis of carbonaceous materials, we have thought and build-up an experimental apparatus to obtain Raman Spectra of frozen hydrocarbons during ion irradiation. The present experimental results point out clearly to the formation of IPHAC already at low T and low energy deposition (approximately equal to a few eV/C-atom).

  2. Can cirrus clouds produce glories?

    PubMed

    Sassen, K; Arnott, W P; Barnett, J M; Aulenbach, S

    1998-03-20

    A vague glory display was photographed over central Utah from an airplane beginning its descent through a cirrus cloud layer with an estimated cloud top temperature of -45 and -55 degrees C. Photographic analysis reveals a single reddish-brown ring of 2.5-3.0 degrees radius around the antisolar point, although a second ring appeared visually to have been present over the brief observation period. Mie and approximate nonspherical theory scattering simulations predict a population of particles with modal diameters between 9 and 15 mum. Although it is concluded that multiple-ringed glories can be accounted for only through the backscattering of light from particles that are strictly spherical in shape, the poor glory colorization in this case could imply the presence of slightly aspherical ice particles. The location of this display over mountainous terrain suggests that it was generated by an orographic wave cloud, which we speculate produced numerous frozen cloud droplets that only gradually took on crystalline characteristics during growth.

  3. Engineering microbes to produce biofuels.

    PubMed

    Wackett, Lawrence P

    2011-06-01

    The current biofuels landscape is chaotic. It is controlled by the rules imposed by economic forces and driven by the necessity of finding new sources of energy, particularly motor fuels. The need is bringing forth great creativity in uncovering new candidate fuel molecules that can be made via metabolic engineering. These next generation fuels include long-chain alcohols, terpenoid hydrocarbons, and diesel-length alkanes. Renewable fuels contain carbon derived from carbon dioxide. The carbon dioxide is derived directly by a photosynthetic fuel-producing organism(s) or via intermediary biomass polymers that were previously derived from carbon dioxide. To use the latter economically, biomass depolymerization processes must improve and this is a very active area of research. There are competitive approaches with some groups using enzyme based methods and others using chemical catalysts. With the former, feedstock and end-product toxicity loom as major problems. Advances chiefly rest on the ability to manipulate biological systems. Computational and modular construction approaches are key. For example, novel metabolic networks have been constructed to make long-chain alcohols and hydrocarbons that have superior fuel properties over ethanol. A particularly exciting approach is to implement a direct utilization of solar energy to make a usable fuel. A number of approaches use the components of current biological systems, but re-engineer them for more direct, efficient production of fuels.

  4. Hydrodynamic Instabilities Produced by Evaporation

    NASA Astrophysics Data System (ADS)

    Romo-Cruz, Julio Cesar Ruben; Hernandez-Zapata, Sergio; Ruiz-Chavarria, Gerardo

    2012-11-01

    When a liquid layer (alcohol in the present work) is in an environment where its relative humidity is less than 100 percent evaporation appears. When RH is above a certain threshold the liquid is at rest. If RH decreases below this threshold the flow becomes unstable, and hydrodynamic cells develop. The aim of this work is to understand the formation of those cells and its main features. Firstly, we investigate how the cell size depends on the layer width. We also study how temperature depends on the vertical coordinate when the cells are present. An inverse temperature gradient is found, that is, the bottom of liquid layer is colder than the free surface. This shows that the intuitive idea that the cells are due to a direct temperature gradient, following a Marangoni-like process, does not work. We propose the hypothesis that the evaporation produce a pressure gradient that is responsible of the cell development. On the other hand, using a Schlieren technique we study the topography of the free surface when cells are present. Finally the alcohol vapor layer adjacent to the liquid surface is explored using scattering experiments, giving some insight on the plausibility of the hypothesis described previously. Authors acknowledge support by DGAPA-UNAM under project IN116312 ``Vorticidad y ondas no lineales en fluidos.''

  5. Process for producing mesophase pitch

    SciTech Connect

    Isumi, T.; Naito, T.; Igarashi, S.

    1988-11-29

    This patient describes process for producing a mesophase pitch having a mesophase content of above 90% and a softening point of below 320/sup 0/ C. comprising the steps of: heat-treating a pitch forming material at elevated temperatures above about 380/sup 0/C for a time sufficient to provide a mixture of mesophase and non-mesophase pitch containing about 20% to about 80% (by weight) of mesophase and a softening point of no greater than 250/sup 0/C; aging and settling the mesophase portion of the mixture of mesophase and non-mesophase pitch obtained in step by maintaining the mixture in a substantially quiescent condition and at a temperature below the temperature in the heat-treating step, at which temperature the mixture is sufficiently liquid so that the separation of the mesophase and non-mesophase portions of the mixture can be substantially accomplished, (and above about 350/sup 0/C) for a time sufficient for the mesophase portion of the mixture to coalesce and accumulate into a substantially lower homogeneous mesophase pitch layer containing at least 90% mesophase and an upper layer comprising the non-mesophase portion of the mixture; and separating the lower mesophase layer from the upper non-mesophase layer whereby a mesophase pitch which has a mesopphase content of above 90% and a softening point below 320/sup 0/C is obtained. heat-treated at a temperature in the range of about 380/sup 0/C to about 460/sup 0/C whereby thermal cracking and polycondensation reaction occur.

  6. Apparatus for producing alcohol fuel

    SciTech Connect

    Horst, F.E.; Krieder, R.M.

    1983-09-06

    An apparatus and method for producing alcohol fuel in an efficient and continuous manner are provided. The apparatus and method utilize otherwise lost heat to reduce the amount of heat required to convert feed stock into alcohol fuel. The apparatus and method utilize the supply of feed stock from a hopper through an auger to a cooker vessel, and then in turn to enzyme and fermenting tanks or vessels, which in turn discharge fermented mash to a strainer for separation of the alcohol beer from the mash. The beer is then discharged to a level controlled beer tank which regulates a residue valve controlling the amount of residue liquid returned to the apparatus and maintained under process. From the beer tank, the flow of the beer is regulated by passage through a non-clogging control valve into a reflux column. A single control in the form of a sensible heat detector in the reflux column operates the non-clogging control valve and simultaneously regulates both the quantity of beer supplied to the reflux column and the amount of reflux supplied thereto. The reflux column utilizes highly efficient spreader and concentrator plates therein which are supplied with reflux from the incoming beer to enhance the efficiency of the reflux column. From the reflux column, uncondensed alcohol vapors may be withdrawn and then treated with a denaturing agent before being condensed so that pottable alcohol is never formed. Additionally, heat exchangers are utilized in the apparatus and method to recapture what would otherwise be lost heat, particularly from the hot residue liquid accumulated and discharged from the reflux column, for heating the various fluids in the apparatus and under process.

  7. 7 CFR 1430.510 - New producers.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false New producers. 1430.510 Section 1430.510 Agriculture Regulations of the Department of Agriculture (Continued) COMMODITY CREDIT CORPORATION, DEPARTMENT OF....510 New producers. Notwithstanding other provisions of this subpart, producers who were new producers...

  8. 7 CFR 1430.510 - New producers.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false New producers. 1430.510 Section 1430.510 Agriculture Regulations of the Department of Agriculture (Continued) COMMODITY CREDIT CORPORATION, DEPARTMENT OF....510 New producers. Notwithstanding other provisions of this subpart, producers who were new producers...

  9. 7 CFR 1430.510 - New producers.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false New producers. 1430.510 Section 1430.510 Agriculture Regulations of the Department of Agriculture (Continued) COMMODITY CREDIT CORPORATION, DEPARTMENT OF....510 New producers. Notwithstanding other provisions of this subpart, producers who were new producers...

  10. 7 CFR 1430.510 - New producers.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false New producers. 1430.510 Section 1430.510 Agriculture Regulations of the Department of Agriculture (Continued) COMMODITY CREDIT CORPORATION, DEPARTMENT OF....510 New producers. Notwithstanding other provisions of this subpart, producers who were new producers...

  11. 7 CFR 1430.510 - New producers.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false New producers. 1430.510 Section 1430.510 Agriculture Regulations of the Department of Agriculture (Continued) COMMODITY CREDIT CORPORATION, DEPARTMENT OF....510 New producers. Notwithstanding other provisions of this subpart, producers who were new producers...

  12. 7 CFR 1032.12 - Producer.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 9 2014-01-01 2013-01-01 true Producer. 1032.12 Section 1032.12 Agriculture... Handling Definitions § 1032.12 Producer. (a) Except as provided in paragraph (b) of this section, producer... from the producer or diverted by the plant operator in accordance with § 1032.13; or (2) Received by...

  13. 7 CFR 1032.12 - Producer.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 9 2010-01-01 2009-01-01 true Producer. 1032.12 Section 1032.12 Agriculture... Handling Definitions § 1032.12 Producer. (a) Except as provided in paragraph (b) of this section, producer... from the producer or diverted by the plant operator in accordance with § 1032.13; or (2) Received by...

  14. 7 CFR 1032.12 - Producer.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 9 2013-01-01 2013-01-01 false Producer. 1032.12 Section 1032.12 Agriculture... Handling Definitions § 1032.12 Producer. (a) Except as provided in paragraph (b) of this section, producer... from the producer or diverted by the plant operator in accordance with § 1032.13; or (2) Received by...

  15. 7 CFR 1032.12 - Producer.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 9 2011-01-01 2011-01-01 false Producer. 1032.12 Section 1032.12 Agriculture... Handling Definitions § 1032.12 Producer. (a) Except as provided in paragraph (b) of this section, producer... from the producer or diverted by the plant operator in accordance with § 1032.13; or (2) Received by...

  16. 7 CFR 1032.12 - Producer.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 9 2012-01-01 2012-01-01 false Producer. 1032.12 Section 1032.12 Agriculture... Handling Definitions § 1032.12 Producer. (a) Except as provided in paragraph (b) of this section, producer... from the producer or diverted by the plant operator in accordance with § 1032.13; or (2) Received by...

  17. Framework for Producing Ecological Nowcasts

    NASA Astrophysics Data System (ADS)

    Votava, P.; Nemani, R. R.; Michaelis, A.; Milesi, C.; Hashimoto, H.; Ichii, K.; Melton, F.

    2007-12-01

    TOPS is a data and modeling software system designed to seamlessly integrate data from satellite, aircraft and ground sensors, and weather/climate models with application models to quickly and reliably produce operational nowcasts and forecasts of ecological conditions. Through automation of the data retrieval, pre-processing, integration, and modeling steps, TOPS is able to reliably provide data on current and predicted ecosystem conditions, allowing TOPS data products to be used in an operational setting for a range of applications. The core of the system is located and maintained by the Ecocast group at NASA Ames Research Center. We have develop a layered approach where at the lowest level the system interacts with the numerous data providers such as the Distributed Active Archive Centers (DAAC), the National Center for Environmental Predictions (NCEP), the National Weather Service (NWS), NOAA, and others. This subsystem is fully autonomous, gathering data through periodic query to the requesting centers sometimes as often as every 15-minutes. Subsets of our input datasets are also available by subscriptions and are being pushed to us as they become available (Oregon State University direct broadcast feed is an example of such interaction). When the data are obtained, they are archived in the database and then further processed to fit the application needs. Due to significant differences in climate and satellite data processing, we have two separate subsystems to accomplish the task. On the climate side, we merge ground station data with model data and grid these to required resolution together with generation of basic statistics and QA/QC information. The satellite processing subsystem performs spatial data tiling and subsetting, as well as composition of data sets based on the QA/QC information supplied, in order to obtain the highest quality inputs. After the climate and satellite data are processed, they are inserted into a database. The model framework

  18. Melatonin analgesia is associated with improvement of the descending endogenous pain-modulating system in fibromyalgia: a phase II, randomized, double-dummy, controlled trial

    PubMed Central

    2014-01-01

    ). Conclusion Melatonin increased the inhibitory endogenous pain-modulating system as assessed by the reduction on NPS(0-10) during the CPM-TASK. Melatonin alone or associated with amitriptyline was better than amitriptyline alone in improving pain on the VAS, whereas its association with amitriptyline produced only marginal additional clinical effects on FIQ and PPT. Trial registration Current controlled trail is registered at clinical trials.gov upon under number NCT02041455. Registered January 16, 2014. PMID:25052847

  19. 7 CFR 1205.309 - Producer.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE COTTON RESEARCH AND PROMOTION Cotton Research and Promotion Order Definitions § 1205.309 Producer. Producer means any person who shares in a...

  20. PRODUCING ENERGY AND RADIOACTIVE FISSION PRODUCTS

    DOEpatents

    Segre, E.; Kennedy, J.W.; Seaborg, G.T.

    1959-10-13

    This patent broadly discloses the production of plutonium by the neutron bombardment of uranium to produce neptunium which decays to plutonium, and the fissionability of plutonium by neutrons, both fast and thermal, to produce energy and fission products.

  1. 7 CFR 1205.309 - Producer.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE COTTON RESEARCH AND PROMOTION Cotton Research and Promotion Order Definitions § 1205.309 Producer. Producer means any person who shares in a...

  2. 7 CFR 946.8 - Producer.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE IRISH POTATOES GROWN IN WASHINGTON Order Regulating Handling Definitions § 946.8 Producer. Producer means any person engaged in the production...

  3. 7 CFR 946.8 - Producer.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE IRISH POTATOES GROWN IN WASHINGTON Order Regulating Handling Definitions § 946.8 Producer. Producer means any person engaged in the production...

  4. Process for producing synthesis gas from wood

    SciTech Connect

    Curran, G.P.; Lancet, M.S.

    1982-06-15

    In a process for producing synthesis gas by reacting a solid carbonaceous fuel with water in the presence of a carbon dioxide acceptor to produce a synthesis gas rich in hydrogen with at least a portion of the carbon dioxide so produced being reacted with the carbon dioxide acceptor to produce calcium carbonate and to provide sufficient heat to maintain a desired reaction temperature, an improvement comprising; the use of finely-divided wood as the solid carbonaceous fuel.

  5. 7 CFR 1219.20 - Producer.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE HASS AVOCADO PROMOTION, RESEARCH, AND INFORMATION Hass Avocado Promotion, Research, and Information Order Definitions § 1219.20 Producer. Producer means any person who is engaged in the business of producing Hass avocados in the United...

  6. 7 CFR 1219.20 - Producer.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE HASS AVOCADO PROMOTION, RESEARCH, AND INFORMATION Hass Avocado Promotion, Research, and Information Order Definitions § 1219.20 Producer. Producer means any person who is engaged in the business of producing Hass avocados in the United...

  7. 7 CFR 1219.20 - Producer.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE HASS AVOCADO PROMOTION, RESEARCH, AND INFORMATION Hass Avocado Promotion, Research, and Information Order Definitions § 1219.20 Producer. Producer means any person who is engaged in the business of producing Hass avocados in the United...

  8. 7 CFR 1219.20 - Producer.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE HASS AVOCADO PROMOTION, RESEARCH, AND INFORMATION Hass Avocado Promotion, Research, and Information Order Definitions § 1219.20 Producer. Producer means any person who is engaged in the business of producing Hass avocados in the United...

  9. 7 CFR 1219.20 - Producer.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE HASS AVOCADO PROMOTION, RESEARCH, AND INFORMATION Hass Avocado Promotion, Research, and Information Order Definitions § 1219.20 Producer. Producer means any person who is engaged in the business of producing Hass avocados in the United...

  10. 7 CFR 1230.21 - Producer.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PORK PROMOTION, RESEARCH, AND CONSUMER INFORMATION Pork Promotion, Research, and Consumer Information Order Definitions § 1230.21 Producer. Producer means a person who produces porcine animals in the United States for sale in commerce. ...

  11. 7 CFR 1230.21 - Producer.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PORK PROMOTION, RESEARCH, AND CONSUMER INFORMATION Pork Promotion, Research, and Consumer Information Order Definitions § 1230.21 Producer. Producer means a person who produces porcine animals in the United States for sale in commerce. ...

  12. 7 CFR 1230.21 - Producer.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PORK PROMOTION, RESEARCH, AND CONSUMER INFORMATION Pork Promotion, Research, and Consumer Information Order Definitions § 1230.21 Producer. Producer means a person who produces porcine animals in the United States for sale in commerce. ...

  13. MANPOWER AND THE GROWTH OF PRODUCER SERVICES.

    ERIC Educational Resources Information Center

    GREENFIELD, HARRY I.

    PRODUCER SERVICES, THOSE SERVICES WHICH BUSINESS FIRMS, NONPROFIT INSTITUTIONS, AND GOVERNMENTS PROVIDE AND USUALLY SELL TO THE PRODUCER RATHER THAN TO THE CONSUMER, AND THE FACTORS AFFECTING THEIR SUPPLY AND DEMAND ARE ANALYZED. APPROXIMATELY 8.5 MILLION WORKERS, OR ABOUT 13 PERCENT OF THE TOTAL, ARE EMPLOYED IN PRODUCER SERVICES. DURING THE…

  14. 7 CFR 1131.13 - Producer milk.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 9 2010-01-01 2009-01-01 true Producer milk. 1131.13 Section 1131.13 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE ARIZONA MARKETING AREA Order Regulating Handling Definitions § 1131.13 Producer milk. Producer milk means the skim milk (or the skim equivalent...

  15. 7 CFR 1006.13 - Producer milk.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 9 2010-01-01 2009-01-01 true Producer milk. 1006.13 Section 1006.13 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE FLORIDA MARKETING AREA Order Regulating Handling Definitions § 1006.13 Producer milk. Producer milk means the skim milk (or the skim equivalent...

  16. 7 CFR 1126.13 - Producer milk.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 9 2010-01-01 2009-01-01 true Producer milk. 1126.13 Section 1126.13 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE SOUTHWEST MARKETING AREA Order Regulating Handling Definitions § 1126.13 Producer milk. Producer milk means the skim milk (or the skim equivalent...

  17. 7 CFR 1033.13 - Producer milk.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 9 2010-01-01 2009-01-01 true Producer milk. 1033.13 Section 1033.13 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE MIDEAST MARKETING AREA Order Regulating Handling Definitions § 1033.13 Producer milk. Producer milk means the skim milk (or the skim equivalent...

  18. 7 CFR 1032.13 - Producer milk.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 9 2010-01-01 2009-01-01 true Producer milk. 1032.13 Section 1032.13 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE CENTRAL MARKETING AREA Order Regulating Handling Definitions § 1032.13 Producer milk. Producer milk means the skim milk (or the skim equivalent...

  19. 7 CFR 1001.13 - Producer milk.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 9 2010-01-01 2009-01-01 true Producer milk. 1001.13 Section 1001.13 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE NORTHEAST MARKETING AREA Order Regulating Handling Definitions § 1001.13 Producer milk. Producer milk means the skim milk (or the skim equivalent...

  20. 7 CFR 1434.4 - Eligible producer.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... FOR HONEY § 1434.4 Eligible producer. (a) To be eligible to receive an individual or joint loan or loan deficiency payments under this part, a person must: (1) Have produced honey in the United States... calendar year; (2) Be responsible for the risk of keeping the bees and producing honey; (3) Have...

  1. 7 CFR 1434.4 - Eligible producer.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... FOR HONEY § 1434.4 Eligible producer. (a) To be eligible to receive an individual or joint loan or loan deficiency payments under this part, a person must: (1) Have produced honey in the United States... calendar year; (2) Be responsible for the risk of keeping the bees and producing honey; (3) Have...

  2. 7 CFR 1434.4 - Eligible producer.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... FOR HONEY § 1434.4 Eligible producer. (a) To be eligible to receive an individual or joint loan or loan deficiency payments under this part, a person must: (1) Have produced honey in the United States... calendar year; (2) Be responsible for the risk of keeping the bees and producing honey; (3) Have...

  3. 29 CFR 780.213 - Produce business.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 3 2014-07-01 2014-07-01 false Produce business. 780.213 Section 780.213 Labor Regulations... Specific Situations Hatchery Operations § 780.213 Produce business. In some instances, hatcheries also engage in the produce business as such and commingle with the culled eggs and chickens other eggs...

  4. 29 CFR 780.213 - Produce business.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 3 2011-07-01 2011-07-01 false Produce business. 780.213 Section 780.213 Labor Regulations... Specific Situations Hatchery Operations § 780.213 Produce business. In some instances, hatcheries also engage in the produce business as such and commingle with the culled eggs and chickens other eggs...

  5. 29 CFR 780.213 - Produce business.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 3 2013-07-01 2013-07-01 false Produce business. 780.213 Section 780.213 Labor Regulations... Specific Situations Hatchery Operations § 780.213 Produce business. In some instances, hatcheries also engage in the produce business as such and commingle with the culled eggs and chickens other eggs...

  6. 29 CFR 780.213 - Produce business.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Produce business. 780.213 Section 780.213 Labor Regulations... Specific Situations Hatchery Operations § 780.213 Produce business. In some instances, hatcheries also engage in the produce business as such and commingle with the culled eggs and chickens other eggs...

  7. 29 CFR 780.213 - Produce business.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 3 2012-07-01 2012-07-01 false Produce business. 780.213 Section 780.213 Labor Regulations... Specific Situations Hatchery Operations § 780.213 Produce business. In some instances, hatcheries also engage in the produce business as such and commingle with the culled eggs and chickens other eggs...

  8. 7 CFR 987.7 - Producer.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Producer. 987.7 Section 987.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... RIVERSIDE COUNTY, CALIFORNIA Order Regulating Handling Definitions § 987.7 Producer. Producer is...

  9. 7 CFR 925.7 - Producer.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Producer. 925.7 Section 925.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... SOUTHEASTERN CALIFORNIA Definitions § 925.7 Producer. Producer is synonymous with grower and means any...

  10. 7 CFR 1280.122 - Seedstock producer.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE LAMB PROMOTION, RESEARCH, AND INFORMATION ORDER Lamb Promotion, Research, and Information Order Definitions § 1280.122 Seedstock producer. Seedstock producer means any lamb producer in the U.S. who engages in the production and sale of breeding...

  11. 9 CFR 114.16 - Producing subsidiaries.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Producing subsidiaries. 114.16 Section... BIOLOGICAL PRODUCTS § 114.16 Producing subsidiaries. A serial or subserial of a biological product may be produced jointly by a licensee and one or more subsidiaries, or by two or more subsidiaries. The...

  12. 7 CFR 1427.4 - Eligible producer.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... deficiency payment documents are signed by the guardian; (3) Any note and security agreement or loan... producer executes a note and security agreement with CCC, each such producer shall be jointly and severally... such producer shall also remain liable for repayment of the entire marketing assistance loan...

  13. 7 CFR 1434.4 - Eligible producer.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... FOR HONEY § 1434.4 Eligible producer. (a) To be eligible to receive an individual or joint loan or loan deficiency payments under this part, a person must: (1) Have produced honey in the United States... calendar year; (2) Be responsible for the risk of keeping the bees and producing honey; (3) Have a...

  14. 7 CFR 1434.4 - Eligible producer.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... FOR HONEY § 1434.4 Eligible producer. (a) To be eligible to receive an individual or joint loan or loan deficiency payments under this part, a person must: (1) Have produced honey in the United States... calendar year; (2) Be responsible for the risk of keeping the bees and producing honey; (3) Have a...

  15. 7 CFR 1131.13 - Producer milk.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 9 2013-01-01 2013-01-01 false Producer milk. 1131.13 Section 1131.13 Agriculture... AND ORDERS; MILK), DEPARTMENT OF AGRICULTURE MILK IN THE ARIZONA MARKETING AREA Order Regulating Handling Definitions § 1131.13 Producer milk. Producer milk means the skim milk (or the skim equivalent of...

  16. 7 CFR 1006.13 - Producer milk.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 9 2014-01-01 2013-01-01 true Producer milk. 1006.13 Section 1006.13 Agriculture... AND ORDERS; MILK), DEPARTMENT OF AGRICULTURE MILK IN THE FLORIDA MARKETING AREA Order Regulating Handling Definitions § 1006.13 Producer milk. Producer milk means the skim milk (or the skim equivalent of...

  17. 7 CFR 1126.13 - Producer milk.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 9 2014-01-01 2013-01-01 true Producer milk. 1126.13 Section 1126.13 Agriculture... AND ORDERS; MILK), DEPARTMENT OF AGRICULTURE MILK IN THE SOUTHWEST MARKETING AREA Order Regulating Handling Definitions § 1126.13 Producer milk. Producer milk means the skim milk (or the skim equivalent of...

  18. 7 CFR 1001.13 - Producer milk.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 9 2014-01-01 2013-01-01 true Producer milk. 1001.13 Section 1001.13 Agriculture... AND ORDERS; MILK), DEPARTMENT OF AGRICULTURE MILK IN THE NORTHEAST MARKETING AREA Order Regulating Handling Definitions § 1001.13 Producer milk. Producer milk means the skim milk (or the skim equivalent of...

  19. 7 CFR 1131.13 - Producer milk.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 9 2014-01-01 2013-01-01 true Producer milk. 1131.13 Section 1131.13 Agriculture... AND ORDERS; MILK), DEPARTMENT OF AGRICULTURE MILK IN THE ARIZONA MARKETING AREA Order Regulating Handling Definitions § 1131.13 Producer milk. Producer milk means the skim milk (or the skim equivalent of...

  20. 7 CFR 1033.13 - Producer milk.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 9 2014-01-01 2013-01-01 true Producer milk. 1033.13 Section 1033.13 Agriculture... AND ORDERS; MILK), DEPARTMENT OF AGRICULTURE MILK IN THE MIDEAST MARKETING AREA Order Regulating Handling Definitions § 1033.13 Producer milk. Producer milk means the skim milk (or the skim equivalent of...

  1. 7 CFR 1032.13 - Producer milk.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 9 2014-01-01 2013-01-01 true Producer milk. 1032.13 Section 1032.13 Agriculture... AND ORDERS; MILK), DEPARTMENT OF AGRICULTURE MILK IN THE CENTRAL MARKETING AREA Order Regulating Handling Definitions § 1032.13 Producer milk. Producer milk means the skim milk (or the skim equivalent of...

  2. 7 CFR 1033.13 - Producer milk.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 9 2013-01-01 2013-01-01 false Producer milk. 1033.13 Section 1033.13 Agriculture... AND ORDERS; MILK), DEPARTMENT OF AGRICULTURE MILK IN THE MIDEAST MARKETING AREA Order Regulating Handling Definitions § 1033.13 Producer milk. Producer milk means the skim milk (or the skim equivalent of...

  3. 7 CFR 1001.13 - Producer milk.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 9 2012-01-01 2012-01-01 false Producer milk. 1001.13 Section 1001.13 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE NORTHEAST MARKETING AREA Order Regulating Handling Definitions § 1001.13 Producer milk. Producer milk means the skim milk (or the skim equivalent of...

  4. 7 CFR 1006.13 - Producer milk.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 9 2013-01-01 2013-01-01 false Producer milk. 1006.13 Section 1006.13 Agriculture... AND ORDERS; MILK), DEPARTMENT OF AGRICULTURE MILK IN THE FLORIDA MARKETING AREA Order Regulating Handling Definitions § 1006.13 Producer milk. Producer milk means the skim milk (or the skim equivalent of...

  5. 7 CFR 1033.13 - Producer milk.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 9 2012-01-01 2012-01-01 false Producer milk. 1033.13 Section 1033.13 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE MIDEAST MARKETING AREA Order Regulating Handling Definitions § 1033.13 Producer milk. Producer milk means the skim milk (or the skim equivalent of...

  6. 7 CFR 1032.13 - Producer milk.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 9 2013-01-01 2013-01-01 false Producer milk. 1032.13 Section 1032.13 Agriculture... AND ORDERS; MILK), DEPARTMENT OF AGRICULTURE MILK IN THE CENTRAL MARKETING AREA Order Regulating Handling Definitions § 1032.13 Producer milk. Producer milk means the skim milk (or the skim equivalent of...

  7. 7 CFR 1126.13 - Producer milk.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 9 2012-01-01 2012-01-01 false Producer milk. 1126.13 Section 1126.13 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE SOUTHWEST MARKETING AREA Order Regulating Handling Definitions § 1126.13 Producer milk. Producer milk means the skim milk (or the skim equivalent of...

  8. 7 CFR 1131.13 - Producer milk.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 9 2012-01-01 2012-01-01 false Producer milk. 1131.13 Section 1131.13 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE ARIZONA MARKETING AREA Order Regulating Handling Definitions § 1131.13 Producer milk. Producer milk means the skim milk (or the skim equivalent of...

  9. 7 CFR 1006.13 - Producer milk.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 9 2012-01-01 2012-01-01 false Producer milk. 1006.13 Section 1006.13 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE FLORIDA MARKETING AREA Order Regulating Handling Definitions § 1006.13 Producer milk. Producer milk means the skim milk (or the skim equivalent of...

  10. 7 CFR 1032.13 - Producer milk.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 9 2012-01-01 2012-01-01 false Producer milk. 1032.13 Section 1032.13 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE CENTRAL MARKETING AREA Order Regulating Handling Definitions § 1032.13 Producer milk. Producer milk means the skim milk (or the skim equivalent of...

  11. 7 CFR 1126.13 - Producer milk.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 9 2013-01-01 2013-01-01 false Producer milk. 1126.13 Section 1126.13 Agriculture... AND ORDERS; MILK), DEPARTMENT OF AGRICULTURE MILK IN THE SOUTHWEST MARKETING AREA Order Regulating Handling Definitions § 1126.13 Producer milk. Producer milk means the skim milk (or the skim equivalent of...

  12. 7 CFR 1001.13 - Producer milk.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 9 2013-01-01 2013-01-01 false Producer milk. 1001.13 Section 1001.13 Agriculture... AND ORDERS; MILK), DEPARTMENT OF AGRICULTURE MILK IN THE NORTHEAST MARKETING AREA Order Regulating Handling Definitions § 1001.13 Producer milk. Producer milk means the skim milk (or the skim equivalent of...

  13. 7 CFR 1032.13 - Producer milk.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 9 2011-01-01 2011-01-01 false Producer milk. 1032.13 Section 1032.13 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE CENTRAL MARKETING AREA Order Regulating Handling Definitions § 1032.13 Producer milk. Producer milk means the skim milk (or the skim equivalent...

  14. 7 CFR 1033.13 - Producer milk.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 9 2011-01-01 2011-01-01 false Producer milk. 1033.13 Section 1033.13 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE MIDEAST MARKETING AREA Order Regulating Handling Definitions § 1033.13 Producer milk. Producer milk means the skim milk (or the skim equivalent...

  15. 7 CFR 1001.13 - Producer milk.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 9 2011-01-01 2011-01-01 false Producer milk. 1001.13 Section 1001.13 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE NORTHEAST MARKETING AREA Order Regulating Handling Definitions § 1001.13 Producer milk. Producer milk means the skim milk (or the skim equivalent...

  16. 7 CFR 1131.13 - Producer milk.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 9 2011-01-01 2011-01-01 false Producer milk. 1131.13 Section 1131.13 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE ARIZONA MARKETING AREA Order Regulating Handling Definitions § 1131.13 Producer milk. Producer milk means the skim milk (or the skim equivalent...

  17. 7 CFR 1126.13 - Producer milk.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 9 2011-01-01 2011-01-01 false Producer milk. 1126.13 Section 1126.13 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE SOUTHWEST MARKETING AREA Order Regulating Handling Definitions § 1126.13 Producer milk. Producer milk means the skim milk (or the skim equivalent...

  18. 7 CFR 1006.13 - Producer milk.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 9 2011-01-01 2011-01-01 false Producer milk. 1006.13 Section 1006.13 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE FLORIDA MARKETING AREA Order Regulating Handling Definitions § 1006.13 Producer milk. Producer milk means the skim milk (or the skim equivalent...

  19. Process for producing ethanol from syngas

    SciTech Connect

    Krause, Theodore R; Rathke, Jerome W; Chen, Michael J

    2013-05-14

    The invention provides a method for producing ethanol, the method comprising establishing an atmosphere containing methanol forming catalyst and ethanol forming catalyst; injecting syngas into the atmosphere at a temperature and for a time sufficient to produce methanol; and contacting the produced methanol with additional syngas at a temperature and for a time sufficient to produce ethanol. The invention also provides an integrated system for producing methanol and ethanol from syngas, the system comprising an atmosphere isolated from the ambient environment; a first catalyst to produce methanol from syngas wherein the first catalyst resides in the atmosphere; a second catalyst to product ethanol from methanol and syngas, wherein the second catalyst resides in the atmosphere; a conduit for introducing syngas to the atmosphere; and a device for removing ethanol from the atmosphere. The exothermicity of the method and system obviates the need for input of additional heat from outside the atmosphere.

  20. Inventory transparency for agricultural produce through IOT

    NASA Astrophysics Data System (ADS)

    Srinivasan, S. P.; Sorna Shanthi, D.; Anand, Aashish V.

    2017-06-01

    Re-structuring the practices of traditional inventory management is becoming more essential to optimize the supply chain transparency and accuracy of agricultural produce. A flexible and transparent inventory management system is becoming the need of any agricultural commodity. It was noticed that the major setback for the farmers who are the suppliers of the farm produce is due to poor supply chain integration. The recent advent technologies and IT explosion can bring up a greater impact in the process of storing, tracking, distributing and monitoring perishable agriculture produce of day to day life. The primary focus of this paper is to integrate IoT into inventory management and other inbound logistics management of agriculture produce. The unique features of agricultural produce like a prediction of supply, demand, the location of warehouses, distribution and tracking of inventory can be integrated through IoT. This paper proposes a conceptual framework for inventory management transparency involved in the supply chain of agriculture produce.

  1. Method for producing oxygen from lunar materials

    NASA Technical Reports Server (NTRS)

    Sullivan, Thomas A. (Inventor)

    1993-01-01

    This invention is related to producing oxygen from lunar or Martian materials, particularly from lunar ilmenite in situ. The process includes producing a slurry of the minerals and hot sulfuric acid, the acid and minerals reacting to form sulfates of the metal. Water is added to the slurry to dissolve the minerals into an aqueous solution, the first aqueous solution is separated from unreacted minerals from the slurry, and the aqueous solution is electrolyzed to produce the metal and oxygen.

  2. The Alga Ochromonas danica Produces Bromosulfolipids.

    PubMed

    White, Alexander R; Duggan, Brendan M; Tsai, Shiou-Chuan; Vanderwal, Christopher D

    2016-03-04

    Many halogenases interchangeably incorporate chlorine and bromine into organic molecules. On the basis of an unsubstantiated report that the alga Ochromonas danica, a prodigious producer of chlorosulfolipids, was able to produce bromosulfolipids, we have investigated the promiscuity of its halogenases toward bromine incorporation. We have found that bromosulfolipids are produced with the exact positional and stereochemical selectivity as in the chlorosulfolipid danicalipin A when this alga is grown under modified conditions containing excess bromide ion.

  3. Two marine Agrobacterium producers of sesbanimide antibiotics.

    PubMed

    Acebal, C; Alcazar, R; Cañedo, L M; de la Calle, F; Rodriguez, P; Romero, F; Fernandez Puentes, J L

    1998-01-01

    Sesbanimides are cytotoxic compounds, originally isolated in 1983 from seeds of the leguminous plants Sesbania drummondii and Sesbania punicea. In this paper we describe the bacterial production of sesbanimides by two "marine Agrobacterium"; strain PH-103 which produces Sesbanimide-A and strain PH-A034C which produces Sesbanimide-C. The isolation and taxonomy of the producing microorganisms, fermentation and isolation of sesbanimides are reported.

  4. Imported PER-1 producing Pseudomonas aeruginosa, PER-1 producing Acinetobacter baumanii and VIM-2-producing Pseudomonas aeruginosa strains in Hungary

    PubMed Central

    Szabó, Dora; Szentandrássy, Julia; Juhász, Zsuzsa; Katona, Katalin; Nagy, Károly; Rókusz, László

    2008-01-01

    Introduction Pseudomonas aeruginosa and Acinetobacter baumanii are important nosocomial pathogens with wide intrinsic resistance. However, due to the dissemination of the acquired resistance mechanisms, such as extended-spectrum beta-lactamase (ESBL) and metallo beta-lactamase (MBL) production, multidrug resistant strains have been isolated more often. Case presentation We report a case of a Hungarian tourist, who was initially hospitalized in Egypt and later transferred to Hungary. On the day of admission PER-1-producing P. aeruginosa, PER-1 producing A. baumannii, SHV-5-producing Klebsiella pneumoniae and VIM-2-producing P. aeruginosa isolates were subcultured from the patient's samples in Hungary. Comparing the pulsed-field gel electrophoresis (PFGE) patterns of the P. aeruginosa strains from the patient to the P. aeruginosa strains occurring in this hospital, we can state that the PER-1-producing P. aeruginosa and VIM-2-producing P. aeruginosa had external origin. Conclusion This is the first report of PER-1-producing P. aeruginosa,and PER-1-producing A. baumanii strains in Hungary. This case highlights the importance of spreading of the beta-lactamase-mediated resistance mechanisms between countries and continents, showing the importance of careful screening and the isolation of patients arriving from a different country. PMID:18513394

  5. 7 CFR 996.16 - Producer.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE MINIMUM QUALITY AND HANDLING.... Producer means any person in the United States engaged in a proprietary capacity in the production...

  6. Stable, fertile, high polyhydroxyalkanoate producing plants and methods of producing them

    DOEpatents

    Bohmert-Tatarev, Karen; McAvoy, Susan; Peoples, Oliver P.; Snell, Kristi D.

    2015-08-04

    Transgenic plants that produce high levels of polyhydroxybutyrate and methods of producing them are provided. In a preferred embodiment the transgenic plants are produced using plastid transformation technologies and utilize genes which are codon optimized. Stably transformed plants able to produce greater than 10% dwt PHS in tissues are also provided.

  7. 7 CFR 1206.16 - Producer.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MANGO PROMOTION, RESEARCH, AND INFORMATION Mango Promotion, Research, and Information Order Definitions § 1206.16 Producer. Producer means any person who is engaged in the production and sale of mangos in the United States and who owns,...

  8. 7 CFR 1206.8 - Foreign producer.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MANGO PROMOTION, RESEARCH, AND INFORMATION Mango Promotion, Research, and Information Order Definitions § 1206.8 Foreign producer. Foreign producer means any person: (1) Who is engaged in the production and sale of mangos outside of the...

  9. 7 CFR 1206.16 - Producer.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MANGO PROMOTION, RESEARCH, AND INFORMATION Mango Promotion, Research, and Information Order Definitions § 1206.16 Producer. Producer means any person who is engaged in the production and sale of mangos in the United States and who owns,...

  10. 7 CFR 1206.16 - Producer.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MANGO PROMOTION, RESEARCH, AND INFORMATION Mango Promotion, Research, and Information Order Definitions § 1206.16 Producer. Producer means any person who is engaged in the production and sale of mangos in the United States and who owns,...

  11. 7 CFR 1206.8 - Foreign producer.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MANGO PROMOTION, RESEARCH, AND INFORMATION Mango Promotion, Research, and Information Order Definitions § 1206.8 Foreign producer. Foreign producer means any person: (1) Who is engaged in the production and sale of mangos outside of the...

  12. 7 CFR 1206.8 - Foreign producer.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MANGO PROMOTION, RESEARCH, AND INFORMATION Mango Promotion, Research, and Information Order Definitions § 1206.8 Foreign producer. Foreign producer means any person: (1) Who is engaged in the production and sale of mangos outside of the...

  13. 7 CFR 1206.8 - Foreign producer.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MANGO PROMOTION, RESEARCH, AND INFORMATION Mango Promotion, Research, and Information Order Definitions § 1206.8 Foreign producer. Foreign producer means any person: (1) Who is engaged in the production and sale of mangos outside of the...

  14. 7 CFR 1206.16 - Producer.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MANGO PROMOTION, RESEARCH, AND INFORMATION Mango Promotion, Research, and Information Order Definitions § 1206.16 Producer. Producer means any person who is engaged in the production and sale of mangos in the United States and who owns,...

  15. 7 CFR 1206.16 - Producer.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MANGO PROMOTION, RESEARCH, AND INFORMATION Mango Promotion, Research, and Information Order Definitions § 1206.16 Producer. Producer means any person who is engaged in the production and sale of mangos in the United States and who owns,...

  16. 7 CFR 1206.8 - Foreign producer.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MANGO PROMOTION, RESEARCH, AND INFORMATION Mango Promotion, Research, and Information Order Definitions § 1206.8 Foreign producer. Foreign producer means any person: (1) Who is engaged in the production and sale of mangos outside of the...

  17. 7 CFR 1124.13 - Producer milk.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 9 2010-01-01 2009-01-01 true Producer milk. 1124.13 Section 1124.13 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE PACIFIC NORTHWEST MARKETING AREA Order Regulating Handling Definitions § 1124.13 Producer milk. Except as provided for in paragraph (f) of...

  18. 7 CFR 1005.13 - Producer milk.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 9 2010-01-01 2009-01-01 true Producer milk. 1005.13 Section 1005.13 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE APPALACHIAN MARKETING AREA Order Regulating Handling Definitions § 1005.13 Producer milk. Except as provided for in paragraph (e) of this...

  19. 7 CFR 1030.13 - Producer milk.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 9 2010-01-01 2009-01-01 true Producer milk. 1030.13 Section 1030.13 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE UPPER MIDWEST MARKETING AREA Order Regulating Handling Definitions § 1030.13 Producer milk. Except as provided for in paragraph (e) of this...

  20. 7 CFR 1007.13 - Producer milk.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 9 2010-01-01 2009-01-01 true Producer milk. 1007.13 Section 1007.13 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE SOUTHEAST MARKETING AREA Order Regulating Handling Definitions § 1007.13 Producer milk. Except as provided for in paragraph (e) of this...

  1. 7 CFR 1210.306 - Producer.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Definitions § 1210.306 Producer. Producer means any person engaged in the growing of 10 acres or more of watermelons including any person who owns or shares the...

  2. 7 CFR 1210.306 - Producer.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Definitions § 1210.306 Producer. Producer means any person engaged in the growing of 10 acres or more of watermelons including any person who owns or shares the...

  3. 7 CFR 1210.306 - Producer.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Definitions § 1210.306 Producer. Producer means any person engaged in the growing of 10 acres or more of watermelons including any person who owns or shares the...

  4. 7 CFR 1218.16 - Producer.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BLUEBERRY PROMOTION, RESEARCH, AND INFORMATION ORDER Blueberry Promotion, Research, and Information Order Definitions § 1218.16 Producer. Producer means any person who grows blueberries in the United States for sale in commerce, or a person...

  5. 7 CFR 1218.16 - Producer.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BLUEBERRY PROMOTION, RESEARCH, AND INFORMATION ORDER Blueberry Promotion, Research, and Information Order Definitions § 1218.16 Producer. Producer means any person who grows blueberries in the United States for sale in commerce, or a person...

  6. 7 CFR 1218.16 - Producer.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BLUEBERRY PROMOTION, RESEARCH, AND INFORMATION ORDER Blueberry Promotion, Research, and Information Order Definitions § 1218.16 Producer. Producer means any person who grows blueberries in the United States for sale in commerce, or a person...

  7. 7 CFR 1218.16 - Producer.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BLUEBERRY PROMOTION, RESEARCH, AND INFORMATION ORDER Blueberry Promotion, Research, and Information Order Definitions § 1218.16 Producer. Producer means any person who grows blueberries in the United States for sale in commerce, or a person...

  8. 7 CFR 1218.16 - Producer.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BLUEBERRY PROMOTION, RESEARCH, AND INFORMATION ORDER Blueberry Promotion, Research, and Information Order Definitions § 1218.16 Producer. Producer means any person who grows blueberries in the United States for sale in commerce, or a person...

  9. 7 CFR 1214.17 - Producer.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE CHRISTMAS TREE PROMOTION, RESEARCH, AND INFORMATION ORDER Christmas Tree Promotion, Research, and Information Order Definitions § 1214.17 Producer. Producer means any person who is engaged in the production of Christmas trees in the United...

  10. 7 CFR 1214.16 - Produce.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE CHRISTMAS TREE PROMOTION, RESEARCH, AND INFORMATION ORDER Christmas Tree Promotion, Research, and Information Order Definitions § 1214.16 Produce. Produce means to engage in the cutting and selling of Christmas trees for the holiday market. ...

  11. 7 CFR 1214.17 - Producer.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE CHRISTMAS TREE PROMOTION, RESEARCH, AND INFORMATION ORDER Christmas Tree Promotion, Research, and Information Order Definitions § 1214.17 Producer. Producer means any person who is engaged in the production of Christmas trees in the United...

  12. 7 CFR 1214.17 - Producer.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE CHRISTMAS TREE PROMOTION, RESEARCH, AND INFORMATION ORDER Christmas Tree Promotion, Research, and Information Order Definitions § 1214.17 Producer. Producer means any person who is engaged in the production of Christmas trees in the United...

  13. 7 CFR 1214.16 - Produce.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE CHRISTMAS TREE PROMOTION, RESEARCH, AND INFORMATION ORDER Christmas Tree Promotion, Research, and Information Order Definitions § 1214.16 Produce. Produce means to engage in the cutting and selling of Christmas trees for the holiday market. ...

  14. 7 CFR 1214.16 - Produce.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE CHRISTMAS TREE PROMOTION, RESEARCH, AND INFORMATION ORDER Christmas Tree Promotion, Research, and Information Order Definitions § 1214.16 Produce. Produce means to engage in the cutting and selling of Christmas trees for the holiday market. ...

  15. 7 CFR 1131.12 - Producer.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Federal order; (2) A dairy farmer whose milk is received at an exempt plant, excluding producer milk diverted to the exempt plant pursuant to § 1131.13(d); (3) A dairy farmer whose milk is received by... designates the dairy farmer as a producer under that order and that milk is allocated by request to...

  16. 7 CFR 1131.12 - Producer.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Federal order; (2) A dairy farmer whose milk is received at an exempt plant, excluding producer milk diverted to the exempt plant pursuant to § 1131.13(d); (3) A dairy farmer whose milk is received by... designates the dairy farmer as a producer under that order and that milk is allocated by request to...

  17. 7 CFR 1124.12 - Producer.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Federal order; (2) A dairy farmer whose milk is received at an exempt plant, excluding producer milk diverted to the exempt plant pursuant to § 1124.13(e); (3) A dairy farmer whose milk is received by... designates the dairy farmer as a producer under that order and that milk is allocated by request to...

  18. 7 CFR 1124.12 - Producer.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Federal order; (2) A dairy farmer whose milk is received at an exempt plant, excluding producer milk diverted to the exempt plant pursuant to § 1124.13(e); (3) A dairy farmer whose milk is received by... designates the dairy farmer as a producer under that order and that milk is allocated by request to...

  19. 7 CFR 1124.12 - Producer.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Federal order; (2) A dairy farmer whose milk is received at an exempt plant, excluding producer milk diverted to the exempt plant pursuant to § 1124.13(e); (3) A dairy farmer whose milk is received by... designates the dairy farmer as a producer under that order and that milk is allocated by request to...

  20. 7 CFR 1001.12 - Producer.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... handler described in § 1000.9(c). (b) Producer shall not include a dairy farmer described in paragraphs (b)(1) through (6) of this section. A dairy farmer described in paragraphs (b)(5) or (6) of this section shall be known as a dairy farmer for other markets. (1) A producer-handler as defined in any...

  1. 7 CFR 1001.12 - Producer.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... handler described in § 1000.9(c). (b) Producer shall not include a dairy farmer described in paragraphs (b)(1) through (6) of this section. A dairy farmer described in paragraphs (b)(5) or (6) of this section shall be known as a dairy farmer for other markets. (1) A producer-handler as defined in any...

  2. 7 CFR 1001.12 - Producer.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... handler described in § 1000.9(c). (b) Producer shall not include a dairy farmer described in paragraphs (b)(1) through (6) of this section. A dairy farmer described in paragraphs (b)(5) or (6) of this section shall be known as a dairy farmer for other markets. (1) A producer-handler as defined in any...

  3. 7 CFR 1210.306 - Producer.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Definitions § 1210.306 Producer. Producer means any person engaged in the growing of 10 acres or more of watermelons including any person who owns or shares...

  4. 7 CFR 1210.306 - Producer.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Definitions § 1210.306 Producer. Producer means any person engaged in the growing of 10 acres or more of watermelons including any person who owns or shares...

  5. 7 CFR 1209.15 - Producer.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MUSHROOM PROMOTION, RESEARCH, AND CONSUMER INFORMATION ORDER Mushroom Promotion, Research, and Consumer Information Order Definitions § 1209.15 Producer. Producer means any person engaged in the production of mushrooms who owns or shares the...

  6. 7 CFR 1209.15 - Producer.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MUSHROOM PROMOTION, RESEARCH, AND CONSUMER INFORMATION ORDER Mushroom Promotion, Research, and Consumer Information Order Definitions § 1209.15 Producer. Producer means any person engaged in the production of mushrooms who owns or shares the...

  7. 7 CFR 1209.15 - Producer.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MUSHROOM PROMOTION, RESEARCH, AND CONSUMER INFORMATION ORDER Mushroom Promotion, Research, and Consumer Information Order Definitions § 1209.15 Producer. Producer means any person engaged in the production of mushrooms who owns or shares the...

  8. Does Bt Corn Really Produce Tougher Residues

    USDA-ARS?s Scientific Manuscript database

    Bt corn hybrids produce insecticidal proteins that are derived from a bacterium, Bacillus thuringiensis. There have been concerns that Bt corn hybrids produce residues that are relatively resistant to decomposition. We conducted four experiments that examined the decomposition of corn residues und...

  9. Method for producing microporous metal bodies

    DOEpatents

    Danko, Joseph C.

    1982-01-01

    Tungsten is vapor-deposited by hydrogen reduction of tungsten hexafluoride (WF.sub.6) to produce a tungsten body having from 40 to 100 ppm fluorine. The tungsten is then heated under vacuum to produce grain boundary porosity for a sufficient period of time to allow the pores along the grain boundaries to become interconnected.

  10. 7 CFR 1208.19 - Producer.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PROCESSED RASPBERRY PROMOTION, RESEARCH, AND INFORMATION ORDER Processed Raspberry Promotion, Research, and Information Order Definitions § 1208.19 Producer. Producer means any person who grows 20,000 pounds or more of raspberries for...

  11. 7 CFR 1208.19 - Producer.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PROCESSED RASPBERRY PROMOTION, RESEARCH, AND INFORMATION ORDER Processed Raspberry Promotion, Research, and Information Order Definitions § 1208.19 Producer. Producer means any person who grows 20,000 pounds or more of raspberries for...

  12. 7 CFR 1221.21 - Producer.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SORGHUM PROMOTION, RESEARCH, AND INFORMATION ORDER Sorghum Promotion, Research, and Information Order Definitions § 1221.21 Producer. Producer means any person who is engaged in the production and sale of sorghum in the United States and who owns...

  13. 7 CFR 1216.22 - Producer.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PEANUT PROMOTION, RESEARCH, AND INFORMATION ORDER Peanut Promotion, Research, and Information Order Definitions § 1216.22 Producer. Producer means any person engaged in the production and sale of peanuts and who owns, or shares the ownership and...

  14. 7 CFR 1216.22 - Producer.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PEANUT PROMOTION, RESEARCH, AND INFORMATION ORDER Peanut Promotion, Research, and Information Order Definitions § 1216.22 Producer. Producer means any person engaged in the production and sale of peanuts and who owns, or shares the ownership and...

  15. 7 CFR 1216.22 - Producer.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PEANUT PROMOTION, RESEARCH, AND INFORMATION ORDER Peanut Promotion, Research, and Information Order Definitions § 1216.22 Producer. Producer means any person engaged in the production and sale of peanuts and who owns, or shares the ownership and...

  16. 7 CFR 1216.22 - Producer.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PEANUT PROMOTION, RESEARCH, AND INFORMATION ORDER Peanut Promotion, Research, and Information Order Definitions § 1216.22 Producer. Producer means any person engaged in the production and sale of peanuts and who owns, or shares the ownership and...

  17. 7 CFR 1216.22 - Producer.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PEANUT PROMOTION, RESEARCH, AND INFORMATION ORDER Peanut Promotion, Research, and Information Order Definitions § 1216.22 Producer. Producer means any person engaged in the production and sale of peanuts and who owns, or shares the ownership and...

  18. 7 CFR 1221.21 - Producer.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SORGHUM PROMOTION, RESEARCH, AND INFORMATION ORDER Sorghum Promotion, Research, and Information Order Definitions § 1221.21 Producer. Producer means any person who is engaged in the production and sale of sorghum in the United States and who...

  19. 7 CFR 1221.21 - Producer.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SORGHUM PROMOTION, RESEARCH, AND INFORMATION ORDER Sorghum Promotion, Research, and Information Order Definitions § 1221.21 Producer. Producer means any person who is engaged in the production and sale of sorghum in the United States and who...

  20. 7 CFR 1221.21 - Producer.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SORGHUM PROMOTION, RESEARCH, AND INFORMATION ORDER Sorghum Promotion, Research, and Information Order Definitions § 1221.21 Producer. Producer means any person who is engaged in the production and sale of sorghum in the United States and who...

  1. 7 CFR 1221.21 - Producer.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SORGHUM PROMOTION, RESEARCH, AND INFORMATION ORDER Sorghum Promotion, Research, and Information Order Definitions § 1221.21 Producer. Producer means any person who is engaged in the production and sale of sorghum in the United States and who...

  2. 7 CFR 1207.305 - Producer.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POTATO RESEARCH AND PROMOTION PLAN Potato Research and Promotion Plan Definitions § 1207.305 Producer. Producer means any person engaged in the growing of 5 or more acres of potatoes who owns or shares the ownership and risk of loss of such...

  3. 7 CFR 1207.305 - Producer.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POTATO RESEARCH AND PROMOTION PLAN Potato Research and Promotion Plan Definitions § 1207.305 Producer. Producer means any person engaged in the growing of 5 or more acres of potatoes who owns or shares the ownership and risk of loss of such...

  4. 7 CFR 1207.305 - Producer.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POTATO RESEARCH AND PROMOTION PLAN Potato Research and Promotion Plan Definitions § 1207.305 Producer. Producer means any person engaged in the growing of 5 or more acres of potatoes who owns or shares the ownership and risk of loss of such...

  5. 7 CFR 1207.305 - Producer.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POTATO RESEARCH AND PROMOTION PLAN Potato Research and Promotion Plan Definitions § 1207.305 Producer. Producer means any person engaged in the growing of 5 or more acres of potatoes who owns or shares the ownership and risk of loss of such...

  6. 7 CFR 1207.305 - Producer.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POTATO RESEARCH AND PROMOTION PLAN Potato Research and Promotion Plan Definitions § 1207.305 Producer. Producer means any person engaged in the growing of 5 or more acres of potatoes who owns or shares the ownership and risk of loss of such...

  7. 7 CFR 760.1202 - Eligible producers.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AGRICULTURE SPECIAL PROGRAMS INDEMNITY PAYMENT PROGRAMS 2005-2007 Catfish Grant Program § 760.1202 Eligible producers. (a) To be considered an eligible catfish producer, an participant must: (1) Raise catfish in a... period; (2) Maintain the catfish for commercial use as part of a farming operation; (3) Have a risk in...

  8. 7 CFR 760.1202 - Eligible producers.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AGRICULTURE SPECIAL PROGRAMS INDEMNITY PAYMENT PROGRAMS 2005-2007 Catfish Grant Program § 760.1202 Eligible producers. (a) To be considered an eligible catfish producer, an participant must: (1) Raise catfish in a... period; (2) Maintain the catfish for commercial use as part of a farming operation; (3) Have a risk in...

  9. 7 CFR 760.1202 - Eligible producers.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AGRICULTURE SPECIAL PROGRAMS INDEMNITY PAYMENT PROGRAMS 2005-2007 Catfish Grant Program § 760.1202 Eligible producers. (a) To be considered an eligible catfish producer, an participant must: (1) Raise catfish in a... period; (2) Maintain the catfish for commercial use as part of a farming operation; (3) Have a risk in...

  10. 7 CFR 760.1202 - Eligible producers.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AGRICULTURE SPECIAL PROGRAMS INDEMNITY PAYMENT PROGRAMS 2005-2007 Catfish Grant Program § 760.1202 Eligible producers. (a) To be considered an eligible catfish producer, an participant must: (1) Raise catfish in a... period; (2) Maintain the catfish for commercial use as part of a farming operation; (3) Have a risk in...

  11. 7 CFR 760.1202 - Eligible producers.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AGRICULTURE SPECIAL PROGRAMS INDEMNITY PAYMENT PROGRAMS 2005-2007 Catfish Grant Program § 760.1202 Eligible producers. (a) To be considered an eligible catfish producer, an participant must: (1) Raise catfish in a... period; (2) Maintain the catfish for commercial use as part of a farming operation; (3) Have a risk in...

  12. Method for producing microporous metal bodies

    SciTech Connect

    Danko, J.C.

    1982-12-07

    Tungsten is vapor-deposited by hydrogen reduction of tungsten hexafluoride (Wf/sub 6/) to produce a tungsten body having from 40 to 100 ppm fluorine. The tungsten is then heated under vacuum produce grain boundary porosity for a sufficient period of time to allow the pores along the grain boundaries to become interconnected.

  13. Flow Caster Produces Custom Alloy Magnetic Ribbon

    NASA Image and Video Library

    2016-12-21

    NASA Glenn’s large-scale, 5 kg planar flow caster cools a vat of molten metallic alloy, producing a magnetic ribbon that spouts into a collection bin. The caster has the ability to produce a magnetized ribbon that measures up to one mile long and 50 mm wide to support NASA’s hybrid electric aircraft propulsion and power management work.

  14. 7 CFR 1220.119 - Producer.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Soybean Promotion and Research Order Definitions § 1220.119 Producer. The term producer means any person engaged in the growing of soybeans in the United States who owns, or who...

  15. 7 CFR 1220.119 - Producer.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Soybean Promotion and Research Order Definitions § 1220.119 Producer. The term producer means any person engaged in the growing of soybeans in the United States who owns, or who...

  16. 7 CFR 1220.119 - Producer.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Soybean Promotion and Research Order Definitions § 1220.119 Producer. The term producer means any person engaged in the growing of soybeans in the United States who owns, or who...

  17. 7 CFR 1220.119 - Producer.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Soybean Promotion and Research Order Definitions § 1220.119 Producer. The term producer means any person engaged in the growing of soybeans in the United States who owns, or who...

  18. 7 CFR 1220.119 - Producer.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Soybean Promotion and Research Order Definitions § 1220.119 Producer. The term producer means any person engaged in the growing of soybeans in the United States who owns, or who...

  19. 7 CFR 1209.15 - Producer.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MUSHROOM PROMOTION, RESEARCH, AND CONSUMER INFORMATION ORDER Mushroom Promotion, Research, and Consumer Information Order Definitions § 1209.15 Producer. Producer means any person engaged in the production of mushrooms who owns or shares...

  20. 7 CFR 1209.15 - Producer.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MUSHROOM PROMOTION, RESEARCH, AND CONSUMER INFORMATION ORDER Mushroom Promotion, Research, and Consumer Information Order Definitions § 1209.15 Producer. Producer means any person engaged in the production of mushrooms who owns or shares...

  1. Music Teacher as Writer and Producer

    ERIC Educational Resources Information Center

    Randles, Clint

    2012-01-01

    In this article I attempt to redefine the role of a music teacher as being more than a director, the more traditional term ascribed to this position. I do this by using descriptions of the role of "writer" and "producer" of student lives borrowed from music education philosophy, screenwriting, and professional music producers. This vision is…

  2. 7 CFR 1124.13 - Producer milk.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 9 2014-01-01 2013-01-01 true Producer milk. 1124.13 Section 1124.13 Agriculture... AND ORDERS; MILK), DEPARTMENT OF AGRICULTURE MILK IN THE PACIFIC NORTHWEST MARKETING AREA Order Regulating Handling Definitions § 1124.13 Producer milk. Except as provided for in paragraph (f) of this...

  3. 7 CFR 1007.13 - Producer milk.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 9 2012-01-01 2012-01-01 false Producer milk. 1007.13 Section 1007.13 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE SOUTHEAST MARKETING AREA Order Regulating Handling Definitions § 1007.13 Producer milk. Except as provided for in paragraph (e) of this section...

  4. 7 CFR 1007.13 - Producer milk.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 9 2014-01-01 2013-01-01 true Producer milk. 1007.13 Section 1007.13 Agriculture... AND ORDERS; MILK), DEPARTMENT OF AGRICULTURE MILK IN THE SOUTHEAST MARKETING AREA Order Regulating Handling Definitions § 1007.13 Producer milk. Except as provided for in paragraph (e) of this section...

  5. 7 CFR 1124.13 - Producer milk.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 9 2012-01-01 2012-01-01 false Producer milk. 1124.13 Section 1124.13 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE PACIFIC NORTHWEST MARKETING AREA Order Regulating Handling Definitions § 1124.13 Producer milk. Except as provided for in paragraph (f) of this...

  6. 7 CFR 1005.13 - Producer milk.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 9 2012-01-01 2012-01-01 false Producer milk. 1005.13 Section 1005.13 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE APPALACHIAN MARKETING AREA Order Regulating Handling Definitions § 1005.13 Producer milk. Except as provided for in paragraph (e) of this section...

  7. 7 CFR 1030.13 - Producer milk.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 9 2012-01-01 2012-01-01 false Producer milk. 1030.13 Section 1030.13 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE UPPER MIDWEST MARKETING AREA Order Regulating Handling Definitions § 1030.13 Producer milk. Except as provided for in paragraph (e) of this section...

  8. 7 CFR 1124.13 - Producer milk.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 9 2013-01-01 2013-01-01 false Producer milk. 1124.13 Section 1124.13 Agriculture... AND ORDERS; MILK), DEPARTMENT OF AGRICULTURE MILK IN THE PACIFIC NORTHWEST MARKETING AREA Order Regulating Handling Definitions § 1124.13 Producer milk. Except as provided for in paragraph (f) of this...

  9. 7 CFR 1007.13 - Producer milk.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 9 2013-01-01 2013-01-01 false Producer milk. 1007.13 Section 1007.13 Agriculture... AND ORDERS; MILK), DEPARTMENT OF AGRICULTURE MILK IN THE SOUTHEAST MARKETING AREA Order Regulating Handling Definitions § 1007.13 Producer milk. Except as provided for in paragraph (e) of this section...

  10. 7 CFR 1030.13 - Producer milk.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 9 2013-01-01 2013-01-01 false Producer milk. 1030.13 Section 1030.13 Agriculture... AND ORDERS; MILK), DEPARTMENT OF AGRICULTURE MILK IN THE UPPER MIDWEST MARKETING AREA Order Regulating Handling Definitions § 1030.13 Producer milk. Except as provided for in paragraph (e) of this section...

  11. 7 CFR 1005.13 - Producer milk.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 9 2013-01-01 2013-01-01 false Producer milk. 1005.13 Section 1005.13 Agriculture... AND ORDERS; MILK), DEPARTMENT OF AGRICULTURE MILK IN THE APPALACHIAN MARKETING AREA Order Regulating Handling Definitions § 1005.13 Producer milk. Except as provided for in paragraph (e) of this section...

  12. 7 CFR 1005.13 - Producer milk.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 9 2014-01-01 2013-01-01 true Producer milk. 1005.13 Section 1005.13 Agriculture... AND ORDERS; MILK), DEPARTMENT OF AGRICULTURE MILK IN THE APPALACHIAN MARKETING AREA Order Regulating Handling Definitions § 1005.13 Producer milk. Except as provided for in paragraph (e) of this section...

  13. 7 CFR 1030.13 - Producer milk.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 9 2014-01-01 2013-01-01 true Producer milk. 1030.13 Section 1030.13 Agriculture... AND ORDERS; MILK), DEPARTMENT OF AGRICULTURE MILK IN THE UPPER MIDWEST MARKETING AREA Order Regulating Handling Definitions § 1030.13 Producer milk. Except as provided for in paragraph (e) of this section...

  14. 7 CFR 1001.12 - Producer.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... handler described in § 1000.9(c). (b) Producer shall not include a dairy farmer described in paragraphs (b)(1) through (6) of this section. A dairy farmer described in paragraphs (b)(5) or (6) of this section shall be known as a dairy farmer for other markets. (1) A producer-handler as defined in any...

  15. 7 CFR 1131.12 - Producer.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Federal order; (2) A dairy farmer whose milk is received at an exempt plant, excluding producer milk diverted to the exempt plant pursuant to § 1131.13(d); (3) A dairy farmer whose milk is received by... designates the dairy farmer as a producer under that order and that milk is allocated by request to...

  16. 7 CFR 1030.13 - Producer milk.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 9 2011-01-01 2011-01-01 false Producer milk. 1030.13 Section 1030.13 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE UPPER MIDWEST MARKETING AREA Order Regulating Handling Definitions § 1030.13 Producer milk. Except as provided for in paragraph (e) of this...

  17. 7 CFR 1005.13 - Producer milk.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 9 2011-01-01 2011-01-01 false Producer milk. 1005.13 Section 1005.13 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE APPALACHIAN MARKETING AREA Order Regulating Handling Definitions § 1005.13 Producer milk. Except as provided for in paragraph (e) of this...

  18. 7 CFR 1124.13 - Producer milk.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 9 2011-01-01 2011-01-01 false Producer milk. 1124.13 Section 1124.13 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE PACIFIC NORTHWEST MARKETING AREA Order Regulating Handling Definitions § 1124.13 Producer milk. Except as provided for in paragraph (f) of...

  19. 7 CFR 1007.13 - Producer milk.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 9 2011-01-01 2011-01-01 false Producer milk. 1007.13 Section 1007.13 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE SOUTHEAST MARKETING AREA Order Regulating Handling Definitions § 1007.13 Producer milk. Except as provided for in paragraph (e) of this...

  20. Particular applications of food irradiation fresh produce

    NASA Astrophysics Data System (ADS)

    Prakash, Anuradha

    2016-12-01

    On fresh fruits and vegetables, irradiation at low and medium dose levels can effectively reduce microbial counts which can enhance safety, inhibit sprouting to extend shelf-life, and eliminate or sterilize insect pests which can serve to facilitate trade between countries. At the dose levels used for these purposes, the impact on quality is negligible. Despite the fact that regulations in many countries allow the use of irradiation for fresh produce, the technology remains under-utilized, even in the light of an increase in produce related disease outbreaks and the economic benefits of extended shelf life and reduced food waste. Putative concerns about consumer acceptance particularly for produce that is labeled as irradiated have deterred many companies from using irradiation and retailers to carry irradiated produce. This section highlights the commercial use of irradiation for fresh produce, other than phytosanitary irradiation which is covered in supplementary sections.

  1. Stretched arc discharge in produced water.

    PubMed

    Cho, Y I; Wright, K C; Kim, H S; Cho, D J; Rabinovich, A; Fridman, A

    2015-01-01

    The objective of the present study was to investigate the feasibility of stretching an arc discharge in produced water to increase the volume of produced water treated by plasma. Produced water is the wastewater generated by hydraulic fracturing of shale during the production phase in shale-oil or shale-gas exploration. The electric conductivity of produced water is in the range of 50-200 mS/cm, which provides both a challenge and opportunity for the application of plasmas. Stretching of an arc discharge in produced water was accomplished using a ground electrode and two high-voltage electrodes: one positioned close to the ground electrode and the other positioned farther away from the ground. The benefit of stretching the arc is that the contact between the arc and water is significantly increased, resulting in more efficient plasma treatment in both performance and energy cost.

  2. Producer breeding objectives and optimal sire selection.

    PubMed

    Tozer, P R; Stokes, J R

    2002-12-01

    Information from an online survey of dairy producers was used to determine how important producers perceived three different objectives in the breeding problem. The objectives were: maximizing expected net merit of the progeny, minimizing the expected progeny inbreeding coefficient, and minimizing semen expenditure. Producers were asked to rank the three objectives and then to weight the importance of each objective relative to the others. This information was then used to determine weights to be used in a multiple-objective integer program designed to select individual mates for a herd of 76 Jersey cows with known genetic background and cow net merit. The results of the multiple-objective models show that rank and relative importance of producer objectives can affect the portfolio of sires selected. Producers whose primary objective was to maximize expected net merit had a range of average expected progeny net merit of $306 to $310, but the level of expected progeny inbreeding was from 6.99 to 10.45%, with a semen cost per conception of $35 to $41. For producers who selected minimizing progeny inbreeding as the primary goal in their breeding programs, the range of inbreeding was from 6.11 to 6.60%, with lower net merit range of $274 to $301 and semen expenditure of $30 to $37 per conception. One producer selected minimizing semen cost as the primary objective. For that producer's portfolio, the semen cost was $27 per conception and net merit was $288, with a progeny inbreeding coefficient of 10.68%. The results of this research suggest that producer information and goals have a substantial impact on the portfolio of sires selected by that producer to attain these goals.

  3. Biocorrosion produced by Thiobacillus-like microorganisms.

    PubMed

    López, A I; Marín, I; Amils, R

    1994-01-01

    Biocorrosion can be produced by many different microorganisms through diverse mechanisms. The biocorrosion produced by acidophilic microorganisms of the genus Thiobacillus is based on the production of sulfuric acid and ferric ion from pyrites or related mineral structures, as a result of the chemolithotrophic metabolism of these microorganisms. The products of this aerobic respiration are also powerful oxidant elements, which can produce chemical oxidations of other metallic structures. The Tinto River, a very unusual extremophilic habitat (pH around 2, and high concentration of ferric ion), product of the growth of strict chemolithotrophic microorganisms, is discussed as a model case.

  4. APPARATUS FOR PRODUCING AND MANIPULATING PLASMAS

    DOEpatents

    Colgate, S.A.; Ferguson, J.P.; Furth, H.P.; Wright, R.E.

    1960-07-26

    An electrical pinch discharge apparatus is described for producing and manipulating high-temperature plasmas. The apparatus may be of either the linear or toroidal pinch discharge type. Arrangements are provided whereby stabilizing fields may be trapped in the plasma external to the main pinch discharge path and the boundary condition of the stabilizing field programed so as to stabilize the discharge or to promote instabilities in the discharge as desired. The produced plasmas may be employed for various purposes, and fusion neutrons have been produced with the apparatus.

  5. Method for producing uranium atomic beam source

    DOEpatents

    Krikorian, Oscar H.

    1976-06-15

    A method for producing a beam of neutral uranium atoms is obtained by vaporizing uranium from a compound UM.sub.x heated to produce U vapor from an M boat or from some other suitable refractory container such as a tungsten boat, where M is a metal whose vapor pressure is negligible compared to that of uranium at the vaporization temperature. The compound, for example, may be the uranium-rhenium compound, URe.sub.2. An evaporation rate in excess of about 10 times that of conventional uranium beam sources is produced.

  6. Laser irradiation to produce amorphous pharmaceuticals.

    PubMed

    Titapiwatanakun, Varin; Tankul, Junlathip; Basit, Abdul W; Gaisford, Simon

    2016-11-30

    Using a high-power CO2 laser to irradiate powder beds, it was possible to induce phase transformation to the amorphous state. Irradiation of a model drug, indometacin, resulted in formation of a glass. Varying the settings of the laser (power and raster speed) was shown to change the physicochemical properties of the glasses produced and all irradiated glasses were found to be more stable than a reference glass produced by melt-quenching. Irradiation of a powder blend of paracetamol and polyvinylpyrrolidone K30 was found to produce a solid amorphous dispersion. The results suggest that laser-irradiation might be a useful method for making amorphous pharmaceuticals.

  7. Mass-producible micro-holographic tags

    SciTech Connect

    Sweatt, W.C.; Ray-Chaudhuri, A.K.; Kravitz, S.H.; Warren, M.E.; Stulen, R.H.; Tichenor, D.A.; Krenz, K.D. |; Descour, M.R.; Underwood, J.H.

    1996-06-01

    Microtags are microscopic computer-generated holograms with 130-nm features and are mass-producible with EUVL. This fabrication method renders microtags difficult to counterfeit. Applications includ tagging and tracking of microprocessors, memory chips, currencey, and credit cards.

  8. Methods and systems for producing syngas

    SciTech Connect

    Hawkes, Grant L; O'Brien, James E; Stoots, Carl M; Herring, J. Stephen; McKellar, Michael G; Wood, Richard A; Carrington, Robert A; Boardman, Richard D

    2013-02-05

    Methods and systems are provided for producing syngas utilizing heat from thermochemical conversion of a carbonaceous fuel to support decomposition of at least one of water and carbon dioxide using one or more solid-oxide electrolysis cells. Simultaneous decomposition of carbon dioxide and water or steam by one or more solid-oxide electrolysis cells may be employed to produce hydrogen and carbon monoxide. A portion of oxygen produced from at least one of water and carbon dioxide using one or more solid-oxide electrolysis cells is fed at a controlled flow rate in a gasifier or combustor to oxidize the carbonaceous fuel to control the carbon dioxide to carbon monoxide ratio produced.

  9. Characteristics of wine produced by mushroom fermentation.

    PubMed

    Okamura, T; Ogata, T; Minamimoto, N; Takeno, T; Noda, H; Fukuda, S; Ohsugi, M

    2001-07-01

    Saccharomyces cerevisiae is the main microorganism used in wine brewing, because this microbe has potent ability to produce alcohol dehydrogenase. We have recently discovered that some genera of mushroom produced alcohol dehydrogenase, and made wine by using a mushroom in place of S. cerevisiae. The highest alcohol concentration in this wine was achieved with Pleurotus ostreatus (2.6 M, 12.2%). In the case of Agaricus blazei, the same alcohol concentration (1.7 M, 8%) was produced under both aerobic and anaerobic conditions. This wine produced by A. blazei contained about 0.68% beta-D-glucan, which is known to have a preventive effects against cancer. The wine made by using Flammulina velutipes showed thrombosis-preventing activity, giving a prolonged thrombin clotting time 2.2-fold that of the control. Thus, the wine made by using mushroom seems to be a functional food which can be expected to have preventive effects against cancer and thrombosis.

  10. Producing X-rays at the APS

    ScienceCinema

    None

    2016-07-12

    An introduction and overview of the Advanced Photon Source at Argonne National Laboratory, the technology that produces the brightest X-ray beams in the Western Hemisphere, and the research carried out by scientists using those X-rays.

  11. Facility produced charge-exchange ions

    NASA Technical Reports Server (NTRS)

    Carruth, M. R., Jr.

    1981-01-01

    These facility produced ions are created by charge-exchange collisions between neutral atoms and energetic thruster beam ions. The result of the electron transfer is an energetic neutral atom and an ion of only thermal energy. There are true charge-exchange ions produced by collisions with neutrals escaping from the ion thruster and being charge-exchange ionized before the neutral intercepts the tank wall. The facility produced charge-exchange ions will not exist in space and therefore, represent a source of error where measurements involving ion thruster plasmas and their density are involved. The quantity of facility produced ions in a test chamber with a 30 cm mercury ion thruster was determined.

  12. Methods of producing compounds from plant materials

    SciTech Connect

    Werpy, Todd A.; Schmidt, Andrew J.; Frye, Jr., John G.; Zacher, Alan H. , Franz; James A. , Alnajjar; Mikhail S. , Neuenschwander; Gary G. , Alderson; Eric V. , Orth; Rick J. , Abbas; Charles A. , Beery; Kyle E. , Rammelsberg; Anne M. , Kim; Catherine J.

    2010-01-26

    The invention includes methods of processing plant material by adding water to form a mixture, heating the mixture, and separating a liquid component from a solid-comprising component. At least one of the liquid component and the solid-comprising component undergoes additional processing. Processing of the solid-comprising component produces oils, and processing of the liquid component produces one or more of glycerol, ethylene glycol, lactic acid and propylene glycol. The invention includes a process of forming glycerol, ethylene glycol, lactic acid and propylene glycol from plant matter by adding water, heating and filtering the plant matter. The filtrate containing starch, starch fragments, hemicellulose and fragments of hemicellulose is treated to form linear poly-alcohols which are then cleaved to produce one or more of glycerol, ethylene glycol, lactic acid and propylene glycol. The invention also includes a method of producing free and/or complexed sterols and stanols from plant material.

  13. Methods of producing compounds from plant material

    DOEpatents

    Werpy, Todd A.; Schmidt, Andrew J.; Frye, Jr., John G.; Zacher, Alan H.; Franz, James A.; Alnajjar, Mikhail S.; Neuenschwander, Gary G.; Alderson, Eric V.; Orth, Rick J.; Abbas, Charles A.; Beery, Kyle E.; Rammelsberg, Anne M.; Kim, Catherine J.

    2006-01-03

    The invention includes methods of processing plant material by adding water to form a mixture, heating the mixture, and separating a liquid component from a solid-comprising component. At least one of the liquid component and the solid-comprising component undergoes additional processing. Processing of the solid-comprising component produces oils, and processing of the liquid component produces one or more of glycerol, ethylene glycol, lactic acid and propylene glycol. The invention includes a process of forming glycerol, ethylene glycol, lactic acid and propylene glycol from plant matter by adding water, heating and filtering the plant matter. The filtrate containing starch, starch fragments, hemicellulose and fragments of hemicellulose is treated to form linear poly-alcohols which are then cleaved to produce one or more of glycerol, ethylene glycol, lactic acid and propylene glycol. The invention also includes a method of producing free and/or complexed sterols and stanols from plant material.

  14. Producing tritium in a homogenous reactor

    DOEpatents

    Cawley, William E.

    1985-01-01

    A method and apparatus are described for the joint production and separation of tritium. Tritium is produced in an aqueous homogenous reactor and heat from the nuclear reaction is used to distill tritium from the lower isotopes of hydrogen.

  15. How To Produce and Characterize Transgenic Plants.

    ERIC Educational Resources Information Center

    Savka, Michael A.; Wang, Shu-Yi; Wilson, Mark

    2002-01-01

    Explains the process of establishing transgenic plants which is a very important tool in plant biology and modern agriculture. Produces transgenic plants with the ability to synthesize opines. (Contains 17 references.) (YDS)

  16. Producing approximate answers to database queries

    NASA Technical Reports Server (NTRS)

    Vrbsky, Susan V.; Liu, Jane W. S.

    1993-01-01

    We have designed and implemented a query processor, called APPROXIMATE, that makes approximate answers available if part of the database is unavailable or if there is not enough time to produce an exact answer. The accuracy of the approximate answers produced improves monotonically with the amount of data retrieved to produce the result. The exact answer is produced if all of the needed data are available and query processing is allowed to continue until completion. The monotone query processing algorithm of APPROXIMATE works within the standard relational algebra framework and can be implemented on a relational database system with little change to the relational architecture. We describe here the approximation semantics of APPROXIMATE that serves as the basis for meaningful approximations of both set-valued and single-valued queries. We show how APPROXIMATE is implemented to make effective use of semantic information, provided by an object-oriented view of the database, and describe the additional overhead required by APPROXIMATE.

  17. Coloured Rings Produced on Transparent Plates

    ERIC Educational Resources Information Center

    Suhr, Wilfried; Schlichting, H. Joachim

    2007-01-01

    Beautiful colored interference rings can be produced by using transparent plates such as window glass. A simple model explains this effect, which was described by Newton but has almost been forgotten. (Contains 11 figures.)

  18. Genetics Home Reference: aldosterone-producing adenoma

    MedlinePlus

    ... produced from these genes transports certain ions across cell membranes . The flow of these ions creates an electrical charge across the cell membrane, which affects certain biochemical processes. In adrenal gland ...

  19. How To Produce and Characterize Transgenic Plants.

    ERIC Educational Resources Information Center

    Savka, Michael A.; Wang, Shu-Yi; Wilson, Mark

    2002-01-01

    Explains the process of establishing transgenic plants which is a very important tool in plant biology and modern agriculture. Produces transgenic plants with the ability to synthesize opines. (Contains 17 references.) (YDS)

  20. 7 CFR 989.11 - Producer.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN IN... proprietary capacity in the production of grapes which are sun-dried or dehydrated by artificial means...