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Sample records for acetate prasterone pregabalin

  1. Pregabalin

    MedlinePlus

    ... treat certain types of seizures in people with epilepsy. Pregabalin is in a class of medications called ... you are taking pregabalin for the treatment of epilepsy, mental illness, or other conditions. A small number ...

  2. Pregabalin (Pfizer).

    PubMed

    Huckle, Richard

    2004-01-01

    Pregabalin is a gamma-aminobutyric acid analog that is under development by Pfizer for the potential treatment of central nervous system disorders, including epilepsy, neuropathic pain, fibromyalgia and generalized anxiety disorder. By April 2003, Pfizer had filed for approval of pregabalin in Europe for neuropathic pain and as an adjunctive therapy for epilepsy, and in October 2003 an NDA was filed for these indications and generalized anxiety disorder. At this time, phase III trials in fibromyalgia were ongoing. PMID:14983979

  3. Pregabalin for the management of fibromyalgia syndrome

    PubMed Central

    Boomershine, Chad S

    2010-01-01

    This last article in a three-part series on approved medications for managing fibromyalgia syndrome (FMS) reviews pregabalin (Lyrica®). Pregabalin was the first drug approved for FMS management and, as an anticonvulsant, differs from the other approved agents that are antidepressants. Pregabalin inhibits presynaptic excitatory neurotransmitter release by blocking α2δ calcium channels. Five randomized, placebo-controlled trials have demonstrated pregabalin reduces pain and improves sleep and health-related quality of life in FMS patients. While indicated dosing is 300–450 mg divided twice daily, initial dosing of 25–50 mg at night is recommended owing to side effects including somnolence, dizziness, and cognitive dysfunction. Since side effects such as weight gain and peripheral edema are dose-related, uptitration in weekly increments based on tolerability and therapeutic response is recommended. Due to its lack of protein binding and negligible hepatic metabolism, pregabalin can be safely combined with other medications and used in patients with renal failure when the dose is appropriate. Pregabalin may worsen sedation when combined with central nervous system depressants. Pregabalin should be discontinued gradually. Pregabalin-treated patients should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior. Pregabalin in combination with the other approved medications may be synergistic in treating FMS. PMID:21197312

  4. Pregabalin for the management of fibromyalgia syndrome.

    PubMed

    Boomershine, Chad S

    2010-01-01

    This last article in a three-part series on approved medications for managing fibromyalgia syndrome (FMS) reviews pregabalin (Lyrica(®)). Pregabalin was the first drug approved for FMS management and, as an anticonvulsant, differs from the other approved agents that are antidepressants. Pregabalin inhibits presynaptic excitatory neurotransmitter release by blocking α(2)δ calcium channels. Five randomized, placebo-controlled trials have demonstrated pregabalin reduces pain and improves sleep and health-related quality of life in FMS patients. While indicated dosing is 300-450 mg divided twice daily, initial dosing of 25-50 mg at night is recommended owing to side effects including somnolence, dizziness, and cognitive dysfunction. Since side effects such as weight gain and peripheral edema are dose-related, uptitration in weekly increments based on tolerability and therapeutic response is recommended. Due to its lack of protein binding and negligible hepatic metabolism, pregabalin can be safely combined with other medications and used in patients with renal failure when the dose is appropriate. Pregabalin may worsen sedation when combined with central nervous system depressants. Pregabalin should be discontinued gradually. Pregabalin-treated patients should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior. Pregabalin in combination with the other approved medications may be synergistic in treating FMS. PMID:21197312

  5. Pregabalin Abuse amongst Opioid Substitution Treatment Patients.

    PubMed

    McNamara, S; Stokes, S; Kilduff, R; Shine, A

    2015-01-01

    Pregabalin (Lyrica®) is used in treating epilepsy, nerve pain and anxiety. Pregabalin was initially thought to have a low misuse potential however there are emerging reports of Pregabalin being abused. A study was commenced at the National Drug Treatment Centre's (NDTC) Drug Analysis Laboratory to determine the level of usage of Pregabalin within the addiction services population in Ireland. A total of 498 urine samples representing samples from 440 individual opioid substitution patients, initially screened by immunoassay for drugs of abuse, were subjected to further analysis for Pregabalin by Liquid Chromatography/Mass Spectrometry (LC/MS). Of 440 patients tested, 39 tested positive for Pregabalin (9.2%). Only 10 patients from this group were prescribed this drug to our knowledge thus giving an estimated rate of misuse of 7.0%. Other drugs detected in the Pregabalin positive patients were Opiates (31.8%), Cocaine (11.4%), Benzodiazepines (79.5%) and Cannabis (77.8%). Our study confirms that Pregabalin abuse is taking place amongst the addiction services population. We believe that misuse of this prescription drug is a serious emerging issue which should be monitored carefully. PMID:26817289

  6. Pregabalin in Chemotherapy Induced Neuropathic Pain

    PubMed Central

    Atreya, Shrikant

    2016-01-01

    Chemotherapeutic agents belonging to vinca alkaloids, taxanes, and antitubulins produce peripheral neuropathy for which there is no validated treatment. Pregabalin, a gamma-aminobutyric acid analog, is known to inhibit theα2δ subunit of the voltage-gated calcium channel. Earlier studies and case reports have shown pregabalin to be effective in treating neuropathic pain. We present a case series of patients with chemotherapy-induced peripheral neuropathy who were successfully treated with pregabalin with reduction in the hyperalgesia, allodynia, and improvement in the quality of life. PMID:26962289

  7. Pregabalin in Chemotherapy Induced Neuropathic Pain.

    PubMed

    Atreya, Shrikant

    2016-01-01

    Chemotherapeutic agents belonging to vinca alkaloids, taxanes, and antitubulins produce peripheral neuropathy for which there is no validated treatment. Pregabalin, a gamma-aminobutyric acid analog, is known to inhibit theα2δ subunit of the voltage-gated calcium channel. Earlier studies and case reports have shown pregabalin to be effective in treating neuropathic pain. We present a case series of patients with chemotherapy-induced peripheral neuropathy who were successfully treated with pregabalin with reduction in the hyperalgesia, allodynia, and improvement in the quality of life. PMID:26962289

  8. [Effect of sodium prasterone on termination of mid-trimester pregnancy].

    PubMed

    Wang, X D

    1993-12-01

    Sodium prasterone sulfate was used before termination of mid-trimester pregnancy in 50 cases, and another 50 cases taking no drug as the control group. Both groups were given intraamniotic rivanol. In the treatment group, the results indicated that the Bishop score was elevated by 1 to 8. There were an effective rate of 86% and satisfactory rate of 98%. In comparison, the control group showed 40% (P < 0.001) and 76% (P < 0.01) respectively, and there was significant difference between the 2 groups. The average induction-abortion time interval was 13.2 hours shorter in treatment group (P < 0.01). Adverse effects such as nausea or fatigue was only seen occasionally. PMID:8137647

  9. Evaluation of the acceptability of intravaginal prasterone ovule administration using an applicator.

    PubMed

    Montesino, Marlene; Labrie, Fernand; Archer, David F; Zerhouni, Jaâfar; Côté, Isabelle; Lavoie, Lyne; Beauregard, Adam; Martel, Céline; Vaillancourt, Mario; Moyneur, Erick; Balser, John

    2016-03-01

    The objective of the study is to evaluate the acceptability of the intravaginal administration of ovules/suppositories of DHEA (dehydroepiandrosterone, prasterone) for the treatment of vulvovaginal atrophy (VVA) in women with moderate to severe dyspareunia who were administered daily for 12 weeks intravaginal 0.50% (6.5 mg) DHEA or placebo. There were a total of 373 women in the per-protocol population who responded to the questionnaire for both treatment groups. While it was planned that the applicator would be evaluated as suitable if at least 80% of participants have a global score  ≤ 2 units, 99% and 100% of participants had a score  ≤ 2 units in the placebo and DHEA groups, respectively, for the global score (mean of 5 questions). When asked about like and dislike the technique of drug administration, 284 comments were positive, while 114 women gave no comment. About 92-94% of women indicated that they were very confident to be able use the applicator successfully in the future. The survey shows a high degree of satisfaction and of confidence to use the applicator successfully in the future. PMID:26634942

  10. Painful legs and moving toes syndrome responsive to pregabalin

    PubMed Central

    Rossi, FH; Liu, W; Geigel, E; Castaneda, S; Rossi, EM; Schnacky, K

    2015-01-01

    Report three cases of painful legs and moving toes (PLMT) syndrome responsive to pregabalin along with a review of its literature. Three patients with PLMT syndrome improved with pregabalin. The first and third patient reported improvement in pain scores, quality of life, and quality of sleep sustained over time. The second and third patient had near complete remission of toe movements, but pregabalin was discontinued in the second patient due to aggravation of leg edema. PLMT is a rare and debilitating disorder characterized by lower limb pain and involuntary toes or feet movements. Its pathophysiology remains unknown and its therapy refractory to most drugs, except for pregabalin, as shown in this case series. PLMT is a rare and incapacitating syndrome due to the lack of an effective pain therapy. We report three patients with PLMT who favorable responded to pregabalin. We propose pregabalin be considered in the management of PLMT. PMID:25766346

  11. Pregabalin in post traumatic neuropathic pain: Case studies

    PubMed Central

    Singh, Rakesh Kumar; Sinha, Vijay Prakash; Pal, U. S.; Yadav, Sharad C.; Singh, Maneesh K.

    2012-01-01

    Pregabalin is effective in the treatment of peripheral and central neuropathic pain. This study evaluated the effectiveness of pregablin in management of post traumatic peripheral nerve injury facial pain not responding to other medication like analgesics. Pregabalin was well tolerated. The most common adverse effects were dizziness and tiredness. PMID:23251069

  12. Teratogenic Effects of Pregabalin in Mice

    PubMed Central

    Etemad, Leila; Mohammad, Afshar; Mohammadpour, Amir Hooshang; Vahdati Mashhadi, Nasser; Moallem, Seyed Adel

    2013-01-01

    Objective(s): Anti-epileptic drugs (AEDs) have the potential to affect fetal development throughout pregnancy. Considering the broad therapeutic indications of pregabalin (PGB), its potential teratogenic effects and the levels of homocysteine have been studied. Materials and Methods: Timed-pregnant mice received one of three doses of PGB (20, 40 or 80 mg/kg/day) or the vehicle control during organogenesis, intraperitoneally. The litters were stained and examined for malformations. Total homocysteine (tHcy) was measured in serum from the pregnant mice on GD18. Results: The rate of fetus malformations increased significantly in all treated groups as compared to the control group. The abnormalities included limb, vertebral column and craniofacial abnormalities. The most common abnormality was limb deformity. The percentage of fetal resorption significantly increased at higher doses. There was no significant difference in tHcy concentrations between the treated and control groups. Conclusion: Pregabalin may have potential teratogenic effects even in lower doses, however with less intensity than other AEDs. Therefore, it is suggested that great caution should be taken when prescribing it in pregnancy and further investigation for possible mechaninsms. PMID:24379963

  13. Pregabalin: a new approach to treatment of the dysautonomic crisis.

    PubMed

    Axelrod, Felicia B; Berlin, Dena

    2009-08-01

    Nausea and dysautonomic crises severely limit function and quality of life for a large number of individuals with familial dysautonomia. We treated a small cohort of 15 patients with familial dysautonomia who suffered frequent dysautonomic crises with pregabalin. Nausea and overt crises markedly decreased in 13 (87%) of these patients and the overall assessments of benefit were extremely favorable, suggesting that pregabalin may be a potentially useful therapeutic agent for this disorder. PMID:19620195

  14. Neuroprotective Effects of Pregabalin on Cerebral Ischemia and Reperfusion

    PubMed Central

    Aşcı, Sanem; Demirci, Serpil; Aşcı, Halil; Doğuç, Duygu Kumbul; Onaran, İbrahim

    2016-01-01

    Background: Stroke is one of the most common causes of death and the leading cause of disability in adults. Cerebral ischemia/reperfusion injury causes cerebral edema, hemorrhage, and neuronal death. Aims: In post-ischemic reperfusion, free radical production causes brain tissue damage by oxidative stress. Pregabalin, an antiepileptic agent was shown to have antioxidant effects. The aim of this study was to evaluate the neuroprotective and antioxidant effects of pregabalin on ischemia and reperfusion in rat brain injury. Study Design: Animal experimentation. Methods: Male Wistar rats weighing (250–300 g) were randomly divided into six groups, each consisting of 6 rats: control (C), pregabalin (P), ischemia (I), pregabalin + ischemia (PI), ischemia + reperfusion (IR) and ischemia + reperfusion + pregabalin (PIR). Rats were initially pre-treated with 50 mg/kg/d pregabalin orally for two days. Then, animals that applied ischemia in I, PI, IR and PIR groups were exposed to carotid clamping for 30 minutes and 20 minutes reperfusion was performed in the relevant reperfusion groups. Results: NR2B receptor levels were significantly lower in the PIR group in comparison to the IR group. In the PIR group, Thiobarbituric acid reactive substance (TBARS) level had statistically significant decrease compared with IR group. Glutathione peroxidase (GSH-PX) levels were also significantly increased in the PIR group compared with I, IR and control groups. In the PI and PIR groups, catalase (CAT) levels were also significantly increased compared with I and IR groups (p=0.03 and p=0.07, respectively). Conclusion: Pregabalin may protect the damage of oxidative stress after ischemia + reperfusion. This result would illuminate clinical studies in the future. PMID:27403394

  15. Pregabalin for acute and chronic pain in adults

    PubMed Central

    Moore, R Andrew; Straube, Sebastian; Wiffen, Philip J; Derry, Sheena; McQuay, Henry J

    2014-01-01

    Background Antiepileptic drugs have been used in pain management since the 1960s. Pregabalin is a recently developed antiepileptic drug also used in management of chronic neuropathic pain conditions. Objectives To assess analgesic efficacy and associated adverse events of pregabalin in acute and chronic pain. Search methods We searched MEDLINE, EMBASE, and CENTRAL to May 2009 for randomised controlled trials (RCTs). Additional studies were identified from the reference lists of retrieved papers and on-line clinical trial databases. Selection criteria Randomised, double blind trials reporting on the analgesic effect of pregabalin, with subjective pain assessment by the patient as either the primary or a secondary outcome. Data collection and analysis Two independent review authors extracted data and assessed trial quality. Numbers-needed-to-treat-to-benefit (NNTs) were calculated, where possible, from dichotomous data for effectiveness, adverse events and study withdrawals. Main results There was no clear evidence of beneficial effects of pregabalin in established acute postoperative pain. No studies evaluated pregabalin in chronic nociceptive pain, like arthritis. Pregabalin at doses of 300 mg, 450 mg, and 600 mg daily was effective in patients with postherpetic neuralgia, painful diabetic neuropathy, central neuropathic pain, and fibromyalgia (19 studies, 7003 participants). Pregabalin at 150 mg daily was generally ineffective. Efficacy was demonstrated for dichotomous outcomes equating to moderate or substantial pain relief, alongside lower rates for lack of efficacy discontinuations with increasing dose. The best (lowest) NNT for each condition for at least 50% pain relief over baseline (substantial benefit) for 600 mg pregabalin daily compared with placebo were 3.9 (95% confidence interval 3.1 to 5.1) for postherpetic neuralgia, 5.0 (4.0 to 6.6) for painful diabetic neuropathy, 5.6 (3.5 to 14) for central neuropathic pain, and 11 (7.1 to 21) for fibromyalgia

  16. Transient Positive Horizontal Head Impulse Test in Pregabalin Intoxication.

    PubMed

    Jeong, Seong-Hae; Kim, Yong Soo; Lee, Ju-Hoen; Jo, Hyunjin; Lee, Ae Young; Kim, Jae-Moon

    2015-12-01

    Head impulse test (HIT) is helpful to understanding high-frequency vestibulo-ocular reflex in patients with dizziness and imbalance. There are some reports on abnormal HITs in cerebellar disorder. To our knowledge, there was no report of transient bilateral positive head impulse related to antiepileptic drugs. A 65-year-old woman developed dizziness and imbalance after treatment with pregabalin for pain control of radiation cystitis. Neurological examination exhibited positive bilateral HIT results, in addition to ataxia and gaze-evoked rebound nystagmus. Pregabalin intoxication can evoke transient positive horizontal head impulse test as another indicator of cerebellar dysfunction. PMID:26819943

  17. Transient Positive Horizontal Head Impulse Test in Pregabalin Intoxication

    PubMed Central

    Jeong, Seong-Hae; Kim, Yong Soo; Lee, Ju-Hoen; Jo, Hyunjin; Lee, Ae Young; Kim, Jae-Moon

    2015-01-01

    Head impulse test (HIT) is helpful to understanding high-frequency vestibulo-ocular reflex in patients with dizziness and imbalance. There are some reports on abnormal HITs in cerebellar disorder. To our knowledge, there was no report of transient bilateral positive head impulse related to antiepileptic drugs. A 65-year-old woman developed dizziness and imbalance after treatment with pregabalin for pain control of radiation cystitis. Neurological examination exhibited positive bilateral HIT results, in addition to ataxia and gaze-evoked rebound nystagmus. Pregabalin intoxication can evoke transient positive horizontal head impulse test as another indicator of cerebellar dysfunction. PMID:26819943

  18. Pregabalin for the treatment of generalized anxiety disorder: an update

    PubMed Central

    Baldwin, David S; Ajel, Khalil; Masdrakis, Vasilios G; Nowak, Magda; Rafiq, Rizwan

    2013-01-01

    A previous review summarized what was then known about the potential role of pregabalin in the treatment of patients with generalized anxiety disorder (GAD): this review provides an update on its pharmacological properties and presumed mechanism of action, the liability for abuse, and efficacy and tolerability in patients with GAD. Pregabalin has a similar molecular structure to the inhibitory neurotransmitter gamma amino butyric acid (GABA) but its mechanism of action does not appear to be mediated through effects on GABA. Instead, its anxiolytic effects may arise through high-affinity binding to the alpha-2-delta sub-unit of the P/Q type voltage-gated calcium channel in “over-excited” presynaptic neurons, thereby reducing the release of excitatory neurotransmitters such as glutamate. The findings of randomized controlled trials and meta-analyses together indicate that pregabalin is efficacious in both acute treatment and relapse prevention in GAD, with some evidence of an early onset of effect, and broad efficacy in reducing the severity of psychological and physical symptoms of anxiety. It also has efficacy as an augmenting agent after non-response to antidepressant treatment in GAD. Continuing vigilance is needed in assessing its potential abuse liability but the tolerability profile of pregabalin may confer some advantages over other pharmacological treatments in the short term for treatment in patients with GAD. PMID:23836974

  19. Quantitative Sensory Testing Predicts Pregabalin Efficacy in Painful Chronic Pancreatitis

    PubMed Central

    Olesen, Søren S.; Graversen, Carina; Bouwense, Stefan A. W.; van Goor, Harry; Wilder-Smith, Oliver H. G.; Drewes, Asbjørn M.

    2013-01-01

    Background A major problem in pain medicine is the lack of knowledge about which treatment suits a specific patient. We tested the ability of quantitative sensory testing to predict the analgesic effect of pregabalin and placebo in patients with chronic pancreatitis. Methods Sixty-four patients with painful chronic pancreatitis received pregabalin (150–300 mg BID) or matching placebo for three consecutive weeks. Analgesic effect was documented in a pain diary based on a visual analogue scale. Responders were defined as patients with a reduction in clinical pain score of 30% or more after three weeks of study treatment compared to baseline recordings. Prior to study medication, pain thresholds to electric skin and pressure stimulation were measured in dermatomes T10 (pancreatic area) and C5 (control area). To eliminate inter-subject differences in absolute pain thresholds an index of sensitivity between stimulation areas was determined (ratio of pain detection thresholds in pancreatic versus control area, ePDT ratio). Pain modulation was recorded by a conditioned pain modulation paradigm. A support vector machine was used to screen sensory parameters for their predictive power of pregabalin efficacy. Results The pregabalin responders group was hypersensitive to electric tetanic stimulation of the pancreatic area (ePDT ratio 1.2 (0.9–1.3)) compared to non-responders group (ePDT ratio: 1.6 (1.5–2.0)) (P = 0.001). The electrical pain detection ratio was predictive for pregabalin effect with a classification accuracy of 83.9% (P = 0.007). The corresponding sensitivity was 87.5% and specificity was 80.0%. No other parameters were predictive of pregabalin or placebo efficacy. Conclusions The present study provides first evidence that quantitative sensory testing predicts the analgesic effect of pregabalin in patients with painful chronic pancreatitis. The method can be used to tailor pain medication based on patient’s individual sensory profile and thus

  20. Pregabalin in Childhood Epilepsy: A Clinical Trial Study

    PubMed Central

    MOLLAMOHAMMADI, Mohsen; TONKABONI, Seyed Hassan; PIRZADEH, Zahra; Vahedian, Mostafa

    2014-01-01

    Objective The prevalence of active epilepsy is about 0.5–1%, and approximately 70% of patients are cured with first anti-epileptic drugs and the remaining patients need multiple drugs. Pregabalin as an add-on therapy has a postive effect on refractory seizures in adults. To the best of our knowledge, there is no research with this drug in childhood epilepsy. We use pregabalin in children with refractory seizures as an add-on therapy. The objective of this study is to evaluate the effects of pregabalin in the reduction of seizures for refractory epilepsy. Material & Methods Forty patients with refractory seizures who were referred to Mofid Children’s Hospital and Hazrat Masoumeh Hospital were selected. A questionnaire based on patient record forms, demographic data (age, gender,…), type of seizure, clinical signs, EEG record, imaging report, drugs that had been used, drugs currently being used, and the number of seizures before and after Pregabalin treatment was completed. We checked the number of seizures after one and four months. Results After one month, 26.8% of patients had more than a 50% reduction in seizures and 14.6% of these patients were seizure-free; 12.2% had a 25–50% reduction; and approximately 61% had less than a 25% reduction or no change in seizures. After the fourth month, 34.1% of patients had more than a 50% reduction in seizures and 24.4% of these patients were seizure-free. Additionally, 65.9% of patients had less than 50% reduction in seizures (9.8% between 25–50% and 56.1% less than 25% or without improvement). Conclusion We recommend Pregabalin as an add-on therapy for refractory seizures (except for myoclonic seizures) for children. PMID:25657772

  1. Gabapentin and pregabalin for the treatment of chronic pruritus.

    PubMed

    Matsuda, Kazuki M; Sharma, Divya; Schonfeld, Ariel R; Kwatra, Shawn G

    2016-09-01

    Chronic pruritus is a distressing symptom that is often refractory to treatment. Patients frequently fail topical therapies and oral over-the-counter antihistamines, prompting the clinician to consider alternative therapies such as neuroactive agents. Herein, the use of gabapentin and pregabalin, 2 medications well known for treating neuropathic pain and epilepsy that are occasionally used for relieving chronic pruritus is explored. The findings from original sources published to date to evaluate the use of gabapentin and pregabalin as antipruritic agents are explored. They are found to be promising alternative treatments for the relief of several forms of chronic pruritus, particularly uremic pruritus and neuropathic or neurogenic itch, in patients who fail conservative therapies. PMID:27206757

  2. Pregabalin in Neuropathic Pain: Evidences and Possible Mechanisms

    PubMed Central

    Verma, Vivek; Singh, Nirmal; Singh Jaggi, Amteshwar

    2014-01-01

    Pregabalin is an antagonist of voltage gated Ca2+ channels and specifically binds to alpha-2-delta subunit to produce antiepileptic and analgesic actions. It successfully alleviates the symptoms of various types of neuropathic pain and presents itself as a first line therapeutic agent with remarkable safety and efficacy. Preclinical studies in various animal models of neuropathic pain have shown its effectiveness in treating the symptoms like allodynia and hyperalgesia. Clinical studies in different age groups and in different types of neuropathic pain (peripheral diabetic neuropathy, fibromyalgia, post-herpetic neuralgia, cancer chemotherapy-induced neuropathic pain) have projected it as the most effective agent either as monotherapy or in combined regimens in terms of cost effectiveness, tolerability and overall improvement in neuropathic pain states. Preclinical studies employing pregabalin in different neuropathic pain models have explored various molecular targets and the signaling systems including Ca2+ channel-mediated neurotransmitter release, activation of excitatory amino acid transporters (EAATs), potassium channels and inhibition of pathways involving inflammatory mediators. The present review summarizes the important aspects of pregabalin as analgesic in preclinical and clinical studies as well as focuses on the possible mechanisms. PMID:24533015

  3. The Role of NMDARs Ligands on Antinociceptive Effects of Pregabalin in the Tail Flick Test

    PubMed Central

    Meymandi, Manzumeh-Shamsi; Keyhanfar, Fariborz; Yazdanpanah, Omid; Heravi, Gioia

    2015-01-01

    Background: Pregabalin as a new anticonvulsant has been used in different pain treatments. Objectives: The aim of this study was to investigate the role of N-methyl-D-aspartate (NMDA) ligands in antinociceptive effect of pregabalin in mice using tail flick. Materials and Methods: NMDA (15 and 30 mg/kg) as an agonist or MK801 (0.02 and 0.05 mg/kg) as an antagonist were injected intraperitoneally either alone or 15 minutes before antinociceptive dose of pregabalin (100 mg/kg). Then the latency times and %MPE were measured in the tail flick assay during 75 minutes. Results: NMDA and MK801 had no effects alone. NMDA pretreatment significantly decreased the latency times of pregabalin till 75th minutes. In NMDA pretreated groups, %MPE30 unlike %MPE75 decreased significantly compared to those of pregabalin. MK801 delayed the latency times in pretreated groups, but %MPE30 and %MPE75 did not change significantly compared to pregabalin alone. Conclusions: Our findings support the role of NMDARs in pregabalin antinociception, because the NMDAR agonist, unlike the antagonist, decreased the antinociceptive effect of pregabalin, even if tail flick is not an adequate pain assessment method in this regard. PMID:26587404

  4. Serum steroid concentrations remain within normal postmenopausal values in women receiving daily 6.5mg intravaginal prasterone for 12weeks.

    PubMed

    Martel, Céline; Labrie, Fernand; Archer, David F; Ke, Yuyong; Gonthier, Renaud; Simard, Jean-Nicolas; Lavoie, Lyne; Vaillancourt, Mario; Montesino, Marlene; Balser, John; Moyneur, Érick

    2016-05-01

    This study integrates all data obtained in women aged 40-80years enrolled with moderate to severe symptoms of vulvovaginal atrophy (VVA) who received daily intravaginal administration of 0.50% (6.5mg) dehydroepiandrosterone (DHEA; prasterone) for 12weeks (n=723; ITT-S population) as compared with placebo (n=266; ITT-S population). To this end, serum steroid levels (DHEA, DHEA-sulfate (DHEA-S), androst-5-ene-3β, 17β-diol (5-diol), testosterone, dihydrotestosterone (DHT), androstenedione (4-dione), estrone (E1), estradiol (E2), estrone sulfate (E1-S), androsterone glucuronide (ADT-G), and androstane-3α, 17β-diol 17-glucuronide (3α-diol-17G)) were measured at Day 1 and Week 12 by liquid chromatography-tandem mass spectrometry (LC-MS/MS) following validation performed according to the FDA guidelines [1-6]. In agreement with the mechanisms of intracrinology where DHEA is exclusively transformed intracellularly into active sex steroids which act and are inactivated locally before being released as glucuronided or sulfated metabolites for elimination by the kidneys and liver, all sex steroids remained well within normal postmenopausal values following administration of intravaginal DHEA. Serum estradiol, the most relevant sex steroid, was measured after 12weeks of treatment at 3.36pg/ml (cITT-S population) or 19% below the normal postmenopausal value of 4.17pg/ml. On the other hand, serum E1-S, the best recognized marker of global estrogenic activity, shows an average value of 209pg/ml at 12 weeks compared to 220pg/ml in normal postmenopausal women. Moreover, serum ADT-G, the main metabolite of androgens, also remains well within normal postmenopausal values. The present data shows that a low daily intravaginal dose (6.5mg) of DHEA (prasterone) which is efficacious on the symptoms and signs of VVA, permits to achieve the desired local efficacy without systemic exposure, in agreement with the stringent mechanisms of menopause established after 500 million years of

  5. Clinical utility, safety, and efficacy of pregabalin in the treatment of fibromyalgia

    PubMed Central

    Bhusal, Santosh; Diomampo, Sherilyn; Magrey, Marina N

    2016-01-01

    Fibromyalgia is a chronic debilitating medical syndrome with limited therapeutic options. Pregabalin, an anticonvulsant and α-2-Δ subunit receptor ligand, is one of the anchor drugs approved by the US Food and Drug Administration for the treatment of fibromyalgia. The drug has shown clinically meaningful benefits across multiple symptom domains of fibromyalgia. Efficacy of pregabalin in fibromyalgia pain has been evaluated in at least five high-quality randomized trials, two long-term extension studies, a meta-analysis, a Cochrane database systematic review, and several post hoc analyses. These studies also hint towards a meaningful benefit on sleep, functioning, quality of life, and work productivity. Side effects of pregabalin, although common, are mild to moderate in intensity. They are noted early during therapy, improve or disappear with dose reduction, and are not usually life- or organ threatening. In most patients, tolerance develops to the most common side effects, dizziness, and somnolence, with time. With close clinical monitoring at initiation or dose titration, pregabalin can be effectively used in primary care setting. Pregabalin is cost saving with long-term use and its cost-effectiveness profile is comparable, if not better, to that of other drugs used in fibromyalgia. In the present era of limited therapeutic options, pregabalin undoubtedly retains its role as one of cardinal drugs used in the treatment of fibromyalgia. This review intends to discuss the clinical utility of pregabalin in the management of fibromyalgia with a focus on efficacy, safety, and cost-effectiveness. PMID:26937205

  6. Postoperative respiratory depression associated with pregabalin: A case series and a preoperative decision algorithm

    PubMed Central

    Eipe, Naveen; Penning, John

    2011-01-01

    Pregabalin is gaining popularity in the perioperative period for its usefulness in treating neuropathic pain and its apparent opioid-sparing effect. The present report describes the perioperative course of three patients who received pregabalin and experienced significant respiratory depression in the postoperative period. All three patients consented to the report and publication of the present case series. The first patient was elderly with borderline renal dysfunction. She experienced respiratory arrest in the immediate postoperative period following a craniotomy for tumour excision. The second patient presented with severe respiratory depression 12 h after receiving a spinal anesthetic for joint replacement, and was later found to have clinically significant obstructive sleep apnea. The third patient, who was an otherwise healthy elderly individual on benzodiazepines for anxiety, experienced respiratory arrest in the postanesthesia care unit after an uneventful anesthesia for lumbar spine decompression. All of these patients were treated successfully with standard resuscitation measures. Although other causes of respiratory depression in these patients were considered, there appears to be an association between pregabalin and this complication. The present article briefly reviews the evidence regarding the perioperative use of pregabalin. Based on the authors’ experience and the available evidence, they believe that pregabalin may be useful in the management of acute pain in carefully selected patients undergoing certain surgeries. A clinical algorithm has been developed to guide the perioperative use of pregabalin. This algorithm may be helpful in increasing the safety of perioperative pregabalin use. PMID:22059207

  7. Comparison of central versus peripheral delivery of pregabalin in neuropathic pain states

    PubMed Central

    2012-01-01

    Background Although pregabalin therapy is beneficial for neuropathic pain (NeP) by targeting the CaVα2δ-1 subunit, its site of action is uncertain. Direct targeting of the central nervous system may be beneficial for the avoidance of systemic side effects. Results We used intranasal, intrathecal, and near-nerve chamber forms of delivery of varying concentrations of pregabalin or saline delivered over 14 days in rat models of experimental diabetic peripheral neuropathy and spinal nerve ligation. As well, radiolabelled pregabalin was administered to determine localization with different deliveries. We evaluated tactile allodynia and thermal hyperalgesia at multiple time points, and then analyzed harvested nervous system tissues for molecular and immunohistochemical changes in CaVα2δ-1 protein expression. Both intrathecal and intranasal pregabalin administration at high concentrations relieved NeP behaviors, while near-nerve pregabalin delivery had no effect. NeP was associated with upregulation of CACNA2D1 mRNA and CaVα2δ-1 protein within peripheral nerve, dorsal root ganglia (DRG), and dorsal spinal cord, but not brain. Pregabalin's effect was limited to suppression of CaVα2δ-1 protein (but not CACNA2D1 mRNA) expression at the spinal dorsal horn in neuropathic pain states. Dorsal root ligation prevented CaVα2δ-1 protein trafficking anterograde from the dorsal root ganglia to the dorsal horn after neuropathic pain initiation. Conclusions Either intranasal or intrathecal pregabalin relieves neuropathic pain behaviours, perhaps due to pregabalin's effect upon anterograde CaVα2δ-1 protein trafficking from the DRG to the dorsal horn. Intranasal delivery of agents such as pregabalin may be an attractive alternative to systemic therapy for management of neuropathic pain states. PMID:22236461

  8. Pregabalin: a review of its use in adults with generalized anxiety disorder.

    PubMed

    Frampton, James E

    2014-09-01

    Pregabalin (Lyrica(®)), a well established anxiolytic agent, has been approved in the EU for the treatment of generalized anxiety disorder (GAD) in adults. It has a distinct mechanism of action relative to other anti-anxiety agents (α2δ binding at presynaptic voltage dependent calcium channels leading to inhibition of excitatory neurotransmission), a rapid onset of effect (typically ≤1 week) and broad spectrum activity against both the psychic and somatic symptoms of GAD. In long-term studies, pregabalin maintained improvements in anxiety symptoms that occurred in response to short-term treatment and delayed the time to relapse of GAD compared with placebo. Common comorbidities of GAD, such as insomnia, gastrointestinal symptoms and subsyndromal depression, have no effect on the anxiolytic efficacy of, and moreover are specifically improved by, pregabalin. Treatment with pregabalin is generally well tolerated; the drug has an adverse event profile that includes dizziness, somnolence and weight gain. The potential for abuse of pregabalin is low; the risk of withdrawal symptoms is generally low when the drug is discontinued gradually (over 1 week). Alongside selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs), pregabalin is considered a first-line agent for the long-term treatment of GAD by the World Federation of Societies of Biological Psychiatry. It should be stressed, however, that definitive head-to-head studies comparing pregabalin with SSRI/SNRIs, including in patients with GAD and co-morbid major depressive disorder, are currently lacking. Recently, a study of SSRI/SNRI augmentation with pregabalin yielded positive results, while another study of switching from long-term benzodiazepine therapy to pregabalin was inconclusive; further investigations on these topics are warranted. PMID:25149863

  9. Preparation and evaluation of floating tablets of pregabalin.

    PubMed

    Kanwar, Navjot; Kumar, Rakesh; Sarwal, Amita; Sinha, V R

    2016-01-01

    Floating tablets of pregabalin were prepared using different concentrations of the gums (xanthan gum and guar gum), Carbopol 974P NF and HPMC K100. Optimized formulations were studied for physical tests, floating time, swelling behavior, in vitro release studies and stability studies. In vitro drug release was higher for tablet batches containing guar and xanthan gum as compared to the batches containing Carbopol 974P NF. Tablet batches were subjected to stability studies and evaluated by different parameters (drug release, drug content, FTIR and DSC studies). The optimized tablet batch was selected for in vivo pharmacodynamic studies (PTZ induced seizures). The results obtained showed that the onset of jerks and clonus were delayed and extensor phase was abolished with time in treated groups. A significant difference (p > 0.05) was observed in control and treated group behavior indicating an excellent activity of the formulation for a longer period (>12 h). PMID:26146770

  10. The potential of pregabalin in neurology, psychiatry and addiction: a qualitative overview.

    PubMed

    Martinotti, Giovanni; Lupi, Matteo; Sarchione, Fabiola; Santacroce, Rita; Salone, Anatolia; De Berardis, Domenico; Serroni, Nicola; Cavuto, Marilde; Signorelli, Maria; Aguglia, Eugenio; Valchera, Alessandro; Iasevoli, Felice; Di Giannantonio, Massimo

    2013-01-01

    Pregabalin is an anticonvulsant drug that binds to the α₂δ (alpha2delta) subunit of the voltage-dependent calcium channel in central nervous system (CNS). Pregabalin decreases the release of neurotransmitters, including glutamate, norepinephrine, substance P and calcitonin gene-related peptide. Purpose of this paper is to offer a qualitative overview of the studies currently available in literature about this drug, examining the effectiveness of pregabalin in its various fields of application. Our analysis, conducted on a final selection of 349 scientific papers, shows that pregabalin may help to reduce pain in diabetic neuropathy, in post-herpetic neuralgia and in some patients affected by fibromyalgia. It is also effective for the treatment of diverse types of seizures and has similar efficacy to benzodiazepines and venlafaxine in anxiety disorder. Moreover, pregabalin may be a therapeutic agent for the treatment of alcohol abuse, in both withdrawal phase and relapse prevention. Possible implications in the treatment of benzodiazepines dependence are emerging, but a potential abuse or misuse of the drug has also been reported. Range of dosage may fluctuate considerably, from 75 mg to 600 mg per day. Further studies are needed to completely understand pregabalin mechanism of action in the different diseases. PMID:23782139

  11. Pregabalin and placebo responders show different effects on central pain processing in chronic pancreatitis patients

    PubMed Central

    Bouwense, Stefan AW; Olesen, Søren S; Drewes, Asbjørn M; van Goor, Harry; Wilder-Smith, Oliver HG

    2015-01-01

    Background Pain control in chronic pancreatitis is a major challenge; the mechanisms behind analgesic treatment are poorly understood. This study aims to investigate the differences in pain sensitivity and modulation in chronic pancreatitis patients, based on their clinical response (responders vs nonresponders) to placebo or pregabalin treatment. Methods This study was part of a randomized, double-blind, placebo-controlled trial evaluating the analgesic effects of pregabalin and placebo in chronic pancreatitis. Post hoc, patients were assigned to one of four groups, ie, responders and nonresponders to pregabalin (n=16; n=15) or placebo (n=12; n=17) treatment. Responders were defined as patients with >30% pain reduction after 3 weeks of treatment. We measured change in pain sensitivity before and after the treatment using electric pain detection thresholds (ePDT) in dermatomes C5 (generalized effects) and Ventral T10 (segmental effects). Descending endogenous pain modulation was quantified via conditioned pain modulation (CPM) paradigm. Results Sixty patients were analyzed in a per-protocol analysis. ePDT change in C5 was significant vs baseline and greater in pregabalin (1.3 mA) vs placebo responders (−0.1 mA; P=0.015). This was not so for ePDT in Ventral T10. CPM increased more in pregabalin (9%) vs placebo responders (−17%; P<0.001). CPM changed significantly vs baseline only for pregabalin responders (P=0.006). Conclusion This hypothesis-generating study provides the first evidence that pain relief with pregabalin is associated with anti-hyperalgesic effects and increased endogenous inhibitory modulation. No such effects were observed in patients experiencing pain relief with the placebo treatment. The mechanisms underlying analgesic response to placebo vs drug treatments are different and, together with their interactions, deserve further study. PMID:26203273

  12. Hemangiosarcoma in mice administered pregabalin: analysis of genotoxicity, tumor incidence, and tumor genetics.

    PubMed

    Pegg, David; Bleavins, Michael; Herman, James; Wojcinski, Zbigniew; Graziano, Michael; Henck, Judith; Criswell, Kay A; Anderson, Timothy; Duddy, Steven

    2012-07-01

    Pregabalin, (S)-3-(aminomethyl)-5-methylhexanoic acid, binds with high affinity to the α(2)δ subunit of voltage-gated calcium channels and exerts analgesic, anxiolytic, and antiseizure activities. Two-year carcinogenicity studies were completed in B6C3F1 and CD-1 mice and two separate studies in Wistar rats. Doses in mice were 200, 1000, and 5000 mg/kg/day, with systemic exposures (AUC(0-24 h)) up to 31 times the mean exposure in humans, given the maximum recommended clinical dose. In rats, doses were 50, 150, and 450 mg/kg/day in males and 100, 300, and 900 mg/kg/day in females; systemic exposures up to 24 times were achieved in clinical trials. In both strains of mice, pregabalin treatment was associated with an increased incidence of hemangiosarcoma primarily in liver, spleen, and bone marrow. The incidence of hemangiosarcoma was higher in B6C3F1 mice than in CD-1 mice, consistent with its spontaneous incidence. Pregabalin did not increase the incidence of any other tumor type in rats and was not genotoxic, based on an extensive battery of in vivo and in vitro tests in bacterial and mammalian systems. Thus, pregabalin is a single-species, single tumor-type, nongenotoxic mouse carcinogen. Hemangiosarcomas occurring in mice treated with pregabalin were genotypically distinct from hemangiosarcomas induced by genotoxic carcinogens in humans with respect to ras and p53 mutation patterns and were similar to spontaneous tumors. Furthermore, there was a strong association between pregabalin treatment and bone marrow changes in these studies in mice, suggesting a possible link between the effects observed in bone marrow and the increase in tumor incidence in pregabalin-treated mice. PMID:22539615

  13. Neuropathic Pain in Elderly Patients with Chronic Low Back Painand Effects of Pregabalin: A Preliminary Study

    PubMed Central

    Ito, Kenyu; Hida, Tetsuro; Ito, Sadayuki; Harada, Atsushi

    2015-01-01

    Study Design Preliminary study. Purpose To assess the association of neuropathic pain with chronic low back pain (LBP) and the effect of pregabalin on neuropathic pain in the elderly. Overview of Literature Of those with chronic LBP, 37% were predominantly presenting with neuropathic pain in young adults. Pregabalin is effective for pain in patients with diabetic neuropathy and peripheral neuralgia. No study has reported on the effects of pregabalin for chronic LBP in elderly patients yet. Methods Pregabalin was administered to 32 patients (age, ≥65 years) with chronic LBP for 4 weeks. Pain and activities of daily living were assessed using the Neuropathic Pain Screening Questionnaire (NePSQ), the pain DETECT questionnaire, visual analog scale, the Japanese Orthopedic Association score, the short form of the McGill Pain Questionnaire and the Roland Morris Disability Questionnaire. Modic change and spinal canal stenosis were investigated using magnetic resonance imaging. Results Altogether, 43.3% of patients had neuropathic pain according to the NePSQ and 15.6% patients had pain according to the pain DETECT. The efficacy rate of pregabalin was 73.3%. A significant effect was observed in patients with neuropathic pain after 4 weeks of administration. Conclusions Neuropathic pain was slightly less frequently associated with chronic LBP in the elderly. Pregabalin was effective in reducing pain in patients with chronic LBP accompanied with neuropathic pain. Lumbar spinal stenosis and lower limb symptoms were observed in patients with neuropathic pain. We recommend the use of pregabalin for patients after evaluating a screening score, clinical symptoms and magnetic resonance imaging studies. PMID:25901238

  14. Double-blind, randomized, controlled, crossover trial of pregabalin for neurogenic claudication

    PubMed Central

    Frazer, Maria E.; Rast, Shirley A.; McDermott, Michael P.; Gewandter, Jennifer S.; Chowdhry, Amit K.; Czerniecka, Kate; Pilcher, Webster H.; Simon, Lee S.; Dworkin, Robert H.

    2015-01-01

    Objectives: To test the effects of pregabalin on the induction of neurogenic claudication. Methods: This study was a randomized, double-blind, active placebo-controlled, 2-period, crossover trial. Twenty-nine subjects were randomized to receive pregabalin followed by active placebo (i.e., diphenhydramine) or active placebo followed by pregabalin. Each treatment period lasted 10 days, including a 2-step titration. Periods were separated by a 10-day washout period, including a 3-day taper phase after the first period. The primary outcome variable was the time to first moderate pain symptom (Numeric Rating Scale score ≥4) during a 15-minute treadmill test (Tfirst). Secondary outcome measures included pain intensity at rest, pain intensity at the end of the treadmill test, distance walked, and validated self-report measures of pain and functional limitation including the Roland-Morris Disability Questionnaire, modified Brief Pain Inventory–Short Form, Oswestry Disability Index, and Swiss Spinal Stenosis Questionnaire. Results: No significant difference was found between pregabalin and active placebo for the time to first moderate pain symptom (difference in median Tfirst = −1.08 [95% confidence interval −2.25 to 0.08], p = 0.61). In addition, none of the secondary outcome measures of pain or functional limitation were significantly improved by pregabalin compared with active placebo. Conclusions: Pregabalin was not more effective than active placebo in reducing painful symptoms or functional limitations in patients with neurogenic claudication associated with lumbar spinal stenosis. Classification of evidence: This study provides Class I evidence that for patients with neurogenic claudication, compared with diphenhydramine, pregabalin does not increase the time to moderate pain during a treadmill test. PMID:25503625

  15. The antiallodynic action of pregabalin in neuropathic pain is independent from the opioid system

    PubMed Central

    Yalcin, Ipek; Nexon, Laurent; Wurtz, Xavier; Ceredig, Rhian Alice; Daniel, Dorothée; Hawkes, Rachael Aredhel; Salvat, Eric; Barrot, Michel

    2016-01-01

    Background Clinical management of neuropathic pain, which is pain arising as a consequence of a lesion or a disease affecting the somatosensory system, partly relies on the use of anticonvulsant drugs such as gabapentinoids. Therapeutic action of gabapentinoids such as gabapentin and pregabalin, which act by the inhibition of calcium currents through interaction with the α2δ-1 subunit of voltage-dependent calcium channels, is well documented. However, some aspects of the downstream mechanisms are still to be uncovered. Using behavioral, genetic, and pharmacological approaches, we tested whether opioid receptors are necessary for the antiallodynic action of acute and/or long-term pregabalin treatment in the specific context of neuropathic pain. Results Using the cuff model of neuropathic pain in mice, we show that acute pregabalin administration at high dose has a transitory antiallodynic action, while prolonged oral pregabalin treatment leads to sustained antiallodynic action, consistent with clinical observations. We show that pregabalin remains fully effective in μ-opioid receptor, in δ-opioid receptor and in κ-opioid receptor deficient mice, either female or male, and its antiallodynic action is not affected by acute naloxone. Our work also shows that long-term pregabalin treatment suppresses tumor necrosis factor-α overproduction induced by sciatic nerve constriction in the lumbar dorsal root ganglia. Conclusions We demonstrate that neither acute nor long-term antiallodynic effect of pregabalin in a context of neuropathic pain is mediated by the endogenous opioid system, which differs from opioid treatment of pain and antidepressant treatment of neuropathic pain. Our data are also supportive of an impact of gabapentinoid treatment on the neuroimmune aspect of neuropathic pain. PMID:27030724

  16. Pregabalin Versus Pramipexole: Effects on Sleep Disturbance in Restless Legs Syndrome

    PubMed Central

    Garcia-Borreguero, Diego; Patrick, Jeffrey; DuBrava, Sarah; Becker, Philip M.; Lankford, Alan; Chen, Crystal; Miceli, Jeffrey; Knapp, Lloyd; Allen, Richard P.

    2014-01-01

    Study Objectives: To compare pregabalin versus placebo and pramipexole for reducing restless legs syndrome (RLS)-related sleep disturbance. Design: Randomized, double-blinded, crossover trial. Setting: Twenty-three US sleep centers. Participants: Eighty-five individuals with moderate to severe idiopathic RLS and associated sleep disturbance. Interventions: Participants were randomized across 6 treatment sequences comprising three 4-week periods on pregabalin 300 mg/day (n = 75), pramipexole 0.5 mg/day (n = 76), or placebo (n = 73). Measurements and Results: Polysomnography was conducted over 2 nights at the end of each period. Primary (wake after sleep onset [WASO], pregabalin vs placebo) and key secondary endpoints were analyzed for statistical significance, with descriptive statistics for other endpoints. Pregabalin improved sleep maintenance, demonstrated by reductions in WASO (-27.1 min vs placebo [P < 0.0001]; -26.9 vs pramipexole) and number of awakenings after sleep onset (-2.7 vs placebo; -7.9 vs pramipexole [P < 0.0001]) by polysomnography, and an increase in subjective total sleep time (30.8 min vs placebo [P < 0.0001]; 26.8 vs pramipexole). Pregabalin also increased slow wave sleep duration (20.9 min vs placebo; 32.1 vs pramipexole [P < 0.0001]). Reduction in periodic limb movement arousal index (PLMAI) with pregabalin was similar to pramipexole and greater than placebo (-3.7 PLMA/h [P < 0.0001]), although reduction in total PLM in sleep was less than for pramipexole. Conclusions: This study demonstrated improvements in objective and subjective measures of sleep maintenance and sleep architecture with pregabalin compared with placebo and pramipexole. Effects of pregabalin on periodic limb movement arousal index were comparable to pramipexole. Trial Registration: ClinicalTrials.gov identifier, NCT00991276; http://clinicaltrials.gov/show/NCT00991276 Citation: Garcia-Borreguero D; Patrick J; DuBrava S; Becker PM; Lankford A; Chen C; Miceli J; Knapp L; Allen

  17. Combination of pregabalin with duloxetine for fibromyalgia: a randomized controlled trial.

    PubMed

    Gilron, Ian; Chaparro, Luis E; Tu, Dongsheng; Holden, Ronald R; Milev, Roumen; Towheed, Tanveer; DuMerton-Shore, Deborah; Walker, Sarah

    2016-07-01

    Fibromyalgia is a syndrome characterized by chronic widespread pain and associated with sleep disturbance, depression, fatigue, and cognitive dysfunction. Polypharmacy is commonly used, but supportive evidence is limited. Most fibromyalgia trials focus primarily on pain reduction with monotherapy. This trial compares a pregabalin-duloxetine combination to each monotherapy. Using a randomized, double-blind, 4-period crossover design, participants received maximally tolerated doses of placebo, pregabalin, duloxetine, and pregabalin-duloxetine combination-for 6 weeks. Primary outcome was daily pain (0-10); secondary outcomes included global pain relief, Fibromyalgia Impact Questionnaire, SF-36 survey, Medical Outcomes Study Sleep Scale, Beck Depression Inventory (BDI-II), adverse events, and other measures. Of 41 participants randomized, 39 completed ≥2 treatments. Daily pain during placebo, pregabalin, duloxetine, and combination was 5.1, 5.0, 4.1, and 3.7, respectively (P < 0.05 only for combination vs placebo, and pregabalin). Participants (%) reporting ≥moderate global pain relief were 18%, 39%, 42%, and 68%, respectively (P < 0.05 for combination vs placebo, pregabalin, and duloxetine). Fibromyalgia Impact Questionnaire scores were 42.9, 37.4, 36.0, and 29.8, respectively (P < 0.05 for combination vs placebo, pregabalin, and duloxetine). SF-36 scores were 50.2, 55.7, 56.0, and 61.2, respectively (P < 0.05 for combination vs placebo, pregabalin, and duloxetine). Medical Outcomes Study Sleep Scale scores were 48.9, 35.2, 46.1, and 32.1, respectively (P < 0.05 only for combination vs placebo, and duloxetine). BDI-II scores were 11.9, 9.9, 10.7, and 8.9, respectively (P < 0.05 only for combination vs placebo). Moderate-severe drowsiness was more frequent during combination vs placebo. Combining pregabalin and duloxetine for fibromyalgia improves multiple clinical outcomes vs monotherapy. Continued research should compare this and other combinations to monotherapy

  18. Efficacy of Pregabalin in the Treatment of Radicular Pain: Results of a Controlled Trial

    PubMed Central

    Malik, Khalid M.; M. Nelson, Ariana; J. Avram, Michael; Lee Robak, Sabrina; T. Benzon, Honorio

    2015-01-01

    Background: Pregabalin is commonly used to treat patients with various neuropathic pain syndromes. Objectives: The purpose of the present study was to evaluate the efficacy of pregabalin in patients with lumbar or cervical radicular pain. Patients and Methods: A prospective, randomized, double-blind trial was conducted in 39 patients with lumbar and cervical radicular pain, who received 3 weeks of either pregabalin (n = 10) or placebo (n = 9) treatment. Baseline pain and disability were evaluated before the treatment and were re-evaluated, along with overall patient satisfaction, after the 3 weeks of treatment. Results: Data on 19 of the 39 patients recruited were available for analysis. No statistically significant differences in the pain, disability, and patient satisfaction scores were found between the groups. When the individual patient scores were assessed, the placebo treatment was found to be efficacious in 4 of the 9 patients and pregabalin was effective in 2 of the 10 patients, but the difference was not statistically significant (P = 0.350). Conclusions: The present data do not suggest that pregabalin is more efficacious than placebo in the treatment of lumbar and cervical radicular pain. However, the small sample size of this study may have affected the ability to detect such a difference. PMID:26478867

  19. Pregabalin and gabapentin for the treatment of sciatica.

    PubMed

    Robertson, Kelvin; Marshman, Laurence A G; Plummer, David

    2016-04-01

    Whilst pregabalin (PGB) and gabapentin (GBP) are both used to treat neuropathic pain, their relative role in sciatica is unclear. Our aim was to extensively review the roles of PGB and GBP in treating sciatica. The efficacy, side effects (SE) profile and cost of PGB and GBP in neuropathic pain states were reviewed with special reference to sciatica. Eleven articles matched the criteria: seven systematic reviews, one retrospective cross-sectional study, one placebo-controlled-crossover study, one randomized placebo-controlled double-blind study and one case report. GBP and PGB appeared to demonstrate comparable efficacy and SE. However, the amount and quality of evidence was low, and only indirect comparisons were available. Importantly, no direct "head-to-head" study existed. Globally, costs varied widely (by up to 31 times) and unpredictably (PGB cheaper than GBP, or vice versa). Formulary regulator rulings were globally disparate; however, many exclusively favoured the more expensive drug (whether GBP or PGB). No studies assessed PGB-GBP interchange. Weak evidence suggests that efficacy and SE with GBP and PGB are probably similar; however, firm conclusions are precluded. Despite weak data, and having cited minor titration, but definite cost, advantages, UK National Institute for Health and Clinical Excellence favoured PGB over GBP. Given that no evidence supports unhindered PGB-GBP interchange, neither drug should probably be favoured. Prospective "head-to-head" studies are urgently required to provide robust evidence-based knowledge for choice of GBP or PGB in sciatica. PMID:26633090

  20. Development and evaluation of in situ gel of pregabalin

    PubMed Central

    Madan, Jyotsana R; Adokar, Bhushan R; Dua, Kamal

    2015-01-01

    Aim and Background: Pregabalin (PRG), an analog of gamma-aminobutyric acid, reduces the release of many neurotransmitters, including glutamate, and noradrenaline. It is used for the treatment of epilepsy; simple and complex partial convulsion. The present research work aims to ensure a high drug absorption by retarding the advancement of PRG formulation through the gastrointestinal tract. The work aims to design a controlled release PRG formulation which is administered as liquid and further gels in the stomach and floats in gastric juice. Materials and Methods: In situ gelling formulations were prepared using sodium alginate, calcium chloride, sodium citrate, hydroxypropyl methylcellulose (HPMC) K100M, and sodium bicarbonate. The prepared formulations were evaluated for solution viscosity, drug content, in vitro gelling studies, gel strength, and in vitro drug release. The final formulation was optimized using a 32 full factorial design. Results: The formulation containing 2.5% w/v sodium alginate and 0.2% w/v calcium chloride were considered optimum since it showed minimum floating lag time (18 s), optimum viscosity (287.3 cps), and gel strength (4087.17 dyne/cm2). The optimized formulation follows Korsmeyer-Peppas kinetic model with n value 0.3767 representing Fickian diffusion mechanism of drug release. Conclusion: Floating in situ gelling system of PRG can be formulated using sodium alginate as a gelling polymer and calcium chloride as a complexing agent to control the drug release for about 12 h for the treatment of epilepsy. PMID:26682193

  1. Effect of Gabapentin and Pregabalin in Rat Model of Taxol Induced Neuropathic Pain

    PubMed Central

    Rameshkannan, S.; Ali, R. Meher

    2015-01-01

    Background Chemotherapy induced neuropathy pain remains as a major dose limiting side effect of many commonly used chemotherapeutic drugs. Presently newer antiepileptic agents have been developed with improved safety and tolerability profiles in alleviating neuropathic pain. Objectives To evaluate the effect of Gabapentin and Pregabalin in Paclitaxel (Taxol) induced neuropathic pain and to compare the effect of these drugs in animal models. Materials and Methods Rats were randomly divided into four groups of six animals each. Group 1- vehicle, Group 2 – Paclitaxel (2mg/kg), Group 3 - Gabapentin (60mg/kg) with Paclitaxel, Group 4 - Pregabalin (30mg/kg) with Paclitaxel. Pain was induced by intraperitoneal injection of Paclitaxel on four alternate days. After taking the baseline values, the drugs treated groups (group 3 and 4) were administered with respective drugs once a day orally for eight consecutive days along with paclitaxel. All the animals were tested for thermal hyperalgesia and cold allodynia on day 0, 7, 14, 21 and 28 with Radiant heat method and Tail immersion test, Acetone drop method respectively. Results In Radiant heat method, gabapentin and pregabalin treated animals found to have significant increase in the tail latency period compared to control and paclitaxel treated groups in all periods of observation. Acetone drop test and tail immersion test also showed significant response similar to Radiant heat method. Pregabalin showed highly significant effect when compared to gabapentin group. Conclusion Both gabapentin and pregabalin produced significant anti-hyperalgesic and anti-allodynic effects in experimental animal models. Pregabalin treated group showed highly significant effect compared to gabapentin treated animals. PMID:26155495

  2. Comparative clinical study of gabapentin and pregabalin for postoperative analgesia in laparoscopic cholecystectomy

    PubMed Central

    Mishra, Rajshree; Tripathi, Manoj; Chandola, H. C.

    2016-01-01

    Background: Reduction in central sensitization by gabapentinoids that include gabapentin and pregabalin may reduce acute postoperative pain. Aims: The aim of this study is to evaluate postoperative analgesic benefit and efficacy in patients administered with oral gabapentin or pregabalin as premedication for laparoscopic cholecystectomy under general anesthesia. Settings and Design: Randomized, prospective, and comparative study. Materials and Methods: In this study, recruited patients were randomly allocated in three groups. Groups A, B, and C received 2 capsules of B complex, 3 capsules of 300 mg gabapentin each, and 2 capsules of 75 mg pregabalin, respectively, each in 30 patients of each group, 1 h before induction of anesthesia. Postoperative efficacy among these three groups was compared with respect to increase in duration of analgesia, reduction in postoperative pain scores, total postoperative requirements of analgesics and side effects. Statistical Analysis: Mean and standard deviation were calculated. Test of analysis between two groups was done by t-test and among three groups by analysis of variance, and then P value was calculated. Results: Pregabalin and gabapentin group had lower visual analog scale (VAS) score (P < 0.05), prolonged timing of first rescue analgesic (4.67 ± 14.79 vs. 158 ± 13.10 vs. 343.16 ± 9.69) min, and less opioid consumption (169.87 ± 20.32 vs. 116.13 ± 14.08 vs. 64.67 ± 16.69) mg compared to placebo group. Between the gabapentinoids, pregabalin group had lower VAS score, prolonged timing of first rescue analgesic, and less opioids consumption than the gabapentin group. Conclusion: It is concluded in this study that pregabalin group had lower VAS score, prolonged timing of first rescue analgesic, and less opioids consumption than the gabapentin group. Both gabapentinoids had better postoperative analgesic profile than placebo. PMID:27212747

  3. Effectiveness of posthemodialysis administration of pregabalin (75 mg) in treatment resistance uremia pruritus.

    PubMed

    Khan, Tahir Mehmood; Aziz, Abdul; Suleiman, Amal K

    2016-01-01

    Uremic pruritus (UP) is one of the complications faced by majority of the patients with end stage renal disease (ESRD). Due to complex pathophysiology of UP, most of the anti-inflammatory and tropical lubricants often not provide a long lasting control over pruritus. Recently the uses of certain anti-epileptics are found to demonstrate promising relief to UP. To test the effect of 75 mg pregabalin in patients with treatment resistance pruritus. Data was prospectively collected from a patient with ESRD and suffering from treatment resistance pruritus. Intensity of pruritus was recorded using 5D-itching scale (5D-IS) and visual analogue scale (VAS). Pre and post assessment was done for this patient, on initial assess the parathyroid hormone level of the patient was 70.5 pg/ml with a serum phosphate level of 2.61 mmol/L. Upon initial assess the VAS score was 8 and 5D-IS score was twenty. After the duration of four weeks of pregabalin 75 mg post hemodialysis, 5D-IS score reduced to 8 and VAS score move down to 3. Pregabalin 75 mg post hemodialysis was found to reduce the intensity of UP. Pregabalin 75 mg post hemodialysis can be another option to treat UP. PMID:26957874

  4. New treatment options in the management of fibromyalgia: role of pregabalin

    PubMed Central

    Zareba, Grazyna

    2008-01-01

    Fibromyalgia (FM) is a common, chronic pain disorder with unknown etiology, characterized by widespread musculoskeletal pain and tenderness, and accompanied by several other symptoms such as sleep disturbance, fatigue, and mood disorders. Pregabalin is the first drug approved for the treatment of FM. Pregabalin has analgesic, anticonvulsant, and anxiolytic activity and has earlier demonstrated efficacy in the management of neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, and as adjuvant therapy for adult patients with partial onset seizures. Pregabalin, a lipophilic gamma-aminobutyric acid (GABA) analog, is α2δ-1 ligand that binds to, and modulates, voltage-gated calcium channels. This modulation is characterized by a reduction of the excessive neurotransmitter release that is observed in certain neurological and psychotic disorders. Several randomized, double-blind, placebo-controlled studies have demonstrated that pregabalin has been effective in pain management, improving sleep quality and fatigue, as well as in several domains of health related quality of life. Because of mild to moderate adverse effects it can be considered a well-tolerated therapy for FM. PMID:19337459

  5. Pregabalin in the treatment of inferior alveolar nerve paraesthesia following overfilling of endodontic sealer

    PubMed Central

    Alonso-Ezpeleta, Oscar; Martín, Pablo J.; López-López, José; Castellanos-Cosano, Lizett; Martín-González, Jenifer; Segura-Egea, Juan J.

    2014-01-01

    A case of orofacial pain and inferior alveolar nerve (IAN) paraesthesia after extrusion of endodontic sealer within the mandibular canal treated with prednisone and pregabalin is described. A 36-year-old woman underwent root canal treatment of the mandibular second right premolar tooth. Post-operative panoramic radiograph revealed the presence of radiopaque canal sealer in the mandibular canal. Damage to IAN consecutive to extrusion of endodontic sealer was diagnosed. Non-surgical management was decided, including: 1 mg/kg/day prednisone 2 times/day, once-daily regimen, and 150 mg/day pregabalin, two doses per day, monitoring the progress with periodic follow-up visits. Six weeks after the incident the signs and symptoms were gone. The complete resolution of paraesthesia and the control of pain achieved suggest that a non-surgical approach, combining prednisone and the GABA analogue pregabalin, is a good option in the management of the IAN damage subsequent to endodontic sealer extrusion. Key words:Endodontics, inferior alveolar nerve, neuropathic pain, orofacial pain, paraesthesia, pregabalin. PMID:24790724

  6. Comparative study between paracetamol and two different doses of pregabalin on postoperative pain in laparoscopic cholecystectomy

    PubMed Central

    Esmat, Ibrahim M.; Farag, Hanan M.

    2015-01-01

    Background: Postoperative pain is the primary reason for prolonged hospital stay after laparoscopic cholecystectomy. This study compared the effect of a single oral preoperative administration of paracetamol (1 g) with 2 different doses of pregabalin (150 or 300 mg) for attenuating postoperative pain and analgesic consumption. Materials and Methods: Seventy-five patients, aged 18-60 years, American Society of Anesthesiologists’ physical status I and II undergoing elective laparoscopic cholecystectomy were included in this randomized controlled study. Patients were divided into three groups, 25 each to receive either oral paracetamol 1 g (group I, control group) or pregabalin 150 (group II) or 300 mg (group III), 2 h before surgery. Postoperative pain was evaluated based on visual analog scale over a period of 6 h and 1st time for rescue analgesia. Postoperative sedation, hemodynamic changes, serum cortisol level, and side effects were also evaluated. Results: There was a significant decrease in mean heart rate, mean systolic blood pressure, sedation score, pain score, and delayed the first request for analgesics postoperatively in group (II) and group (III) compared to group (I) 2 h postoperatively. There was no significant difference in group (III) compared to group (II) postoperatively. The incidence of postoperative side effects was more in group (III). Conclusion: The single oral preoperative dose administration of pregabalin had significant opioid-sparing effect in the first 6 h after surgery, whereas side effects were more common with administration of pregabalin 300 mg. PMID:26543452

  7. Premedication With Oral Pregabalin for the Prevention of Acute Postsurgical Pain in Coronary Artery Bypass Surgery

    PubMed Central

    Ziyaeifard, Mohsen; Mehrabanian, Mohammad Javad; Faritus, Seyedeh Zahra; Khazaei Koohpar, Mehrdad; Ferasatkish, Rasool; Hosseinnejad, Heidar; Mehrabanian, Mohammadreza

    2015-01-01

    Background: For coronary artery bypass grafting (CABG) sternotomy should be performed. The pain after surgery is severe and requires medical intervention. Use of the analgesics is limited by their side effects and studies suggest that prevention with some medications before surgery is effective in controlling the postoperative pain. Objectives: We investigated the efficacy of pregabalin administration before surgery in the treatment of acute postoperative pain after CABG surgery. Patients and Methods: Sixty patients indicated for elective CABG surgery were randomly allocated to two groups. One group received placebo and the other received 150 mg of oral pregabalin before surgery. Heart rates, blood pressure, respiratory rate, intensive care unit (ICU) stay duration, morphine consumption, and pain score according to the visual analog scale (VAS) were measured and recorded at 4, 12, and 24 hours of surgery. Results: Pregabalin consumption did not alter hemodynamic parameters and was safe in patients after CABG. Its consumption was associated with significant reduction in the pain score (P values were 0.035, 0.026, and 0.047 respectively at 4, 12, and 24 hours of surgery). Its use was not associated with changes in the morphine consumption at 4, 12, and 24 hours of surgery (P > 0.05). Conclusions: Premedication with studied dose of pregabalin is effective for the prevention of postoperative pain in patients after CABG and has no adverse effects. Trials with other treating schedule and doses of the drug should be performed to determine the best treatment plan. PMID:25830118

  8. Systemic Pregabalin Attenuates Sensorimotor Responses and Medullary Glutamate Release in Inflammatory Tooth Pain Model

    PubMed Central

    Narita, Noriyuki; Kumar, Naresh; Cherkas, Pavel S.; Chiang, Chen Yu; Dostrovsky, Jonathan O.; Coderre, Terence J.; Sessle, Barry J.

    2012-01-01

    Our previous studies have demonstrated that application to the tooth pulp of the inflammatory irritant mustard oil (MO) induces medullary glutamate release and central sensitization in the rat medullary dorsal horn (MDH), as well as nociceptive sensorimotor responses in craniofacial muscles in rats. There is recent evidence that anticonvulsant drugs such as pregabalin that influence glutamatergic neurotransmission are effective in several pain states. The aim of this study was to examine whether systemic administration of pregabalin attenuated glutamate release in the medulla as well as these nociceptive effects reflected in increased electromyographic (EMG) activity induced by MO application to the tooth pulp. Male adult rats were anesthetized with isofluorane (1.0~1.2 %), and jaw and tongue muscle EMG activities were recorded by needle electrodes inserted bilaterally into masseter and anterior digastric muscles and into the genioglossus muscle, and also the medullary release of glutamate was assessed by in vivo microdialysis. Pregabalin or vehicle control (isotonic saline) was administered 30 min before the pulpal application of MO or vehicle control (mineral oil). Application of mineral oil to the maxillary first molar tooth pulp produced no change in baseline EMG activity and glutamate release. However, application of MO to the pulp significantly increased both the medullary release of glutamate and EMG activity in the jaw and tongue muscles for several minutes. In contrast, pre-medication with pregabalin, but not vehicle control, significantly and dose-dependently attenuated the medullary glutamate release and EMG activity in these muscles after MO application to the tooth pulp (ANOVA, p<0.05). These results suggest that pregabalin may attenuate the medullary release of glutamate and associated nociceptive sensorimotor responses in this acute inflammatory pulpal pain model, and that it may prove useful for the treatment of orofacial inflammatory pain states

  9. Systemic pregabalin attenuates sensorimotor responses and medullary glutamate release in inflammatory tooth pain model.

    PubMed

    Narita, N; Kumar, N; Cherkas, P S; Chiang, C Y; Dostrovsky, J O; Coderre, T J; Sessle, B J

    2012-08-30

    Our previous studies have demonstrated that application of inflammatory irritant mustard oil (MO) to the tooth pulp induces medullary glutamate release and central sensitization in the rat medullary dorsal horn (MDH), as well as nociceptive sensorimotor responses in craniofacial muscles in rats. There is recent evidence that anticonvulsant drugs such as pregabalin that influence glutamatergic neurotransmission are effective in several pain states. The aim of this study was to examine whether systemic administration of pregabalin attenuated glutamate release in the medulla as well as these nociceptive effects reflected in increased electromyographic (EMG) activity induced by MO application to the tooth pulp. Male adult rats were anesthetized with isofluorane (1.0-1.2%), and jaw and tongue muscle EMG activities were recorded by needle electrodes inserted bilaterally into masseter and anterior digastric muscles and into the genioglossus muscle, and also the medullary release of glutamate was assessed by in vivo microdialysis. Pregabalin or vehicle control (isotonic saline) was administered 30 min before the pulpal application of MO or vehicle control (mineral oil). Application of mineral oil to the maxillary first molar tooth pulp produced no change in baseline EMG activity and glutamate release. However, application of MO to the pulp significantly increased both the medullary release of glutamate and EMG activity in the jaw and tongue muscles for several minutes. In contrast, pre-medication with pregabalin, but not vehicle control, significantly and dose-dependently attenuated the medullary glutamate release and EMG activity in these muscles after MO application to the tooth pulp (analysis of variance (ANOVA), p<0.05). These results suggest that pregabalin may attenuate the medullary release of glutamate and associated nociceptive sensorimotor responses in this acute inflammatory pulpal pain model, and that it may prove useful for the treatment of orofacial

  10. Effect of pregabalin on contextual memory deficits and inflammatory state-related protein expression in streptozotocin-induced diabetic mice.

    PubMed

    Sałat, Kinga; Gdula-Argasińska, Joanna; Malikowska, Natalia; Podkowa, Adrian; Lipkowska, Anna; Librowski, Tadeusz

    2016-06-01

    Diabetes mellitus is a metabolic disease characterized by hyperglycemia due to defects in insulin secretion or its action. Complications from long-term diabetes consist of numerous biochemical, molecular, and functional tissue alterations, including inflammation, oxidative stress, and neuropathic pain. There is also a link between diabetes mellitus and vascular dementia or Alzheimer's disease. Hence, it is important to treat diabetic complications using drugs which do not aggravate symptoms induced by the disease itself. Pregabalin is widely used for the treatment of diabetic neuropathic pain, but little is known about its impact on cognition or inflammation-related proteins in diabetic patients. Thus, this study aimed to evaluate the effect of intraperitoneal (ip) pregabalin on contextual memory and the expression of inflammatory state-related proteins in the brains of diabetic, streptozotocin (STZ)-treated mice. STZ (200 mg/kg, ip) was used to induce diabetes mellitus. To assess the impact of pregabalin (10 mg/kg) on contextual memory, a passive avoidance task was applied. Locomotor and exploratory activities in pregabalin-treated diabetic mice were assessed by using activity cages. Using Western blot analysis, the expression of cyclooxygenase-2 (COX-2), cytosolic prostaglandin E synthase (cPGES), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), nuclear factor-ĸB (NF-ĸB) p50 and p65, aryl hydrocarbon receptor (AhR), as well as glucose transporter type-4 (GLUT4) was assessed in mouse brains after pregabalin treatment. Pregabalin did not aggravate STZ-induced learning deficits in vivo or influence animals' locomotor activity. We observed significantly lower expression of COX-2, cPGES, and NF-κB p50 subunit, and higher expression of AhR and Nrf2 in the brains of pregabalin-treated mice in comparison to STZ-treated controls, which suggested immunomodulatory and anti-inflammatory effects of pregabalin. Antioxidant properties of pregabalin in the brains of

  11. Efficacy of Pregabalin in Acute Postoperative Pain Under Different Surgical Categories

    PubMed Central

    Lam, David M.H.; Choi, Siu-Wai; Wong, Stanley S.C.; Irwin, Michael G.; Cheung, Chi-Wai

    2015-01-01

    Abstract The efficacy of pregabalin in acute postsurgical pain has been demonstrated in numerous studies; however, the analgesic efficacy and adverse effects of using pregabalin in various surgical procedures remain uncertain. We aim to assess the postsurgical analgesic efficacy and adverse events after pregabalin administration under different surgical categories using a systematic review and meta-analysis of randomized controlled trials. A search of the literature was performed between August 2014 to April 2015, using PubMed, Ovid via EMBASE, Google Scholar, and ClinicalTrials.gov with no limitation on publication year or language. Studies considered for inclusion were randomized controlled trials, reporting on relevant outcomes (2-, 24-hour pain scores, or 24 hour morphine-equivalent consumption) with treatment with perioperative pregabalin. Seventy-four studies were included. Pregabalin reduced pain scores at 2 hours in all categories: cardiothoracic (Hedge's g and 95%CI, −0.442 [−0.752 to −0.132], P = 0.005), ENT (Hedge g and 95%CI, −0.684 [−1.051 to −0.316], P < 0.0001), gynecologic (Hedge g, 95%CI, −0.792 [−1.235 to −0.350], P < 0.0001), laparoscopic cholecystectomy (Hedge g, 95%CI, –0.600 [–0.989 to –0.210], P = 0.003), orthopedic (Hedge g, 95%CI, −0.507 [−0.812 to −0.202], P = 0.001), spine (Hedge g, 95%CI, −0.972 [−1.537 to −0.407], P = 0.001), and miscellaneous procedures (Hedge g, 95%CI, −1.976 [−2.654 to −1.297], P < 0.0001). Pregabalin reduced 24-hour morphine consumption in gynecologic (Hedge g, 95%CI, −1.085 [−1.582 to −0.441], P = 0.001), laparoscopic cholecystectomy (Hedge g, 95%CI, –0.886 [–1.652 to –0.120], P = 0.023), orthopedic (Hedge g, 95%CI, −0.720 [−1.118 to −0.323], P < 0.0001), spine (Hedge g, 95%CI, −1.016 [−1.732 to −0.300], P = 0.005), and miscellaneous procedures (Hedge g, 95%CI, −1.329 [−2.286 to −0.372], P = 0

  12. Ammonium acetate

    Integrated Risk Information System (IRIS)

    Ammonium acetate ; CASRN 631 - 61 - 8 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic

  13. Vinyl acetate

    Integrated Risk Information System (IRIS)

    Vinyl acetate ; CASRN 108 - 05 - 4 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Eff

  14. Ethyl acetate

    Integrated Risk Information System (IRIS)

    Ethyl acetate ; CASRN 141 - 78 - 6 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Eff

  15. Phenylmercuric acetate

    Integrated Risk Information System (IRIS)

    Phenylmercuric acetate ; CASRN 62 - 38 - 4 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinog

  16. Thallium acetate

    Integrated Risk Information System (IRIS)

    Jump to main content . Integrated Risk Information System Recent Additions | Contact Us Search : All EPA IRIS • You are here : EPA Home • Research • Environmental Assessment • IRIS • IRIS Summaries Redirect Page As of September 30 , 2009 , the assessment summary for Thallium acetate is included in t

  17. Pregabalin for the treatment of patients with generalized anxiety disorder with inadequate treatment response to antidepressants and severe depressive symptoms.

    PubMed

    Olivares, José M; Álvarez, Enrique; Carrasco, José L; Pérez Páramo, María; López-Gómez, Vanessa

    2015-09-01

    To evaluate the effectiveness of pregabalin in patients with resistant generalized anxiety disorder (GAD) and severe depressive symptoms, we carried out a post-hoc analysis of a multicenter, prospective, and observational 6-month study. We included patients who were at least 18 years old, fulfilled the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria for GAD, showed inadequate responses to previous courses of antidepressant treatment, had Montgomery-Asberg Rating Scale scores of at least 35, had not received pregabalin previously, and were prescribed pregabalin upon entry into this study. We included 1815 patients fulfilling the DSM-IV criteria for GAD, and 133 (7.3%) fulfilled the selection criteria for these analyses. Ninety-seven percent of the patients received pregabalin (mean dose: 222 mg/day) in combination with other psychotropics. The Hamilton Anxiety Scale total score was reduced by a mean of 20.3 points (95% confidence interval, 22.1-18.4) (57.2% reduction) at month 6. Pregabalin also ameliorated comorbid depressive symptoms, with a reduction in the mean score of the Montgomery-Asberg Rating Scale of 22.3 points (95% confidence interval, 24.2-20.4) (56.6% reduction). Our results suggest that pregabalin, as part of a combination regimen with antidepressants and/or benzodiazepines, might be effective for the treatment of patients with GAD who have shown inadequate response to previous antidepressants and have severe depressive symptoms. PMID:26111356

  18. Comparison of propranolol and pregabalin for prophylaxis of childhood migraine: a randomised controlled trial.

    PubMed

    Bakhshandeh Bali, MohammadKazem; Rahbarimanesh, Ali Akbar; Sadeghi, Manelie; Sedighi, Mostafa; Karimzadeh, Parvaneh; Ghofrani, Mohammad

    2015-01-01

    Migraine involves 5-10% of children and adolescents. Thirty percent of children with severe migraine attacks have school absence and reduced quality of life that need preventive therapy. The purpose of this randomised control trial study is to compare the effectiveness, safety and the tolerability of pregabalin toward Propranolol in migraine prophylaxis of children. From May 2011 to October 2012, 99 children 3-15 years referred to the neurology clinic of Mofid Children's Hospital with a diagnosis of migraine enrolled the study. Patients randomly divided into two groups (A&B). We treated children of group A with capsule of pregabalin as children of group B with tablet of propranolol for at least 8 weeks. In this study, 99 patients were examined that 91 children reached the last stage. The group A consistsed of 46 patients, 12(26.1%) girls, 34 (73.9%) boys and the group B consisted of 45 patients, 14(31.1%) girls, 31 (68.9%) boys. Basis of age, gender, headache onset, headache frequency, migraine type, triggering and relieving factors there was no significant difference among these groups (P>0.05). After 4 and 8 weeks of Pregabalin usage monthly headache frequency decreased to 2.2±4.5 and 1.76±6.2 respectively. Propranolol reduced monthly headache frequency up to 3.73±6.11 and 3.34±5.95 later 4 and 8 weeks respectively. There was a significant difference between these two groups according to headache frequency reduction (P=0.04). Pregabalin efficacy in reducing the frequency and duration of pediatric migraine headache is considerable in comparison with propranolol. PMID:26024701

  19. Gabapentin vs pregabalin as a premedication in lower limb orthopaedics surgery under combined spinal epidural technique

    PubMed Central

    Khetarpal, Ranjana; Kataria, Amar Parakash; Bajaj, Samita; Kaur, Harjinder; Singh, Sudha

    2016-01-01

    Background: Pregabalin and gabapentin are the gamma-aminobutyric acid analogs used as a part of multimodal analgesic regimen. Aim: To compare the postoperative analgesic benefits of gabapentin or pregabalin as a premedication for lower limb orthopedic surgery under combined spinal-epidural techniques. Settings and Design: Randomized double-blind study. Materials and Methods: A total of 90 patients were divided into three groups: G, P, C who received gabapentin 1200 mg, pregabalin 300 mg, and placebo, respectively 1.5 h before surgery. All patients received combined spinal-epidural block with 3 ml of 0.5% intrathecal bupivacaine. Assessment of pain was made with visual analog scale (VAS). Postoperative analgesia was provided with epidural top-ups with 2.5 ml of 0.5% bupivacaine and fentanyl 25 μg when VAS >3. Rescue analgesia in the form of injection diclofenac (75 mg) intramuscularly was given if VAS >3 even after epidural top-up. A total number of epidural top-ups, rescue analgesia, pain-free interval postspinal anesthesia, and sedation score were noted. Statistical Analysis: This was done using SPSS version 17. Mean and standard deviation were calculated using Chi-square test and analysis of variance. Results: The total postoperative analgesic time was 7.23 h in Group G, 14.80 h in Group P, and 4.17 h in Group C. A total number of epidural top-ups were 2.43 in Group G, 0.77 in Group P, and 4.43 in Group C. Conclusion: Pregabalin 300 mg and gabapentin 1200 mg significantly reduce the need of postoperative rescue analgesia, epidural top-ups, and increase the duration of postspinal anesthesia without altering hemodynamics with sedation as a major side effect. PMID:27212758

  20. Pregabalin, the lidocaine plaster and duloxetine in patients with refractory neuropathic pain: a systematic review

    PubMed Central

    2010-01-01

    Background Patients frequently fail to receive adequate pain relief from, or are intolerant of, first-line therapies prescribed for neuropathic pain (NeP). This refractory chronic pain causes psychological distress and impacts patient quality of life. Published literature for treatment in refractory patients is sparse and often published as conference abstracts only. The aim of this study was to identify published data for three pharmacological treatments: pregabalin, lidocaine plaster, and duloxetine, which are typically used at 2nd line or later in UK patients with neuropathic pain. Methods A systematic review of the literature databases MEDLINE, EMBASE and CCTR was carried out and supplemented with extensive conference and grey literature searching. Studies of any design (except single patient case studies) that enrolled adult patients with refractory NeP were included in the review and qualitatively assessed. Results Seventeen studies were included in the review: nine of pregabalin, seven of the lidocaine plaster, and one of duloxetine. No head-to-head studies of these treatments were identified. Only six studies included treatments within UK licensed indications and dose ranges. Reported efficacy outcomes were not consistent between studies. Pain scores were most commonly assessed in studies including pregabalin; trials of pregabalin and the lidocaine plaster reported the proportion of responders. Significant improvements in the total, sensory and affective scores of the Short-form McGill Pain Questionnaire, and in function interference, sleep interference and pain associated distress, were associated with pregabalin treatment; limited or no quality of life data were available for the other two interventions. Limitations to the review are the small number of included studies, which are generally small, of poor quality and heterogeneous in patient population and study design. Conclusions Little evidence is available relevant to the treatment of refractory

  1. Effect of Pregabalin on Cardiovascular Responses to Exercise and Postexercise Pain and Fatigue in Fibromyalgia: A Randomized, Double-Blind, Crossover Pilot Study

    PubMed Central

    White, Andrea T.; Light, Kathleen C.; Bateman, Lucinda; Hughen, Ronald W.; Vanhaitsma, Timothy A.; Light, Alan R.

    2015-01-01

    Pregabalin, an approved treatment for fibromyalgia (FM), has been shown to decrease sympathetic nervous system (SNS) activity and inhibit sympathetically maintained pain, but its effects on exercise responses have not been reported. Methods. Using a randomized double-blind crossover design, we assessed the effect of 5 weeks of pregabalin (versus placebo) on acute cardiovascular and subjective responses to moderate exercise in 19 FM patients. Blood pressure (BP), heart rate (HR), and ratings of perceived exertion (RPE) during exercise and ratings of pain, physical fatigue, and mental fatigue before, during, and for 48 hours after exercise were compared in patients on pregabalin versus placebo and also versus 18 healthy controls. Results. On placebo, exercise RPE and BP were significantly higher in FM patients than controls (p < 0.04). Pregabalin responders (n = 12, defined by patient satisfaction and symptom changes) had significantly lower exercise BP, HR, and RPE on pregabalin versus placebo (p < 0.03) and no longer differed from controls (p > 0.26). Cardiovascular responses of nonresponders (n = 7) were not altered by pregabalin. In responders, pregabalin improved ratings of fatigue and pain (p < 0.04), but negative effects on pain and fatigue were seen in nonresponders. Conclusions. These preliminary findings suggest that pregabalin may normalize cardiovascular and subjective responses to exercise in many FM patients. PMID:27026828

  2. Successful use of pregabalin by the rectal route to treat chronic neuropathic pain in a patient with complete intestinal failure.

    PubMed

    Doddrell, Charlotte; Tripathi, Shiva Shankar

    2015-01-01

    Pregabalin is widely used for treatment of neuropathic pain and is only approved for oral use. This is the first reported case of using pregabalin by the rectal route for treatment in a 70-year-old patient with chronic neuropathic pain and complete intestinal failure. Therapies used in an attempt to manage his chronic pain have included a variety of doses and strengths of opioid preparations and cannabinoids, plus topical and alternative therapies. These were not effective, so it was decided to start a trial of pregabalin administered by the rectal route. Serum levels were measured to assess absorption. Within a few weeks of starting the treatment, the patient had improved pain control and appeared more comfortable and calm. PMID:26516246

  3. Pregabalin and Tranexamic Acid Evaluation by Two Simple and Sensitive Spectrophotometric Methods

    PubMed Central

    Sher, Nawab; Fatima, Nasreen; Perveen, Shahnaz; Siddiqui, Farhan Ahmed; Wafa Sial, Alisha

    2015-01-01

    This paper demonstrates colorimetric visible spectrophotometric quantification methods for amino acid, namely, tranexamic acid and pregabalin. Both drugs contain the amino group, and when they are reacted with 2,4-dinitrophenol and 2,4,6-trinitrophenol, they give rise to yellow colored complexes showing absorption maximum at 418 nm and 425 nm, respectively, based on the Lewis acid base reaction. Detailed optimization process and stoichiometric studies were conducted along with investigation of thermodynamic features, that is, association constant and standard free energy changes. The method was linear over the concentration range of 0.02–200 µgmL−1 with correlation coefficient of more than 0.9990 in all of the cases. Limit of detection was in range from 0.0041 to 0.0094 µgmL−1 and limit of quantification was in the range from 0.0137 to 0.0302 µgmL−1. Excellent recovery in Placebo spiked samples indicated that there is no interference from common excipients. The analytical methods under proposal were successfully applied to determine tranexamic acid and pregabalin in commercial products. t-test and F ratio were evaluated without noticeable difference between the proposed and reference methods. PMID:25873964

  4. Impact of pregabalin treatment on synaptic plasticity and glial reactivity during the course of experimental autoimmune encephalomyelitis

    PubMed Central

    Silva, Gleidy A A; Pradella, Fernando; Moraes, Adriel; Farias, Alessandro; dos Santos, Leonilda M B; de Oliveira, Alexandre L R

    2014-01-01

    Background Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease that affects young adults. It is characterized by generating a chronic demyelinating autoimmune inflammation in the central nervous system. An experimental model for studying MS is the experimental autoimmune encephalomyelitis (EAE), induced by immunization with antigenic proteins from myelin. Aims The present study investigated the evolution of EAE in pregabalin treated animals up to the remission phase. Methods and results The results demonstrated a delay in the onset of the disease with statistical differences at the 10th and the 16th day after immunization. Additionally, the walking track test (CatWalk) was used to evaluate different parameters related to motor function. Although no difference between groups was obtained for the foot print pressure, the regularity index was improved post treatment, indicating a better motor coordination. The immunohistochemical analysis of putative synapse preservation and glial reactivity revealed that pregabalin treatment improved the overall morphology of the spinal cord. A preservation of circuits was depicted and the glial reaction was downregulated during the course of the disease. qRT-PCR data did not show immunomodulatory effects of pregabalin, indicating that the positive effects were restricted to the CNS environment. Conclusions Overall, the present data indicate that pregabalin is efficient for reducing the seriousness of EAE, delaying its course as well as reducing synaptic loss and astroglial reaction. PMID:25365796

  5. A randomised controlled trial of peri-operative pregabalin vs. placebo for video-assisted thoracoscopic surgery.

    PubMed

    Konstantatos, A H; Howard, W; Story, D; Mok, L Y H; Boyd, D; Chan, M T V

    2016-02-01

    We allocated 52 participants to oral pregabalin 300 mg and 48 participants to placebo tablets before thoracoscopic surgery and for five postoperative days. The median (IQR [range]) cumulative pain scores at rest for nine postoperative months were 184 (94-274 [51-1454]) after pregabalin and 166 (66-266 [48-1628]) after placebo, p = 0.39. The corresponding scores on deep breathing were 468 (281-655 [87-2870]) and 347 (133-561 [52-3666]), respectively, p = 0.16. After three postoperative months, 29/100 participants had persistent surgical site pain, 19/52 after pregabalin and 10/48 after placebo, p = 0.12, of whom four and five, respectively, attended a pain management clinic, p = 0.24. The median (IQR [range]) morphine equivalent consumption six days after surgery was 273 (128-619 [39-2243]) mg after pregabalin and 319 (190-663 [47-2258]) mg after placebo, p = 0.35. PMID:26566754

  6. Effect of Oral Pregabalin as Preemptive Analgesic in Patients Undergoing Lower Limb Orthopedic Surgeries under Spinal Anaesthesia

    PubMed Central

    Sebastian, Bon; Nelamangala, Kiran; Krishnamurthy, Dinesh

    2016-01-01

    Introduction Conquering postoperative pain which has significant impact on the surgery outcome can be challenging for the clinicians. Pregabalin is a GABA analogue used for various neuropathic pain syndromes. Very few studies are there with the use of pregabalin as a preemptive analgesic for orthopedic surgeries. Aim To compare pregabalin 150 mg with placebo for postoperative pain control in patients undergoing elective lower limb orthopedic surgeries under spinal anaesthesia and to assess any side effects. Materials and Methods A randomized double blinded prospective study was undertaken. Ninety patients with ASA physical status I, II, aged between 18–50 years were enrolled in the study. One hour prior to spinal anaesthesia Group C - received colour matched empty capsules, Group P – received 150mg of oral pregabalin. Spinal anaesthesia was administered in sitting position in L3-L4 space with Inj. Bupivacaine heavy (0.5%) at a dose of 0.3mg/kg body weight with 20 mg being the maximum dose using 25 gauge spinal needle. Rescue analgesia was provided with using Inj. Diclofenac 1.5 mg/kg intramuscular. Results Time for rescue analgesia (VAS score >3) was significantly increased in Group P than in Group C. The total dose of diclofenac required in the 24 hour postoperative period was significantly lower in Group P than in Group C. The sedation scores and patient satisfaction scores were also more in Group P than in Group C. Conclusion Preemptive pregabalin in an oral dose of 150 mg offers good postoperative analgesia in lower limb orthopedic surgeries under spinal anaesthesia.

  7. Comparative efficacy and tolerability of duloxetine, pregabalin, and milnacipran for the treatment of fibromyalgia: a Bayesian network meta-analysis of randomized controlled trials.

    PubMed

    Lee, Young Ho; Song, Gwan Gyu

    2016-05-01

    The aim of this study was to assess the relative efficacy and tolerability of duloxetine, pregabalin, and milnacipran at the recommended doses in patients with fibromyalgia. Randomized controlled trials (RCTs) examining the efficacy and safety of duloxetine 60 mg, pregabalin 300 mg, pregabalin 150 mg, milnacipran 200 mg, and milnacipran 100 mg compared to placebo in patients with fibromyalgia were included in this Bayesian network meta-analysis. Nine RCTs including 5140 patients met the inclusion criteria. The proportion of patients with >30 % improvement from baseline in pain was significantly higher in the duloxetine 60 mg, pregabalin 300 mg, milnacipran 100 mg, and milnacipran 200 mg groups than in the placebo group [pairwise odds ratio (OR) 2.33, 95 % credible interval (CrI) 1.50-3.67; OR 1.68, 95 % CrI 1.25-2.28; OR 1.62, 95 % CrI 1.16-2.25; and OR 1.61; 95 % CrI 1.15-2.24, respectively]. Ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that duloxetine 60 mg had the highest probability of being the best treatment for achieving the response level (SUCRA = 0.9431), followed by pregabalin 300 mg (SUCRA = 0.6300), milnacipran 100 mg (SUCRA = 0.5680), milnacipran 200 mg (SUCRA = 0.5617), pregabalin 150 mg (SUCRA = 0.2392), and placebo (SUCRA = 0.0580). The risk of withdrawal due to adverse events was lower in the placebo group than in the pregabalin 300 mg, duloxetine 60 mg, milnacipran 100 mg, and milnacipran 200 mg groups. However, there was no significant difference in the efficacy and tolerability between the medications at the recommended doses. Duloxetine 60 mg, pregabalin 300 mg, milnacipran 100 mg, and milnacipran 200 mg were more efficacious than placebo. However, there was no significant difference in the efficacy and tolerability between the medications at the recommended doses. PMID:27000046

  8. Impact of potential pregabalin or duloxetine drug–drug interactions on health care costs and utilization among Medicare members with fibromyalgia

    PubMed Central

    Ellis, Jeffrey J; Sadosky, Alesia B; Ten Eyck, Laura L; Cappelleri, Joseph C; Brown, Courtney R; Suehs, Brandon T; Parsons, Bruce

    2014-01-01

    Purpose To examine the impact of newly initiated pregabalin or duloxetine treatment on fibromyalgia (FM) patients’ encounters with potential drug–drug interactions (DDIs), the health care cost and utilization consequences of those interactions, and the impact of treatment on opioid utilization. Patients and methods Subjects included those with an FM diagnosis, a pregabalin or duloxetine prescription claim (index event), ≥1 inpatient or ≥2 outpatient medical claims, and ≥12 months preindex and ≥6 postindex enrollment. Propensity score matching was used to help balance the pregabalin and duloxetine cohorts on baseline demographics and comorbidities. Potential DDIs were defined based on Micromedex 2.0 software and were identified by prescription claims. Results No significant differences in baseline characteristics were found between matched pregabalin (n=794) and duloxetine cohorts (n=794). Potential DDI prevalence was significantly greater (P<0.0001) among duloxetine subjects (71.9%) than among pregabalin subjects (4.0%). There were no significant differences in all-cause health care utilization or costs between pregabalin subjects with and without a potential DDI. By contrast, duloxetine subjects with a potential DDI had higher mean all-cause costs ($9,373 versus $7,228; P<0.0001) and higher mean number of outpatient visits/member (16.0 versus 13.0; P=0.0009) in comparison to duloxetine subjects without a potential DDI. There was a trend toward a statistically significant difference between pregabalin and duloxetine subjects in their respective pre- versus post-differences in use of ≥1 long-acting opioids (1.6% and 3.4%, respectively; P=0.077). Conclusion The significantly higher prevalence of potential DDIs and potential cost impact found in FM duloxetine subjects, relative to pregabalin subjects, underscore the importance of considering DDIs when selecting a treatment. PMID:25339847

  9. Systemic pregabalin attenuates facial hypersensitivity and noxious stimulus-evoked release of glutamate in medullary dorsal horn in a rodent model of trigeminal neuropathic pain.

    PubMed

    Kumar, Naresh; Cherkas, Pavel S; Varathan, Vidya; Miyamoto, Makiko; Chiang, Chen Yu; Dostrovsky, Jonathan O; Sessle, Barry J; Coderre, Terence J

    2013-05-01

    Pregabalin is effective in treating many neuropathic pain conditions. However, the mechanisms of its analgesic effects remain poorly understood. The aim of the present study was to determine whether pregabalin suppresses facial mechanical hypersensitivity and evoked glutamate release in the medullary dorsal horn (MDH) in a rodent model of trigeminal neuropathic pain. Nociceptive mechanical sensitivity was assessed pre-operatively, and then post-operatively 1h following pregabalin or vehicle (saline) treatment on post-operative days 2 and 5 following infraorbital nerve transection (IONX). In addition, an in vivo microdialysis probe was inserted into the exposed medulla post-operatively and dialysate samples were collected. Glutamate release was then evoked by mustard oil (MO) application to the tooth pulp, and the effects of pregabalin or vehicle were examined on the MDH glutamate release. Glutamate concentrations in the dialysated samples were determined by HPLC, and data analyzed by ANOVA. IONX animals (but not control animals) showed facial mechanical hypersensitivity for several days post-operatively. In addition, tooth pulp stimulation with MO evoked a transient release of glutamate in the MDH of IONX animals. Compared to vehicle, administration of pregabalin significantly attenuated the facial mechanical hypersensitivity as well as the MO-evoked glutamate release in MDH. This study provides evidence in support of recent findings pointing to the usefulness of pregabalin in the treatment of orofacial neuropathic pain. PMID:23454190

  10. Pregabalin attenuates place escape/avoidance behavior in a rat model of spinal cord injury.

    PubMed

    Baastrup, Cathrine; Jensen, Troels Staehelin; Finnerup, Nanna Brix

    2011-01-25

    Spinal cord injury (SCI) pain in humans is difficult to treat, and the lack of valid methods to measure behavior comparable to the complex human pain experience preclinically represents an important obstacle to finding better treatments for this type of central pain. The place escape/avoidance paradigm (PEAP) relies on the active choice of an animal between its natural preference for a dark environment or pain relief, and it has been suggested to measure the affective-motivational component of pain. We have modified the method to a T10 spinal cord contusion model (SCC) of at-level central neuropathic pain in Sprague-Dawley rats. In order to demonstrate sensitivity to change in escape/avoidance behavior and thus the applicability of the PEAP method to predict drug efficacy, we investigated the effect of pregabalin (30 mg/kg) treatment in a randomized design. SCC animals displayed increased escape/avoidance behavior postinjury, indicating at-level mechanical hypersensitivity. Second, we found no correlation between state anxiety levels in SCC animals (elevated plus maze) and PEAP behavior, suggesting that the PEAP measurement is not biased by differences in anxiety levels. Third, we demonstrated a decrease in escape/avoidance behavior in response to treatment with the analgesic drug pregabalin. Thus, the PEAP may be applicable as a surrogate correlate of human pain. In conclusion, the primary finding in this study was a sensitivity to change in escape/avoidance behavior induced by pharmacological modulation with analgesics, supporting the use of the PEAP as a central outcome measure in preclinical SCI pain research. PMID:21070753

  11. Neuronal hyperexcitability in the ventral posterior thalamus of neuropathic rats: modality selective effects of pregabalin

    PubMed Central

    Dickenson, Anthony H.

    2016-01-01

    Neuropathic pain represents a substantial clinical challenge; understanding the underlying neural mechanisms and back-translation of therapeutics could aid targeting of treatments more effectively. The ventral posterior thalamus (VP) is the major termination site for the spinothalamic tract and relays nociceptive activity to the somatosensory cortex; however, under neuropathic conditions, it is unclear how hyperexcitability of spinal neurons converges onto thalamic relays. This study aimed to identify neural substrates of hypersensitivity and the influence of pregabalin on central processing. In vivo electrophysiology was performed to record from VP wide dynamic range (WDR) and nociceptive-specific (NS) neurons in anesthetized spinal nerve-ligated (SNL), sham-operated, and naive rats. In neuropathic rats, WDR neurons had elevated evoked responses to low- and high-intensity punctate mechanical stimuli, dynamic brushing, and innocuous and noxious cooling, but less so to heat stimulation, of the receptive field. NS neurons in SNL rats also displayed increased responses to noxious punctate mechanical stimulation, dynamic brushing, noxious cooling, and noxious heat. Additionally, WDR, but not NS, neurons in SNL rats exhibited substantially higher rates of spontaneous firing, which may correlate with ongoing pain. The ratio of WDR-to-NS neurons was comparable between SNL and naive/sham groups, suggesting relatively few NS neurons gain sensitivity to low-intensity stimuli leading to a “WDR phenotype.” After neuropathy was induced, the proportion of cold-sensitive WDR and NS neurons increased, supporting the suggestion that changes in frequency-dependent firing and population coding underlie cold hypersensitivity. In SNL rats, pregabalin inhibited mechanical and heat responses but not cold-evoked or elevated spontaneous activity. PMID:27098028

  12. Liquid chromatographic separation of pregabalin and its possible impurities with fluorescence detection after postcolumn derivatization with o-phtaldialdehyde.

    PubMed

    Dousa, Michal; Gibala, Petr; Lemr, K

    2010-11-01

    A rapid procedure based on direct extraction and RP-HPLC separation of pregabalin and its possible impurities with fluorescence detection has been developed. The separation conditions and parameters of derivatization reaction for postcolumn derivatization of pregabalin with o-phtaldialdehyde/2-mercaptoethanol were studied. Purospher STAR RP-8e column with isocratic elution was employed. Fluorescence detection was performed at excitation and emission wavelength of 345 nm and 450 nm, respectively. The proposed method has an advantage of a simple sample pre-treatment and a quick and very sensitive HPLC method. The applicability of developed method was successfully verified during analysis of commercial samples of tablets of Lyrica (Pfizer, USA). PMID:20435423

  13. Effectiveness of pregabalin for the treatment of chronic low back pain with accompanying lower limb pain (neuropathic component): a non-interventional study in Japan

    PubMed Central

    Taguchi, Toshihiko; Igarashi, Ataru; Watt, Stephen; Parsons, Bruce; Sadosky, Alesia; Nozawa, Kazutaka; Hayakawa, Kazuhiro; Yoshiyama, Tamotsu; Ebata, Nozomi; Fujii, Koichi

    2015-01-01

    Objective To evaluate the impact of pregabalin on sleep, pain, function, and health status in patients with chronic low back pain with accompanying neuropathic pain (CLBP-NeP) under routine clinical practice. Methods This prospective, non-interventional, observational study enrolled Japanese adults (≥18 years) with CLBP-NeP of duration ≥3 months and severity ≥5 on a numerical rating scale (0= no pain, 10= worst possible pain). Treatment was 8 weeks with pregabalin (n=157) or usual care alone (n=174); choice of treatment was determined by the physician. The primary efficacy outcome was change from baseline to 8 weeks in pain-related interference with sleep, assessed using the Pain-Related Sleep Interference Scale (PRSIS; 0= did not interfere with sleep, 10= completely interferes with sleep). Secondary endpoints were changes in PRSIS at week 4, and changes at weeks 4 and 8 in pain (numerical rating scale), function (Roland-Morris Disability Questionnaire), and quality of life (EuroQol 5D-5L); global assessments of change were evaluated from the clinician and patient perspectives at the final visit. Results Demographic characteristics were similar between cohorts, but clinical characteristics suggested greater disease severity in the pregabalin group including a higher mean (standard deviation) pain score, 6.3 (1.2) versus 5.8 (1.1) (P<0.001). For the primary endpoint, pregabalin resulted in significantly greater improvements in PRSIS at week 8, least-squares mean changes of −1.3 versus −0.4 for usual care (P<0.001); pregabalin also resulted in greater PRSIS improvement at week 4 (P=0.012). Relative to usual care at week 8, pregabalin improved pain and function (both P<0.001), and showed global improvements since beginning study medication (P<0.001). Pregabalin was well tolerated. Conclusion In clinical practice in patients with CLBP-NeP, pregabalin showed significantly greater improvements in pain-related interference with sleep relative to usual care. In

  14. Modeling the longitudinal latent effect of pregabalin on self-reported changes in sleep disturbances in outpatients with generalized anxiety disorder managed in routine clinical practice

    PubMed Central

    Ruiz, Miguel A; Álvarez, Enrique; Carrasco, Jose L; Olivares, José M; Pérez, María; Rejas, Javier

    2015-01-01

    Background Anxiety disorders are among the most common psychiatric illnesses, with generalized anxiety disorder (GAD) being one of the most common. Sleep disturbances are highly prevalent in GAD patients. While treatment with pregabalin has been found to be associated with significant improvement in GAD-related sleep disturbance across many controlled clinical trials, mediational analysis has suggested that a substantial portion of this effect could be the result of a direct effect of pregabalin. Thus, the objective of this study was to model the longitudinal latent effect of pregabalin or usual care (UC) therapies on changes in sleep in outpatients with GAD under routine clinical practice. Methods Male and female GAD outpatients, aged 18 years or above, from a 6-month prospective noninterventional trial were analyzed. Direct and indirect effects of either pregabalin or UC changes in anxiety symptoms (assessed with Hamilton Anxiety Scale) and sleep disturbances (assessed with Medical Outcomes Study-Sleep Scale [MOS-S]) were estimated by a conditional latent curve model applying structural equation modeling. Results A total of 1,546 pregabalin-naïve patients were analyzed, 984 receiving pregabalin and 562 UC. Both symptoms of anxiety and sleep disturbances were significantly improved in both groups, with higher mean (95% confidence interval) score reductions in subjects receiving pregabalin: −15.9 (−15.2; −16.6) vs −14.5 (−13.5; −15.5), P=0.027, in Hamilton Anxiety Scale; and −29.7 (−28.1; −31.3) vs −24.0 (−21.6; −26.4), P<0.001, in MOS-S. The conditional latent curve model showed that the pregabalin effect on sleep disturbances was significant (γ =−3.99, P<0.001), after discounting the effect on reduction in anxiety symptoms. A mediation model showed that 70% of the direct effect of pregabalin on sleep remained after discounting the mediated effect of anxiety improvement. Conclusion A substantial proportion of the incremental

  15. Evaluation of the safety and efficacy of pregabalin in older patients with neuropathic pain: results from a pooled analysis of 11 clinical studies

    PubMed Central

    2010-01-01

    Background Older patients are typically underrepresented in clinical trials of medications for chronic pain. A post hoc analysis of multiple clinical studies of pregabalin in patients with painful diabetic peripheral neuropathy (DPN) or postherpetic neuralgia (PHN) was conducted to evaluate the efficacy and safety of pregabalin in older patients. Methods Data from 11 double-blind, randomized, placebo-controlled clinical studies of pregabalin in patients with DPN or PHN were pooled. Efficacy outcomes included change in Daily Pain Rating Scale score, ≥30% and ≥50% responders, and endpoint pain score ≤3. Safety was based on adverse events (AEs). Primary efficacy was analyzed by analysis of covariance with terms for treatment, age category, protocol, baseline pain, and treatment-by-age category interaction. Results 2516 patients (white, n = 2344 [93.2%]; men, n = 1347 [53.5%]; PHN, n = 1003 [39.9%]; pregabalin, n = 1595) were included in the analysis. Patients were grouped by age: 18 to 64 years (n = 1236), 65 to 74 years (n = 766), and ≥75 years (n = 514). Baseline mean pain and sleep interference scores were comparable across treatment and age groups. Significant improvements in endpoint mean pain were observed for all pregabalin dosages versus placebo in all age groups (p ≤ 0.0009), except for the lowest dosage (150 mg/day) in the youngest age group. Clinically meaningful pain relief, defined as ≥30% and ≥50% pain response, was observed in all age groups. The most common AEs were dizziness, somnolence, peripheral edema, asthenia, dry mouth, weight gain, and infections. The relative risks for these AEs increased with pregabalin dose, but did not appear related to older age or type of neuropathic pain. Conclusions Pregabalin (150-600 mg/day) significantly reduced pain in older patients (age ≥65 years) with neuropathic pain and improvements in pain were comparable to those observed in younger patients. Titration of pregabalin to the lowest effective

  16. Formulation of a modified-release pregabalin tablet using hot-melt coating with glyceryl behenate.

    PubMed

    Jeong, Kyu Ho; Woo, Hye Seung; Kim, Chae Jin; Lee, Kyung Hwa; Jeon, Jun Young; Lee, Sang Young; Kang, Jae-Hoon; Lee, Sangkil; Choi, Young Wook

    2015-11-10

    A modified-release (MR) tablet of the anti-anxiety drug pregabalin (PRE) was prepared by hot-melt coating PRE with glyceryl behenate (GB) as a release retardant and compressing to form a matrix with microcrystalline cellulose (MCC) as a hydrophilic diluent. GB-coated PRE had a size in the range of 177-290 μm with good to acceptable flowability. Tablet hardness decreased slightly as GB content increased. PRE release from the tablet matrices was successfully modified by altering the ratio of MCC and GB, and it was found that dissolution- or diffusion-controlled release depended on the amount of GB used. Drug release was pH-independent. An accelerated stability test on the most promising MR tablet at 40°C and 75% relative humidity for 6 months showed no significant changes in PRE content, and the occurrence of total impurities--including PRE-lactam--was within acceptable limits. After oral administration of the selected MR tablet or a commercial IR capsule (Lyrica) to healthy human volunteers, pharmacokinetic parameters including Tmax, Cmax, AUC0-24, and T1/2 were compared. The confidence interval of AUC0-24 was within the adequate range, but that of Cmax was inadequate. This study demonstrated the potential use of GB for PRE-containing MR formulations. PMID:26315121

  17. Pregabalin for Refractory Radicular Leg Pain due to Lumbar Spinal Stenosis: A Preliminary Prospective Study

    PubMed Central

    Orita, Sumihisa; Yamashita, Masaomi; Eguchi, Yawara; Suzuki, Miyako; Inoue, Gen; Miyagi, Masayuki; Watanabe, Tomoko; Ozawa, Tomoyuki; Kamoda, Hiroto; Ishikawa, Tetsuhiro; Aoki, Yasuchika; Ito, Toshinori; Kubota, Go; Suzuki, Munetaka; Yamauchi, Kazuyo; Hanaoka, Eiji; Sakuma, Yoshihiro; Shimbo, Jun; Oikawa, Yasuhiro; Suzuki, Takane; Takahashi, Kazuhisa; Ohtori, Seiji

    2016-01-01

    We investigated the efficacy of pregabalin (PGB) for neuropathic leg pain in lumbar spinal stenosis (LSS) patients with disturbed activities of daily living (ADL)/quality of life (QOL) in a prospective observational study. Subjects were a total of 104 LSS patients with neuropathic pain (NeP) in leg and neurological intermittent claudication (IMC) refractory to nonsteroidal anti-inflammatory drugs (NSAIDs) for at least a month. NeP was identified using screening tool, Pain DETECT questionnaire. Visual analog scale (VAS) scores and responses to the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) were assessed before and 6 weeks after PGB treatment initiation. Changes in IMC distance and adverse events were also recorded. PGB significantly improved their VAS scores for pain and sleep quality (P < 0.001). With respect to JOABPEQ, significant improvements were observed with regard to the following dimensions: pain-related disorders (P < 0.01), lumbar spine dysfunction (P = 0.031), gait disturbance (P = 0.028), and psychological disorders (P = 0.014). The IMC distance showed an improvement tendency after PGB treatment, albeit with no significance (P = 0.063). Minor adverse events such as dizziness were observed. PGB can be effective for neuropathic leg pain refractory to NSAIDs in LSS patients, resulting in not only pain control but also improving lower back pain-related ADL/QOL scores. PMID:27445615

  18. Preparation of vinyl acetate

    DOEpatents

    Tustin, Gerald Charles; Zoeller, Joseph Robert; Depew, Leslie Sharon

    1998-01-01

    This invention pertains to the preparation of vinyl acetate by contacting a mixture of hydrogen and ketene with a heterogeneous catalyst containing a transition metal to produce acetaldehyde, which is then reacted with ketene in the presence of an acid catalyst to produce vinyl acetate.

  19. Preparation of vinyl acetate

    DOEpatents

    Tustin, G.C.; Zoeller, J.R.; Depew, L.S.

    1998-03-24

    This invention pertains to the preparation of vinyl acetate by contacting a mixture of hydrogen and ketene with a heterogeneous catalyst containing a transition metal to produce acetaldehyde, which is then reacted with ketene in the presence of an acid catalyst to produce vinyl acetate.

  20. Quantitation of pregabalin in dried blood spots and dried plasma spots by validated LC-MS/MS methods.

    PubMed

    Kostić, Nađa; Dotsikas, Yannis; Jović, Nebojša; Stevanović, Galina; Malenović, Anđelija; Medenica, Mirjana

    2015-05-10

    In this paper, novel LC-MS/MS methods for the determination of antiepileptic drug pregabalin in dried matrix spots (DMS) are presented. This attractive technique of sample collection in micro amount was utilized in the form of dried blood spots (DBS) and dried plasma spots (DPS). Following a pre-column derivatization procedure, using n-propyl chloroformate in the presence of n-propanol, and consecutive liquid-liquid extraction, derivatized pregabalin and its internal standard, 4-aminocyclohexanecarboxylic acid, were detected in positive ion mode by applying two SRM transitions per analyte. A YMC-Pack Octyl column (50mm×4.0mm, 3μm particle size) maintained at 30°C, was utilized with running mobile phase composed of acetonitrile: 0.15% formic acid (85:15, v/v). Flow rate was 550μL/min and total run time 2min. Established methods were fully validated over the concentration range of 0.200-20.0μg/mL for DBS and 0.400-40.0μg/mL for DPS, respectively, while specificity, accuracy, precision, recovery, matrix-effect, stability, dilution integrity and spot homogeneity were found within acceptance criteria. Validated methods were applied for the determination of pregabalin levels in dried blood and plasma samples obtained from patients with epilepsy, after per os administration of commercial capsules. Comparison of drug level in blood and plasma, as well as correction steps undertaken in order to overcome hematocrit issue, when analyzing DBS, are also given. PMID:25767905

  1. Efficacy and safety of premedication with single dose of oral pregabalin in children with dental anxiety: A randomized double-blind placebo-controlled crossover clinical trial

    PubMed Central

    Eskandarian, Tahereh; Eftekharian, Hamidreza; Soleymanzade, Rojin

    2015-01-01

    Background: Dental anxiety is a relatively frequent problem that can lead to more serious problems such as a child entering a vicious cycle as he/she becomes reluctant to accept the required dental treatments. The aim of this randomized double-blind clinical trial study was to evaluate the anxiolytic and sedative effect of pregabalin in children. Materials and Methods: Twenty-five children were randomized to a double-blind placebo-controlled crossover clinical trial. Two visits were scheduled for each patient. At the first visit, 75 mg pregabalin or placebo was given randomly, and the alternative was administered at the next visit. Anxiolytic and sedative effects were measured using the visual analogue scale. The child's behavior was rated with the Frankl behavioral rating scale and the sedation level during the dental procedure was scored using the Ramsay sedation scale. The unpaired, two-tailed Student's t-test was used to compare the mean changes of visual analog scale (VAS) for anxiety in the pregabalin group with that of the placebo group. A repeated measures MANOVA model was used to detect differences in sedation level in the pregabalin and placebo groups regarding the interaction of 3-time measurements; sub-group analysis was performed using Student's t-test. The Mann–Whitney U-test was used to analyze the nonparametric data of the Frankl and Ramsay scales. A P < 0.05 was considered significant. Results: The reduction of the VAS-anxiety score from 2 h post-dose was statistically significant in the pregabalin group. From 2 h to 4 h post-dose, the VAS-sedation score increased significantly in the pregabalin group. The child's behavior rating was not significantly different between the groups. The number of “successful” treatment visits was higher in the pregabalin group compared to the placebo group. Conclusion: Significant anxiolytic and sedative effects can be anticipated 2 h after oral administration of pregabalin without serious side effects. PMID

  2. Process and formulation variables of pregabalin microspheres prepared by w/o/o double emulsion solvent diffusion method and their clinical application by animal modeling studies.

    PubMed

    Aydogan, Ebru; Comoglu, Tansel; Pehlivanoglu, Bilge; Dogan, Murat; Comoglu, Selcuk; Dogan, Aysegul; Basci, Nursabah

    2015-01-01

    Pregabalin is an anticonvulsant drug used for neuropathic pain and as an adjunct therapy for partial seizures with or without secondary generalization in adults. In conventional therapy recommended dose for pregabalin is 75 mg twice daily or 50 mg three times a day, with maximum dosage of 600 mg/d. To achieve maximum therapeutic effect with a low risk of adverse effects and to reduce often drug dosing, modified release preparations; such as microspheres might be helpful. However, most of the microencapsulation techniques have been used for lipophilic drugs, since hydrophilic drugs like pregabalin, showed low-loading efficiency and rapid dissolution of compounds into the aqueous continous phase. The purpose of this study was to improve loading efficiency of a water-soluble drug and modulate release profiles, and to test the efficiency of the prepared microspheres with the help of animal modeling studies. Pregabalin is a water soluble drug, and it was encapsulated within anionic acrylic resin (Eudragit S 100) microspheres by water in oil in oil (w/o/o) double emulsion solvent diffusion method. Dichloromethane and corn oil were chosen primary and secondary oil phases, respectively. The presence of internal water phase was necessary to form stable emulsion droplets and it accelerated the hardening of microspheres. Tween 80 and Span 80 were used as surfactants to stabilize the water and corn oil phases, respectively. The optimum concentration of Tween 80 was 0.25% (v/v) and Span 80 was 0.02% (v/v). The volume of the continous phase was affected the size of the microspheres. As the volume of the continous phase increased, the size of microspheres decreased. All microsphere formulations were evaluated with the help of in vitro characterization parameters. Microsphere formulations (P1-P5) exhibited entrapment efficiency ranged between 57.00 ± 0.72 and 69.70 ± 0.49%; yield ranged between 80.95 ± 1.21 and 93.05 ± 1.42%; and mean particle size were

  3. Joint modeling of dizziness, drowsiness, and dropout associated with pregabalin and placebo treatment of generalized anxiety disorder.

    PubMed

    Frame, Bill; Miller, Raymond; Hutmacher, Matthew M

    2009-12-01

    Dizziness and drowsiness are cited as being predictors of dropout from clinical trials for the medicine pregabalin. These adverse events are typically recorded daily on a four point ordinal scale (0 = none, 1 = mild, 2 = moderate, 3 = severe), with most subjects never reporting either adverse event. We modeled the dizziness, drowsiness, and dropout associated with pregabalin use in generalized anxiety disorder using piecewise Weibull distributions for the time to first non-zero dizziness or drowsiness score, after which the dizziness or drowsiness was modeled with ordinal regression with a Markovian element. Dropout was modeled with a Weibull distribution. Platykurtosis was encountered in the estimated random effects distributions for the ordinal regression models and was addressed with dynamic John-Draper transformations. The only identified predictor for the time to first non-zero dizziness or drowsiness score was daily titrated dose. Predictors for dropout included creatinine clearance and maximum daily adverse event score. Tolerance to adverse events over time was modeled by including a non-stationary component for the dizziness ordinal Markov regression while the piecewise Weibull distributions allowed a change point in the median time to first non-zero dizziness or drowsiness score. PMID:19904583

  4. Identification of the alpha2-delta-1 subunit of voltage-dependent calcium channels as a molecular target for pain mediating the analgesic actions of pregabalin.

    PubMed

    Field, Mark J; Cox, Peter J; Stott, Emma; Melrose, Heather; Offord, James; Su, Ti-Zhi; Bramwell, Steve; Corradini, Laura; England, Steven; Winks, Joanna; Kinloch, Ross A; Hendrich, Jan; Dolphin, Annette C; Webb, Tony; Williams, Dic

    2006-11-14

    Neuropathic pain is a debilitating condition affecting millions of people around the world and is defined as pain that follows a lesion or dysfunction of the nervous system. This type of pain is difficult to treat, but the novel compounds pregabalin (Lyrica) and gabapentin (Neurontin) have proven clinical efficacy. Unlike traditional analgesics such as nonsteroidal antiinflammatory drugs or narcotics, these agents have no frank antiinflammatory actions and no effect on physiological pain. Although extensive preclinical studies have led to a number of suggestions, until recently their mechanism of action has not been clearly defined. Here, we describe studies on the analgesic effects of pregabalin in a mutant mouse containing a single-point mutation within the gene encoding a specific auxiliary subunit protein (alpha2-delta-1) of voltage-dependent calcium channels. The mice demonstrate normal pain phenotypes and typical responses to other analgesic drugs. We show that the mutation leads to a significant reduction in the binding affinity of pregabalin in the brain and spinal cord and the loss of its analgesic efficacy. These studies show conclusively that the analgesic actions of pregabalin are mediated through the alpha2-delta-1 subunit of voltage-gated calcium channels and establish this subunit as a therapeutic target for pain control. PMID:17088553

  5. Cost-Effectiveness of Capsaicin 8% Patch Compared with Pregabalin for the Treatment of Patients with Peripheral Neuropathic Pain in Scotland.

    PubMed

    Mankowski, Colette; Patel, Sachin; Trueman, David; Bentley, Anthony; Poole, Chris

    2016-01-01

    We evaluated the cost-effectiveness of capsaicin 8% patch (QUTENZA™) versus pregabalin in patients with PNP from the perspective of the National Health Service (NHS) and Personal and Social Services in Scotland, UK. A decision-tree cost-effectiveness model was developed for non-diabetic patients with peripheral neuropathic pain (PNP) who were pregabalin-naïve and had not achieved adequate pain relief or tolerated conventional first- or second-line treatments. Patients entering the model received either a single application of capsaicin 8% patch or titrated daily dosing with pregabalin; after 8 weeks patients were classified as responders, non-responders, or were assumed to discontinue treatment due to intolerable adverse events. Responders continued to receive baseline treatment at intervals observed in clinical practice. Non-responders and those who discontinued treatment were assumed to receive last-line therapy (duloxetine). The base-case time horizon was 2 years. Model inputs for effectiveness, discontinuations and health-state utilities were taken from a head-to-head non-inferiority study (ELEVATE, NCT01713426). Other inputs were obtained from published sources or clinical expert opinion. Costs were expressed in GBP 2013/14. Results were presented as incremental cost-effectiveness ratios (ICER), i.e. cost per quality-adjusted life-year (QALY) gained. Model assumptions were tested with scenario analyses. Parameter uncertainty was tested using one-way and probabilistic sensitivity analyses. Compared with dose-optimized pregabalin, capsaicin 8% patch was the dominant treatment strategy (total cost difference, -£11; total QALY gain, 0.049). Capsaicin 8% patch was also the dominant treatment strategy versus pregabalin in 6 out of 7 scenario analyses. The model was most sensitive to variation in time to capsaicin 8% patch retreatment (maximum ICER, £7,951/QALY at lower-bound 95% confidence interval). At a willingness-to-pay threshold of £20,000/QALY, the

  6. Cost-Effectiveness of Capsaicin 8% Patch Compared with Pregabalin for the Treatment of Patients with Peripheral Neuropathic Pain in Scotland

    PubMed Central

    Mankowski, Colette; Patel, Sachin; Trueman, David; Bentley, Anthony; Poole, Chris

    2016-01-01

    We evaluated the cost-effectiveness of capsaicin 8% patch (QUTENZA™) versus pregabalin in patients with PNP from the perspective of the National Health Service (NHS) and Personal and Social Services in Scotland, UK. A decision-tree cost-effectiveness model was developed for non-diabetic patients with peripheral neuropathic pain (PNP) who were pregabalin-naïve and had not achieved adequate pain relief or tolerated conventional first- or second-line treatments. Patients entering the model received either a single application of capsaicin 8% patch or titrated daily dosing with pregabalin; after 8 weeks patients were classified as responders, non-responders, or were assumed to discontinue treatment due to intolerable adverse events. Responders continued to receive baseline treatment at intervals observed in clinical practice. Non-responders and those who discontinued treatment were assumed to receive last-line therapy (duloxetine). The base-case time horizon was 2 years. Model inputs for effectiveness, discontinuations and health-state utilities were taken from a head-to-head non-inferiority study (ELEVATE, NCT01713426). Other inputs were obtained from published sources or clinical expert opinion. Costs were expressed in GBP 2013/14. Results were presented as incremental cost-effectiveness ratios (ICER), i.e. cost per quality-adjusted life-year (QALY) gained. Model assumptions were tested with scenario analyses. Parameter uncertainty was tested using one-way and probabilistic sensitivity analyses. Compared with dose-optimized pregabalin, capsaicin 8% patch was the dominant treatment strategy (total cost difference, –£11; total QALY gain, 0.049). Capsaicin 8% patch was also the dominant treatment strategy versus pregabalin in 6 out of 7 scenario analyses. The model was most sensitive to variation in time to capsaicin 8% patch retreatment (maximum ICER, £7,951/QALY at lower-bound 95% confidence interval). At a willingness-to-pay threshold of £20,000/QALY, the

  7. Guidelines in the management of diabetic nerve pain: clinical utility of pregabalin

    PubMed Central

    Vinik, Aaron I; Casellini, Carolina M

    2013-01-01

    Neurology and the Toronto Consensus Panel on Diabetic Neuropathy were included. Unfortunately, the results of evidence-based studies do not necessarily take into account the presence of comorbidities, the cost of treatment, or the role of third-party payers in decision-making. Thus, this review attempts to give a more balanced view of the management of pain in the diabetic patient with neuropathy and in particular the role of pregabalin. PMID:23467255

  8. Real-life efficacy of pregabalin for the treatment of peripheral neuropathic pain in daily clinical practice in Denmark: the NEP-TUNE study

    PubMed Central

    Crawford, Michael E; Poulsen, Peter Bo; Schiøttz-Christensen, Berit; Habicht, Andreas; Strand, Mette; Bach, Flemming W

    2016-01-01

    Objective The aim of this study was to provide evidence regarding the real-life efficacy of pregabalin in the treatment of peripheral neuropathic pain (NeP) in Denmark. Methods In this prospective, observational, noninterventional study, pregabalin (Lyrica®) was prescribed following usual clinical practice. Compared with baseline, the primary study end points after 3 months of observation were changes in 1) the average level of pain during the past week, 2) the worst level of pain during the past week, and 3) the least level of pain during the past week. The Wilcoxon signed-rank test was used to perform paired analyses, and a multivariate regression analysis investigated factors driving change in pain. Results A total of 86 of the 128 patients included were regarded as efficacy evaluable (those completing 3 months of pregabalin treatment). Patients (59 years) were long-time sufferers of peripheral NeP, and 38% of them had comorbidities. The majority had previously been treated with tricyclic antidepressants or gabapentin. The average dose of pregabalin was 81.5 mg/d at baseline and 240 mg/d after 3 months. A clinically and statistically significant improvement of 2.2 points in the average level of pain intensity was found after 3 months. The higher the pain intensity at baseline, the higher was the reduction of the pain score. Positive results were also found for pain-related sleep interference, patients’ global impression of change, quality of life, and work and productivity impairment. Twenty-one patients reported 28 adverse events. Conclusion This real-life study indicates that for some patients (two-thirds), addition of pregabalin for peripheral NeP helps to reduce their pain intensity significantly. PMID:27284265

  9. Pain relief and functional improvement in patients with neuropathic pain associated with spinal cord injury: an exploratory analysis of pregabalin clinical trials

    PubMed Central

    Sadosky, Alesia; Parsons, Bruce; Emir, Birol; Nieshoff, Edward C

    2016-01-01

    Background Characterizing relationships between pain relief and function can inform patient management decisions. This analysis explored graphically the relationship between pain relief and functional improvement in patients with neuropathic pain associated with spinal cord injury in two clinical trials of pregabalin. Methods This was a post hoc analysis of two randomized, double-blind, clinical trials in patients who were treated with pregabalin (n=181) or placebo (n=172) for neuropathic pain associated with spinal cord injury. The bivariate relationship between percent pain relief and absolute change in the functional outcomes with placebo and pregabalin was evaluated graphically using scatter plots, and loess curves illustrated the extent of the relationship between pain and function. Linear trend analysis evaluated the statistical significance of these relationships using Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT)-based thresholds of pain reduction (<15%, 15% <30%, 30% to <50%, and ≥50%). Outcome measures included modified Brief Pain Inventory pain interference with function in one of the studies and the Medical Outcomes Study Sleep Scale (an 11-point Numeric Rating Scale) and the Hospital Anxiety and Depression Scale (HADS) for the pooled studies. Results Data ellipses showed a shift with pregabalin relative to placebo toward greater improvement with increasing pain relief for all outcome measures except HADS. Loess curves suggested a relationship between increased pain relief and improved function except for HADS, with the clearest relationship observed for sleep. Linear trend analysis showed significant relationships between pain and Medical Outcomes Study Sleep Scale (P<0.0001) and between pain and function on the modified Brief Pain Inventory Interference Index and most individual items (P<0.05). Conclusion Greater functional improvements were generally achieved at higher levels of clinically significant pain

  10. A randomized, double-blind, placebo-controlled trial and open-label extension study to evaluate the efficacy and safety of pregabalin in the treatment of neuropathic pain associated with human immunodeficiency virus neuropathy.

    PubMed

    Simpson, David M; Rice, Andrew S C; Emir, Birol; Landen, Jaren; Semel, David; Chew, Marci L; Sporn, Jonathan

    2014-10-01

    The objective of these studies was to assess the efficacy and safety of pregabalin in the treatment of human immunodeficiency virus (HIV)-associated neuropathic pain. Patients with HIV-associated distal sensory polyneuropathy (DSP) were randomized to treatment with flexible-dose pregabalin (150-600 mg/day) or placebo for 17 weeks in a single-blind, placebo lead-in, randomized, double-blind, parallel-group, placebo-controlled multinational trial. The primary efficacy outcome was the change in mean pain score on an 11-point numeric rating scale (NRS) from baseline to study endpoint. Participants who completed this trial were invited to participate in a 6-month open-label extension study with pregabalin. Of the 377 patients enrolled in the randomized controlled trial (pregabalin, n=183; placebo, n=194), 68.4% completed treatment. In the open-label extension, 217 patients were treated and 59.4% completed treatment. Both studies were terminated by the sponsor after a preplanned interim analysis indicated trial futility. At endpoint, the change from baseline in least-squares mean NRS pain scores in the intent-to-treat population was -2.04 for pregabalin versus -2.11 for placebo (P=.709). There were no significant differences between the pregabalin and placebo groups in the secondary efficacy measures. Incidence of adverse events was lower than seen in previous pregabalin studies. Overall, this trial did not show pregabalin to be more efficacious than placebo in treating HIV-associated DSP. Studies such as these, which fail to support their primary hypotheses, may be important in informing the methodology of future trials, especially when novel approaches to limit variability in the control group are included. ClinicalTrials.gov identifiers: NCT01049217 and NCT01145417. PMID:24907403

  11. The antiallodynic action of pregabalin may depend on the suppression of spinal neuronal hyperexcitability in rats with spared nerve injury

    PubMed Central

    Ding, Lei; Cai, Jie; Guo, Xiang-Yang; Meng, Xiu-Li; Xing, Guo-Gang

    2014-01-01

    BACKGROUND: Pregabalin (PGB) is a novel antiepileptic drug and is also used as a first-line medication for the treatment of neuropathic pain. However, the mechanisms of its analgesic effects remain largely unknown. OBJECTIVES: To elucidate the mechanisms underlying the antiallodynic action of PGB in rats with neuropathic pain. METHODS: In a rat model of neuropathic pain induced by spared nerve injury, mechanical allodynia, as a behavioural sign of neuropathic pain, was assessed by measuring 50% paw withdrawal threshold with von Frey filaments. Activities of dorsal horn wide dynamic range (WDR) neurons were examined by extracellular electrophysiological recording in vivo. RESULTS: Spinal administration of PGB exerted a significant antiallodynic effect and a prominent inhibitory effect on the hypersensitivity of dorsal horn WDR neurons in rats with spared nerve injury. CONCLUSION: The antiallodynic action of PGB is likely dependent on the suppression of WDR neuron hyperexcitability in rats with neuropathic pain. PMID:24851240

  12. Separation and characterization of modified pregabalins in terms of cyclodextrin complexation, using capillary electrophoresis and nuclear magnetic resonance.

    PubMed

    Béni, Szabolcs; Sohajda, Tamás; Neumajer, Gábor; Iványi, Róbert; Szente, Lajos; Noszál, Béla

    2010-03-11

    The (S)-(+)-isomer of 3-isobutyl-GABA (pregabalin), the blockbuster drug in the treatment of neuropathic pain has been separated from its R isomer by cyclodextrin modified capillary zone electrophoresis (CZE) using uncoated fused-silica capillary. Derivatization of the single isomer and the racemate with tosyl- and dansyl-chloride was carried out to introduce strong UV chromophores of different size. CE-pH titrations were performed to determine the dissociation constants for both derivatives. 30 cyclodextrin (CD) derivatives as chiral agents were used at four different pH values to study the enantioseparation of the differently protonated guest molecules. The separation was optimized as a function of CD concentration, buffer type and concentration, pH and applied voltage. For the tosylated derivate the best resolution (R(s)=2.76) was found with 6-monodeoxy-6-mono-(3-hydroxy)-propylamino-beta-cyclodextrin hydrochloride (PA-beta-CD) at pH 6.8, while with the same selector at pH 7.2 enantioseparation with an R(s) value of 4.32 could be achieved for the dansylated pregabalin. At pH 2.5 for the dansylated derivative trimethylated alpha- and beta-CD systems resulted the most significant separation (R(s)=7.38 and R(s)=7.74, respectively). Experiments with dual CD systems were carried out as well. The stoichiometry of the complexes was determined using the Job plot method and resulted in a 1:1 complex in both cases. The structures of the inclusion complexes were elucidated using 2D ROESY NMR experiments. PMID:19914021

  13. Cost-effectiveness analysis of pregabalin for treatment of chronic low back pain in patients with accompanying lower limb pain (neuropathic component) in Japan

    PubMed Central

    Igarashi, Ataru; Akazawa, Manabu; Murata, Tatsunori; Taguchi, Toshihiko; Sadosky, Alesia; Ebata, Nozomi; Willke, Richard; Fujii, Koichi; Doherty, Jim; Kobayashi, Makoto

    2015-01-01

    Objective To assess the cost-effectiveness of pregabalin for the treatment of chronic low back pain with accompanying neuropathic pain (CLBP-NeP) from the health care payer and societal perspectives. Methods The cost-effectiveness of pregabalin versus usual care for treatment of CLBP-NeP was evaluated over a 12-month time horizon using the incremental cost-effectiveness ratio (ICER). Quality-adjusted life years (QALYs), derived from the five-dimension, five-level EuroQol (EQ-5D-5L) questionnaire, was the measure of effectiveness. Medical costs and productivity losses were both calculated. Expected costs and outcomes were estimated via cohort simulation using a state-transition model, which mimics pain state transitions among mild, moderate, and severe pain. Distributions of pain severity were obtained from an 8-week noninterventional study. Health care resource consumption for estimation of direct medical costs for pain severity levels was derived from a physician survey. The ICER per additional QALY gained was calculated and sensitivity analyses were performed to evaluate the robustness of the assumptions across a range of values. Results Direct medical costs and hospitalization costs were both lower in the pregabalin arm compared with usual care. The estimated ICERs in the base case scenarios were approximately ¥2,025,000 and ¥1,435,000 per QALY gained with pregabalin from the payer and societal perspectives, respectively; the latter included indirect costs related to lost productivity. Sensitivity analyses using alternate values for postsurgical pain scores (0 and 5), initial pain severity levels (either all moderate or all severe), and the actual EQ-5D-5L scores from the noninterventional study showed robustness of results, with ICERs that were similar to the base case. Development of a cost-effectiveness acceptability curve showed high probability (≥75%) of pregabalin being cost-effective. Conclusion Using data and assumptions from routine clinical

  14. Acetate Dependence of Tumors

    PubMed Central

    Comerford, Sarah A.; Huang, Zhiguang; Du, Xinlin; Wang, Yun; Cai, Ling; Witkiewicz, Agnes; Walters, Holly; Tantawy, Mohammed N.; Fu, Allie; Manning, H. Charles; Horton, Jay D.; Hammer, Robert E.; McKnight, Steven L.; Tu, Benjamin P.

    2014-01-01

    SUMMARY Acetyl-CoA represents a central node of carbon metabolism that plays a key role in bioenergetics, cell proliferation and the regulation of gene expression. How highly glycolytic or hypoxic tumors are able to produce sufficient quantities of this metabolite to support cell growth and survival under nutrient-limiting conditions remains poorly understood. Here we show that the nucleocytosolic acetyl-CoA synthetase enzyme, ACSS2, supplies a key source of acetyl-CoA for tumors by capturing acetate as a carbon source. Despite exhibiting no gross deficits in growth or development, adult mice lacking ACSS2 exhibit a significant reduction in tumor burden in two different models of hepatocellular carcinoma. ACSS2 is expressed in a large proportion of human tumors and its activity is responsible for the majority of cellular acetate uptake into both lipids and histones. These observations may qualify ACSS2 as a targetable metabolic vulnerability of a wide spectrum of tumors. PMID:25525877

  15. Synthesis of new fluorinated analogs of GABA, Pregabalin bioisosteres, and their effects on [(3)H]GABA uptake by rat brain nerve terminals.

    PubMed

    Borisova, T; Pozdnyakova, N; Shaitanova, E; Gerus, I; Dudarenko, M; Mironets, R; Haufe, G; Kukhar, V

    2015-08-01

    Fluorinated analogs of natural substances take an essential place in the design of new biologically active compounds. New fluorinated analogs of γ-aminobutyric acid, that is, β-polyfluoroalkyl-GABAs (FGABAs), were synthesized with substituents: β-CF3-β-OH (1), β-CF3 (2); β-CF2CF2H (3). FGABAs are bioisosteres of Pregabalin (Lyrica®, Pfizer's blockbuster drug, β-i-Bu-GABA), and have lipophilicity close to this medicine. The effects of synthesized FGABAs on [(3)H]GABA uptake by isolated rat brain nerve terminals (synaptosomes) were assessed and compared with those of Pregabalin. FGABAs 1-3 (100μM) did not influence the initial velocity of [(3)H]GABA uptake when applied acutely, whereas an increase in this parameter was found after preliminary incubation of FGABAs with synaptosomes. Pregabalin after preliminary incubation with synaptosomes caused unidirectional changes in the initial velocity of [(3)H]GABA uptake. Using specific inhibitors of GAT1 and GAT3, NO-711 and SNAP5114, respectively, the ability of FGABAs 1-3 to influence non-GAT1 and non-GAT3 uptake activity of nerve terminals was analyzed, but no specificity was found. Therefore, new synthesized FGABAs are structural but not functional analogs of GABA (because they did not inhibit synaptosomal [(3)H]GABA uptake). Moreover, FGABAs are able to increase the initial velocity of [(3)H]GABA uptake by synaptosomes, and this effect is higher than that of Pregabalin. PMID:26138193

  16. Five Patients With Burning Mouth Syndrome in Whom an Antidepressant (Serotonin-Noradrenaline Reuptake Inhibitor) Was Not Effective, but Pregabalin Markedly Relieved Pain.

    PubMed

    Ito, Mikiko; Tokura, Tatsuya; Yoshida, Keizo; Nagashima, Wataru; Kimura, Hiroyuki; Umemura, Eri; Tachibana, Masako; Miyauchi, Tomoya; Kobayashi, Yuka; Arao, Munetaka; Ozaki, Norio; Kurita, Kenichi

    2015-01-01

    Burning mouth syndrome (BMS) causes idiopathic pain or a burning sensation in clinically normal oral mucosa. Burning mouth syndrome is a chronic disease with an unknown etiology. Burning mouth syndrome is also idiopathic, and a consensus regarding diagnosis/treatment has not been reached yet. Recent studies have supported the suggestion that BMS is a neuropathic pain disorder in which both the peripheral and central nervous systems are involved. Tricyclic antidepressants (nortriptyline and amitriptyline), serotonin-noradrenaline reuptake inhibitors (SNRIs) (duloxetine and milnacipran), and antiepileptic drugs, potential-dependent calcium channel α2δ subunit ligands (gabapentine and pregabalin), are currently recommended as the first-choice drugs for neuropathic pain. In this study, we report 5 patients with BMS in whom there was no response to SNRI (milnacipran or duloxetine), or administration was discontinued because of adverse reactions, but in whom pregabalin therapy markedly reduced or led to the disappearance of pain in a short period. Pregabalin, whose mechanism of action differs from that of SNRIs, may become a treatment option for BMS patients who are not responsive to or are resistant to SNRIs. PMID:26166242

  17. Clinically relevant concentration of pregabalin has no acute inhibitory effect on excitation of dorsal horn neurons under normal or neuropathic pain conditions: An intracellular calcium-imaging study in spinal cord slices from adult rats.

    PubMed

    Baba, Hiroshi; Petrenko, Andrey B; Fujiwara, Naoshi

    2016-10-01

    Pregabalin is thought to exert its therapeutic effect in neuropathic pain via binding to α2δ-1 subunits of voltage-gated calcium (Ca(2+)) channels. However, the exact analgesic mechanism after its binding to α2δ-1 subunits remains largely unknown. Whether a clinical concentration of pregabalin (≈10μM) can cause acute inhibition of dorsal horn neurons in the spinal cord is controversial. To address this issue, we undertook intracellular Ca(2+)-imaging studies using spinal cord slices with an intact attached L5 dorsal root, and examined if pregabalin acutely inhibits the primary afferent stimulation-evoked excitation of dorsal horn neurons in normal rats and in rats with streptozotocin-induced painful diabetic neuropathy. Under normal conditions, stimulation of a dorsal root evoked Ca(2+) signals predominantly in the superficial dorsal horn. Clinically relevant (10μM) and a very high concentration of pregabalin (100μM) did not affect the intensity or spread of dorsal root stimulation-evoked Ca(2+) signals, whereas an extremely high dose of pregabalin (300μM) slightly but significantly attenuated Ca(2+) signals in normal rats and in diabetic neuropathic (DN) rats. There was no difference between normal rats and DN rats with regard to the extent of signal attenuation at all concentrations tested. These results suggest that the activity of dorsal horn neurons in the spinal cord is not inhibited acutely by clinical doses of pregabalin under normal or DN conditions. It is very unlikely that an acute inhibitory action in the dorsal horn is the main analgesic mechanism of pregabalin in neuropathic pain states. PMID:27543338

  18. Effects of 2 Different Doses of Pregabalin on Morphine Consumption and Pain After Abdominal Hysterectomy: A Randomized, Double-Blind Clinical Trial

    PubMed Central

    Yücel, Aytaç; Özturk, Erdoğan; Aydoğan, M. Said; Durmuş, Mahmut; Çolak, Cemil; Ersoy, M. Özcan

    2011-01-01

    Background Pregabalin has a similar pharmacologic profile to that of its developmental predecessor gabapentin but has shown greater analgesic activity in rodent models of neuropathic pain. Objective The objective of the study was to compare the effects of 2 different doses of pregabalin and placebo on postoperative pain and morphine consumption. Methods Ninety patients who underwent abdominal hysterectomy were included in the study and randomly divided into 3 groups in a doubled-blinded manner. They were given 150 mg of pregabalin (group P300, n = 30), 300 mg of pregabalin (group P600, n = 30), or placebo capsules (group C, n = 30) 4 hours before the induction of anesthesia; they received a second dose of the drug 12 hours postoperatively. Morphine consumption, nausea, and vomiting, visual analogue scale-pain intensity (VAS-PI), sedation scores, and dissatisfaction scores were recorded in the postanesthesia care unit (PACU) and at 2, 4, 6, and 24 hours after operation. Results Morphine consumption at 24 hours was 40.80 (3.42) mg, 33.79 (5.77) mg, and 46.97 (6.67) mg in groups P300, P600, and C, respectively (P < 0.001). VAS-PI scores at movement and at rest in the PACU and at 2, 4, and 6 hours decreased in group P600 (P < 0.01). In the PACU and at 2, 4, and 6 hours, the sedation scores were increased in group P600 compared with the scores in group C (P < 0.001, P < 0.001, P = 0.01, P = 0.006, respectively). Patient satisfaction was higher in group P600 than in group C for all time points (P < 0.001, P < 0.001, P < 0.001, P = 0.001, P < 0.001, respectively). There were no statistically significant differences between the groups for side effects such as nausea, vomiting, and dizziness (P = 0.58). Conclusions Pregabalin at a total dose of 600 mg, administered before operation and at 12 hours postoperatively after abdominal hysterectomy, reduced morphine consumption and pain intensity and increased patient satisfaction. No significant differences in side effects were

  19. Pregabalin versus SSRIs and SNRIs in benzodiazepine-refractory outpatients with generalized anxiety disorder: a post hoc cost-effectiveness analysis in usual medical practice in Spain

    PubMed Central

    De Salas-Cansado, Marina; Olivares, José M; Álvarez, Enrique; Carrasco, Jose L; Barrueta, Andoni; Rejas, Javier

    2012-01-01

    Background Generalized anxiety disorder (GAD) is a prevalent health condition which seriously affects both patient quality of life and the National Health System. The aim of this research was to carry out a post hoc cost-effectiveness analysis of the effect of pregabalin versus selective serotonin reuptake inhibitors (SSRIs)/serotonin norepinephrine reuptake inhibitors (SNRIs) in treated benzodiazepine-refractory outpatients with GAD. Methods This post hoc cost-effectiveness analysis used secondary data extracted from the 6-month cohort, prospective, noninterventional ADAN study, which was conducted to ascertain the cost of illness in GAD subjects diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria. Benzodiazepine-refractory subjects were those who claimed persistent symptoms of anxiety and showed a suboptimal response (Hamilton Anxiety Rating Scale ≥ 16) to benzodiazepines, alone or in combination, over 6 months. Patients could switch to pregabalin (as monotherapy or addon) or to an SSRI or SNRI, alone or in combination. Effectiveness was expressed as quality-adjusted life years gained, and the perspective was that of the National Health System in the year 2008. A sensitivity analysis was performed using bootstrapping techniques (10,000 resamples were obtained) in order to obtain a cost-effectiveness plane and a corresponding acceptability curve. Results A total of 282 subjects (mean Hamilton Anxiety Rating Scale score 25.8) were identified, comprising 157 in a pregabalin group and 125 in an SSRI/SNRI group. Compared with SSRI/SNRI, pregabalin (average dose 163 mg/day) was associated with higher quality-adjusted life years gained (0.1086 ± 0.0953 versus 0.0967 ± 0.1003, P = 0.334), but increased health care costs (€1014 ± 762 versus €846 ± 620, P = 0.166) and drug costs (€376 ± 252 versus 220 ± 140, P < 0.001), resulting in an incremental cost-effectiveness ratio of €25,304 (95% confidence interval

  20. [Nomegestrol acetate: clinical pharmacology].

    PubMed

    Lello, S

    2009-10-01

    Progestogens are used in clinical practice in some conditions. Their effects depend on their chemical structure, pharmacokinetics, pharmacodynamics, with important differences among various progestogens. Generally, progestins are classified according to their parent molecule, of which often they keep some features. Derivatives of 19-nor-progesterone are characterized by high selectivity of action on progestin receptor. In particular, nomegestrol acetate (NomAc) shows an important progestational potency, neutral gluco-lipid profile, and antigonadotropic activity. It is used for treating menstrual cycle disorders and for hormone replacement therapy in menopause in association with an estrogen. In future, thanks to its antigonadotropic activity, NomAc will be used in estroprogestin combinations in fertile women, thus taking advantage of its tolerability profile and obtaining numerous non-contraceptive benefits as well. PMID:19749678

  1. Visible-light-induced synthesis of pH-responsive composite hydrogels for controlled delivery of the anticonvulsant drug pregabalin.

    PubMed

    Cevik, Ozlem; Gidon, Dogan; Kizilel, Seda

    2015-01-01

    We report here a novel method for the synthesis of a pH-responsive composite using visible light. Formation of the pH-responsive layer is based on poly(methacrylic acid-g-ethylene glycol) as the macromer, eosin Y as the photoinitiator and triethanolamine as the co-initiator. The hydrogel was functionalized with hydrophobic domains through incorporation of crosslinked styrene-butadiene-styrene (SBS) copolymer into the pH-responsive prepolymer. Swelling ratios were decreased with the addition of SBS, and resulted in high hydrogel crosslink density. The composite allowed for controlled release of an anticonvulsant model drug, pregabalin, under neutral pH condition and the release was analyzed to describe the mode of transport through the network. In vitro human fibroblast survival assay and in vivo rabbit implantation experiments demonstrated that this hybrid network is not toxic and has desirable biocompatibility properties. This is the first report about the synthesis of a pH-responsive network incorporating crosslinked SBS synthesized under visible light. The approach for multifunctional membranes could allow the incorporation of molecules with specific functionalities so that sequential molecule delivery in response to specific stimuli could be achieved. PMID:25242648

  2. Analgesic effectiveness and tolerability of oral oxycodone/naloxone and pregabalin in patients with lung cancer and neuropathic pain: an observational analysis

    PubMed Central

    De Santis, Stefano; Borghesi, Cristina; Ricciardi, Serena; Giovannoni, Daniele; Fulvi, Alberto; Migliorino, Maria Rita; Marcassa, Claudio

    2016-01-01

    Introduction Cancer-related pain has a severe negative impact on quality of life. Combination analgesic therapy with oxycodone and pregabalin is effective for treating neuropathic cancer pain. We investigated the efficacy and tolerability of a dose-escalation combination therapy with prolonged-release oxycodone/naloxone (OXN-PR) and pregabalin in patients with non-small-cell lung cancer and severe neuropathic pain. Methods This was a 4-week, open-label, observational study. Patients were treated with OXN-PR and pregabalin. Average pain intensity ([API] measured on a 0–10 numerical rating scale) and neuropathic pain (Douleur Neuropathique 4) were assessed at study entry and at follow-up visits. The primary endpoint was response to treatment, defined as a reduction of API at T28 ≥30% from baseline. Secondary endpoints included other efficacy measures, as well as patient satisfaction and quality of life (Brief Pain Inventory Short Form), Hospital Anxiety and Depression Scale, and Symptom Distress Scale; bowel function was also assessed. Results A total of 56 patients were enrolled. API at baseline was 8.0±0.9, and decreased after 4 weeks by 48% (4.2±1.9; P<0.0001 vs baseline); 46 (82.1%) patients responded to treatment. Significant improvements were also reported in number/severity of breakthrough cancer pain episodes (P=0.001), Brief Pain Inventory Short Form (P=0.0002), Symptom Distress Scale (P<0.0001), Hospital Anxiety and Depression Scale depression (P=0.0006) and anxiety (P<0.0001) subscales, and bowel function (P=0.0003). At study end, 37 (66.0%) patients were satisfied/very satisfied with the new analgesic treatment. Combination therapy had a good safety profile. Conclusion OXN-PR and pregabalin were safe and highly effective in a real-world setting of severe neuropathic cancer pain, with a high rate of satisfaction, without interference on bowel function. PMID:27445495

  3. 21 CFR 184.1185 - Calcium acetate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    .... No. 62-54-4), also known as acetate of lime or vinegar salts, is the calcium salt of acetic acid. It may be produced by the calcium hydroxide neutralization of acetic acid. (b) The ingredient meets...

  4. Long-term cost-effectiveness of initiating treatment for painful diabetic neuropathy with pregabalin, duloxetine, gabapentin, or desipramine.

    PubMed

    Bellows, Brandon K; Nelson, Richard E; Oderda, Gary M; LaFleur, Joanne

    2016-01-01

    Painful diabetic neuropathy (PDN) affects nearly half of patients with diabetes. The objective of this study was to compare the cost-effectiveness of starting patients with PDN on pregabalin (PRE), duloxetine (DUL), gabapentin (GABA), or desipramine (DES) over a 10-year time horizon from the perspective of third-party payers in the United States. A Markov model was used to compare the costs (2013 $US) and effectiveness (quality-adjusted life-years [QALYs]) of first-line PDN treatments in 10,000 patients using microsimulation. Costs and QALYs were discounted at 3% annually. Probabilities and utilities were derived from the published literature. Costs were average wholesale price for drugs and national estimates for office visits and hospitalizations. One-way and probabilistic (PSA) sensitivity analyses were used to examine parameter uncertainty. Starting with PRE was dominated by DUL as DUL cost less and was more effective. Starting with GABA was extendedly dominated by a combination of DES and DUL. DES and DUL cost $23,468 and $25,979, while yielding 3.05 and 3.16 QALYs, respectively. The incremental cost-effectiveness ratio for DUL compared with DES was $22,867/QALY gained. One-way sensitivity analysis showed that the model was most sensitive to the adherence threshold and utility for mild pain. PSA showed that, at a willingness-to-pay (WTP) of $50,000/QALY, DUL was the most cost-effective option in 56.3% of the simulations, DES in 29.2%, GABA in 14.4%, and PRE in 0.1%. Starting with DUL is the most cost-effective option for PDN when WTP is greater than $22,867/QALY. Decision makers may consider starting with DUL for PDN patients. PMID:26397932

  5. Antibiofilm Properties of Acetic Acid

    PubMed Central

    Bjarnsholt, Thomas; Alhede, Morten; Jensen, Peter Østrup; Nielsen, Anne K.; Johansen, Helle Krogh; Homøe, Preben; Høiby, Niels; Givskov, Michael; Kirketerp-Møller, Klaus

    2015-01-01

    Bacterial biofilms are known to be extremely tolerant toward antibiotics and other antimicrobial agents. These biofilms cause the persistence of chronic infections. Since antibiotics rarely resolve these infections, the only effective treatment of chronic infections is surgical removal of the infected implant, tissue, or organ and thereby the biofilm. Acetic acid is known for its antimicrobial effect on bacteria in general, but has never been thoroughly tested for its efficacy against bacterial biofilms. In this article, we describe complete eradication of both Gram-positive and Gram-negative biofilms using acetic acid both as a liquid and as a dry salt. In addition, we present our clinical experience of acetic acid treatment of chronic wounds. In conclusion, we here present the first comprehensive in vitro and in vivo testing of acetic acid against bacterial biofilms. PMID:26155378

  6. Inferior ST-Elevation Acute Myocardial Infarction or an Inferior-Lead Brugada-like Electrocardiogram Pattern Associated With the Use of Pregabalin and Quetiapine?

    PubMed

    Brunetti, Natale D; Ieva, Riccardo; Correale, Michele; Cuculo, Andrea; Santoro, Francesco; Guaricci, Andrea I; De Gennaro, Luisa; Gaglione, Antonio; Di Biase, Matteo

    2016-01-01

    The Brugada electrocardiogram pattern is characterized by coved-type ST-elevation (>2 mm) in the right precordial leads. We report the case of a 62-year-old man, with bipolar disorder, admitted to the emergency department because of dyspnea and chest discomfort. The patient was on treatment with pregabalin and quetiapine. Unexpectedly, electrocardiogram at admission showed diffuse ST-elevation, more evident in inferior leads, where a Brugada-like pattern was present. The patient underwent coronary angiography with a diagnosis of suspected acute coronary syndrome. Coronary angiography, however, showed mild coronary artery disease not requiring coronary angioplasty. Echocardiography did not reveal left ventricular dysfunction or pericardial effusion. Troponin levels remained normal over serial controls. Eventually, chest radiography showed lung opacities and consolidation suggestive for pneumonia. To the best of our knowledge, this is one of the first cases showing a transient Brugada-like electrocardiogram pattern in inferior leads, probably amplified by the administration of pregabalin and quetiapine. PMID:26291591

  7. 21 CFR 184.1185 - Calcium acetate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium acetate. 184.1185 Section 184.1185 Food and... Substances Affirmed as GRAS § 184.1185 Calcium acetate. (a) Calcium acetate (Ca (C2H3O2)2, CAS Reg. No. 62-54-4), also known as acetate of lime or vinegar salts, is the calcium salt of acetic acid. It may...

  8. Desmopressin Acetate in Intracranial Haemorrhage

    PubMed Central

    Kapapa, Thomas; Röhrer, Stefan; Struve, Sabine; Petscher, Matthias; König, Ralph; Wirtz, Christian Rainer; Woischneck, Dieter

    2014-01-01

    Introduction. The secondary increase in the size of intracranial haematomas as a result of spontaneous haemorrhage or trauma is of particular relevance in the event of prior intake of platelet aggregation inhibitors. We describe the effect of desmopressin acetate as a means of temporarily stabilising the platelet function. Patients and Methods. The platelet function was analysed in 10 patients who had received single (N = 4) or multiple (N = 6) doses of acetylsalicylic acid and 3 patients (control group) who had not taken acetylsalicylic acid. All subjects had suffered intracranial haemorrhage. Analysis was performed before, half an hour and three hours after administration of desmopressin acetate. Statistical analysis was performed by applying a level of significance of P ≤ 0.05. Results. (1) Platelet function returned to normal 30 minutes after administration of desmopressin acetate. (2) The platelet function worsened again after three hours. (3) There were no complications related to electrolytes or fluid balance. Conclusion. Desmopressin acetate can stabilise the platelet function in neurosurgical patients who have received acetylsalicylic acid prior to surgery without causing transfusion-related side effects or a loss of time. The effect is, however, limited and influenced by the frequency of drug intake. Further controls are needed in neurosurgical patients. PMID:25610644

  9. Reductive opening of carbohydrate phenylsulfonylethylidene (PSE) acetals.

    PubMed

    Chéry, Florence; Cabianca, Elena; Tatibouët, Arnaud; De Lucchi, Ottorino; Lindhorst, Thisbe K; Rollin, Patrick

    2015-11-19

    The phenylsulfonylethylidene (PSE) acetal is a relatively new protecting group in carbohydrate chemistry. However, carbohydrate-derived phenylsulfonylethylidene (PSE) acetals show a different behavior in reductive desulfonylation than simple symmetrical acetals. Here we have investigated various SET-type reaction conditions in order to open PSE acetals regioselectively and to produce chiral ω-hydroxyethenyl ethers. Whereas sodium amalgam leads to a mixture of regioisomeric vinyl ethers besides the ethylidene acetal, samarium iodide is suited for regioselective ring opening. This is shown with seven different carbohydrate PSE acetals, both of the 1,3-dioxane and the 1,3-dioxolane type. PMID:26469209

  10. [Prasterone (dihydroepiandrosterone): a modern source of eternal youth?].

    PubMed

    Keppel Hesselink, J M

    1997-12-20

    The function of adrenal cortical hormone dihydroepiandrosterone (DHEA) is currently unknown. The use of this hormone as a food supplement is widely recommended in the USA for the elderly, as DHEA serum concentrations decrease dramatically after the age of about fourty. DHEA is available without prescription. Many sources suggest a causal relation between the decrease of DHEA production during aging and the emergence of degenerative disorders. To substantiate this relationship animal experimental and epidemiological literature is cited. However, data from clinical trials are rare and neither the safety nor the efficacy of DHEA is documented. Via the modern media such as the Internet the consumer is stimulated to use and order DHEA, 'the fountain of youth'. Consumers willing to follow this recommendation should be informed about the absence of proof of safety and efficacy. However, the compelling suggestions from animal and epidemiological literature of DHEA activity are intriguing, and further clinical trials to document the efficacy and safety of DHEA are urgently needed. PMID:9555138

  11. 21 CFR 522.533 - Deslorelin acetate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Deslorelin acetate. (a) Specifications. Each implant contains 2.1 milligrams deslorelin acetate. (b) Sponsor.... One implant per mare. (ii) Indications for use. For inducing ovulation within 48 hours in...

  12. Carbon-isotopic analysis of dissolved acetate

    NASA Technical Reports Server (NTRS)

    Gelwicks, J. T.; Hayes, J. M.

    1990-01-01

    Heating of dried, acetate-containing solids together with oxalic acid dihydrate conveniently releases acetic acid for purification by gas chromatography. For determination of the carbon-isotopic composition of total acetate, the acetate-containing zone of the chromatographic effluent can be routed directly to a combustion furnace coupled to a vacuum system allowing recovery, purification, and packaging of CO2 for mass-spectrometric analysis. For analysis of methyl carbon, acetic acid can be cryogenically trapped from the chromatographic effluent, then transferred to a tube containing excess NaOH. The tube is evacuated, sealed, and heated to 500 degrees C to produce methane by pyrolysis of sodium acetate. Subsequent combustion of the methane allows determination of the 13C content at the methyl position in the parent acetate. With typical blanks, the standard deviation of single analyses is less than 0.4% for acetate samples larger than 5 micromoles. A full treatment of uncertainties is outlined.

  13. Ozone decomposition in aqueous acetate solutions

    SciTech Connect

    Sehested, K.; Holcman, J.; Bjergbakke, E.; Hart, E.J.

    1987-01-01

    The acetate radical ion reacts with ozone with a rate constant of k = (1.5 +/- 0.5) x 10Z dmT mol s . The products from this reaction are CO2, HCHO, and O2 . By subsequent reaction of the peroxy radical with ozone the acetate radical ion is regenerated through the OH radical. A chain decomposition of ozone takes place. It terminates when the acetate radical ion reacts with oxygen forming the unreactive peroxy acetate radical. The chain is rather short as oxygen is developed, as a result of the ozone consumption. The inhibiting effect of acetate on the ozone decay is rationalized by OH scavenging by acetate and successive reaction of the acetate radical ion with oxygen. Some products from the bimolecular disappearance of the peroxy acetate radicals, however, react further with ozone, reducing the effectiveness of the stabilization.

  14. 21 CFR 184.1721 - Sodium acetate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Sodium acetate. 184.1721 Section 184.1721 Food and....1721 Sodium acetate. (a) Sodium acetate (C2H3O2Na, CAS Reg. No. 127-09-3 or C2H3O2Na·3H2O, CAS Reg. No. 6131-90-4) is the sodium salt of acetic acid and occurs naturally in plant and animal tissues....

  15. 21 CFR 582.6185 - Calcium acetate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium acetate. 582.6185 Section 582.6185 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Calcium acetate. (a) Product. Calcium acetate. (b) Conditions of use. This substance is...

  16. Kinetics of the Methanogenic Fermentation of Acetate

    PubMed Central

    Fukuzaki, Satoshi; Nishio, Naomichi; Nagai, Shiro

    1990-01-01

    Inhibition of the fermentation of acetate to methane and carbon dioxide by acetate was analyzed with an acetate-acclimatized sludge and with Methanosarcina barkeri Fusaro under mesophilic conditions. A second-order substrate inhibition model, qch4 = qmS/[Ks + S + (S2/Ki)], where S was the concentration of undissociated acetic acid, not ionized acetic acid, could be applicable in both cases. The analysis resulted in substrate saturation constants, Ks, of 4.0 μM for the acclimatized sludge and 104 μM for M. barkeri. The threshold concentrations of undissociated acetic acid when no further acetate utilization was observed were 0.078 μM (pH 7.50) for the acclimatized sludge and 4.43 μM (pH 7.45) for M. barkeri. These kinetic results suggested that the concentration of undissociated acetic acid became a key factor governing the actual threshold acetate concentration for acetate utilization and that the acclimatized sludge in which Methanothrix spp. appeared dominant could utilize acetate better and survive at a lower concentration of undissociated acetic acid than could M. barkeri. Images PMID:16348323

  17. 21 CFR 522.2476 - Trenbolone acetate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... days. (A) 140 milligrams (mg) trenbolone acetate (one implant consisting of 7 pellets, each pellet containing 20 mg trenbolone acetate) per implant dose. (B) 140 mg trenbolone acetate (one implant consisting... 29 mg tylosin tartrate) per implant dose. (ii) Indications for use. For improved feed...

  18. 21 CFR 522.2476 - Trenbolone acetate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... days. (A) 140 milligrams (mg) trenbolone acetate (one implant consisting of 7 pellets, each pellet containing 20 mg trenbolone acetate) per implant dose. (B) 140 mg trenbolone acetate (one implant consisting... 29 mg tylosin tartrate) per implant dose. (ii) Indications for use. For improved feed...

  19. 21 CFR 522.2476 - Trenbolone acetate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... days. (A) 140 milligrams (mg) trenbolone acetate (one implant consisting of 7 pellets, each pellet containing 20 mg trenbolone acetate) per implant dose. (B) 140 mg trenbolone acetate (one implant consisting... 29 mg tylosin tartrate) per implant dose. (ii) Indications for use. For improved feed...

  20. 21 CFR 522.2476 - Trenbolone acetate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... days. (A) 140 milligrams (mg) trenbolone acetate (one implant consisting of 7 pellets, each pellet containing 20 mg trenbolone acetate) per implant dose. (B) 140 mg trenbolone acetate (one implant consisting... 29 mg tylosin tartrate) per implant dose. (ii) Indications for use. For improved feed...

  1. 21 CFR 582.1721 - Sodium acetate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Sodium acetate. 582.1721 Section 582.1721 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1721 Sodium acetate. (a) Product. Sodium acetate. (b) Conditions of use. This substance is...

  2. 21 CFR 582.1721 - Sodium acetate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Sodium acetate. 582.1721 Section 582.1721 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1721 Sodium acetate. (a) Product. Sodium acetate. (b) Conditions of use. This substance is...

  3. 21 CFR 582.1721 - Sodium acetate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sodium acetate. 582.1721 Section 582.1721 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1721 Sodium acetate. (a) Product. Sodium acetate. (b) Conditions of use. This substance is...

  4. 21 CFR 582.1721 - Sodium acetate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Sodium acetate. 582.1721 Section 582.1721 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1721 Sodium acetate. (a) Product. Sodium acetate. (b) Conditions of use. This substance is...

  5. 21 CFR 582.1721 - Sodium acetate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Sodium acetate. 582.1721 Section 582.1721 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1721 Sodium acetate. (a) Product. Sodium acetate. (b) Conditions of use. This substance is...

  6. 21 CFR 582.1005 - Acetic acid.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Acetic acid. 582.1005 Section 582.1005 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1005 Acetic acid. (a) Product. Acetic acid. (b) Conditions of use. This substance is...

  7. 21 CFR 184.1005 - Acetic acid.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Acetic acid. 184.1005 Section 184.1005 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DIRECT FOOD....1005 Acetic acid. (a) Acetic acid (C2H4O2, CAS Reg. No. 64-19-7) is known as ethanoic acid. It...

  8. 21 CFR 582.1005 - Acetic acid.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Acetic acid. 582.1005 Section 582.1005 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1005 Acetic acid. (a) Product. Acetic acid. (b) Conditions of use. This substance is...

  9. 21 CFR 582.1005 - Acetic acid.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Acetic acid. 582.1005 Section 582.1005 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1005 Acetic acid. (a) Product. Acetic acid. (b) Conditions of use. This substance is...

  10. 21 CFR 582.1005 - Acetic acid.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Acetic acid. 582.1005 Section 582.1005 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1005 Acetic acid. (a) Product. Acetic acid. (b) Conditions of use. This substance is...

  11. 21 CFR 582.1005 - Acetic acid.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Acetic acid. 582.1005 Section 582.1005 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1005 Acetic acid. (a) Product. Acetic acid. (b) Conditions of use. This substance is...

  12. Acet-oxy-γ-valerolactone.

    PubMed

    Tristram, Cameron; Gainsford, Graeme J; Hinkley, Simon

    2013-06-01

    Levulinyl cellulose esters have been produced as an effective renewable binder for architectural coatings. The title compound, C7H10O4 (systematic name: 2-methyl-5-oxo-tetra-hydro-furan-2-yl acetate), assigned as the esterifying species, was isolated and crystallized to confirm the structure. In the crystal, the mol-ecules pack in layers parallel to (102) utilizing weak C-H⋯O inter-actions. PMID:23795112

  13. Understanding Palladium Acetate from a User Perspective.

    PubMed

    Carole, William A; Colacot, Thomas J

    2016-06-01

    The behavior of palladium acetate is reviewed with respect to its synthesis, characterization, structure (in both solution and solid state), and activation pathways. In addition, comparisons of catalytic activities between pure palladium acetate and two common byproducts, Pd3 (OAc)5 (NO2 ) and polymeric [Pd(OAc)2 ]n , typically present in commercially available material are reviewed. Hence, this minireview serves as a concise guide for the users of palladium acetate from both academia and industry. PMID:27125630

  14. 21 CFR 184.1721 - Sodium acetate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... sodium sulfate and sodium bicarbonate. (b) The ingredient meets the specifications of the Food Chemicals... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Sodium acetate. 184.1721 Section 184.1721 Food and... Substances Affirmed as GRAS § 184.1721 Sodium acetate. (a) Sodium acetate (C2H3O2Na, CAS Reg. No. 127-09-3...

  15. 21 CFR 184.1721 - Sodium acetate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... sodium sulfate and sodium bicarbonate. (b) The ingredient meets the specifications of the Food Chemicals... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Sodium acetate. 184.1721 Section 184.1721 Food and... Substances Affirmed as GRAS § 184.1721 Sodium acetate. (a) Sodium acetate (C2H3O2Na, CAS Reg. No. 127-09-3...

  16. 21 CFR 184.1721 - Sodium acetate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... sodium sulfate and sodium bicarbonate. (b) The ingredient meets the specifications of the Food Chemicals... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Sodium acetate. 184.1721 Section 184.1721 Food and... Substances Affirmed as GRAS § 184.1721 Sodium acetate. (a) Sodium acetate (C2H3O2Na, CAS Reg. No. 127-09-3...

  17. 21 CFR 184.1005 - Acetic acid.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Acetic acid. 184.1005 Section 184.1005 Food and... Substances Affirmed as GRAS § 184.1005 Acetic acid. (a) Acetic acid (C2H4O2, CAS Reg. No. 64-19-7) is known as ethanoic acid. It occurs naturally in plant and animal tissues. It is produced by fermentation...

  18. 21 CFR 184.1005 - Acetic acid.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Acetic acid. 184.1005 Section 184.1005 Food and... Substances Affirmed as GRAS § 184.1005 Acetic acid. (a) Acetic acid (C2H4O2, CAS Reg. No. 64-19-7) is known as ethanoic acid. It occurs naturally in plant and animal tissues. It is produced by fermentation...

  19. Positron scattering from vinyl acetate

    NASA Astrophysics Data System (ADS)

    Chiari, L.; Zecca, A.; Blanco, F.; García, G.; Brunger, M. J.

    2014-09-01

    Using a Beer-Lambert attenuation approach, we report measured total cross sections (TCSs) for positron scattering from vinyl acetate (C4H6O2) in the incident positron energy range 0.15-50 eV. In addition, we also report an independent atom model with screening corrected additivity rule computation results for the TCSs, differential and integral elastic cross sections, the positronium formation cross section and inelastic integral cross sections. The energy range of these calculations is 1-1000 eV. While there is a reasonable qualitative correspondence between measurement and calculation for the TCSs, in terms of the energy dependence of those cross sections, the theory was found to be a factor of ˜2 larger in magnitude at the lower energies, even after the measured data were corrected for the forward angle scattering effect.

  20. Extractive fermentation of acetic acid

    SciTech Connect

    Busche, R.M.

    1991-12-31

    In this technoeconomic evaluation of the manufacture of acetic acid by fermentation, the use of the bacterium: Acetobacter suboxydans from the old vinegar process was compared with expected performance of the newer Clostridium thermoaceticum bacterium. Both systems were projected to operate as immobilized cells in a continuous, fluidized bed bioreactor, using solvent extraction to recover the product. Acetobacter metabolizes ethanol aerobically to produce acid at 100 g/L in a low pH medium. This ensures that the product is in the form of a concentrated extractable free acid, rather than as an unextractable salt. Unfortunately, yields from glucose by way of the ethanol fermentation are poor, but near the biological limits of the organisms involved. Conversely, C. thermoaceticum is a thermophilic anaerobe that operates at high fermentation rates on glucose at neutral pH to produce acetate salts directly in substantially quantitative yields. However, it is severely inhibited by product, which restricts concentration to a dilute 20 g/L. An improved Acetobacter system operating with recycled cells at 50 g/L appears capable of producing acid at $0.38/lb, as compared with a $0.29/lb price for synthetic acid. However, this system has only a limited margin for process improvement. The present Clostridium system cannot compete, since the required selling price would be $0.42/lb. However, if the organism could be adapted to tolerate higher product concentrations at acid pH, selling price could be reduced to $0.22/lb, or about 80% of the price of synthetic acid.

  1. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2002-11-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abacavir sulfate, abarelix, adalimumab, adefovir dipivoxil, AdGVVEGF121.10, anastrozole, anecortave acetate, aripiprazole, asulacrine isethionate, atazanavir, ATL-962, 16-Aza-epothilone B; Bevacizumab, bicalutamide, blonanserin, BMS-188667, bosentan; Celecoxib, celmoleukin, cetuximab, cilomilast, cinacalcet hydrochloride, CNTF(Ax15), colesevelam hydrochloride; Daclizumab, delavirdine mesilate, desogestrel, desoxyepothilone B, dexmethylphenidate hydrochloride, duloxetine hydrochloride; Ecogramostim, emtricitabine, epalrestat, escitalopram oxalate, examorelin, exendin-4, ezetimibe; Fidarestat, frovatriptan; HIV-1 Immunogen; Iloperidone, insulin detemir, insulin lispro, irinotecan hydrochloride; Keratinocyte growth factor; Lasofoxifene tartrate, levetiracetam, levormeloxifene, levosimendan, lumiracoxib, LY-307161 SR; Memantine hydrochloride, MEN-10755, metformin hydrochloride, metreleptin, motexafin gadolinium; Naratriptan hydrochloride, natalizumab, nesiritide, nicotine, NN-2211, NN-414; Olanzapine, omalizumab; Pegaptanib sodium, peginterferon alfa-2a, peginterferon alfa-2b, pegvisomant, pimecrolimus, pirfenidone, pramlintide acetate prasterone, pregabalin; Quetiapine fumarate; Rabeprazole sodium, raloxifene hydrochloride, raltitrexed, rDNA insulin, rFGF-2, risedronate sodium, rofecoxib, roflumilast, rosiglitazone maleate; SN-22995; Tacrolimus, tadalafil, tegaserod maleate, tiotropium bromide, tomoxetine hydrochloride, trastuzumab, trimegestone; Voglibose, Voriconazole; Ziprasidone hydrochloride. PMID:12616707

  2. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2006-06-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 131-I-chlorotoxin; Ad5CMV-p53, adalimumab, albumin interferon alfa, alemtuzumab, aliskiren fumarate, aminolevulinic acid methyl ester, anakinra, AR-C126532, atomoxetine hydrochloride; Bevacizumab, bosentan, botulinum toxin type B, brimonidine tartrate/timolol maleate; Calcipotriol/betamethasone dipropionate, cangrelor tetrasodium, cetuximab, ciclesonide, cinacalcet hydrochloride, collagen-PVP, Cypher; Darbepoetin alfa, darusentan, dasatinib, denosumab, desloratadine, dexosome vaccine (lung cancer), dexrazoxane, dextromethorphan/quinidine sulfate, duloxetine hydrochloride; ED-71, eel calcitonin, efalizumab, entecavir, etoricoxib; Falciparum merozoite protein-1/AS02A, fenretinide, fondaparinux sodium; gamma-Hydroxybutyrate sodium, gefitinib, ghrelin (human); hLM609; Icatibant acetate, imatinib mesylate, ipsapirone, irofulven; LBH-589, LE-AON, levocetirizine, LY-450139; Malaria vaccine, mapatumumab, motexafin gadolinium, muraglitazar, mycophenolic acid sodium salt; nab-paclitaxel, nelarabine; O6-Benzylguanine, olmesartan medoxomil, orbofiban acetate; Panitumumab, peginterferon alfa-2a, peginterferon alfa-2b, pemetrexed disodium, peptide YY3-36, pleconaril, prasterone, pregabalin; Ranolazine, rebimastat, recombinant malaria vaccine, rosuvastatin calcium; SQN-400; Taxus, tegaserod maleate, tenofovir disoproxil fumarate, teriparatide, troxacitabine; Valganciclovir hydrochloride, Val-Tyr sardine peptidase, VNP-40101M, vorinostat. PMID:16845450

  3. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2007-11-01

    1-Octanol, 9vPnC-MnCc; Abiraterone acetate, Adalimumab, Adefovir dipivoxil, Alemtuzumab, Aliskiren fumarate, Aminolevulinic acid hexyl ester, Amlodipine besylate/atorvastatin calcium, Amrubicin hydrochloride, Anakinra, Aripiprazole, ARRY-520, AS-1404, Asimadoline, Atazanavir sulfate, AVE-0277, Azelnidipine; Bevacizumab, Bimatoprost, Boceprevir, Bortezomib, Bosentan, Botulinum toxin type B; Certolizumab pegol, Cetuximab, Clevudine, Contusugene ladenovec, CP-751871, Crofelemer, Cypher, CYT006-AngQb; Darbepoetin alfa, Desmopressin, Dexlansoprazole, DG-041; E-5555, Ecogramostim, Entecavir, Erlotinib hydrochloride, Escitalopram oxalate, Eszopiclone, Everolimus, Ezetimibe, Ezetimibe/simvastatin; Falecalcitriol, Fampridine, Fesoterodine fumarate, Fingolimod hydrochloride; Gefitinib, Ghrelin (human), GS-7904L, GV-1001; HT-1001; Insulin detemir, ISIS-112989, Istradefylline; Laquinimod sodium, Latanoprost/timolol maleate, Lenalidomide, Levobetaxolol hydrochloride, Liposomal doxorubicin, Liposomal morphine sulfate, Lubiprostone, Lumiracoxib, LY-518674; MEM-1003, Mesna disulfide, Mipomersen sodium, MM-093, Mycophenolic acid sodium salt; Naptumomab estafenatox, Natalizumab; Olmesartan medoxomil, Olmesartan medoxomil/hydrochlorothiazide; Paclitaxel nanoparticles, Paclitaxel poliglumex, Pasireotide, Pazufloxacin mesilate, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Peginterferon alfa-2b/ribavirin, Pegvisomant, Pemetrexed disodium, Pimagedine, Pimecrolimus, Pramlintide acetate, Prasterone, Pregabalin, Prulifloxacin; QAE-397; Rec-15/2615, RFB4(dsFv)-PE38, rhGAD65, Roflumilast, Romiplostim, Rosuvastatin calcium, Rotigotine, Rupatadine fumarate; Safinamide mesilate, SIR-Spheres, Sitagliptin phosphate, Sodium phenylacetate, Sodium phenylacetate/Sodium benzoate, Sorafenib, SSR-244738; Taribavirin hydrochloride, Taxus, Teduglutide, Tegaserod maleate, Telaprevir, Telbivudine, Tenofovir disoproxil fumarate, Tigecycline, Tiotropium bromide, Trabectedin, Travoprost

  4. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2005-12-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity. prous.com. This issue focuses on the following selection of drugs: 131I-chTNT; Abatacept, adalimumab, alemtuzumab, APC-8015, aprepitant, atazanavir sulfate, atomoxetine hydrochloride, azimilide hydrochloride; Bevacizumab, bortezomib, bosentan, buserelin; Caspofungin acetate, CC-4047, ChAGCD3, ciclesonide, clopidogrel, curcumin, Cypher; Dabigatran etexilate, dapoxetine hydrochloride, darbepoetin alfa, darusentan, denosumab, DMXB-Anabaseine, drospirenone, drospirenone/estradiol, duloxetine hydrochloride, dutasteride; Edodekin alfa, efaproxiral sodium, elaidic acid-cytarabine, erlotinib hydrochloride, ertapenem sodium, escitalopram oxalate, eszopiclone, etonogestrel/testosterone decanoate, exenatide; Fulvestrant; Gefitinib, glycine, GVS-111; Homoharringtonine; ICC-1132, imatinib mesylate, iodine (I131) tositumomab, i.v. gamma-globulin; Levetiracetam, levocetirizine, lintuzumab, liposomal nystatin, lumiracoxib, lurtotecan; Manitimus, mapatumumab, melatonin, micafungin sodium, mycophenolic acid sodium salt; Oblimersen sodium, OGX-011, olmesartan medoxomil, omalizumab, omapatrilat, oral insulin; Parathyroid hormone (human recombinant), pasireotide, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, phVEGF-A165, pimecrolimus, pitavastatin calcium, plerixafor hydrochloride, posaconazole, pramlintide acetate, prasterone, pregabalin, PT-141; Quercetin; Ranolazine, rosuvastatin calcium, rubitecan, rupatadine fumarate; Sardomozide, sunitinib malate; Tadalafil, talactoferrin alfa, tegaserod maleate, telithromycin, testosterone transdermal patch, TH-9507, tigecycline, tiotropium bromide, tipifarnib, tocilizumab, treprostinil sodium; Valdecoxib, vandetanib

  5. 21 CFR 556.380 - Melengestrol acetate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Melengestrol acetate. 556.380 Section 556.380 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Tolerances for Residues of New Animal Drugs § 556.380 Melengestrol acetate. A tolerance of 25 parts...

  6. 21 CFR 556.380 - Melengestrol acetate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Melengestrol acetate. 556.380 Section 556.380 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Tolerances for Residues of New Animal Drugs § 556.380 Melengestrol acetate. A tolerance of 25 parts...

  7. 21 CFR 556.380 - Melengestrol acetate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Melengestrol acetate. 556.380 Section 556.380 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Tolerances for Residues of New Animal Drugs § 556.380 Melengestrol acetate. A tolerance of 25 parts...

  8. 21 CFR 556.380 - Melengestrol acetate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Melengestrol acetate. 556.380 Section 556.380 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Tolerances for Residues of New Animal Drugs § 556.380 Melengestrol acetate. A tolerance of 25 parts...

  9. 21 CFR 173.228 - Ethyl acetate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... the specifications of the Food Chemicals Codex, 1 (Ethyl Acetate; p. 372, 3d Ed., 1981), which are... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Ethyl acetate. 173.228 Section 173.228 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR...

  10. Manufacturing Ethyl Acetate From Fermentation Ethanol

    NASA Technical Reports Server (NTRS)

    Rohatgi, Naresh K.; Ingham, John D.

    1991-01-01

    Conceptual process uses dilute product of fermentation instead of concentrated ethanol. Low-concentration ethanol, extracted by vacuum from fermentation tank, and acetic acid constitutes feedstock for catalytic reaction. Product of reaction goes through steps that increases ethyl acetate content to 93 percent by weight. To conserve energy, heat exchangers recycle waste heat to preheat process streams at various points.

  11. The pharmacology of nomegestrol acetate.

    PubMed

    Ruan, Xiangyan; Seeger, Harald; Mueck, Alfred O

    2012-04-01

    Nomegestrol acetate (NOMAC) is a 19-norprogesterone derivative with high biological activity at the progesterone receptor, a weak anti-androgenic effect, but with no binding to estrogen, glucocorticoid or mineralocorticoid receptors. At dosages of 1.5mg/day or more, NOMAC effectively suppresses gonadotropic activity and ovulation in women of reproductive age. Hemostasis, lipids and carbohydrate metabolism remain largely unchanged. In normal and cancerous human breast cells, NOMAC has shown favorable effects on estrogen metabolism. Like natural progesterone (but in contrast to some other synthetic progestogens), it does not appear stimulate the proliferation of cancerous breast cells. While there has been some experience of the use of NOMAC in combination with estrogens as a hormone replacement therapy, most of the data on the compound are reported in the context of its inclusion as a component of a new contraceptive pill comprising 2.5mg NOMAC combined with 1.5mg estradiol. Because of its strong endometrial efficacy, and due to its high antigonadotropic activity and long elimination half-life (about 50h), the contraceptive efficacy of the new pill is maintained even when dosages are missed. Furthermore, for the first time with a monophasic 24/4 regimen containing estradiol, cyclical stability can be achieved comparable with that obtained using pills containing ethinyl estradiol and progestogens like levonorgestrel or drospirenone. The addition of NOMAC to estradiol means that the beneficial effects of estrogen are not lost, which is of especial importance in relation to the cardiovascular system. On the basis both of its pharmacology and of studies performed during the development of the NOMAC/estradiol pill, involving some 4000 women in total, good long-term tolerability can be expected for NOMAC, although its safety profile is still to be fully ascertained, as the clinical endpoint studies are yet to be completed. PMID:22364709

  12. Conversion to eslicarbazepine acetate monotherapy

    PubMed Central

    French, Jacqueline; Jacobson, Mercedes P.; Pazdera, Ladislav; Gough, Mallory; Cheng, Hailong; Grinnell, Todd; Blum, David

    2016-01-01

    Objective: To assess the efficacy and safety of eslicarbazepine acetate (ESL) monotherapy. Methods: This post hoc pooled analysis of 2 randomized double-blind studies (093-045 and -046) included adults with partial-onset seizures medically uncontrolled by 1 or 2 antiepileptic drugs (AEDs). Following the baseline period (8 weeks), eligible patients were randomized 2:1 to receive ESL 1,600 mg or 1,200 mg once daily for 18 weeks; the primary endpoint was study exit by meeting predefined exit criteria (signifying worsening seizure control). In each study, treatment was considered effective if the upper 95% confidence limit for exit rate was lower than the historical control threshold (65.3%). Results: Pooled exit rates were as follows: ESL 1,600 mg = 20.6% (95% confidence interval: 15.6%–26.8%); ESL 1,200 mg = 30.8% (23.0%–40.5%). Use of 2 baseline AEDs or rescue medication, US location, epilepsy duration ≥20 years, and higher maximum baseline seizure frequency were associated with higher exit risks. Median percent reductions in standardized seizure frequency between baseline and the 18-week double-blind period were as follows: ESL 1,600 mg = 43.2%; ESL 1,200 mg = 35.7%; baseline carbamazepine use was associated with smaller reductions. Safety profiles were similar between ESL doses. Conclusions: Exit rates for ESL monotherapy (1,600 mg and 1,200 mg once daily) were lower than the historical control threshold, irrespective of baseline AED use and region, with no additional safety concerns identified. Clinical factors and location clearly influence treatment responses in conversion-to-monotherapy trials. Classification of evidence: This pooled analysis provides Class IV evidence that for adults with medically uncontrolled partial-onset seizures, ESL monotherapy is well tolerated and effective. PMID:26911639

  13. Clostridium thermosaccharolyticum strain deficient in acetate production

    SciTech Connect

    Rothstein, D.M.

    1986-01-01

    A mutant of Clostridium thermosaccharolyticum that is blocked in acetate production was isolated after treatment with nitrosoguanidine and selection for fluoroacetate resistance. The mutant produced more ethanol than the parent strain did.

  14. Acetate Causes Alcohol Hangover Headache in Rats

    PubMed Central

    Maxwell, Christina R.; Spangenberg, Rebecca Jay; Hoek, Jan B.; Silberstein, Stephen D.; Oshinsky, Michael L.

    2010-01-01

    Background The mechanism of veisalgia cephalgia or hangover headache is unknown. Despite a lack of mechanistic studies, there are a number of theories positing congeners, dehydration, or the ethanol metabolite acetaldehyde as causes of hangover headache. Methods We used a chronic headache model to examine how pure ethanol produces increased sensitivity for nociceptive behaviors in normally hydrated rats. Results Ethanol initially decreased sensitivity to mechanical stimuli on the face (analgesia), followed 4 to 6 hours later by inflammatory pain. Inhibiting alcohol dehydrogenase extended the analgesia whereas inhibiting aldehyde dehydrogenase decreased analgesia. Neither treatment had nociceptive effects. Direct administration of acetate increased nociceptive behaviors suggesting that acetate, not acetaldehyde, accumulation results in hangover-like hypersensitivity in our model. Since adenosine accumulation is a result of acetate formation, we administered an adenosine antagonist that blocked hypersensitivity. Discussion Our study shows that acetate contributes to hangover headache. These findings provide insight into the mechanism of hangover headache and the mechanism of headache induction. PMID:21209842

  15. Mafenide acetate allergy presenting as recurrent chondritis.

    PubMed

    Pickus, Evan J; Lionelli, Gerald T; Charles, E Woodall; Korentager, Richard A

    2002-02-01

    Acute chondritis has a strong predilection for recurrence. Mafenide acetate has been implicated in causing reactions that mimic this condition; however, these hypersensitivity reactions lack fever, fluctuance, and pain. The authors report a case of mafenide acetate allergy presenting as recurrent chondritis in a patient who had previously been treated successfully for this condition. In this patient, the allergic response resolved within 3 days after cessation of mafenide acetate. If unappreciated, it may have led to unnecessary operative intervention. Therefore, auricular edema and erythema, without fever, fluctuance, and pain, must be recognized by surgeons as a possible mafenide acetate allergy and must be considered in the differential diagnosis for patients who present with recurrent acute suppurative chondritis. PMID:11910229

  16. Nomegestrol acetate/estradiol: in oral contraception.

    PubMed

    Yang, Lily P H; Plosker, Greg L

    2012-10-01

    Nomegestrol acetate/estradiol is a combined oral contraceptive with approval in many countries. This fixed-dose combination tablet contains nomegestrol acetate, a highly selective progestogen, and estradiol, a natural estrogen. It is the first monophasic combined oral contraceptive to contain estradiol, and is taken in 28-day cycles, consisting of 24 active therapy days with 4 placebo days (i.e. 24/4-day cycles). In two large, 1-year, randomized, open-label, multicentre, phase III trials in healthy adult women (aged 18-50 years), nomegestrol acetate/estradiol was at least as effective as drospirenone/ethinylestradiol as contraceptive therapy, as the pregnancy rates in women aged 18-35 years (primary efficacy population) in terms of the Pearl Index (primary endpoint) were numerically lower with nomegestrol acetate/estradiol, although the between-group difference was not statistically significant. In both trials, nomegestrol acetate/estradiol was given in a 24/4-day cycle, and drospirenone/ethinylestradiol was given in a 21/7-day cycle. The criteria for using condoms in case of forgotten doses were less stringent in the nomegestrol acetate/estradiol group than in the drospirenone/ethinylestradiol group. Nomegestrol acetate/estradiol therapy for up to 1 year was generally well tolerated in healthy adult women, with an acceptable tolerability profile in line with that expected for a combined oral contraceptive. The most commonly reported adverse events were acne and abnormal withdrawal bleeding (most often shorter, lighter or absent periods). Overall, compared with drospirenone/ethinylestradiol, nomegestrol acetate/estradiol appeared to be associated with less favourable acne-related outcomes, and shorter, lighter or absent periods. PMID:22950535

  17. Methanogenesis from acetate: a nonmethanogenic bacterium from an anaerobic acetate enrichment.

    PubMed

    Ward, D M; Mah, R A; Kaplan, I R

    1978-06-01

    A methanogenic acetate enrichment was initiated by inoculation of an acetate-mineral salts medium with domestic anaerobic digestor sludge and maintained by weekly transfer for 2 years. The enrichment culture contained a Methanosarcina and several obligately anaerobic nonmethanogenic bacteria. These latter organisms formed varying degrees of association with the Methanosarcina, ranging from the nutritionally fastidious gram-negative rod called the satellite bacterium to the nutritionally nonfastidious Eubacterium limosum. The satellite bacterium had growth requirements for amino acids, a peptide, a purine base, vitamin B12, and other B vitamins. Glucose, mannitol, starch, pyruvate, cysteine, lysine, leucine, isoleucine, arginine, and asparagine stimulated growth and hydrogen production. Acetate was neither incorporated nor metabolized by the satellite organism. Since acetate was the sole organic carbon source in the enrichment culture, organism(s) which metabolize acetate (such as the Methanosarcina) must produce substrates and growth factors for associated organisms which do not metabolize acetate. PMID:677881

  18. Determination of γ-hydroxybutyrate (GHB), β-hydroxybutyrate (BHB), pregabalin, 1,4-butane-diol (1,4BD) and γ-butyrolactone (GBL) in whole blood and urine samples by UPLC-MSMS.

    PubMed

    Dahl, Sandra Rinne; Olsen, Kirsten Midtbøen; Strand, Dag Helge

    2012-02-15

    The demand of high throughput methods for the determination of gamma-hydroxybutyrate (GHB) and its precursors gamma-butyrolactone (GBL) and 1,4-butane-diol (1,4BD) as well as for pregabalin is increasing. Here we present two analytical methods using ultra-high pressure liquid chromatography (UPLC) and tandem mass spectrometric (MS/MS) detection for the determination of GHB, beta-hydroxybutyrate (BHB), pregabalin, 1,4BD and GBL in whole blood and urine. Using the 96-well formate, the whole blood method is a simple high-throughput method suitable for screening of large sample amounts. With an easy sample preparation for urine including only dilution and filtration of the sample, the method is suitable for fast screening of urine samples. Both methods showed acceptable linearity, acceptable limits of detection, and limits of quantification. The within-day and between-day precisions of all analytes were lower than 10% RSD. The analytes were extracted from matrices with recoveries near 100%, and no major matrix effects were observed. Both methods have been used as routine screening analyses of whole blood and urine samples since January 2010. PMID:22226469

  19. Adrenocortical suppression in cats given megestrol acetate.

    PubMed

    Chastain, C B; Graham, C L; Nichols, C E

    1981-12-01

    Megestrol acetate was given orally to 8 cats at a dose of 2.5 mg every other day for 2 weeks and to 8 cats at a dose of 5.0 mg every day for 2 weeks. Four cats were designated nontreated controls. Pre-ACTH-stimulated plasma concentrations of cortisol (hydrocortisone) and ACTH-stimulated cortisol and tolerance to large-dose glucose infusion (IV) were determined on each of the 20 cats given megestrol acetate. Cats were restrained with acepromazine maleate and ketamine hydrochloride during blood sample collection and large-dose glucose infusion. Adrenocortical function and tolerance to large-dose glucose infusion were reevaluated for 4 weeks--after 1st and 2nd weeks of megestrol acetate treatment of the treated groups, and after 1st and 2nd weeks when treatment was stopped (ie, experiment weeks 3 and 4). Each week a cat from the control group and 2 cats from the 2 treated groups were selected to determine the changes occurring during the experiment for that week; after collection of plasma samples, each week's 5 selected cats were euthanatized and necropsied. Significant impairment of adrenocortical function and alteration of adrenocortical morphology occurred with both treated groups. The most severe adrenocortical alterations occurred in the cats 1 week after megestrol acetate was no longer given (ie, experiment week 3). Megestrol acetate-induced adrenocortical suppression contributed to the death of 1 cat. It was concluded that if stress occurs to cats on treatment or soon after treatment with megestrol acetate, glucocorticoids should be supplemented. The effects of megestrol acetate on glucose tolerance were overshadowed by the unforeseen intolerance caused by chemical restraint with acepromazine maleate and ketamine hydrochloride. PMID:6280517

  20. Gateways to clinical trials. March 2003.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2003-03-01

    Gateways to clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and devlopment protal, http://integrity.prous.com. This issue focuses on the following selection of drugs: AAV-CF, adalimumab, ademetionine, afeletecan hydrochloride, agomelatine, alemtuzumab, almotriptan, amdoxovir, aplidine, aranose, arsenic sulfide, atazanavir, atlizumab; Bimatoprost, BMS-181176, BMS-188667, bortezomib, bryostatin 1; Combretastatin A-4 phosphate; Darbepoetin alfa, darusentan, deferasirox, desloratadine, DTaP-HBV-IPV/Hib-vaccine, DTI-0009; Eculizumab, edodekin alfa, emtricitabine, enfuvirtide, epoetin, esomeprazole magnesium etoricoxib; Fampridine, fenretinide, FR-146687; Galiximab, gamma-Hydroxybutyrate sodium, ganirelix acetate, gefitinib, Gemtuzumab ozogamicin, gimatecan; HEA125xOKT3, hIL-13-PE38QQR, HSV-2 theracine, Hu14.18-IL-2, human gammaglobulin; Idraparinux sodium, imatinib mesylate, IMiD3, insulin detemir, interleukin-4, irofulven, ISAtx-247; JT-1001; Levetiracetam, levosimendan, liposomal doxorubicin, liposomal vincristine sulfate, lixivaptan, lopinavir, lumiracoxib; Maxacalcitol, melatonin, midostaurin, MLN-518; Neridronic acid, nesiritide, nitronaproxen; Oblimersen sodium, oregovomab; PEG-filgrastim polyglutamate paclitaxel, prasterone, pregabalin; Rosuvastatin calcium, rotigotine hydrochloride; SGN-30; T-1249, tenofovir disoproxil fumarate, teriparatide, tiotropium bromide, tipranavir, TMC-114, trabectedin, transdermal selegiline; UK-427857; Valdecoxib, valganciclovir hydrochloride, vardenafil, vatalanib succinate, vincristine sulfate TCS; Zofenopril calcium. PMID:12731460

  1. Acetate Transport and Utilization in the Rat Brain

    PubMed Central

    Deelchand, Dinesh K.; Shestov, Alexander A.; Koski, Dee M.; Uğurbil, Kâmil; Henry, Pierre-Gilles

    2009-01-01

    Acetate, a glial-specific substrate, is an attractive alternative to glucose for the study of neuronal-glial interactions. The present study investigates the kinetics of acetate uptake and utilization in the rat brain in vivo during infusion of [2-13C]acetate using NMR spectroscopy. When plasma acetate concentration was increased, the rate of brain acetate utilization (CMRace) increased progressively and reached close to saturation for plasma acetate concentration > 2-3 mM, whereas brain acetate concentration continued to increase. The Michaelis-Menten constant for brain acetate utilization ( KMutil=0.01±0.14mM) was much smaller than for acetate transport through the blood-brain barrier ( KMt=4.18±0.83mM). The maximum transport capacity of acetate through the blood-brain barrier ( Vmaxt=0.96±0.18μmol/g/min) was nearly two-fold higher than the maximum rate of brain acetate utilization ( Vmaxutil=0.50±0.08μmol/g/min). We conclude that, under our experimental conditions, brain acetate utilization is saturated when plasma acetate concentrations increase above 2-3 mM. At such high plasma acetate concentration, the rate-limiting step for glial acetate metabolism is not the blood-brain barrier, but occurs after entry of acetate into the brain. PMID:19393008

  2. Acetylation of Starch with Vinyl Acetate in Imidazolium Ionic Liquids and Characterization of Acetate Distribution

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Starch was acetylated with vinyl acetate in different 1-butyl-3-methylimidazolium (BMIM) salts as solvent in effort to produce starches with different acetylation patterns. Overall degree of substitution was much higher for basic anions such as acetate and dicyanimide (dca) than for neutral anions ...

  3. 40 CFR 721.10001 - 2-Ethoxyethanol, 2-ethoxyethanol acetate, 2-methoxyethanol, and 2-methoxyethanol acetate.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... new uses subject to reporting. (1) The chemical substances identified as 2-ethoxyethanol (CAS No. 110-80-5), 2-ethoxyethanol acetate (CAS No. 111-15-9), 2-methoxyethanol (CAS No. 109-86-4), and 2-methoxyethanol acetate (CAS No. 110-49-6) are subject to reporting under this section for the significant new...

  4. 40 CFR 721.10001 - 2-Ethoxyethanol, 2-ethoxyethanol acetate, 2-methoxyethanol, and 2-methoxyethanol acetate.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... new uses subject to reporting. (1) The chemical substances identified as 2-ethoxyethanol (CAS No. 110-80-5), 2-ethoxyethanol acetate (CAS No. 111-15-9), 2-methoxyethanol (CAS No. 109-86-4), and 2-methoxyethanol acetate (CAS No. 110-49-6) are subject to reporting under this section for the significant new...

  5. Tested Demonstrations: Buffer Capacity of Various Acetic Acid-Sodium Acetate Systems: A Lecture Experiment.

    ERIC Educational Resources Information Center

    Donahue, Craig J.; Panek, Mary G.

    1985-01-01

    Background information and procedures are provided for a lecture experiment which uses indicators to illustrate the concept of differing buffer capacities by titrating acetic acid/sodium acetate buffers with 1.0 molar hydrochloric acid and 1.0 molar sodium hydroxide. A table with data used to plot the titration curve is included. (JN)

  6. [Degradation of thiometon in ethyl acetate].

    PubMed

    Satoh, M; Shimokawa, S; Kobata, M; Tanaka, T; Nakanishi, Y

    2001-04-01

    When performing multiresidue analysis of pesticides, the recovery of thiometon was less than 20% from carrots and eggplants, but about 100% from garlic chives and welsh onions. The recovery of thiometon was found to depend on the lot of ethyl acetate. A 2-year-old lot of ethyl acetate caused degradation of thiometon, but a fresh lot of ethyl acetate did not. Analysis showed that ethyl acetate stored for 2 years contained about 5 microL/mL of acetaldehyde. Thiometon was also degraded by acetone or acetonitrile, when acetaldehyde was added to them, in the same manner as by aged ethyl acetate. The fact that the recovery of thiometon from welsh onions was about 100% indicated that some of the mercaptans in allium vegetables may prevent thiometon degradation. Mercaptans such as L-cysteine and 3-mercaptoproionic acid were confirmed to prevent the degradation of thiometon and disulfoton. These findings show that mercaptans may be useful additives for analyzing thiometon and disulfoton. PMID:11486375

  7. Megestrol acetate for treatment of endometriosis.

    PubMed

    Schlaff, W D; Dugoff, L; Damewood, M D; Rock, J A

    1990-04-01

    Between 1977-1989, 29 women with symptomatic endometriosis were treated with megestrol acetate by the Johns Hopkins Division of Reproductive Endocrinology. All had previously received one or more alternative medical treatments for endometriosis, in each case discontinued because of poor response or development of unacceptable side effects. Treatment consisted of a daily dose of 40 mg megestrol acetate orally for up to 24 months. Disease-related symptoms (dysmenorrhea, noncyclic pelvic pain, and dyspareunia) were relieved in 86% of the subjects treated with an adequate course of therapy. Side effects were fairly well tolerated, although eight women discontinued treatment within 2 months and two others stopped the drug by 4 months. These preliminary findings suggest that megestrol acetate may be an effective treatment for patients with endometriosis, even those who have been unresponsive to other modes of therapy. PMID:2314784

  8. 21 CFR 556.380 - Melengestrol acetate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Melengestrol acetate. 556.380 Section 556.380 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs §...

  9. Heat Bonding of Irradiated Ethylene Vinyl Acetate

    NASA Technical Reports Server (NTRS)

    Slack, D. H.

    1986-01-01

    Reliable method now available for joining parts of this difficult-tobond material. Heating fixture encircles ethylene vinyl acetate multiplesocket part, providing heat to it and to tubes inserted in it. Fixtures specially designed to match parts to be bonded. Tube-and-socket bonds made with this technique subjected to tensile tests. Bond strengths of 50 percent that of base material obtained consistently.

  10. 21 CFR 522.1881 - Prednisolone acetate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Prednisolone acetate. 522.1881 Section 522.1881 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... used as supportive therapy pre- and postoperatively and for various stress conditions...

  11. Fragrance material review on phenethyl acetate.

    PubMed

    McGinty, D; Vitale, D; Letizia, C S; Api, A M

    2012-09-01

    A toxicologic and dermatologic review of phenethyl acetate when used as a fragrance ingredient is presented. Phenethyl acetate is a member of the fragrance structural group aryl alkyl alcohol simple acid esters (AAASAE). The AAASAE fragrance ingredients are prepared by reacting an aryl alkyl alcohol with a simple carboxylic acid (a chain of 1-4 carbons) to generate formate, acetate, propionate, butyrate, isobutyrate and carbonate esters. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for phenethyl acetate were evaluated, then summarized, and includes: physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, elicitation, toxicokinetics, repeated dose, genotoxicity, and carcinogenicity data. A safety assessment of the entire AAASAE will be published simultaneously with this document. Please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all AAASAE in fragrances. PMID:22414644

  12. Synthesis of Cellulose Acetate from Cotton Byproducts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cotton burr and cottonseed hull are relatively inexpensive cotton byproducts. In an effort to derive greater value out of these natural renewable materials, we have succeeded in converting part of them into cellulose acetate without prior chemical breakdown or physical separation of cellulose, ligni...

  13. Advanced Colloids Experiment (ACE-T1)

    NASA Technical Reports Server (NTRS)

    Meyer, William V.; Sicker, Ron; Brown, Dan; Eustace, John

    2015-01-01

    Increment 45 - 46 Science Symposium presentation of Advanced Colloids Experiment (ACE-T1) to RPO. The purpose of this event is for Principal Investigators to present their science objectives, testing approach, and measurement methods to agency scientists, managers, and other investigators.

  14. 21 CFR 184.1185 - Calcium acetate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Calcium acetate. 184.1185 Section 184.1185 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) DIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE Listing of Specific Substances Affirmed as GRAS...

  15. 21 CFR 184.1721 - Sodium acetate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Sodium acetate. 184.1721 Section 184.1721 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) DIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE Listing of Specific Substances Affirmed as GRAS §...

  16. Process for the preparation of vinyl acetate

    DOEpatents

    Tustin, G.C.; Zoeller, J.R.; Depew, L.S.

    1998-02-17

    This invention pertains to the preparation of vinyl acetate by contacting within a contact zone a mixture of ketene and acetaldehyde with an acid catalyst at about one bar pressure and between about 85 and 200 C and removing the reaction products from the contact zone.

  17. Process for the preparation of vinyl acetate

    DOEpatents

    Tustin, Gerald Charles; Zoeller, Joseph Robert; Depew, Leslie Sharon

    1998-01-01

    This invention pertains to the preparation of vinyl acetate by contacting within a contact zone a mixture of ketene and acetaldehyde with an acid catalyst at about one bar pressure and between about 85.degree. and 200.degree. C. and removing the reaction products from the contact zone.

  18. Reactions of germanium tetrahalides with ketene acetals

    SciTech Connect

    Efimova, I.V.; Kazankova, M.A.; Lutsenko, I.F.

    1985-05-01

    Recently, the authors reported that alkyl vinyl ethers and terminal alkynes are readily germylated by germanium tetrahalides in the presence of a tertiary amine. To extend the range of applicability of this reaction and to obtain additional information on its mechanism, the authors study reactions of ketene acetals with germanium tetrachloride and tetrabromide in the presence of triethylamine.

  19. Phenyl Acetate Preparation from Phenol and Acetic Acid: Reassessment of a Common Textbook Misconception.

    ERIC Educational Resources Information Center

    Hocking, M. B.

    1980-01-01

    Reassesses a common textbook misconception that "...phenols cannot be esterified directly." Results of experiments are discussed and data tables provided of an effective method for the direct preparation of phenyl acetate. (CS)

  20. 21 CFR 582.5892 - a-Tocopherol acetate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5892 a-Tocopherol acetate. (a) Product. a-Tocopherol acetate. (b) Conditions of use....

  1. Expression of acetate permease-like (apl) genes in subsurface communities of Geobacter species under fluctuating acetate concentrations

    SciTech Connect

    Elifantz, H.; N'Guessan, L.A.; Mouser, P.J.; Williams, K H.; Wilkins, M J.; Risso, C.; Holmes, D.E.; Long, P.E.; Lovley, D.R.

    2010-03-01

    The addition of acetate to uranium-contaminated aquifers in order to stimulate the growth and activity of Geobacter species that reduce uranium is a promising in situ bioremediation option. Optimizing this bioremediation strategy requires that sufficient acetate be added to promote Geobacter species growth. We hypothesized that under acetate-limiting conditions, subsurface Geobacter species would increase the expression of either putative acetate symporters genes (aplI and aplII). Acetate was added to a uranium-contaminated aquifer (Rifle, CO) in two continuous amendments separated by 5 days of groundwater flush to create changing acetate concentrations. While the expression of aplI in monitoring well D04 (high acetate) weakly correlated with the acetate concentration over time, the transcript levels for this gene were relatively constant in well D08 (low acetate). At the lowest acetate concentrations during the groundwater flush, the transcript levels of aplII were the highest. The expression of aplII decreased 2-10-fold upon acetate reintroduction. However, the overall instability of acetate concentrations throughout the experiment could not support a robust conclusion regarding the role of apl genes in response to acetate limitation under field conditions, in contrast to previous chemostat studies, suggesting that the function of a microbial community cannot be inferred based on lab experiments alone.

  2. Expression of Acetate Permease-like (apl) Genes in Subsurface Communities of Geobacter Species Under Fluctuating Acetate Concentrations

    SciTech Connect

    Elifantz, H; N'Guessan, A L; Mouser, Paula; Williams, Kenneth H; Wilkins, Michael J; Risso, Carla; Holmes, Dawn; Long, Philip E; Lovley, Derek R

    2010-09-01

    The addition of acetate to uranium-contaminated aquifers in order to stimulate the growth and activity of Geobacter species that reduce uranium is a promising in situ bioremediation option. Optimizing this bioremediation strategy requires that sufficient acetate be added to promote Geobacter species growth. We hypothesized that under acetate-limiting conditions, subsurface Geobacter species would increase the expression of either putative acetate symporters genes (aplI and aplII). Acetate was added to a uranium-contaminated aquifer (Rifle, CO) in two continuous amendments separated by 5 days of groundwater flush to create changing acetate concentrations. While the expression of aplI in monitoring well D04 (high acetate) weakly correlated with the acetate concentration over time, the transcript levels for this gene were relatively constant in well D08 (low acetate). At the lowest acetate concentrations during the groundwater flush, the transcript levels of aplII were the highest. The expression of aplII decreased 2–10-fold upon acetate reintroduction. However, the overall instability of acetate concentrations throughout the experiment could not support a robust conclusion regarding the role of apl genes in response to acetate limitation under field conditions, in contrast to previous chemostat studies, suggesting that the function of a microbial community cannot be inferred based on lab experiments alone.

  3. Separating acetic acid from furol (furfural) by electrodialysis method

    SciTech Connect

    Guan, S.F.; Li, C.S. Ye, S.T.; Shen, S.Y.; Wang, Y.T.; Yu, S.H.

    1981-01-01

    Furfural production by hydrolysis of fibrous plant materials is accompanied by formation of acetic acid in amounts depending on the material used. The amount of acetic formed in the hydrolysis of the fruit shell of oil-tea camellia (Camellia oleosa) (an oilseed-bearing tree) is equal to the amount of furfural. The acetic acid can be separated from the furfural and concentrated to 10% by electrodialysis. A smaller amount of furfural is separated with acetic acid.

  4. Cyproterone acetate in treatment of precocious puberty.

    PubMed Central

    Kauli, R; Pertzelan, A; Prager-Lewin, R; Grünebaum, M; Laron, Z

    1976-01-01

    Twenty-nine children (23 girls, 6 boys) with precocious puberty were treated with cyproterone acetate for various periods of time ranging from 6 months to 3 years 4 months. They received an oral dose ranging from 70-150 mg/m2 per day, or an intramuscular depot injection once a fortnight or once a month at a dose ranging from 107-230 mg/m2. Both forms of therapy were found to suppress the signs of sexual maturation, but the oral form proved to be superior. Only the younger patients with a bone age under 11 years showed a beneficial effect upon linear growth and bone maturation. No side effects were noted, but additional advantageous effects upon behaviour and sociability were. It is concluded that at present cyproterone acetate by mouth is the drug of choice in the treatment of precocious puberty. The treatment should be initiated as early as possible to attain maximum benefit. PMID:952553

  5. Facile hydrolysis and alcoholysis of palladium acetate.

    PubMed

    Bedford, Robin B; Bowen, John G; Davidson, Russell B; Haddow, Mairi F; Seymour-Julen, Annabelle E; Sparkes, Hazel A; Webster, Ruth L

    2015-05-26

    Palladium(II) acetate is readily converted into [Pd3 (μ(2) -OH)(OAc)5 ] (1) in the presence of water in a range of organic solvents and is also slowly converted in the solid state. Complex 1 can also be formed in nominally anhydrous solvents. Similarly, the analogous alkoxide complexes [Pd3 (μ(2) -OR)(OAc)5 ] (3) are easily formed in solutions of palladium(II) acetate containing a range of alcohols. An examination of a representative Wacker-type oxidation shows that the Pd-OH complex 1 and a related Pd-oxo complex 4 can be excluded as potential catalytic intermediates in the absence of exogenous water. PMID:25865439

  6. 21 CFR 584.200 - Ethyl alcohol containing ethyl acetate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Ethyl alcohol containing ethyl acetate. The feed additive ethyl alcohol containing ethyl acetate meets the requirement of 27 CFR 21.62, being not less than 92.5 percent ethyl alcohol, each 100 gallons... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ethyl alcohol containing ethyl acetate....

  7. 21 CFR 584.200 - Ethyl alcohol containing ethyl acetate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Ethyl alcohol containing ethyl acetate. The feed additive ethyl alcohol containing ethyl acetate meets the requirement of 27 CFR 21.62, being not less than 92.5 percent ethyl alcohol, each 100 gallons... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Ethyl alcohol containing ethyl acetate....

  8. 21 CFR 582.5933 - Vitamin A acetate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Vitamin A acetate. 582.5933 Section 582.5933 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5933 Vitamin A acetate. (a) Product. Vitamin A acetate. (b) Conditions of use....

  9. 21 CFR 582.5933 - Vitamin A acetate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Vitamin A acetate. 582.5933 Section 582.5933 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5933 Vitamin A acetate. (a) Product. Vitamin A acetate. (b) Conditions of use....

  10. 21 CFR 582.5933 - Vitamin A acetate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Vitamin A acetate. 582.5933 Section 582.5933 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5933 Vitamin A acetate. (a) Product. Vitamin A acetate. (b) Conditions of use....

  11. 21 CFR 582.5933 - Vitamin A acetate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Vitamin A acetate. 582.5933 Section 582.5933 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5933 Vitamin A acetate. (a) Product. Vitamin A acetate. (b) Conditions of use....

  12. 21 CFR 582.5933 - Vitamin A acetate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Vitamin A acetate. 582.5933 Section 582.5933 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5933 Vitamin A acetate. (a) Product. Vitamin A acetate. (b) Conditions of use....

  13. Thermochemical characteristics of cellulose acetates with different degrees of acetylation

    NASA Astrophysics Data System (ADS)

    Larina, V. N.; Ur'yash, V. F.; Kushch, D. S.

    2012-12-01

    The standard enthalpies of combustion and formation of cellulose acetates with different degrees of acetylation are determined. It is established that there is a proportional dependence of these thermochemical characteristics vs. the degree of acetylation, weight fraction of bonded acetic acid, and molar mass of the repeating unit of cellulose acetates.

  14. Acetate concentrations and oxidation in salt marsh sediments

    NASA Technical Reports Server (NTRS)

    1992-01-01

    Acetate concentrations and rates of acetate oxidation and sulfate reduction were measured in S. alterniflora sediments in New Hampshire and Massachusetts. Pore water extracted from cores by squeezing or centrifugation contained in greater than 0.1 mM acetate and, in some instances, greater than 1.0 mM. Pore water sampled nondestructively contained much less acetate, often less than 0.01 mM. Acetate was associated with roots, and concentrations varied with changes in plant physiology. Acetate turnover was very low whether whole core or slurry incubations were used. Radiotracers injected directly into soils yielded rates of sulfate reduction and acetate oxidation not significantly different from core incubation techniques. Regardless of incubation method, acetate oxidation did not account for a substantial percentage of sulfate reduction. These results differ markedly from data for unvegetated coastal sediments where acetate levels are low, oxidation rate constants are high, and acetate oxication rates greatly exceed rates of sulfate reduction. The discrepancy between rates of acetate oxidation and sulfate reduction in these marsh soils may be due either to the utilization of substrates other than acetate by sulfate reducers or artifacts associated with measurements of organic utilization by rhizosphere bacteria. Care must be taken when interpreting data from salt marsh sediments since the release of material from roots during coring may affect the concentrations of certain compounds as well as influencing results obtained when sediment incubations are employed.

  15. 21 CFR 584.200 - Ethyl alcohol containing ethyl acetate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Ethyl alcohol containing ethyl acetate. The feed additive ethyl alcohol containing ethyl acetate meets the requirement of 27 CFR 21.62, being not less than 92.5 percent ethyl alcohol, each 100 gallons... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Ethyl alcohol containing ethyl acetate....

  16. 21 CFR 584.200 - Ethyl alcohol containing ethyl acetate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Ethyl alcohol containing ethyl acetate. The feed additive ethyl alcohol containing ethyl acetate meets the requirement of 27 CFR 21.62, being not less than 92.5 percent ethyl alcohol, each 100 gallons... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Ethyl alcohol containing ethyl acetate....

  17. 21 CFR 584.200 - Ethyl alcohol containing ethyl acetate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Ethyl alcohol containing ethyl acetate. The feed additive ethyl alcohol containing ethyl acetate meets the requirement of 27 CFR 21.62, being not less than 92.5 percent ethyl alcohol, each 100 gallons... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Ethyl alcohol containing ethyl acetate....

  18. Kinetics of Ethyl Acetate Synthesis Catalyzed by Acidic Resins

    ERIC Educational Resources Information Center

    Antunes, Bruno M.; Cardoso, Simao P.; Silva, Carlos M.; Portugal, Ines

    2011-01-01

    A low-cost experiment to carry out the second-order reversible reaction of acetic acid esterification with ethanol to produce ethyl acetate is presented to illustrate concepts of kinetics and reactor modeling. The reaction is performed in a batch reactor, and the acetic acid concentration is measured by acid-base titration versus time. The…

  19. Co-fermentation of acetate and sugars facilitating microbial lipid production on acetate-rich biomass hydrolysates.

    PubMed

    Gong, Zhiwei; Zhou, Wenting; Shen, Hongwei; Yang, Zhonghua; Wang, Guanghui; Zuo, Zhenyu; Hou, Yali; Zhao, Zongbao K

    2016-05-01

    The process of lignocellulosic biomass routinely produces a stream that contains sugars plus various amounts of acetic acid. As acetate is known to inhibit the culture of microorganisms including oleaginous yeasts, little attention has been paid to explore lipid production on mixtures of acetate and sugars. Here we demonstrated that the yeast Cryptococcus curvatus can effectively co-ferment acetate and sugars for lipid production. When mixtures of acetate and glucose were applied, C. curvatus consumed both substrates simultaneously. Similar phenomena were also observed for acetate and xylose mixtures, as well as acetate-rich corn stover hydrolysates. More interestingly, the replacement of sugar with equal amount of acetate as carbon source afforded higher lipid titre and lipid content. The lipid products had fatty acid compositional profiles similar to those of cocoa butter, suggesting their potential for high value-added fats and biodiesel production. This co-fermentation strategy should facilitate lipid production technology from lignocelluloses. PMID:26874438

  20. Multiple-anion nonvolatile acetal (MANA) resists

    NASA Astrophysics Data System (ADS)

    Guevremont, Jeffrey M.; Brainard, Robert L.; Reeves, Scott D.; Zhou, Xin; Nguyen, Thinh B.; Mackevich, Joseph F.; Anderson, Erik H.; Taylor, Gary N.

    2001-08-01

    New acetal or ketal blocking reagents were investigated for use in e-beam lithography and compared with the performance of ethyl vinyl either (EVE). Three blocking groups, (alpha) -Angelicalactone (AL), 6-methylene-5,6-benzo-1,4- dioxane (MBD), and MANA50 (an undisclosed blocking group used to show the potential of this chemistry) were reacted with poly(p-hydroxystyrene) (PHS) under acid catalyzed conditions to form AL-PHS, MBD-PHS, MANA50-PHS. The performance objectives pursued in the design of these new materials was to use acetal (ketal) chemistry to deliver wide process latitudes (e.g. good PED performance and minimal PEB sensitivity), use high molecular weight blocking groups to eliminate outgassing, and use the novel concept of multiple anions to deliver lithographic performance. These new materials are called Multiple Anion Nonvolatile Acetal (MANA) resists. Resists films were exposed with 50kV electrons, post exposure baked (PEB), and developed with 0.26 N TMAH. Resists prepared with the third blocking group, MANA50, gave contrast and imaging performance independent of PEB humidity and were relatively insensitive to PEB temperature and post exposure delay (PED). These resists gave the best resolution (90 nm) and profiles of all the materials tested, as well as showing no outgassing (as measured by film thickness loss).

  1. Gateways to clinical trials.

    PubMed

    Moral, M A; Tomillero, A

    2008-03-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 131-I-Chlorotoxin, 423557; Abatacept, Ad.Egr.TNF.11D, Adalimumab, AE-941, Ambrisentan, AMR-001, Anacetrapib, Anakinra, Aripiprazole, Atazanavir sulfate; BAY-639044, Bazedoxifene acetate, Belimumab, Bevacizumab, Bortezomib, Botulinum toxin type B, Brivaracetam, Bucindolol hydrochloride; Carfilzomib, Carisbamate, CCX-282, CD20Bi, Ceftobiprole, Certolizumab pegol, CF-101, Cinacalcet hydrochloride, Cypher; Darifenacin hydrobromide, Degarelix acetate, Denosumab, Desvenlafaxine succinate, Dexlansoprazole, Dexverapamil, Drotrecogin alfa (activated), Duloxetine hydrochloride, Dutasteride; Efalizumab, EPs-7630, Escitalopram oxalate, Etoricoxib; Fluticasone furoate, Fondaparinux sodium, Fospropofol disodium; Hexadecyloxypropyl-cidofovir, HIV gp120/NefTat/AS02A, HPV-6/11/16/18; INCB-18424, Incyclinide, Inhalable human insulin, Insulin detemir; KNS-760704, KW-0761; Lacosamide, Lenalidomide, Levetiracetam, Licofelone, Lidocaine/prilocaine; mAb 216, MEDI-528, Men ACWY, Meningococcal C-CRM197 vaccine, Methylnaltrexone bromide; Nemifitide ditriflutate, Nicotine conjugate vaccine, Nilotinib hydrochloride monohydrate; Octaparin; Parathyroid hormone (human recombinant), Pegaptanib octasodium, Pitrakinra, Prasterone, Pregabalin; Ranelic acid distrontium salt, Rasagiline mesilate, Retigabine, Rimonabant, RTS,S/AS02D; Sarcosine, Sitaxentan sodium, Solifenacin succinate, Sunitinib malate; Taranabant, Taxus, Teduglutide, Teriparatide, Ticagrelor, Travoprost, TRU-015; USlipristal acetate, Urocortin 2; Vardenafil hydrochloride hydrate; YM-155, Yttrium 90 (90Y) ibritumomab tiuxetan; Zanolimumab, Zoledronic acid monohydrate, Zotarolimus

  2. Overview on mechanisms of acetic acid resistance in acetic acid bacteria.

    PubMed

    Wang, Bin; Shao, Yanchun; Chen, Fusheng

    2015-02-01

    Acetic acid bacteria (AAB) are a group of gram-negative or gram-variable bacteria which possess an obligate aerobic property with oxygen as the terminal electron acceptor, meanwhile transform ethanol and sugar to corresponding aldehydes, ketones and organic acids. Since the first genus Acetobacter of AAB was established in 1898, 16 AAB genera have been recorded so far. As the main producer of a world-wide condiment, vinegar, AAB have evolved an elegant adaptive system that enables them to survive and produce a high concentration of acetic acid. Some researches and reviews focused on mechanisms of acid resistance in enteric bacteria and made the mechanisms thoroughly understood, while a few investigations did in AAB. As the related technologies with proteome, transcriptome and genome were rapidly developed and applied to AAB research, some plausible mechanisms conferring acetic acid resistance in some AAB strains have been published. In this review, the related mechanisms of AAB against acetic acid with acetic acid assimilation, transportation systems, cell morphology and membrane compositions, adaptation response, and fermentation conditions will be described. Finally, a framework for future research for anti-acid AAB will be provided. PMID:25575804

  3. [Degradation of oxytetracycline with ozonation in acetic acid solvent].

    PubMed

    Li, Shi-Yin; Li, Xiao-Rong; Zhu, Yi-Ping; Zhu, Jiang-Peng; Wang, Guo-Xiang

    2012-12-01

    Use acetic acid as the media of ozone degradation of oxytetracycline (OTC), and effects of the initial dosing ratio of ozone/OTC, ozone flow, free radical scavenger, metal ions on the removal rate of OTC were investigated respectively. The results showed that acetic acid had a high ozone stability and solubility. OTC had a high removal rate and degradation rate in acetic acid solution. With the increase of OTC dosage, the removal rate of OTC decreased in acetic acid. Removal rate of OTC was increased distinctly when ozone flow increased properly. It was also observed that free radical scavenger had a significantly negative effect on OTC ozonation degradation in acetic acid. Furthermore the main reactions of OTC ozone oxidation were direct oxidation and indirect oxidation in acetic acid. When Fe3+ and Co2+ were existent in acetic acid, the degradation of OTC was inhibited significantly. PMID:23379161

  4. Acetic acid removal from corn stover hydrolysate using ethyl acetate and the impact on Saccharomyces cerevisiae bioethanol fermentation.

    PubMed

    Aghazadeh, Mahdieh; Ladisch, Michael R; Engelberth, Abigail S

    2016-07-01

    Acetic acid is introduced into cellulose conversion processes as a consequence of composition of lignocellulose feedstocks, causing significant inhibition of adapted, genetically modified and wild-type S. cerevisiae in bioethanol fermentation. While adaptation or modification of yeast may reduce inhibition, the most effective approach is to remove the acetic acid prior to fermentation. This work addresses liquid-liquid extraction of acetic acid from biomass hydrolysate through a pathway that mitigates acetic acid inhibition while avoiding the negative effects of the extractant, which itself may exhibit inhibition. Candidate solvents were selected using simulation results from Aspen Plus™, based on their ability to extract acetic acid which was confirmed by experimentation. All solvents showed varying degrees of toxicity toward yeast, but the relative volatility of ethyl acetate enabled its use as simple vacuum evaporation could reduce small concentrations of aqueous ethyl acetate to minimally inhibitory levels. The toxicity threshold of ethyl acetate, in the presence of acetic acid, was found to be 10 g L(-1) . The fermentation was enhanced by extracting 90% of the acetic acid using ethyl acetate, followed by vacuum evaporation to remove 88% removal of residual ethyl acetate along with 10% of the broth. NRRL Y-1546 yeast was used to demonstrate a 13% increase in concentration, 14% in ethanol specific production rate, and 11% ethanol yield. This study demonstrated that extraction of acetic acid with ethyl acetate followed by evaporative removal of ethyl acetate from the raffinate phase has potential to significantly enhance ethanol fermentation in a corn stover bioethanol facility. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:929-937, 2016. PMID:27090191

  5. Temperature dependence of ion transport in dilute tetrabutylammonium triflate-acetate solutions and self-diffusion in pure acetate liquids.

    PubMed

    Bopege, Dharshani N; Petrowsky, Matt; Fleshman, Allison M; Frech, Roger; Johnson, Matthew B

    2012-01-12

    Conductivities and static dielectric constants for 0.0055 M tetrabutylammonium trifluoromethanesulfonate in n-butyl acetate, n-pentyl acetate, n-hexyl acetate, n-octyl acetate, and n-decyl acetate have been collected over the temperature range of 0-80 °C. Self-diffusion coefficients and static dielectric constants of pure acetates were obtained over the same temperature range. Both temperature-dependent diffusion coefficients and ionic conductivities of these pure acetates and dilute acetate solutions can be accurately described by the compensated Arrhenius formalism. Activation energies were calculated from compensated Arrhenius plots for both conductivity and diffusion data. Activation energies are higher for conductivity data of 0.0055 M TbaTf-acetates compared to diffusion data of pure acetates. The plot of the exponential prefactor versus the dielectric constant yields a single master curve for both conductivity and diffusion data. These data support the argument that mass and charge transport are thermally activated processes in the acetates, as previously observed in alcohol-based electrolytes. PMID:22145961

  6. Chemoselectivities in acetalization, thioacetalization, oxathioacetalization and azathioacetalization.

    PubMed

    Roy, Ram Kinkar; Bagaria, Priyanka; Naik, Sarala; Kavala, Veerababurao; Patel, Bhisma K

    2006-02-16

    In the present article (experimental as well theoretical) the relative yields of cyclic (O,O), (S,S), (S,O), and (S,N) acetals, formed from p-(NO2)C6H4CHO and p-(OH)C6H4CHO, are compared. Atomic charges, global electrophilicity descriptor (w) [as proposed by Parr et al., J. Am. Chem. Soc. 1999, 121, 1922] and hard-soft acid-base concept of Pearson (J. Am. Chem. Soc. 1963, 85, 3533) are used to explain the experimental observations. Although the w values can explain the yields, charge and local softness values of the interacting sites explain the plausible reaction mechanism. The bisnucleophiles chosen for acetalization are CH2(OH)-CH2(OH) (glycol), CH2(SH)-CH2(SH) (dithiol), CH2(OH)-CH2(SH) (oxathiol) and CH2(SH)-CH2(NH2) (azathiol). For p-(NO2)C6H4CHO, the experimental yield of cyclic acetals were found to follow the trend as (S,N) > (S,O) > (O,O) > (S,S), which is also supported by theoretical explanation based on the w values and applying the concept of hard-hard (i.e., charge-controlled) and soft-soft (i.e., orbital-controlled) interaction between the interacting sites of the substrates (i.e., aldehydes) and the reactants (bisnucleophiles). Similarly, for p-(OH)C6H4CHO the relative yields of cyclic acetals follow the trend (S,N) approximately (S,S) > (S,O) > (O,O). It is argued that the attack on C(CHO) (i.e., C-atom of the CHO group) in p-(NO2)C6H4CHO by O(OH) (i.e., O-atom of OH group) or N(NH2) (i.e., N-atom of NH2 group) is mainly charge-controlled but the attack on C(CHO) in p-(OH)C6H4CHO) by S(SH) (i.e., S-atom of SH group) is orbital-controlled. PMID:16466254

  7. Sphingolipids contribute to acetic acid resistance in Zygosaccharomyces bailii.

    PubMed

    Lindahl, Lina; Genheden, Samuel; Eriksson, Leif A; Olsson, Lisbeth; Bettiga, Maurizio

    2016-04-01

    Lignocellulosic raw material plays a crucial role in the development of sustainable processes for the production of fuels and chemicals. Weak acids such as acetic acid and formic acid are troublesome inhibitors restricting efficient microbial conversion of the biomass to desired products. To improve our understanding of weak acid inhibition and to identify engineering strategies to reduce acetic acid toxicity, the highly acetic-acid-tolerant yeast Zygosaccharomyces bailii was studied. The impact of acetic acid membrane permeability on acetic acid tolerance in Z. bailii was investigated with particular focus on how the previously demonstrated high sphingolipid content in the plasma membrane influences acetic acid tolerance and membrane permeability. Through molecular dynamics simulations, we concluded that membranes with a high content of sphingolipids are thicker and more dense, increasing the free energy barrier for the permeation of acetic acid through the membrane. Z. bailii cultured with the drug myriocin, known to decrease cellular sphingo-lipid levels, exhibited significant growth inhibition in the presence of acetic acid, while growth in medium without acetic acid was unaffected by the myriocin addition. Furthermore, following an acetic acid pulse, the intracellular pH decreased more in myriocin-treated cells than in control cells. This indicates a higher inflow rate of acetic acid and confirms that the reduction in growth of cells cultured with myriocin in the medium with acetic acid was due to an increase in membrane permeability, thereby demonstrating the importance of a high fraction of sphingolipids in the membrane of Z. bailii to facilitate acetic acid resistance; a property potentially transferable to desired production organisms suffering from weak acid stress. PMID:26416641

  8. Phytogenic biosynthesis and emission of methyl acetate.

    PubMed

    Jardine, Kolby; Wegener, Frederik; Abrell, Leif; van Haren, Joost; Werner, Christiane

    2014-02-01

    Acetylation of plant metabolites fundamentally changes their volatility, solubility and activity as semiochemicals. Here we present a new technique termed dynamic (13) C-pulse chasing to track the fate of C1-3 carbon atoms of pyruvate into the biosynthesis and emission of methyl acetate (MA) and CO2 . (13) C-labelling of MA and CO2 branch emissions respond within minutes to changes in (13) C-positionally labelled pyruvate solutions fed through the transpiration stream. Strong (13) C-labelling of MA emissions occurred only under pyruvate-2-(13) C and pyruvate-2,3-(13) C feeding, but not pyruvate-1-(13) C feeding. In contrast, strong (13) CO2 emissions were only observed under pyruvate-1-(13) C feeding. These results demonstrate that MA (and other volatile and non-volatile metabolites) derive from the C2,3 atoms of pyruvate while the C1 atom undergoes decarboxylation. The latter is a non-mitochondrial source of CO2 in the light generally not considered in studies of CO2 sources and sinks. Within a tropical rainforest mesocosm, we also observed atmospheric concentrations of MA up to 0.6 ppbv that tracked light and temperature conditions. Moreover, signals partially attributed to MA were observed in ambient air within and above a tropical rainforest in the Amazon. Our study highlights the potential importance of acetyl coenzyme A (CoA) biosynthesis as a source of acetate esters and CO2 to the atmosphere. PMID:23862653

  9. Immunotoxicity of trenbolone acetate in Japanese quail

    USGS Publications Warehouse

    Quinn, M.J.; McKernan, M.; Lavoie, E.T.; Ottinger, M.A.

    2007-01-01

    Trenbolone acetate is a synthetic androgen that is currently used as a growth promoter in many meat-exporting countries. Despite industry laboratories classifying trenbolone as nonteratogenic, data showed that embryonic exposure to this androgenic chemical altered development of the immune system in Japanese quail. Trenbolone is lipophilic, persistent, and released into the environment in manure used as soil fertilizer. This is the first study to date to assess this chemical's immunotoxic effects in an avian species. A one-time injection of trenbolone into yolks was administered to mimic maternal deposition, and subsequent effects on the development and function of the immune system were determined in chicks and adults. Development of the bursa of Fabricius, an organ responsible for development of the humoral arm of the immune system, was disrupted, as indicated by lower masse, and smaller and fewer follicles at day 1 of hatch. Morphological differences in the bursas persisted in adults, although no differences in either two measures of immune function were observed. Total numbers of circulating leukocytes were reduced and heterophil-lymphocyte ratios were elevated in chicks but not adults. This study shows that trenbolone acetate is teratogenic and immunotoxic in Japanese quail, and provides evidence that the quail immune system may be fairly resilient to embryonic endocrine-disrupting chemical-induced alterations following no further exposure posthatch.

  10. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2006-05-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com/. This issue focuses on the following selection of drugs: Adalimumab, adenosine triphosphate, alemtuzumab, alendronate sodium/cholecalciferol, aliskiren fumarate, AMGN-0007, aminolevulinic acid methyl ester, anakinra, anidulafungin, aripiprazole, atomoxetine hydrochloride; Bevacizumab, bosentan; Calcipotriol/beta methasone dipropionate, caldaret hydrate, caspofungin acetate, cetuximab, cinacalcet hydrochloride, clopidogrel, cocaine-BSA conjugate, conivaptan hydrochloride, Cypher; Darbepoetin alfa, delmitide, desloratadine, desmoteplase, desoxyepothilone B, disufenton sodium, DU-176b, duloxetine hydrochloride, dutasteride; EBV-specific CTLs, ecogramostim, edodekin alfa, efalizumab, eletriptan, emtricitabine, entecavir, erlotinib hydrochloride, ertapenem sodium, escitalopram oxalate, etoricoxib, everolimus, ezetimibe; Fanapanel, fondaparinux sodium; Gefitinib, GTI-2040, GW-501516; Her2 E75-peptide vaccine, human insulin; Ibogaine, icatibant acetate, Id-KLH vaccine, imatinib mesylate, immune globulin subcutaneous [human], indacaterol, inolimomab, ipilimumab, i.v. gamma-globulin, ivabradine hydrochloride, ixabepilone; Lacosamide, lanthanum carbonate, lenalidomide, levocetirizine, levodopa methyl ester hydrochloride/carbidopa, levodopa/carbidopa/entacapone, lidocaine/prilocaine; Maraviroc, mecasermin, melevodopa hydrochloride, mepolizumab, mitumomab; Nesiritide; Omalizumab, oral insulin; Parathyroid hormone (human recombinant), patupilone, pegaptanib sodium, PEG-filgrastim, pemetrexed disodium, photochlor, pimecrolimus, posaconazole, prasterone, prasugrel, pregabalin, prilocaine, PRX-00023; QS-21; Ranibizumab, ranirestat, rhodamine 123, rotigaptide; Sarcosine, sirolimus

  11. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-03-01

    , polyglutamate paclitaxel, posurdex, pramlintide acetate, prasterone, pregabalin; Rasburicase, rimonabant hydrochloride, rostaporfin, rosuvastatin calcium; SDZ-SID-791, sibrotuzumab, sorafenib, SU-11248; Tadalafil, targinine, tegaserod maleate, telithromycin, TheraCIM, tigecycline, tiotropium bromide, tipifarnib, tirapazamine, treprostinil sodium; Valdecoxib, Valganciclovir hydrochloride, Vardenafil hydrochloride hydrate; Ximelagatran; Zofenopril calcium, Zoledronic acid monohydrate. PMID:15071612

  12. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2003-09-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abetimus sodium, adefovir dipivoxil, AGI-1067, alefacept, alemtuzumab, ALVAC-p53, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, Anti-CTLA-4 Mab, AOD-9604, apafant, aprinocarsen sodium, arsenic trioxide; Balaglitazone, BIM-23190, bimatoprost, bortezomib, bosentan, BR-1; Canertinib dihydrochloride, CDP-850, cevimeline hydrochloride, cinacalcet hydrochloride, clenoliximab, clevudine, CN-787; D-003, darusentan, deferasirox, desloratadine dexanabinol, duloxetine hydrochloride; E-5564, edaravone, efaproxiral sodium, elvucitabine emfilermin, EN-101, enfuvirtide, entecavir, epithalon, eplerenone, erlotinib hydrochloride, escitalopram oxalate, esomeprazole magnesium, eszopiclone, etilefrine pivalate hydrochloride etoricoxib, everolimus, exenatide; Fidarestat, fondaparinux sodium; Ganstigmine hydrochloride; Homoharringtonine, HuMax-IL-15, hyperimmune IVIG; Imatinib mesylate, IMC-1C11, Inhaled insulin, irofulven, iseganan hydrochloride, ISIS-14803, ISIS-5132, ivabradine hydrochloride; Keratinocyte growth factor; Lafutidine, lanthanum carbonate, LAS-34475, levocetirizine, liraglutide, LY-307161 SR; Magnesium sulfate, maribavir, melatonin, mycobacterium cell wall complex; NN-414, NO-aspirin, nociceptin, nolomirole hydrochloride; Olmesartan medoxomil oral insulin, ospemifene; PDX, perillyl alcohol, pimecrolimus, pitavastatin calcium, pramlintide acetate, prasterone, pregabalin, PRO-542, PV-701, pyrazoloacridine; R-744, ranelic acid distrontium salt, rasburicase, rDNA insulin, resiniferatoxin, reslizumab, ridogrel, riplizumab ropivacaine, rosuvastatin calcium, roxifiban acetate, ruboxistaurin mesilate

  13. Synthesis and regeneration of lead (IV) acetate

    SciTech Connect

    Boyle, T.J.; Al-Shareef, H.N.; Moore, G.J.

    1996-11-01

    Lead acetate [Pb(O{sub 2}CMe){sub 4}] was easily synthesized from a warm solution of Pb{sub 3}O{sub 4}, HO{sub 2}CMe and O(OCMe){sub 2} following literature preparations when the appropriate measures to minimize water contamination were followed. Furthermore, Pb(O{sub 2}CMe){sub 4} which has been decomposed (evidenced by the appearance of a purple color due to oxidation) can be regenerated using a similar preparatory route. Introduction of Pb(O{sub 2}CMe){sub 4} from the two routes outlined above into the IMO process for production of PZT thin films gave films with comparable ferroelectric properties to commercially available Pb(O{sub 2}CMe){sub 4} precursors. However, the freshly synthesized material yields PZT films with better properties compared to the recycled material.

  14. Breast cancer and depot-medroxyprogesterone acetate

    PubMed Central

    1985-01-01

    The preliminary results of a study of the incidence of breast cancer in relation to use of depot-medroxyprogesterone acetate (DMPA) are presented. The findings are based on data from three participating centres in Thailand, and one each in Kenya and Mexico. A relative risk for breast cancer of 0.7 was observed in women who had ever used DMPA; this was not statistically significant. Although no consistent decrease in risk with duration of use was observed, the lowest relative risk (0.5) was observed in women who had used DMPA for three or more years. These findings are based on small numbers and must be considered preliminary. However, they provide no evidence that DMPA increases the risk of breast cancer, and suggest that it may exert a protective effect, particularly in long-term users. PMID:2931206

  15. A radioimmunoassay for serum medroxyprogesterone acetate.

    PubMed

    Shrimanker, K; Saxena, B N; Fotherby, K

    1978-04-01

    When injected intramuscularly in a dose of 150 mg, Depo Provera, a microcrystalline suspension of medroxyprogesterone acetate (MPA), will provide a contraceptive effect for at least 3 months. This paper describes a sensitive radioimmunoassay for MPA which has been used in the author's laboratory for the past 2 years. MPA was converted to MPA-3-CMO and the oxime was conjugated with bovine serum albumin (BSA) by the mixed anahydride method. 4 rabbits were immunized with the antiserum. A high titre of MPA antibodies was detected 6 months after immunization. Serum from the rabbit with the highest titre of antibodies to MPA was subjected to radioimmunoassay. 7 days after the intramuscular injection of 150 mg Depo-Provera, serum levels of MPA were found in the range of 1750 to 9000 pg/ml. By 75 days, the levels had decreased to 680-2600 pg/ml. The method was found to have adequate accuracy, precision and sensitivity. PMID:661315

  16. Oxidation of indole-3-acetic acid to oxindole-3-acetic acid by an enzyme preparation from Zea mays

    NASA Technical Reports Server (NTRS)

    Reinecke, D. M.; Bandurski, R. S.

    1988-01-01

    Indole-3-acetic acid is oxidized to oxindole-3-acetic acid by Zea mays tissue extracts. Shoot, root, and endosperm tissues have enzyme activities of 1 to 10 picomoles per hour per milligram protein. The enzyme is heat labile, is soluble, and requires oxygen for activity. Cofactors of mixed function oxygenase, peroxidase, and intermolecular dioxygenase are not stimulatory to enzymic activity. A heat-stable, detergent-extractable component from corn enhances enzyme activity 6- to 10-fold. This is the first demonstration of the in vitro enzymic oxidation of indole-3-acetic acid to oxindole-3-acetic acid in higher plants.

  17. Heterogeneous catalyst for the production of acetic anhydride from methyl acetate

    DOEpatents

    Ramprasad, Dorai; Waller, Francis Joseph

    1999-01-01

    This invention relates to a process for producing acetic anhydride by the reaction of methyl acetate, carbon monoxide, and hydrogen at elevated temperatures and pressures in the presence of an alkyl halide and a heterogeneous, bifunctional catalyst that contains an insoluble polymer having pendant quaternized phosphine groups, some of which phosphine groups are ionically bonded to anionic Group VIII metal complexes, the remainder of the phosphine groups being bonded to iodide. In contrast to prior art processes, no accelerator (promoter) is necessary to achieve the catalytic reaction and the products are easily separated from the catalyst by filtration. The catalyst can be recycled for consecutive runs without loss in activity. Bifunctional catalysts for use in carbonylating dimethyl ether are also provided.

  18. Heterogeneous catalyst for the production of acetic anhydride from methyl acetate

    DOEpatents

    Ramprasad, D.; Waller, F.J.

    1999-04-06

    This invention relates to a process for producing acetic anhydride by the reaction of methyl acetate, carbon monoxide, and hydrogen at elevated temperatures and pressures in the presence of an alkyl halide and a heterogeneous, bifunctional catalyst that contains an insoluble polymer having pendant quaternized phosphine groups, some of which phosphine groups are ionically bonded to anionic Group VIII metal complexes, the remainder of the phosphine groups being bonded to iodide. In contrast to prior art processes, no accelerator (promoter) is necessary to achieve the catalytic reaction and the products are easily separated from the catalyst by filtration. The catalyst can be recycled for consecutive runs without loss in activity. Bifunctional catalysts for use in carbonylating dimethyl ether are also provided.

  19. Transition-Metal-Catalyzed Carbonylation of Methyl Acetate.

    ERIC Educational Resources Information Center

    Polichnowski, S. W.

    1986-01-01

    Presents a study of the rhodium-catalyzed, ioding-promoted carbonylation of methyl acetate. This study provides an interesting contrast between the carbonylation of methyl acetate and the carbonylation of methanol when similar rhodium/iodine catalyst systems are used. (JN)

  20. Proteomic Analysis on Acetate Metabolism in Citrobacter sp. BL-4

    PubMed Central

    Kim, Young-Man; Lee, Sung-Eun; Park, Byeoung-Soo; Son, Mi-Kyung; Jung, Young-Mi; Yang, Seung-Ok; Choi, Hyung-Kyoon; Hur, Sung-Ho; Yum, Jong Hwa

    2012-01-01

    Mass production of glucosamine (GlcN) using microbial cells is a worthy approach to increase added values and keep safety problems in GlcN production process. Prior to set up a microbial cellular platform, this study was to assess acetate metabolism in Citrobacter sp. BL-4 (BL-4) which has produced a polyglucosamine PGB-2. The LC-MS analysis was conducted after protein separation on the 1D-PAGE to accomplish the purpose of this study. 280 proteins were totally identified and 188 proteins were separated as acetate-related proteins in BL-4. Acetate was converted to acetyl-CoA by acetyl-CoA synthetase up-regulated in the acetate medium. The glyoxylate bypass in the acetate medium was up-regulated with over-expression of isocitrate lyases and 2D-PAGE confirmed this differential expression. Using 1H-NMR analysis, the product of isocitrate lyases, succinate, increased about 15 times in the acetate medium. During acetate metabolism proteins involved in the lipid metabolism and hexosamine biosynthesis were over-expressed in the acetate medium, while proteins involved in TCA cycle, pentose phosphate cycle and purine metabolism were down-regulated. Taken together, the results from the proteomic analysis can be applied to improve GlcN production and to develop metabolic engineering in BL-4. PMID:22211106

  1. 21 CFR 182.8892 - α-Tocopherol acetate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false α-Tocopherol acetate. 182.8892 Section 182.8892 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8892 α-Tocopherol acetate. (a) Product....

  2. 21 CFR 522.960b - Flumethasone acetate injection.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Flumethasone acetate injection. 522.960b Section 522.960b Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.960b Flumethasone acetate injection....

  3. 21 CFR 522.960b - Flumethasone acetate solution.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Flumethasone acetate solution. 522.960b Section 522.960b Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.960b Flumethasone acetate solution....

  4. 40 CFR 721.303 - Substituted acetate (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.303 Substituted acetate (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as a substituted acetate (PMN...

  5. 40 CFR 721.303 - Substituted acetate (generic).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.303 Substituted acetate (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as a substituted acetate (PMN...

  6. Homogeneous gold-catalyzed efficient oxidative dimerization of propargylic acetates.

    PubMed

    Cui, Li; Zhang, Guozhu; Zhang, Liming

    2009-07-15

    A highly efficient gold-catalyzed oxidative dimerization of propargylic acetates is developed. In this chemistry, Selectfluor oxidation of Au(I) to Au(III) is readily incorporated into Au-catalyzed tandem reactions of propargylic acetates, and transmetallation and reductive elimination on Au(III) intermediates are likely involved. PMID:19362834

  7. 21 CFR 522.2478 - Trenbolone acetate and estradiol benzoate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... ANIMAL DRUGS § 522.2478 Trenbolone acetate and estradiol benzoate. (a) Specifications. Each implant dose...) For an implant as described in paragraph (a)(1) of this section: (A) Amount. 200 mg trenbolone acetate... feed efficiency. (C) Limitations. Implant subcutaneously in ear only. Safety and effectiveness have...

  8. 21 CFR 522.2478 - Trenbolone acetate and estradiol benzoate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... ANIMAL DRUGS § 522.2478 Trenbolone acetate and estradiol benzoate. (a) Specifications. Each implant dose...) For an implant as described in paragraph (a)(1) of this section: (A) Amount. 200 mg trenbolone acetate... feed efficiency. (C) Limitations. Implant subcutaneously in ear only. Safety and effectiveness have...

  9. 21 CFR 522.2478 - Trenbolone acetate and estradiol benzoate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... ANIMAL DRUGS § 522.2478 Trenbolone acetate and estradiol benzoate. (a) Specifications. Each implant dose...) For an implant as described in paragraph (a)(1) of this section: (A) Amount. 200 mg trenbolone acetate... feed efficiency. (C) Limitations. Implant subcutaneously in ear only. Safety and effectiveness have...

  10. 21 CFR 522.2478 - Trenbolone acetate and estradiol benzoate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... ANIMAL DRUGS § 522.2478 Trenbolone acetate and estradiol benzoate. (a) Specifications. Each implant dose...) For an implant as described in paragraph (a)(1) of this section: (A) Amount. 200 mg trenbolone acetate... feed efficiency. (C) Limitations. Implant subcutaneously in ear only. Safety and effectiveness have...

  11. Pharmacokinetics of depot medroxyprogesterone acetate contraception.

    PubMed

    Mishell, D R

    1996-05-01

    Depot medroxyprogesterone acetate (DMPA) is an aqueous suspension of 17-acetoxy 6-methyl progestin administered by intramuscular injection for long-term contraception. This highly effective injectable formulation of medroxyprogesterone acetate (MPA) has a prolonged duration of action since the progestin is released slowly from the muscle. MPA is detected in the serum within 30 minutes after an injection of 150 mg. Serum concentrations vary between individual women but generally plateau at about 1.0 ng/mL for about three months, after which there is a gradual decline. In some women, MPA can be detected in the serum for as long as nine months after a single injection of 150 mg. The circulating MPA initially inhibits the midcycle leutinizing hormone (LH) peak, but LH and follicle stimulating hormone (FSH) levels remain in the range of those for the luteal phase of a pretreatment control cycle. Since ovulation is inhibited, serum progesterone levels remain low (< 0.4 ng/mL) for several months following an injection of DMPA. When MPA levels fall below 0.1 ng/mL, ovulation resumes. Thus, return to fertility is delayed for several months if a woman wishes to conceive after receiving one or more injections of DMPA. Following an injection of DMPA, serum estradiol levels initially are in the early to midfollicular phase range (mean approximately 50 pg/nL). Serum estradiol levels begin to rise about four months after a single injection when MPA levels fall below 0.5 ng/mL. For women who have used DMPA for several years, serum estradiol levels range between 10 and 92 pg/mL, with mean levels of about 40 pg/mL. Despite these low levels of estradiol, hot flushes are a rare event, and the vaginal epithelium remains moist and well rugated. Women using DMPA for several years do not observe a change in breast size. DMPA causes the endometrium to become atrophic, with small, straight endometrial glands and decidualized stroma. The cervical mucus remains thick and viscid. DMPA is a

  12. The clinical use of PET with 11C-acetate

    PubMed Central

    Grassi, Ilaria; Nanni, Cristina; Allegri, Vincenzo; Morigi, Joshua James; Montini, Gian Carlo; Castellucci, Paolo; Fanti, Stefano

    2012-01-01

    The aim of this review is to evaluate clinical applications of 11C-acetate positron emission tomography (PET). Acetate is quickly metabolized into acetyl-CoA in human cells. In this form it can either enter into the tricarboxylic acid cycle, thus producing energy, as happens in the myocardium, or participate in cell membrane lipid synthesis, as happens in tumor cells. 11C-acetate PET was originally employed in cardiology, to study myocardial oxygen metabolism. More recently it has also been used to evaluate myocardial perfusion, as well as in oncology. The first studies of 11C-acetate focused on its use in prostate cancer. Subsequently, 11C-acetate was studied in other urological malignancies, as well as renal cell carcinoma and bladder cancer. Well differentiated hepatocellular carcinoma represents an 18F-fluoro-deoxyglucose (18F-FDG) PET pitfall, so many authors have proposed to use 11C-acetate in addition to 18F-FDG in studying this tumor. 11C-acetate PET has also been used in other malignancies, such as brain tumors and lung carcinoma. Some authors reported a few cases in which 11C-acetate PET incidentally found multiple myeloma or rare tumors, such as thymoma, multicentric angiomyolipoma of the kidney and cerebellopontine angle schwannoma. Lastly, 11C-acetate PET was also employed in a differential diagnosis case between glioma and encephalitis. The numerous studies on 11C-acetate have demonstrated that it can be used in cardiology and oncology with no contraindications apart from pregnancy and the necessity of a rapid scan. Despite its limited availability, this tracer can surely be considered to be a promising one, because of its versatility and capacity to even detect non 18F-FDG-avid neoplasm, such as differentiated lung cancer or hepatocellular carcinoma. PMID:23133801

  13. Fermentation of lignocellulosic sugars to acetic acid by Moorella thermoacetica.

    PubMed

    Ehsanipour, Mandana; Suko, Azra Vajzovic; Bura, Renata

    2016-06-01

    A systematic study of bioconversion of lignocellulosic sugars to acetic acid by Moorella thermoacetica (strain ATCC 39073) was conducted. Four different water-soluble fractions (hydrolysates) obtained after steam pretreatment of lignocellulosic biomass were selected and fermented to acetic acid in batch fermentations. M. thermoacetica can effectively ferment xylose and glucose in hydrolysates from wheat straw, forest residues, switchgrass, and sugarcane straw to acetic acid. Xylose and glucose were completely utilized, with xylose being consumed first. M. thermoacetica consumed up to 62 % of arabinose, 49 % galactose and 66 % of mannose within 72 h of fermentation in the mixture of lignocellulosic sugars. The highest acetic acid yield was obtained from sugarcane straw hydrolysate, with 71 % of theoretical yield based on total sugars (17 g/L acetic acid from 24 g/L total sugars). The lowest acetic acid yield was observed in forest residues hydrolysate, with 39 % of theoretical yield based on total sugars (18 g/L acetic acid from 49 g/L total sugars). Process derived compounds from steam explosion pretreatment, including 5-hydroxymethylfurfural (0.4 g/L), furfural (0.1 g/L) and total phenolics (3 g/L), did not inhibit microbial growth and acetic acid production yield. This research identified two major factors that adversely affected acetic acid yield in all hydrolysates, especially in forest residues: (i) glucose to xylose ratio and (ii) incomplete consumption of arabinose, galactose and mannose. For efficient bioconversion of lignocellulosic sugars to acetic acid, it is imperative to have an appropriate balance of sugars in a hydrolysate. Hence, the choice of lignocellulosic biomass and steam pretreatment design are fundamental steps for the industrial application of this process. PMID:26992903

  14. Gas-Phase Structures of Ketene and Acetic Acid from Acetic Anhydride Using Very-High-Temperature Gas Electron Diffraction.

    PubMed

    Atkinson, Sandra J; Noble-Eddy, Robert; Masters, Sarah L

    2016-03-31

    The gas-phase molecular structure of ketene has been determined using samples generated by the pyrolysis of acetic anhydride (giving acetic acid and ketene), using one permutation of the very-high-temperature (VHT) inlet nozzle system designed and constructed for the gas electron diffraction (GED) apparatus based at the University of Canterbury. The gas-phase structures of acetic anhydride, acetic acid, and ketene are presented and compared to previous electron diffraction and microwave spectroscopy data to show improvements in data extraction and manipulation with current methods. Acetic anhydride was modeled with two conformers, rather than a complex dynamic model as in the previous study, to allow for inclusion of multiple pyrolysis products. The redetermined gas-phase structure of acetic anhydride (obtained using the structure analysis restrained by ab initio calculations for electron diffraction method) was compared to that from the original study, providing an improvement on the description of the low vibrational torsions compared to the dynamic model. Parameters for ketene and acetic acid (both generated by the pyrolysis of acetic anhydride) were also refined with higher accuracy than previously reported in GED studies, with structural parameter comparisons being made to prior experimental and theoretical studies. PMID:26916368

  15. An energy-conserving pyruvate-to-acetate pathway in Entamoeba histolytica. Pyruvate synthase and a new acetate thiokinase.

    PubMed

    Reeves, R E; Warren, L G; Susskind, B; Lo, H S

    1977-01-25

    Under anaerobic conditions, cells of Entamoeba histolytica grown with bacteria produce H2 and acetate while cells grown axenically produce neither. Aerobically, acetate is produced and O2 is consumed by amebae from either type of cells. Centrifuged extracts, 2.4 x 106 x g x min, from both types of cells contain pyruvate synthase (EC 1.2.7.1) and an acetate thiokinase which, together, form a system capable of converting pyruvate to acetate. Pyruvate synthase catalyzes the reaction: pyruvate + CoA leads to CO2 + acetyl-CoA + 2E. Electron acceptors which function with this enzyme are FAD, FMN, riboflavin, ferredoxin, and methyl viologen, but not NAD or NADP. The amebal acetate thiokinase catalyzes the reaction acetyl-CoA + ADP + Pi leads to acetate + ATP + CoA. For this apparently new enzyme we suggest the trivial name acetyl-CoA-synthetase (ADP-forming). Extracts from axenic amebae do not contain hydrogenase, but extracts from cells grown with bacteria do. It is postulated that in bacteria-grown amebae electrons generated at the pyruvate synthase step are utilized anaerobically to produce H2 via the hydrogenase and that the acetyl-CoA is converted to acetate in an energy-conserving step catalyzed by amebal acetyl-CoA synthetase. Aerobically, cells grown under either regimen may utilize the energy-conserving pyruvate-to-acetate pathway since O2 then serves as the ultimate electron acceptor. PMID:13076

  16. Biological Function of Acetic Acid-Improvement in Obesity and Glucose Tolerance by Acetic Acid in Type 2 Diabetic Rats.

    PubMed

    Yamashita, Hiromi

    2016-07-29

    Fatty acids derived from adipose tissue are oxidized by β-oxidation to form ketone bodies as final products under the starving condition. Previously, we found that free acetic acid was formed concomitantly with the production of ketone bodies in isolated rat liver perfusion, and mitochondrial acetyl CoA hydrolase was appeared to be involved with the acetic acid production. It was revealed that acetic acid was formed as a final product of enhanced β-oxidation of fatty acids and utilized as a fuel in extrahepatic tissues under the starving condition. Under the fed condition, β-oxidation is suppressed and acetic acid production is decreased. When acetic acid was taken daily by obesity-linked type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats under the fed condition, it protected OLETF rats against obesity. Furthermore, acetic acid contributed to protect from the accumulation of lipid in the liver as well as abdominal fat in OLETF rats. Transcripts of lipogenic genes in the liver were decreased, while transcripts of myoglobin and Glut4 genes in abdominal muscles were increased in the acetic acid-administered OLETF rats. It is indicated that exogenously administered acetic acid would have effects on lipid metabolism in both the liver and the skeletal muscles, and have function that works against obesity and obesity-linked type 2 diabetes. PMID:26176799

  17. Measurement of the rates of oxindole-3-acetic acid turnover, and indole-3-acetic acid oxidation in Zea mays seedlings

    NASA Technical Reports Server (NTRS)

    Nonhebel, H. M.; Bandurski, R. S. (Principal Investigator)

    1986-01-01

    Oxindole-3-acetic acid is the principal catabolite of indole-3-acetic acid in Zea mays seedlings. In this paper measurements of the turnover of oxindole-3-acetic acid are presented and used to calculate the rate of indole-3-acetic acid oxidation. [3H]Oxindole-3-acetic acid was applied to the endosperm of Zea mays seedlings and allowed to equilibrate for 24 h before the start of the experiment. The subsequent decrease in its specific activity was used to calculate the turnover rate. The average half-life of oxindole-3-acetic acid in the shoots was found to be 30 h while that in the kernels had an average half-life of 35h. Using previously published values of the pool sizes of oxindole-3-acetic acid in shoots and kernels from seedlings of the same age and variety, and grown under the same conditions, the rate of indole-3-acetic acid oxidation was calculated to be 1.1 pmol plant-1 h-1 in the shoots and 7.1 pmol plant-1 h-1 in the kernels.

  18. The effect of oral sodium acetate administration on plasma acetate concentration and acid-base state in horses

    PubMed Central

    Waller, Amanda; Lindinger, Michael I

    2007-01-01

    Aim Sodium acetate (NaAcetate) has received some attention as an alkalinizing agent and possible alternative energy source for the horse, however the effects of oral administration remain largely unknown. The present study used the physicochemical approach to characterize the changes in acid-base status occurring after oral NaAcetate/acetic acid (NAA) administration in horses. Methods Jugular venous blood was sampled from 9 exercise-conditioned horses on 2 separate occasions, at rest and for 24 h following a competition exercise test (CET) designed to simulate the speed and endurance test of 3-day event. Immediately after the CETs horses were allowed water ad libitum and either: 1) 8 L of a hypertonic NaAcetate/acetic acid solution via nasogastric tube followed by a typical hay/grain meal (NAA trial); or 2) a hay/grain meal alone (Control trial). Results Oral NAA resulted in a profound plasma alkalosis marked by decreased plasma [H+] and increased plasma [TCO2] and [HCO3-] compared to Control. The primary contributor to the plasma alkalosis was an increased [SID], as a result of increased plasma [Na+] and decreased plasma [Cl-]. An increased [Atot], due to increased [PP] and a sustained increase in plasma [acetate], contributed a minor acidifying effect. Conclusion It is concluded that oral NaAcetate could be used as both an alkalinizing agent and an alternative energy source in the horse. PMID:18096070

  19. Oxidation of indole-3-acetic acid and oxindole-3-acetic acid to 2,3-dihydro-7-hydroxy-2-oxo-1H indole-3-acetic acid-7'-O-beta-D-glucopyranoside in Zea mays seedlings

    NASA Technical Reports Server (NTRS)

    Nonhebel, H. M.; Bandurski, R. S.

    1984-01-01

    Radiolabeled oxindole-3-acetic acid was metabolized by roots, shoots, and caryopses of dark grown Zea mays seedlings to 2,3-dihydro-7-hydroxy-2-oxo-1H indole-3-acetic acid-7'-O-beta-D-glycopyranoside with the simpler name of 7-hydroxyoxindole-3-acetic acid-glucoside. This compound was also formed from labeled indole-3-acetic acid supplied to intact seedlings and root segments. The glucoside of 7-hydroxyoxindole-3-acetic acid was also isolated as an endogenous compound in the caryopses and shoots of 4-day-old seedlings. It accumulates to a level of 4.8 nanomoles per plant in the kernel, more than 10 times the amount of oxindole-3-acetic acid. In the shoot it is present at levels comparable to that of oxindole-3-acetic acid and indole-3-acetic acid (62 picomoles per shoot). We conclude that 7-hydroxyoxindole-3-acetic acid-glucoside is a natural metabolite of indole-3-acetic acid in Z. mays seedlings. From the data presented in this paper and in previous work, we propose the following route as the principal catabolic pathway for indole-3-acetic acid in Zea seedlings: Indole-3-acetic acid --> Oxindole-3-acetic acid --> 7-Hydroxyoxindole-3-acetic acid --> 7-Hydroxyoxindole-3-acetic acid-glucoside.

  20. Micelles Protect and Concentrate Activated Acetic Acid

    NASA Astrophysics Data System (ADS)

    Todd, Zoe; House, C.

    2014-01-01

    As more and more exoplanets are discovered and the habitability of such planets is considered, one can turn to searching for the origin of life on Earth in order to better understand what makes a habitable planet. Activated acetic acid, or methyl thioacetate, has been proposed to be central to the origin of life on Earth, and also as an important energy currency molecule in early cellular evolution. We have investigated the hydrolysis of methyl thioacetate under various conditions. Its uncatalyzed rate of hydrolysis is about three orders of magnitude faster (K = 0.00663 s^-1; 100°C, pH 7.5, concentration = 0.33mM) than published rates for its catalyzed production making it unlikely to accumulate under prebiotic conditions. However, we also observed that methyl thioacetate was protected from hydrolysis when inside its own hydrophobic droplets. We found that methyl thioacetate protection from hydrolysis was also possible in droplets of hexane and in the membranes of nonanoic acid micelles. Thus, the hydrophobic regions of prebiotic micelles and early cell membranes could have offered a refuge for this energetic molecule increasing its lifetime in close proximity to the reactions for which it would be needed. Methyl thioacetate could thus be important for the origin of life on Earth and perhaps for better understanding the potential habitability of other planets.

  1. Dexamethasone acetate encapsulation into Trojan particles.

    PubMed

    Gómez-Gaete, Carolina; Fattal, Elias; Silva, Lídia; Besnard, Madeleine; Tsapis, Nicolas

    2008-05-22

    We have combined the therapeutic potential of nanoparticles systems with the ease of manipulation of microparticles by developing a hybrid vector named Trojan particles. We aim to use this new delivery vehicle for intravitreal administration of dexamethasone. Initialy, dexamethasone acetate (DXA) encapsulation into biodegradable poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles was optimized. Then, Trojan particles were formulated by spray drying 1,2-Dipalmitoyl-sn-Glycero-3-Phosphocholine (DPPC), hyaluronic acid (HA) and different concentrations of nanoparticle suspensions. The effect of nanoparticles concentration on Trojan particle physical characteristics was investigated as well as the effect of the spray drying process on nanoparticles size. Finally, DXA in vitro release from nanoparticles and Trojan particles was evaluated under sink condition. SEM and confocal microscopy show that most of Trojan particles are spherical, hollow and possess an irregular surface due to the presence of nanoparticles. Neither Trojan particle tap density nor size distribution are significantly modified as a function of nanoparticles concentration. The mean nanoparticles size increase significantly after spray drying. Finally, the in vitro release of DXA shows that the excipient matrix provides protection to encapsulated nanoparticles by slowing drug release. PMID:18374442

  2. Eslicarbazepine acetate for partial-onset seizures.

    PubMed

    Rauchenzauner, Markus; Luef, Gerhard

    2011-12-01

    Eslicarbazepine acetate (ESL), a new voltage-gated sodium channel blocker that is chemically related to carbamazepine and partially metabolized to oxcarbazepine, has attracted attention as results of previous Phase II and III studies demonstrated and confirmed efficacy and tolerability of ESL 800 and 1200 mg once daily as add-on therapy for adult patients with drug-resistant partial-onset seizures. In children, efficacy data point towards a dose-dependent decrease in seizure frequency and tolerability analyses showed a low incidence of mild drug-related adverse effects at 5 and 15 mg/kg/day. The most frequently reported adverse effects were dizziness, somnolence, headache, diplopia, nausea and vomiting. The convenience of once-daily dosing and a short/simple titration regimen in combination with a comparative efficacy and tolerability profile might promote ESL as a valid alternative to the current adjunctive antiepileptic drug therapy armamentarium for drug-resistant partial seizures in adults. Since clinical trials in children and adolescents on ESL efficacy and safety are ongoing and data already published are far from conclusive, the therapeutic value of ESL in this special population has to be established in the near future. PMID:22091592

  3. Pharmacokinetics and drug interactions of eslicarbazepine acetate.

    PubMed

    Bialer, Meir; Soares-da-Silva, Patricio

    2012-06-01

    Eslicarbazepine acetate (ESL) is a novel once-daily antiepileptic drug (AED) approved in Europe since 2009 that was found to be efficacious and well tolerated in a phase III clinical program in adult patients with partial onset seizures previously not controlled with treatment with one to three AEDs, including carbamazepine (CBZ). ESL shares with CBZ and oxcarbazepine (OXC) the dibenzazepine nucleus bearing the 5-carboxamide substitute, but is structurally different at the 10,11 position. This molecular variation results in differences in metabolism, preventing the formation of toxic epoxide metabolites such as carbamazepine-10,11-epoxide. Unlike OXC, which is metabolized to both eslicarbazepine and (R)-licarbazepine, ESL is extensively converted to eslicarbazepine. The systemic exposure to eslicarbazepine after ESL oral administration is approximately 94% of the parent dose, with minimal exposure to (R)-licarbazepine and OXC. After ESL oral administration, the effective half-life (t(1/2,eff) ) of eslicarbazepine was 20-24 h, which is approximately two times longer than its terminal half-life (t(1/2)). At clinically relevant doses (400-1,600 mg/day) ESL has linear pharmacokinetics (PK) with no effects of gender or moderate liver impairment. However, because eslicarbazepine is eliminated primarily (66%) by renal excretion, dose adjustment is recommended for patients with renal impairment. Eslicarbazepine clearance is induced by phenobarbital, phenytoin, and CBZ and it dose-dependently decreases plasma exposure of oral contraceptive and simvastatin. PMID:22612290

  4. Biodegradable cellulose acetate nanofiber fabrication via electrospinning.

    PubMed

    Christoforou, Theopisti; Doumanidis, Charalabos

    2010-09-01

    Nanofiber manufacturing is one of the key advancements in nanotechnology today. Over the past few years, there has been a tremendous growth of research activities to explore electrospinning for nanofiber formation from a rich variety of materials. This quite simple and cost effective process operates on the principle that the solution is extracted under the action of a high electric field. Once the voltage is sufficiently high, a charged jet is ejected following a complicated looping trajectory. During its travel, the solvent evaporates leaving behind randomly oriented nanofibers accumulated on the collector. The combination of their nanoscale dimensionality, high surface area, porosity, flexibility and superior strength makes the electrospun fibers suitable for several value-added applications, such as filters, protecting clothes, high performance structures and biomedical devices. In this study biodegradable cellulose acetate (CA) nanofibrous membranes were produced using electrospinning. The device utilized consisted of a syringe equipped with a metal needle, a microdialysis pump, a high voltage supply and a collector. The morphology of the yielded fibers was determined using SEM. The effect of various parameters, including electric field strength, tip-to-collector distance, solution feed rate and composition on the morphological features of the electrospun fibers was examined. The optimum operating conditions for the production of uniform, non-beaded fibers with submicron diameter were also explored. The biodegradable CA nanofiber membranes are suitable as tissue engineering scaffolds and as reinforcements of biopolymer matrix composites in foils by ultrasonic welding methods. PMID:21133179

  5. Quantitative Structure of an Acetate Dye Molecule Analogue at the TiO2–Acetic Acid Interface

    PubMed Central

    2016-01-01

    The positions of atoms in and around acetate molecules at the rutile TiO2(110) interface with 0.1 M acetic acid have been determined with a precision of ±0.05 Å. Acetate is used as a surrogate for the carboxylate groups typically employed to anchor monocarboxylate dye molecules to TiO2 in dye-sensitized solar cells (DSSC). Structural analysis reveals small domains of ordered (2 × 1) acetate molecules, with substrate atoms closer to their bulk terminated positions compared to the clean UHV surface. Acetate is found in a bidentate bridge position, binding through both oxygen atoms to two 5-fold titanium atoms such that the molecular plane is along the [001] azimuth. Density functional theory calculations provide adsorption geometries in excellent agreement with experiment. The availability of these structural data will improve the accuracy of charge transport models for DSSC. PMID:27110318

  6. Nomegestrol acetate: pharmacology, safety profile and therapeutic efficacy.

    PubMed

    Lello, Stefano

    2010-03-26

    This review summarizes the pharmacology, safety and clinical efficacy of nomegestrol acetate, based on the available published literature, and assesses the pharmacological characteristics that underlie a role in different gynaecological disorders and hormone replacement therapy (HRT), and a potential role in combination estrogen/progestogen oral contraception. Nomegestrol acetate is a potent, orally active progestogen with a favourable tolerability profile and neutral metabolic characteristics. Unlike the majority of older progestogens, which were 19-nortestosterone derivatives synthesized primarily for their antigonadotropic activity as a component of hormonal contraception in combination with an estrogen, nomegestrol acetate is a 19-norprogesterone derivative designed to bind specifically to the progesterone receptor, and is relatively lacking in affinity for other steroid receptors. Nomegestrol acetate exerts strong antiestrogenic effects at the level of the endometrium and has potent antigonadotropic activity, but without any residual androgenic or glucocorticoid properties. At a dosage of 1.25 mg/day, nomegestrol acetate inhibits ovulation while permitting follicle growth, whereas at dosages of 2.5 or 5 mg/day, both ovulation and follicle development are suppressed. The antigonadotropic action of nomegestrol acetate is mediated, like other progestins, at the hypothalamic and pituitary level. Moreover, nomegestrol acetate has partial antiandrogenic activity. Absorption of nomegestrol acetate is rapid after oral administration, reaching a peak serum concentration within 4 hours, with a terminal half-life of approximately 50 hours. Nomegestrol acetate has been used successfully for the treatment of some gynaecological disorders (menstrual disturbances, dysmenorrhoea, premenstrual syndrome) and as a component of HRT in combination with estradiol for the relief of menopausal symptoms; it has been approved in Europe as monotherapy for the treatment of the menopausal

  7. Simultaneous production of acetic and gluconic acids by a thermotolerant Acetobacter strain during acetous fermentation in a bioreactor.

    PubMed

    Mounir, Majid; Shafiei, Rasoul; Zarmehrkhorshid, Raziyeh; Hamouda, Allal; Ismaili Alaoui, Mustapha; Thonart, Philippe

    2016-02-01

    The activity of bacterial strains significantly influences the quality and the taste of vinegar. Previous studies of acetic acid bacteria have primarily focused on the ability of bacterial strains to produce high amounts of acetic acid. However, few studies have examined the production of gluconic acid during acetous fermentation at high temperatures. The production of vinegar at high temperatures by two strains of acetic acid bacteria isolated from apple and cactus fruits, namely AF01 and CV01, respectively, was evaluated in this study. The simultaneous production of gluconic and acetic acids was also examined in this study. Biochemical and molecular identification based on a 16s rDNA sequence analysis confirmed that these strains can be classified as Acetobacter pasteurianus. To assess the ability of the isolated strains to grow and produce acetic acid and gluconic acid at high temperatures, a semi-continuous fermentation was performed in a 20-L bioreactor. The two strains abundantly grew at a high temperature (41°C). At the end of the fermentation, the AF01 and CV01 strains yielded acetic acid concentrations of 7.64% (w/v) and 10.08% (w/v), respectively. Interestingly, CV01 was able to simultaneously produce acetic and gluconic acids during acetic fermentation, whereas AF01 mainly produced acetic acid. In addition, CV01 was less sensitive to ethanol depletion during semi-continuous fermentation. Finally, the enzymatic study showed that the two strains exhibited high ADH and ALDH enzyme activity at 38°C compared with the mesophilic reference strain LMG 1632, which was significantly susceptible to thermal inactivation. PMID:26253254

  8. Computerized image analysis for acetic acid induced intraepithelial lesions

    NASA Astrophysics Data System (ADS)

    Li, Wenjing; Ferris, Daron G.; Lieberman, Rich W.

    2008-03-01

    Cervical Intraepithelial Neoplasia (CIN) exhibits certain morphologic features that can be identified during a visual inspection exam. Immature and dysphasic cervical squamous epithelium turns white after application of acetic acid during the exam. The whitening process occurs visually over several minutes and subjectively discriminates between dysphasic and normal tissue. Digital imaging technologies allow us to assist the physician analyzing the acetic acid induced lesions (acetowhite region) in a fully automatic way. This paper reports a study designed to measure multiple parameters of the acetowhitening process from two images captured with a digital colposcope. One image is captured before the acetic acid application, and the other is captured after the acetic acid application. The spatial change of the acetowhitening is extracted using color and texture information in the post acetic acid image; the temporal change is extracted from the intensity and color changes between the post acetic acid and pre acetic acid images with an automatic alignment. The imaging and data analysis system has been evaluated with a total of 99 human subjects and demonstrate its potential to screening underserved women where access to skilled colposcopists is limited.

  9. Methane Production and Syntrophic Acetate Oxidation in the Florida Everglades

    NASA Astrophysics Data System (ADS)

    Holmes, M. E.; Chanton, J.; Bae, H.; Ogram, A.

    2012-12-01

    Methane production pathways in the Florida Everglades are influenced by factors such as nutrient levels, H2 concentrations, and temperature. Syntrophic acetate oxidizers can outcompete methanogens for acetate when conditions are right (high temperatures and low H2). During syntrophic acetate oxidation (SAO), which becomes more exergonic with increasing temperature, acetate is oxidized to carbon dioxide and H2, which can be utilized to produce methane via CO2 reduction. Everglades soil from along a nutrient gradient was incubated at 25°C and 45°C. The shift to the CO2 reduction pathway for methane formation that would be expected in high temperature incubations due to SAO should result in a decrease in δ13C-CH4 and increase in δ2H-CH4. Instead, we observed higher δ13C and lower δ2H in the methane produced in high temperature incubations. The higher than expected δ13C may be partly explained by lower kinetic isotope effects caused by temperature. Coupling between the syntrophic acetate oxidizers and the CO2 reducers, whereby isotopically light hydrogen from acetate is used in methane formation could lower δ2H-CH4. Separate experiments using 13C-labelled acetate revealed that potential SAO activity is low in soils collected from the Everglades.

  10. The Effects of Acetate Buffer Concentration on Lysozyme Solubility

    NASA Technical Reports Server (NTRS)

    Forsythe, Elizabeth L.; Pusey, Marc L.

    1996-01-01

    The micro-solubility column technique was employed to systematically investigate the effects of buffer concentration on tetragonal lysozyme solubility. While keeping the NaCl concentrations constant at 2%, 3%, 4%, 5% and 7%, and the pH at 4.0, we have studied the solubility of tetragonal lysozyme over an acetate buffer concentration range of 0.01M to 0.5M as a function of temperature. The lysozyme solubility decreased with increasing acetate concentration from 0.01M to 0.1M. This decrease may simply be due to the net increase in solvent ionic strength. Increasing the acetate concentration beyond 0.1M resulted in an increase in the lysozyme solubility, which reached a peak at - 0.3M acetate concentration. This increase was believed to be due to the increased binding of acetate to the anionic binding sites of lysozyme, preventing their occupation by chloride. In keeping with the previously observed reversal of the Hoffmeister series for effectiveness of anions in crystallizing lysozyme, acetate would be a less effective precipitant than chloride. Further increasing the acetate concentration beyond 0.3M resulted in a subsequent gradual decrease in the lysozyme solubility at all NaCl concentrations.